TY  - JOUR
AU  - Milenković, Mila
AU  - Ciasca, Gabriele
AU  - Bonasera, Aurelio
AU  - Scopelliti, Michelangelo
AU  - Marković, Olivera
AU  - Verbić, Tatjana
AU  - Todorović Marković, Biljana
AU  - Jovanović, Svetlana
PY  - 2024
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6414
AB  - The widespread abuse of traditional antibiotics has led to a global rise in antibiotic-resistant bacteria, which give in return unprecedented health risks. Therefore, there is a large and urgent need for the development of new, smart antibacterial agents able to efficiently kill or inhibit bacterial growth. In this study, we investigated the antibacterial activity of S, N-doped Graphene Quantum Dots (GQDs) as a light-triggered antibacterial agent. Gamma irradiation was employed as a tool to achieve one-step modification of GQDs in the presence of L-cysteine amino acid as a source of heteroatoms. X-ray Photoelectron Spectroscopy (XPS), nuclear magnetic resonance (NMR), and zeta potential measurements provided the necessary data to clarify the structure of modified dots and verify the introduction of both S- and N-atoms in GQDs structure, but also severe changes in the aromatic, sp2 domains. Namely, γ-irradiation caused a bonding of S atoms in 1.14 at.% mainly as thiol groups, and N in 1.81 at.% as amino groups, but sp2 contribution in GQD structure was lowered from 63.00 to 4.86 at.%, as measured in dots irradiated at a dose of 200 kGy. Fluorescence quenching measurements showed that L-cysteine-modified dots are able to bind to human serum albumin. The antibacterial activity of GQDs combined with 1 and 6 h of blue light (470 nm) irradiation was tested against 8 bacterial strains. GQD-cys-25 sample provided the best results, with minimum inhibitory concentration (MIC) as low as 125 μg/mL against S. aureus, E. faecalis, and E. coli after only 1 h of blue light exposure.
PB  - Elsevier
T2  - Journal of Photochemistry and Photobiology B: Biology
T1  - Blue-light-driven photoactivity of L-cysteine-modified graphene quantum dots and their antibacterial effects
VL  - 250
SP  - 112818
DO  - 10.1016/j.jphotobiol.2023.112818
ER  - 

@article{
author = "Milenković, Mila and Ciasca, Gabriele and Bonasera, Aurelio and Scopelliti, Michelangelo and Marković, Olivera and Verbić, Tatjana and Todorović Marković, Biljana and Jovanović, Svetlana",
year = "2024",
abstract = "The widespread abuse of traditional antibiotics has led to a global rise in antibiotic-resistant bacteria, which give in return unprecedented health risks. Therefore, there is a large and urgent need for the development of new, smart antibacterial agents able to efficiently kill or inhibit bacterial growth. In this study, we investigated the antibacterial activity of S, N-doped Graphene Quantum Dots (GQDs) as a light-triggered antibacterial agent. Gamma irradiation was employed as a tool to achieve one-step modification of GQDs in the presence of L-cysteine amino acid as a source of heteroatoms. X-ray Photoelectron Spectroscopy (XPS), nuclear magnetic resonance (NMR), and zeta potential measurements provided the necessary data to clarify the structure of modified dots and verify the introduction of both S- and N-atoms in GQDs structure, but also severe changes in the aromatic, sp2 domains. Namely, γ-irradiation caused a bonding of S atoms in 1.14 at.% mainly as thiol groups, and N in 1.81 at.% as amino groups, but sp2 contribution in GQD structure was lowered from 63.00 to 4.86 at.%, as measured in dots irradiated at a dose of 200 kGy. Fluorescence quenching measurements showed that L-cysteine-modified dots are able to bind to human serum albumin. The antibacterial activity of GQDs combined with 1 and 6 h of blue light (470 nm) irradiation was tested against 8 bacterial strains. GQD-cys-25 sample provided the best results, with minimum inhibitory concentration (MIC) as low as 125 μg/mL against S. aureus, E. faecalis, and E. coli after only 1 h of blue light exposure.",
publisher = "Elsevier",
journal = "Journal of Photochemistry and Photobiology B: Biology",
title = "Blue-light-driven photoactivity of L-cysteine-modified graphene quantum dots and their antibacterial effects",
volume = "250",
pages = "112818",
doi = "10.1016/j.jphotobiol.2023.112818"
}

Milenković, M., Ciasca, G., Bonasera, A., Scopelliti, M., Marković, O., Verbić, T., Todorović Marković, B.,& Jovanović, S.. (2024). Blue-light-driven photoactivity of L-cysteine-modified graphene quantum dots and their antibacterial effects. in Journal of Photochemistry and Photobiology B: Biology
Elsevier., 250, 112818.
https://doi.org/10.1016/j.jphotobiol.2023.112818

Milenković M, Ciasca G, Bonasera A, Scopelliti M, Marković O, Verbić T, Todorović Marković B, Jovanović S. Blue-light-driven photoactivity of L-cysteine-modified graphene quantum dots and their antibacterial effects. in Journal of Photochemistry and Photobiology B: Biology. 2024;250:112818.
doi:10.1016/j.jphotobiol.2023.112818 .

Milenković, Mila, Ciasca, Gabriele, Bonasera, Aurelio, Scopelliti, Michelangelo, Marković, Olivera, Verbić, Tatjana, Todorović Marković, Biljana, Jovanović, Svetlana, "Blue-light-driven photoactivity of L-cysteine-modified graphene quantum dots and their antibacterial effects" in Journal of Photochemistry and Photobiology B: Biology, 250 (2024):112818,
https://doi.org/10.1016/j.jphotobiol.2023.112818 . .

TY  - JOUR
AU  - Milenković, Mila
AU  - Ciasca, Gabriele
AU  - Bonasera, Aurelio
AU  - Scopelliti, Michelangelo
AU  - Marković, Olivera
AU  - Verbić, Tatjana
AU  - Todorović Marković, Biljana
AU  - Jovanović, Svetlana
PY  - 2024
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6303
AB  - The widespread abuse of traditional antibiotics has led to a global rise in antibiotic-resistant bacteria, which give 
in return unprecedented health risks. Therefore, there is a large and urgent need for the development of new, 
smart antibacterial agents able to efficiently kill or inhibit bacterial growth. In this study, we investigated the 
antibacterial activity of S, N-doped Graphene Quantum Dots (GQDs) as a light-triggered antibacterial agent. 
Gamma irradiation was employed as a tool to achieve one-step modification of GQDs in the presence of L cysteine amino acid as a source of heteroatoms. X-ray Photoelectron Spectroscopy (XPS), nuclear magnetic 
resonance (NMR), and zeta potential measurements provided the necessary data to clarify the structure of 
modified dots and verify the introduction of both S- and N-atoms in GQDs structure, but also severe changes in 
the aromatic, sp2 domains. Namely, γ-irradiation caused a bonding of S atoms in 1.14 at.% mainly as thiol 
groups, and N in 1.81 at.% as amino groups, but sp2 contribution in GQD structure was lowered from 63.00 to 
4.86 at.%, as measured in dots irradiated at a dose of 200 kGy. Fluorescence quenching measurements showed 
that L-cysteine-modified dots are able to bind to human serum albumin. The antibacterial activity of GQDs 
combined with 1 and 6 h of blue light (470 nm) irradiation was tested against 8 bacterial strains. GQD-cys-25 
sample provided the best results, with minimum inhibitory concentration (MIC) as low as 125 μg/mL against 
S. aureus, E. faecalis, and E. coli after only 1 h of blue light exposure.
PB  - Elsevier
T2  - Journal of Photochemistry & Photobiology, B: Biology
T1  - Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects
VL  - 250
SP  - 112818
DO  - 10.1016/j.jphotobiol.2023.112818
ER  - 

@article{
author = "Milenković, Mila and Ciasca, Gabriele and Bonasera, Aurelio and Scopelliti, Michelangelo and Marković, Olivera and Verbić, Tatjana and Todorović Marković, Biljana and Jovanović, Svetlana",
year = "2024",
abstract = "The widespread abuse of traditional antibiotics has led to a global rise in antibiotic-resistant bacteria, which give 
in return unprecedented health risks. Therefore, there is a large and urgent need for the development of new, 
smart antibacterial agents able to efficiently kill or inhibit bacterial growth. In this study, we investigated the 
antibacterial activity of S, N-doped Graphene Quantum Dots (GQDs) as a light-triggered antibacterial agent. 
Gamma irradiation was employed as a tool to achieve one-step modification of GQDs in the presence of L cysteine amino acid as a source of heteroatoms. X-ray Photoelectron Spectroscopy (XPS), nuclear magnetic 
resonance (NMR), and zeta potential measurements provided the necessary data to clarify the structure of 
modified dots and verify the introduction of both S- and N-atoms in GQDs structure, but also severe changes in 
the aromatic, sp2 domains. Namely, γ-irradiation caused a bonding of S atoms in 1.14 at.% mainly as thiol 
groups, and N in 1.81 at.% as amino groups, but sp2 contribution in GQD structure was lowered from 63.00 to 
4.86 at.%, as measured in dots irradiated at a dose of 200 kGy. Fluorescence quenching measurements showed 
that L-cysteine-modified dots are able to bind to human serum albumin. The antibacterial activity of GQDs 
combined with 1 and 6 h of blue light (470 nm) irradiation was tested against 8 bacterial strains. GQD-cys-25 
sample provided the best results, with minimum inhibitory concentration (MIC) as low as 125 μg/mL against 
S. aureus, E. faecalis, and E. coli after only 1 h of blue light exposure.",
publisher = "Elsevier",
journal = "Journal of Photochemistry & Photobiology, B: Biology",
title = "Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects",
volume = "250",
pages = "112818",
doi = "10.1016/j.jphotobiol.2023.112818"
}

Milenković, M., Ciasca, G., Bonasera, A., Scopelliti, M., Marković, O., Verbić, T., Todorović Marković, B.,& Jovanović, S.. (2024). Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects. in Journal of Photochemistry & Photobiology, B: Biology
Elsevier., 250, 112818.
https://doi.org/10.1016/j.jphotobiol.2023.112818

Milenković M, Ciasca G, Bonasera A, Scopelliti M, Marković O, Verbić T, Todorović Marković B, Jovanović S. Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects. in Journal of Photochemistry & Photobiology, B: Biology. 2024;250:112818.
doi:10.1016/j.jphotobiol.2023.112818 .

Milenković, Mila, Ciasca, Gabriele, Bonasera, Aurelio, Scopelliti, Michelangelo, Marković, Olivera, Verbić, Tatjana, Todorović Marković, Biljana, Jovanović, Svetlana, "Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects" in Journal of Photochemistry & Photobiology, B: Biology, 250 (2024):112818,
https://doi.org/10.1016/j.jphotobiol.2023.112818 . .

TY  - CONF
AU  - Verbić, Tatjana
AU  - Avdeef, Alex
AU  - Tam, Kin Y.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Topalović, Igor A.
AU  - Veljković, Dušan Ž.
AU  - Kathawala, Mufaddal
AU  - Serajuddin, Abu T. M.
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5993
AB  - Since the introduction of combinatorial chemistry and high-throughput screening in drug 
discovery in the early 1990s, the solubility of new chemical entities (NCE) decreased drastically 
while their lipophilicities increased greatly. Characterizing physicochemical properties of low soluble molecules can be especially challenging, since such molecules can undergo 
complicated reactions in aqueous solution, such as forming precipitates or complexes with 
buffer species or undergoing self-aggregation (dimer, trimer, etc.)1,2 or micelle formations. 
Most drugs are ionizable. Foremost to the rational interpretation of solution behavior of 
ionizable drugs in a physiologically-relevant pH domain requires an accurate aqueous pKa, 
determined by a suitable method. In a pH-dependent measurement of a property (e.g. 
solubility-, lipophilicity-, permeability-pH), when the apparent pKa value is different from the 
true aqueous pKa value, it may be an early clue that nonideal solution behavior may be taking 
place. In pharmaceutical research, it may seem cost-effective to use calculated pKa instead of 
measured values, but paradoxically, such preference can lead to inaccurate rationalization of 
the pH-dependent behavior of the drug molecule. For simple molecules, calculated values can 
be useful, but for today’s new drugs or for molecules prone to complicated solution behavior, 
the use of calculated pKas can substantially wrench the interpretation of solution properties. 
Clofazimine (CFZ), although discovered about 66 years ago, and used therapeutically for nearly 
40 years, exhibits some of the properties of relatively recent drug molecules by being 
extremely water insoluble and having variable pKa values reported. We have recently 
combined potentiometric titrations and UV/Vis spectrophotometry in methanol-water 
cosolvent media, accompanied by DFT calculations, to assess the hypothesis of CFZ free base 
dimerization. We reasoned that a soluble dimer might form from drug-drug adhesion along 
the hydrophobic molecular surface. With lessened exposure of the hydrophobic surface to 
water, the dimer would be more water soluble than the monomeric free base. In saturated 
solutions, the apparent solubility in alkaline pH would be elevated due to the presence of the 
dimer. The effect of that would be a lower pKa and reverse pKa cosolvent dependence – the 
behaviour we have noticed in CFZ aqueous solutions. These findings are of paramount 
importance for understanding of CFZ speciation and the future progress in developing its 
improved formulations which is the subject of our ongoing studies.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023
T1  - Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH
SP  - 15
EP  - 15
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5993
ER  - 

@conference{
author = "Verbić, Tatjana and Avdeef, Alex and Tam, Kin Y. and Marković, Olivera S. and Pešić, Miloš P. and Topalović, Igor A. and Veljković, Dušan Ž. and Kathawala, Mufaddal and Serajuddin, Abu T. M.",
year = "2023",
abstract = "Since the introduction of combinatorial chemistry and high-throughput screening in drug 
discovery in the early 1990s, the solubility of new chemical entities (NCE) decreased drastically 
while their lipophilicities increased greatly. Characterizing physicochemical properties of low soluble molecules can be especially challenging, since such molecules can undergo 
complicated reactions in aqueous solution, such as forming precipitates or complexes with 
buffer species or undergoing self-aggregation (dimer, trimer, etc.)1,2 or micelle formations. 
Most drugs are ionizable. Foremost to the rational interpretation of solution behavior of 
ionizable drugs in a physiologically-relevant pH domain requires an accurate aqueous pKa, 
determined by a suitable method. In a pH-dependent measurement of a property (e.g. 
solubility-, lipophilicity-, permeability-pH), when the apparent pKa value is different from the 
true aqueous pKa value, it may be an early clue that nonideal solution behavior may be taking 
place. In pharmaceutical research, it may seem cost-effective to use calculated pKa instead of 
measured values, but paradoxically, such preference can lead to inaccurate rationalization of 
the pH-dependent behavior of the drug molecule. For simple molecules, calculated values can 
be useful, but for today’s new drugs or for molecules prone to complicated solution behavior, 
the use of calculated pKas can substantially wrench the interpretation of solution properties. 
Clofazimine (CFZ), although discovered about 66 years ago, and used therapeutically for nearly 
40 years, exhibits some of the properties of relatively recent drug molecules by being 
extremely water insoluble and having variable pKa values reported. We have recently 
combined potentiometric titrations and UV/Vis spectrophotometry in methanol-water 
cosolvent media, accompanied by DFT calculations, to assess the hypothesis of CFZ free base 
dimerization. We reasoned that a soluble dimer might form from drug-drug adhesion along 
the hydrophobic molecular surface. With lessened exposure of the hydrophobic surface to 
water, the dimer would be more water soluble than the monomeric free base. In saturated 
solutions, the apparent solubility in alkaline pH would be elevated due to the presence of the 
dimer. The effect of that would be a lower pKa and reverse pKa cosolvent dependence – the 
behaviour we have noticed in CFZ aqueous solutions. These findings are of paramount 
importance for understanding of CFZ speciation and the future progress in developing its 
improved formulations which is the subject of our ongoing studies.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023",
title = "Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH",
pages = "15-15",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5993"
}

Verbić, T., Avdeef, A., Tam, K. Y., Marković, O. S., Pešić, M. P., Topalović, I. A., Veljković, D. Ž., Kathawala, M.,& Serajuddin, A. T. M.. (2023). Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH. in 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023
International Association of Physical Chemists., 15-15.
https://hdl.handle.net/21.15107/rcub_cherry_5993

Verbić T, Avdeef A, Tam KY, Marković OS, Pešić MP, Topalović IA, Veljković DŽ, Kathawala M, Serajuddin ATM. Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH. in 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023. 2023;:15-15.
https://hdl.handle.net/21.15107/rcub_cherry_5993 .

Verbić, Tatjana, Avdeef, Alex, Tam, Kin Y., Marković, Olivera S., Pešić, Miloš P., Topalović, Igor A., Veljković, Dušan Ž., Kathawala, Mufaddal, Serajuddin, Abu T. M., "Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH" in 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023 (2023):15-15,
https://hdl.handle.net/21.15107/rcub_cherry_5993 .

TY  - CONF
AU  - Topalović, Igor A.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Kathawala, Mufaddal
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5994
AB  - Methods for drug solubilization have become important part of modern drug discovery and 
development due to increasing number of extremely insoluble drugs and drug candidates. 
One of such methods is acid-base supersolubilization (ABS) [1]. Clofazimine (CFZ) is weakly 
basic antibiotic and anti-inflammatory drug, most notably used in the treatment of leprosy
and tuberculosis, with recently proven inhibitory activity against several coronaviruses [2].
We have recently unraveled its aqueous pKa value and its unique cosolvent dependence [3]. 
The aim of the present study was to investigate CFZ solubilization using the ABS approach. 
Eight small organic acids were tested for the ABS effect (glutaric, malic, tartaric, citric, 
malonic, maleic, succinic, adipic) but only glutaric (GA), malic (MA), and tartaric (TA) acids 
showed some solubilization effect. The effect of their concentration (and the solution pH 
value) was further tested. The solubility of CFZ was determined in GA, MA, and TA solutions 
in wide concentration (1.0×10-2 – 5.0 M) and pH range (~0.2 – 4.8). Equilibration time was 
24 hours (6 h of stirring + 18 h of sedimentation). Phases were separated by filtration. The 
CFZ concentration in supernatant was determined by HPLC-UV/VIS. Results show that CFZ 
solubility increases as acid concentration increases: from 3.04×10-3 to 10.68 mg/mL (in GA), 
from 9.06×10-3 to 1.23 mg/mL (in MA) and from 4.76×10-3 to 0.32 mg/mL (in TA). The effect 
of CFZ solubilization is much more pronounced when the acid concentration is raised above 
2 M. These results can be used as the basis for further CFZ formulation optimization.
Furthermore, our ongoing research is focused on the type of interactions and other possible 
factors that can influence CFZ and other prectically insoluble drugs, embracing (super)solu bilization as a general methodology in drug design and development.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023
T1  - Clofazimine acid-base solubilization: influence  of small organic acids’ concentration
SP  - 66
EP  - 66
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5994
ER  - 

@conference{
author = "Topalović, Igor A. and Marković, Olivera S. and Pešić, Miloš P. and Kathawala, Mufaddal and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2023",
abstract = "Methods for drug solubilization have become important part of modern drug discovery and 
development due to increasing number of extremely insoluble drugs and drug candidates. 
One of such methods is acid-base supersolubilization (ABS) [1]. Clofazimine (CFZ) is weakly 
basic antibiotic and anti-inflammatory drug, most notably used in the treatment of leprosy
and tuberculosis, with recently proven inhibitory activity against several coronaviruses [2].
We have recently unraveled its aqueous pKa value and its unique cosolvent dependence [3]. 
The aim of the present study was to investigate CFZ solubilization using the ABS approach. 
Eight small organic acids were tested for the ABS effect (glutaric, malic, tartaric, citric, 
malonic, maleic, succinic, adipic) but only glutaric (GA), malic (MA), and tartaric (TA) acids 
showed some solubilization effect. The effect of their concentration (and the solution pH 
value) was further tested. The solubility of CFZ was determined in GA, MA, and TA solutions 
in wide concentration (1.0×10-2 – 5.0 M) and pH range (~0.2 – 4.8). Equilibration time was 
24 hours (6 h of stirring + 18 h of sedimentation). Phases were separated by filtration. The 
CFZ concentration in supernatant was determined by HPLC-UV/VIS. Results show that CFZ 
solubility increases as acid concentration increases: from 3.04×10-3 to 10.68 mg/mL (in GA), 
from 9.06×10-3 to 1.23 mg/mL (in MA) and from 4.76×10-3 to 0.32 mg/mL (in TA). The effect 
of CFZ solubilization is much more pronounced when the acid concentration is raised above 
2 M. These results can be used as the basis for further CFZ formulation optimization.
Furthermore, our ongoing research is focused on the type of interactions and other possible 
factors that can influence CFZ and other prectically insoluble drugs, embracing (super)solu bilization as a general methodology in drug design and development.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023",
title = "Clofazimine acid-base solubilization: influence  of small organic acids’ concentration",
pages = "66-66",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5994"
}

Topalović, I. A., Marković, O. S., Pešić, M. P., Kathawala, M., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2023). Clofazimine acid-base solubilization: influence  of small organic acids’ concentration. in 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023
International Association of Physical Chemists., 66-66.
https://hdl.handle.net/21.15107/rcub_cherry_5994

Topalović IA, Marković OS, Pešić MP, Kathawala M, Serajuddin ATM, Avdeef A, Verbić T. Clofazimine acid-base solubilization: influence  of small organic acids’ concentration. in 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023. 2023;:66-66.
https://hdl.handle.net/21.15107/rcub_cherry_5994 .

Topalović, Igor A., Marković, Olivera S., Pešić, Miloš P., Kathawala, Mufaddal, Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Clofazimine acid-base solubilization: influence  of small organic acids’ concentration" in 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023 (2023):66-66,
https://hdl.handle.net/21.15107/rcub_cherry_5994 .

TY  - JOUR
AU  - Pešić, Miloš P.
AU  - Krstić, Jugoslav
AU  - Verbić, Tatjana
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5817
AB  - Molecularly imprinting technology was applied for preparing selec­tive sorbents for benzophenone-4 (BP4), an organic UV filter used in sun­screens and cosmetics. Several imprinted polymers were prepared by bulk polymerization, using BP4 as template. Combination of stability (mechanical and chemical), selectivity and robustness of the imprinted polymers with BP4 properties resulted in a successful imprinting process (imprinting factors in range 1.05–2.60). The prepared polymers were characterised by infrared spec­tro­scopy, elemental analysis, conductometric titrations and nitrogen physi­sorp­tion at 77 K. Adsorption capacities and selectivity towards 7 other organic UV filters (benzophenone-3, benzophenone-8, homosalate, butyl methoxydi­ben­zo­ylmethane, ethyl hexyl salicylate, ethyl hexyl p-dimethylamino benzoate and ethyl hexyl p-methoxycinnamate) were determined, proving high adsorption capacity and high selectivity for BP4 binding. The highest adsorption capacity was observed for 4-vinylpyridine/ethylene glycol dimethacrylate co-polymer prepared in dimethyl sulfoxide (1.108 mmol g-1). The imprinted polymer with the highest binding capacity was applied to solid phase extraction of BP4 from aqueous solutions with 98.5 % efficiency.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper
VL  - 88
IS  - 1
SP  - 55
EP  - 68
DO  - 10.2298/JSC22032540P
ER  - 

@article{
author = "Pešić, Miloš P. and Krstić, Jugoslav and Verbić, Tatjana",
year = "2023",
abstract = "Molecularly imprinting technology was applied for preparing selec­tive sorbents for benzophenone-4 (BP4), an organic UV filter used in sun­screens and cosmetics. Several imprinted polymers were prepared by bulk polymerization, using BP4 as template. Combination of stability (mechanical and chemical), selectivity and robustness of the imprinted polymers with BP4 properties resulted in a successful imprinting process (imprinting factors in range 1.05–2.60). The prepared polymers were characterised by infrared spec­tro­scopy, elemental analysis, conductometric titrations and nitrogen physi­sorp­tion at 77 K. Adsorption capacities and selectivity towards 7 other organic UV filters (benzophenone-3, benzophenone-8, homosalate, butyl methoxydi­ben­zo­ylmethane, ethyl hexyl salicylate, ethyl hexyl p-dimethylamino benzoate and ethyl hexyl p-methoxycinnamate) were determined, proving high adsorption capacity and high selectivity for BP4 binding. The highest adsorption capacity was observed for 4-vinylpyridine/ethylene glycol dimethacrylate co-polymer prepared in dimethyl sulfoxide (1.108 mmol g-1). The imprinted polymer with the highest binding capacity was applied to solid phase extraction of BP4 from aqueous solutions with 98.5 % efficiency.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper",
volume = "88",
number = "1",
pages = "55-68",
doi = "10.2298/JSC22032540P"
}

Pešić, M. P., Krstić, J.,& Verbić, T.. (2023). Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 88(1), 55-68.
https://doi.org/10.2298/JSC22032540P

Pešić MP, Krstić J, Verbić T. Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper. in Journal of the Serbian Chemical Society. 2023;88(1):55-68.
doi:10.2298/JSC22032540P .

Pešić, Miloš P., Krstić, Jugoslav, Verbić, Tatjana, "Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper" in Journal of the Serbian Chemical Society, 88, no. 1 (2023):55-68,
https://doi.org/10.2298/JSC22032540P . .

TY  - DATA
AU  - Pešić, Miloš P.
AU  - Krstić, Jugoslav
AU  - Verbić, Tatjana
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5841
AB  - Molecularly imprinting technology was applied for preparing selec­tive sorbents for benzophenone-4 (BP4), an organic UV filter used in sun­screens and cosmetics. Several imprinted polymers were prepared by bulk polymerization, using BP4 as template. Combination of stability (mechanical and chemical), selectivity and robustness of the imprinted polymers with BP4 properties resulted in a successful imprinting process (imprinting factors in range 1.05–2.60). The prepared polymers were characterised by infrared spec­tro­scopy, elemental analysis, conductometric titrations and nitrogen physi­sorp­tion at 77 K. Adsorption capacities and selectivity towards 7 other organic UV filters (benzophenone-3, benzophenone-8, homosalate, butyl methoxydi­ben­zo­ylmethane, ethyl hexyl salicylate, ethyl hexyl p-dimethylamino benzoate and ethyl hexyl p-methoxycinnamate) were determined, proving high adsorption capacity and high selectivity for BP4 binding. The highest adsorption capacity was observed for 4-vinylpyridine/ethylene glycol dimethacrylate co-polymer prepared in dimethyl sulfoxide (1.108 mmol g-1). The imprinted polymer with the highest binding capacity was applied to solid phase extraction of BP4 from aqueous solutions with 98.5 % efficiency.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Supplementary material for: Pešić, M. P., Krstić, J.,& Verbić, T.. (2023). Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper. in Journal of the Serbian Chemical Society Belgrade : Serbian Chemical Society., 88(1), 55-68. https://doi.org/10.2298/JSC22032540P
VL  - 88
IS  - 1
SP  - 55
EP  - 68
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5841
ER  - 

@misc{
author = "Pešić, Miloš P. and Krstić, Jugoslav and Verbić, Tatjana",
year = "2023",
abstract = "Molecularly imprinting technology was applied for preparing selec­tive sorbents for benzophenone-4 (BP4), an organic UV filter used in sun­screens and cosmetics. Several imprinted polymers were prepared by bulk polymerization, using BP4 as template. Combination of stability (mechanical and chemical), selectivity and robustness of the imprinted polymers with BP4 properties resulted in a successful imprinting process (imprinting factors in range 1.05–2.60). The prepared polymers were characterised by infrared spec­tro­scopy, elemental analysis, conductometric titrations and nitrogen physi­sorp­tion at 77 K. Adsorption capacities and selectivity towards 7 other organic UV filters (benzophenone-3, benzophenone-8, homosalate, butyl methoxydi­ben­zo­ylmethane, ethyl hexyl salicylate, ethyl hexyl p-dimethylamino benzoate and ethyl hexyl p-methoxycinnamate) were determined, proving high adsorption capacity and high selectivity for BP4 binding. The highest adsorption capacity was observed for 4-vinylpyridine/ethylene glycol dimethacrylate co-polymer prepared in dimethyl sulfoxide (1.108 mmol g-1). The imprinted polymer with the highest binding capacity was applied to solid phase extraction of BP4 from aqueous solutions with 98.5 % efficiency.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Supplementary material for: Pešić, M. P., Krstić, J.,& Verbić, T.. (2023). Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper. in Journal of the Serbian Chemical Society Belgrade : Serbian Chemical Society., 88(1), 55-68. https://doi.org/10.2298/JSC22032540P",
volume = "88",
number = "1",
pages = "55-68",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5841"
}

Pešić, M. P., Krstić, J.,& Verbić, T.. (2023). Supplementary material for: Pešić, M. P., Krstić, J.,& Verbić, T.. (2023). Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper. in Journal of the Serbian Chemical Society Belgrade : Serbian Chemical Society., 88(1), 55-68. https://doi.org/10.2298/JSC22032540P. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 88(1), 55-68.
https://hdl.handle.net/21.15107/rcub_cherry_5841

Pešić MP, Krstić J, Verbić T. Supplementary material for: Pešić, M. P., Krstić, J.,& Verbić, T.. (2023). Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper. in Journal of the Serbian Chemical Society Belgrade : Serbian Chemical Society., 88(1), 55-68. https://doi.org/10.2298/JSC22032540P. in Journal of the Serbian Chemical Society. 2023;88(1):55-68.
https://hdl.handle.net/21.15107/rcub_cherry_5841 .

Pešić, Miloš P., Krstić, Jugoslav, Verbić, Tatjana, "Supplementary material for: Pešić, M. P., Krstić, J.,& Verbić, T.. (2023). Highly selective water-compatible molecularly imprinted polymers for benzophenone-4: Scientific paper. in Journal of the Serbian Chemical Society Belgrade : Serbian Chemical Society., 88(1), 55-68. https://doi.org/10.2298/JSC22032540P" in Journal of the Serbian Chemical Society, 88, no. 1 (2023):55-68,
https://hdl.handle.net/21.15107/rcub_cherry_5841 .

TY  - JOUR
AU  - Marković, Olivera S.
AU  - Patel, Nirali G.
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5039
AB  - The solubility of a model basic drug, nortriptyline
(Nor), was investigated as a function of pH in phosphate and/or a
chloride-containing aqueous suspension using experimental
practices recommended in the previously published “white
paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,
2019), was applied. An improved and more detailed experimental
design of the Nor solubility measurement allowed us to exploit the
full capacity of the pH-RSF method. Complex equilibria in the
aqueous phase (cationic and anionic complex formation between
Nor and the phosphate) and solid-phase transformations (Nor free
base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)
were characterized by a detailed analysis of the solubility
measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,
differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate
the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,
on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the
formulation of drug products.
PB  - American Chemical Society
T2  - Molecular pharmaceutics
T1  - Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints
VL  - 19
IS  - 2
SP  - 710
EP  - 719
DO  - 10.1021/acs.molpharmaceut.1c00919
ER  - 

@article{
author = "Marković, Olivera S. and Patel, Nirali G. and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2022",
abstract = "The solubility of a model basic drug, nortriptyline
(Nor), was investigated as a function of pH in phosphate and/or a
chloride-containing aqueous suspension using experimental
practices recommended in the previously published “white
paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,
2019), was applied. An improved and more detailed experimental
design of the Nor solubility measurement allowed us to exploit the
full capacity of the pH-RSF method. Complex equilibria in the
aqueous phase (cationic and anionic complex formation between
Nor and the phosphate) and solid-phase transformations (Nor free
base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)
were characterized by a detailed analysis of the solubility
measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,
differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate
the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,
on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the
formulation of drug products.",
publisher = "American Chemical Society",
journal = "Molecular pharmaceutics",
title = "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints",
volume = "19",
number = "2",
pages = "710-719",
doi = "10.1021/acs.molpharmaceut.1c00919"
}

Marković, O. S., Patel, N. G., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2022). Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular pharmaceutics
American Chemical Society., 19(2), 710-719.
https://doi.org/10.1021/acs.molpharmaceut.1c00919

Marković OS, Patel NG, Serajuddin ATM, Avdeef A, Verbić T. Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular pharmaceutics. 2022;19(2):710-719.
doi:10.1021/acs.molpharmaceut.1c00919 .

Marković, Olivera S., Patel, Nirali G., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints" in Molecular pharmaceutics, 19, no. 2 (2022):710-719,
https://doi.org/10.1021/acs.molpharmaceut.1c00919 . .

TY  - CONF
AU  - Marković, Olivera S.
AU  - Gajić, Brankica P.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5936
AB  - Experimental studies of solubility are important in all phases of drug design and 
development. Solubility data are used to screen out drug-like candidates, 
biopharmaceutical classification and formulation optimization. The development of oral 
and parenteral dosage forms can be challenging, especially when drugs are poorly 
soluble, ionizable, exhibiting pH-dependent solubility and when multiple counterions 
are present in drug suspension. The influence of different counterions on the existing 
equilibria and on pH-dependent drug solubility must be defined in such systems. To 
investigate the effect of multiple ions on the solubility of a model basic drug – tricyclic 
antidepressant imipramine (Im), we conducted a systematic study of the Im solubility as 
a function of pH in the presence of both chloride and phosphate ions as well as in 
chloride-free and phosphate-free suspensions. The pH–Ramp shake–flask method1,2 was 
used for solubility determination. The computer program pDISOL–X was used for data 
analysis. It is shown that distinct pH-dependent solubility profiles were obtained in 
studied systems. Depending on the pH and the total concentration of chloride and/or 
phosphate ions, Im can precipitate as chloride and phosphate salt or free base. 
Furthermore, pH values of solid phase transitions (pHmax) varied as well. For instance, 
pHmax of solid phase transition of (ImH)H2PO4(s) to (ImH)2HPO4(s) change from 5.15 
(chloride and phosphate-containing suspensions) to 5.73 (chloride-free suspensions). 
The intensive self-aggregation of Im in acidic region was suppressed by raising chloride 
or phosphate ions concentration (Iavg 1.42–1.64 M). In that way, solubility of Im was 
decreased due to the common-ion effect. This study illustrates the influence of 
competing counterions on Im solubility and on interconversions in solid phase. Hence, 
such factors must be taken into account during formulation optimization in drug 
research.
PB  - Belgrade : Serbian Chemical Society
PB  - Belgrade : Serbian Young Chemists’ Club
C3  - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
T1  - The influence of  competing counterions on the solubility of imipramine
SP  - 27
EP  - 27
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5936
ER  - 

@conference{
author = "Marković, Olivera S. and Gajić, Brankica P. and Pešić, Miloš P. and Verbić, Tatjana",
year = "2022",
abstract = "Experimental studies of solubility are important in all phases of drug design and 
development. Solubility data are used to screen out drug-like candidates, 
biopharmaceutical classification and formulation optimization. The development of oral 
and parenteral dosage forms can be challenging, especially when drugs are poorly 
soluble, ionizable, exhibiting pH-dependent solubility and when multiple counterions 
are present in drug suspension. The influence of different counterions on the existing 
equilibria and on pH-dependent drug solubility must be defined in such systems. To 
investigate the effect of multiple ions on the solubility of a model basic drug – tricyclic 
antidepressant imipramine (Im), we conducted a systematic study of the Im solubility as 
a function of pH in the presence of both chloride and phosphate ions as well as in 
chloride-free and phosphate-free suspensions. The pH–Ramp shake–flask method1,2 was 
used for solubility determination. The computer program pDISOL–X was used for data 
analysis. It is shown that distinct pH-dependent solubility profiles were obtained in 
studied systems. Depending on the pH and the total concentration of chloride and/or 
phosphate ions, Im can precipitate as chloride and phosphate salt or free base. 
Furthermore, pH values of solid phase transitions (pHmax) varied as well. For instance, 
pHmax of solid phase transition of (ImH)H2PO4(s) to (ImH)2HPO4(s) change from 5.15 
(chloride and phosphate-containing suspensions) to 5.73 (chloride-free suspensions). 
The intensive self-aggregation of Im in acidic region was suppressed by raising chloride 
or phosphate ions concentration (Iavg 1.42–1.64 M). In that way, solubility of Im was 
decreased due to the common-ion effect. This study illustrates the influence of 
competing counterions on Im solubility and on interconversions in solid phase. Hence, 
such factors must be taken into account during formulation optimization in drug 
research.",
publisher = "Belgrade : Serbian Chemical Society, Belgrade : Serbian Young Chemists’ Club",
journal = "8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts",
title = "The influence of  competing counterions on the solubility of imipramine",
pages = "27-27",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5936"
}

Marković, O. S., Gajić, B. P., Pešić, M. P.,& Verbić, T.. (2022). The influence of  competing counterions on the solubility of imipramine. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
Belgrade : Serbian Chemical Society., 27-27.
https://hdl.handle.net/21.15107/rcub_cherry_5936

Marković OS, Gajić BP, Pešić MP, Verbić T. The influence of  competing counterions on the solubility of imipramine. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts. 2022;:27-27.
https://hdl.handle.net/21.15107/rcub_cherry_5936 .

Marković, Olivera S., Gajić, Brankica P., Pešić, Miloš P., Verbić, Tatjana, "The influence of  competing counterions on the solubility of imipramine" in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts (2022):27-27,
https://hdl.handle.net/21.15107/rcub_cherry_5936 .

TY  - CONF
AU  - Topalović, Igor A.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5937
AB  - Nowadays, more than two-thirds of potential drugs currently being discovered are 
practically insoluble in water with solubility <100 μg/mL. Despite that, compounds with 
even lower solubility (<0.1 μg/mL) are commonly selected for further development 
which is very challenging, especially in the pharmaceutical formulation process1
. 
Clofazimine (CFZ), an anti-leprosy drug with inhibitory activity against several 
coronaviruses, has a favourable safety profile2
, but it is poorly soluble in aqueous media. 
Hence, it is important to develop a method for increasing its solubility. In this work, a 
relatively novel approach of enhancing solubility of weakly basic drugs by using weak 
acids that would not form salts with the drug (acid-base supersolubilization (ABS)) has
been applied. CFZ aqueous solubility was determined in solutions of tartaric, citric, 
malic, malonic or maleic acid: in set I acid solutions had the same concentration (2.5 
mol/L), and in the set II they were scaled to the same pH (1.0). The drug was added in 
stirred acid solution until a precipitate was noticed and, after filtration, CFZ 
concentration in samples was determined by HPLC. Based on set I, it was found that the 
solubility of CFZ had the highest value in the case of tartaric acid (0.46 mg/mL) 
compared to other acid solutions of the same concentration. In set II the highest CFZ 
concentration was determined in the malic acid solution which had the highest 
concentration (2.8 mol/L) among other acids. On contrary, maleic acid solution at 
pH=1.0 had the lowest molar concentration (0.5 mol/L) and therefore CFZ was 
minimally dissolved. Further research will be directed toward the examination of acid 
structure effect on CFZ solubility.
PB  - Belgrade : Serbian Chemical Society
PB  - Belgrade : Serbian Young Chemists’ Club
C3  - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
T1  - Investigation of  clofazimine acid-base supersolubilization using various weak organic acids
SP  - 37
EP  - 37
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5937
ER  - 

@conference{
author = "Topalović, Igor A. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana",
year = "2022",
abstract = "Nowadays, more than two-thirds of potential drugs currently being discovered are 
practically insoluble in water with solubility <100 μg/mL. Despite that, compounds with 
even lower solubility (<0.1 μg/mL) are commonly selected for further development 
which is very challenging, especially in the pharmaceutical formulation process1
. 
Clofazimine (CFZ), an anti-leprosy drug with inhibitory activity against several 
coronaviruses, has a favourable safety profile2
, but it is poorly soluble in aqueous media. 
Hence, it is important to develop a method for increasing its solubility. In this work, a 
relatively novel approach of enhancing solubility of weakly basic drugs by using weak 
acids that would not form salts with the drug (acid-base supersolubilization (ABS)) has
been applied. CFZ aqueous solubility was determined in solutions of tartaric, citric, 
malic, malonic or maleic acid: in set I acid solutions had the same concentration (2.5 
mol/L), and in the set II they were scaled to the same pH (1.0). The drug was added in 
stirred acid solution until a precipitate was noticed and, after filtration, CFZ 
concentration in samples was determined by HPLC. Based on set I, it was found that the 
solubility of CFZ had the highest value in the case of tartaric acid (0.46 mg/mL) 
compared to other acid solutions of the same concentration. In set II the highest CFZ 
concentration was determined in the malic acid solution which had the highest 
concentration (2.8 mol/L) among other acids. On contrary, maleic acid solution at 
pH=1.0 had the lowest molar concentration (0.5 mol/L) and therefore CFZ was 
minimally dissolved. Further research will be directed toward the examination of acid 
structure effect on CFZ solubility.",
publisher = "Belgrade : Serbian Chemical Society, Belgrade : Serbian Young Chemists’ Club",
journal = "8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts",
title = "Investigation of  clofazimine acid-base supersolubilization using various weak organic acids",
pages = "37-37",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5937"
}

Topalović, I. A., Marković, O. S., Pešić, M. P.,& Verbić, T.. (2022). Investigation of  clofazimine acid-base supersolubilization using various weak organic acids. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
Belgrade : Serbian Chemical Society., 37-37.
https://hdl.handle.net/21.15107/rcub_cherry_5937

Topalović IA, Marković OS, Pešić MP, Verbić T. Investigation of  clofazimine acid-base supersolubilization using various weak organic acids. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts. 2022;:37-37.
https://hdl.handle.net/21.15107/rcub_cherry_5937 .

Topalović, Igor A., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana, "Investigation of  clofazimine acid-base supersolubilization using various weak organic acids" in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts (2022):37-37,
https://hdl.handle.net/21.15107/rcub_cherry_5937 .

TY  - CONF
AU  - Marjanović, Nemanja Ž.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5938
AB  - In the modern drug research the number of practically insoluble potential drugs is 
increasing. Poor aqueous solubility can cause poor oral absorption and low 
bioavailability of drugs. Hence, solubility enhancement is considered as one of the most 
important challenges in the formulation and development of the dosage forms of drugs. 
Clofazimine (CFZ) is an antibiotic drug which is used in the treatment of tuberculosis 
and leprosy. It is recently shown that CFZ has inhibitory activity against certain 
coronaviruses and can antagonize the replication of SARS-CoV-2.1 Since CFZ is highly 
lipophilic molecule with extremely low solubility, it is quite a challenge to find 
appropriate method for CFZ solubilization. The aim of this work was to investigate the 
effect of methanesulfonic (MSA) and glutaric (GA) acids on the solubility of CFZ. The 
effect of MSA on the solubility of CFZ was studied by the pH-Ramp shake-flask method 
(pH-RSF).2 The solubility of CFZ was determined in the presence of GA in two ways: 
1) by melting a mixture of CFZ and GA in different molar ratios, and then dissolving in 
water; 2) using the pH-RSF method. Interactions between CZ and GA were investigated 
by IR spectroscopy. It is shown that both MSA and GA increase the solubility of CFZ 
in acidic suspensions prepared by pH-RSF method. Also, solubility enhancement was 
observed in the molten CFZ-GA mixtures (molar ratio 1:1 and 1:4) compared to mixtures 
prepared without melting. Besides that, the IR spectra of these mixtures revealed that 
characteristic CFZ band was shifted in molted CFZ-GA mixture (molar ratio 1:1) 
probably due to CFZ-GA interactions. Preliminary results presented in this study 
illustrate that MSA and GA can be used for solubility improvement of CFZ.
PB  - Belgrade : Serbian Chemical Society
PB  - Belgrade : Serbian Young Chemists’ Club
C3  - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
T1  - The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine
SP  - 40
EP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5938
ER  - 

@conference{
author = "Marjanović, Nemanja Ž. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana",
year = "2022",
abstract = "In the modern drug research the number of practically insoluble potential drugs is 
increasing. Poor aqueous solubility can cause poor oral absorption and low 
bioavailability of drugs. Hence, solubility enhancement is considered as one of the most 
important challenges in the formulation and development of the dosage forms of drugs. 
Clofazimine (CFZ) is an antibiotic drug which is used in the treatment of tuberculosis 
and leprosy. It is recently shown that CFZ has inhibitory activity against certain 
coronaviruses and can antagonize the replication of SARS-CoV-2.1 Since CFZ is highly 
lipophilic molecule with extremely low solubility, it is quite a challenge to find 
appropriate method for CFZ solubilization. The aim of this work was to investigate the 
effect of methanesulfonic (MSA) and glutaric (GA) acids on the solubility of CFZ. The 
effect of MSA on the solubility of CFZ was studied by the pH-Ramp shake-flask method 
(pH-RSF).2 The solubility of CFZ was determined in the presence of GA in two ways: 
1) by melting a mixture of CFZ and GA in different molar ratios, and then dissolving in 
water; 2) using the pH-RSF method. Interactions between CZ and GA were investigated 
by IR spectroscopy. It is shown that both MSA and GA increase the solubility of CFZ 
in acidic suspensions prepared by pH-RSF method. Also, solubility enhancement was 
observed in the molten CFZ-GA mixtures (molar ratio 1:1 and 1:4) compared to mixtures 
prepared without melting. Besides that, the IR spectra of these mixtures revealed that 
characteristic CFZ band was shifted in molted CFZ-GA mixture (molar ratio 1:1) 
probably due to CFZ-GA interactions. Preliminary results presented in this study 
illustrate that MSA and GA can be used for solubility improvement of CFZ.",
publisher = "Belgrade : Serbian Chemical Society, Belgrade : Serbian Young Chemists’ Club",
journal = "8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts",
title = "The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine",
pages = "40-40",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5938"
}

Marjanović, N. Ž., Marković, O. S., Pešić, M. P.,& Verbić, T.. (2022). The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
Belgrade : Serbian Chemical Society., 40-40.
https://hdl.handle.net/21.15107/rcub_cherry_5938

Marjanović NŽ, Marković OS, Pešić MP, Verbić T. The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts. 2022;:40-40.
https://hdl.handle.net/21.15107/rcub_cherry_5938 .

Marjanović, Nemanja Ž., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana, "The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine" in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts (2022):40-40,
https://hdl.handle.net/21.15107/rcub_cherry_5938 .

TY  - CONF
AU  - Mrđinac, Jelena Ž.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5939
AB  - The ionization constant (usually expressed in logarithmic form, pKa) is important 
physicochemical parameter which is used to characterize the acid-base chemistry of a 
compound. Since most drugs contain one or more ionizable functional groups, 
knowledge of pKa values is necessary in drug research. The most common techniques 
used for pKa determination are potentiometry and spectrophotometry. Potentiometry is 
a method of choice when ionization processes are overlapping, as in such case it is not 
possible to obtain the absorption spectrum of each species present in solution. The aim 
of this work was the comparative analysis of pKa determination using potentiometry and 
spectrophotometry for model compounds with overlapping ionization processes: 3-
aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. The potentiometric
titrations were performed with pSOL Model 3 instrument (pION) equipped with pS 
software package for titration data analysis.1 Avdeef–Bucher four–parameter equation 
was used for electrode standardization.2 To overcome the above-mentioned limitation of 
spectrophotometry, the alternative approach was applied in this study. The new 
aminocaproate phosphate buffer (containing phosphoric and ε-aminocaproic acids) was 
used for the solutions preparation of the model compounds in pH range 1 – 12. This 
buffer has numerous advantages like UV-transparency, resistance to pH changes upon 
standing for several days, useful buffer capacity and constant ionic strength in the wide 
range of pH values. Absorption spectra were recorded according to specific procedure 
which was carefully designed to avoid systematic errors. Collected absorption spectra 
will be used for the development of the algorithm for the spectral deconvolution (using 
MATLAB). Such software can be very useful tool in the drug research, especially for 
the analysis of the compounds which pKa values cannot be determined by potentiometry.
PB  - Belgrade : Serbian Chemical Society
PB  - Belgrade : Serbian Young Chemists’ Club
C3  - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
T1  - Comparative  analysis of ionization constants determination using spectrophotometry and potentiometry: 3- aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine
SP  - 42
EP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5939
ER  - 

@conference{
author = "Mrđinac, Jelena Ž. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana",
year = "2022",
abstract = "The ionization constant (usually expressed in logarithmic form, pKa) is important 
physicochemical parameter which is used to characterize the acid-base chemistry of a 
compound. Since most drugs contain one or more ionizable functional groups, 
knowledge of pKa values is necessary in drug research. The most common techniques 
used for pKa determination are potentiometry and spectrophotometry. Potentiometry is 
a method of choice when ionization processes are overlapping, as in such case it is not 
possible to obtain the absorption spectrum of each species present in solution. The aim 
of this work was the comparative analysis of pKa determination using potentiometry and 
spectrophotometry for model compounds with overlapping ionization processes: 3-
aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. The potentiometric
titrations were performed with pSOL Model 3 instrument (pION) equipped with pS 
software package for titration data analysis.1 Avdeef–Bucher four–parameter equation 
was used for electrode standardization.2 To overcome the above-mentioned limitation of 
spectrophotometry, the alternative approach was applied in this study. The new 
aminocaproate phosphate buffer (containing phosphoric and ε-aminocaproic acids) was 
used for the solutions preparation of the model compounds in pH range 1 – 12. This 
buffer has numerous advantages like UV-transparency, resistance to pH changes upon 
standing for several days, useful buffer capacity and constant ionic strength in the wide 
range of pH values. Absorption spectra were recorded according to specific procedure 
which was carefully designed to avoid systematic errors. Collected absorption spectra 
will be used for the development of the algorithm for the spectral deconvolution (using 
MATLAB). Such software can be very useful tool in the drug research, especially for 
the analysis of the compounds which pKa values cannot be determined by potentiometry.",
publisher = "Belgrade : Serbian Chemical Society, Belgrade : Serbian Young Chemists’ Club",
journal = "8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts",
title = "Comparative  analysis of ionization constants determination using spectrophotometry and potentiometry: 3- aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine",
pages = "42-42",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5939"
}

Mrđinac, J. Ž., Marković, O. S., Pešić, M. P.,& Verbić, T.. (2022). Comparative  analysis of ionization constants determination using spectrophotometry and potentiometry: 3- aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
Belgrade : Serbian Chemical Society., 42-42.
https://hdl.handle.net/21.15107/rcub_cherry_5939

Mrđinac JŽ, Marković OS, Pešić MP, Verbić T. Comparative  analysis of ionization constants determination using spectrophotometry and potentiometry: 3- aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts. 2022;:42-42.
https://hdl.handle.net/21.15107/rcub_cherry_5939 .

Mrđinac, Jelena Ž., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana, "Comparative  analysis of ionization constants determination using spectrophotometry and potentiometry: 3- aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine" in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts (2022):42-42,
https://hdl.handle.net/21.15107/rcub_cherry_5939 .

TY  - CONF
AU  - Marković, Olivera S.
AU  - Gajić, Brankica P.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5940
AB  - Cilj ovog rada bio je proučavanje ravnoteža u heterogenim sistemima tricikličnog 
antidepresiva amitriptilina (Am) koji sadrže hloride i/ili fosfate. Rastvorljivost Am u 
uslovima povećane jonske sile određena je pH–Ramp shake–flask metodom.1, 2 Veća 
rastvorljivost Am u kiseloj sredini od očekivane, posledica je agregacije – analiza 
eksperimentalnih podataka pomoću programa pDISOL–XTM ukazuje na verovatno 
građenje pentamera Am5H5
5+. Kritična micelarna koncentracija i stepen disocijacije 
agregata određeni su primenom konduktometrijskih titracija. U baznoj sredini primećena je 
delimična degradacija Am. Eksperimentalno dobijeni podaci o rastvorljivosti biološki 
aktivnih supstanci i postojećim ravnotežama u heterogenim sistemima važni su u svim 
fazama dizajna i razvoja lekova.
AB  - The aim of this work was to study the equilibria in tricyclic antidepressant amitriptyline 
(Am) heterogeneous systems containing chloride and/or phosphate ions. Solubility of Am 
in high ionic strength conditions was determined using pH–Ramp shake–flask method.1, 2
Higher solubility of Am than expected in an acidic media is a consequence of self aggregation – pentamer formation (Am5H5
5+) according to pDISOL–XTM analysis. Critical 
micelle concentration and the degree of the aggregate dissociation were determined by 
conductometric titrations. Partial degradation of Am in alkaline suspensions was observed. 
Experimental studies of solubility as well as the existing equilibria in heterogeneous 
systems of biologically active compounds are important at all stages of drug design and 
development.
PB  - Beograd : Srpsko hemijsko društvo
C3  - 58. Savetovanje Srpskog hemijskog društva, Kratki izvodi radova, Beograd 9. i 10. jun 2022. godine
T1  - Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina
SP  - 53
EP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5940
ER  - 

@conference{
author = "Marković, Olivera S. and Gajić, Brankica P. and Pešić, Miloš P. and Verbić, Tatjana",
year = "2022",
abstract = "Cilj ovog rada bio je proučavanje ravnoteža u heterogenim sistemima tricikličnog 
antidepresiva amitriptilina (Am) koji sadrže hloride i/ili fosfate. Rastvorljivost Am u 
uslovima povećane jonske sile određena je pH–Ramp shake–flask metodom.1, 2 Veća 
rastvorljivost Am u kiseloj sredini od očekivane, posledica je agregacije – analiza 
eksperimentalnih podataka pomoću programa pDISOL–XTM ukazuje na verovatno 
građenje pentamera Am5H5
5+. Kritična micelarna koncentracija i stepen disocijacije 
agregata određeni su primenom konduktometrijskih titracija. U baznoj sredini primećena je 
delimična degradacija Am. Eksperimentalno dobijeni podaci o rastvorljivosti biološki 
aktivnih supstanci i postojećim ravnotežama u heterogenim sistemima važni su u svim 
fazama dizajna i razvoja lekova., The aim of this work was to study the equilibria in tricyclic antidepressant amitriptyline 
(Am) heterogeneous systems containing chloride and/or phosphate ions. Solubility of Am 
in high ionic strength conditions was determined using pH–Ramp shake–flask method.1, 2
Higher solubility of Am than expected in an acidic media is a consequence of self aggregation – pentamer formation (Am5H5
5+) according to pDISOL–XTM analysis. Critical 
micelle concentration and the degree of the aggregate dissociation were determined by 
conductometric titrations. Partial degradation of Am in alkaline suspensions was observed. 
Experimental studies of solubility as well as the existing equilibria in heterogeneous 
systems of biologically active compounds are important at all stages of drug design and 
development.",
publisher = "Beograd : Srpsko hemijsko društvo",
journal = "58. Savetovanje Srpskog hemijskog društva, Kratki izvodi radova, Beograd 9. i 10. jun 2022. godine",
title = "Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina",
pages = "53-53",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5940"
}

Marković, O. S., Gajić, B. P., Pešić, M. P.,& Verbić, T.. (2022). Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina. in 58. Savetovanje Srpskog hemijskog društva, Kratki izvodi radova, Beograd 9. i 10. jun 2022. godine
Beograd : Srpsko hemijsko društvo., 53-53.
https://hdl.handle.net/21.15107/rcub_cherry_5940

Marković OS, Gajić BP, Pešić MP, Verbić T. Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina. in 58. Savetovanje Srpskog hemijskog društva, Kratki izvodi radova, Beograd 9. i 10. jun 2022. godine. 2022;:53-53.
https://hdl.handle.net/21.15107/rcub_cherry_5940 .

Marković, Olivera S., Gajić, Brankica P., Pešić, Miloš P., Verbić, Tatjana, "Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina" in 58. Savetovanje Srpskog hemijskog društva, Kratki izvodi radova, Beograd 9. i 10. jun 2022. godine (2022):53-53,
https://hdl.handle.net/21.15107/rcub_cherry_5940 .

TY  - CONF
AU  - Мрђан, Горана
AU  - Ваштаг, Ђенђи
AU  - Апостолов, Сузана
AU  - Рашета, Милена
AU  - Вербић, Татјана
AU  - Марковић, Оливера С.
AU  - Матијевић, Борко
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5968
AB  - Карбохидразони и њихови тио-аналози представљају
једињења добијена кондензацијом карбохидразида, односно тиокарбохи-
дразида са карбонилним једињењима. Захваљујући њиховој структури,
релативно једноставној синтези и великој реактивности, поменути дери-
вати имају широк спектар примене у свим сферама. У оквиру овог рада,
за четири новосинтетисана моно(тио)карбохидразона, одређене су кисе-
линске константе применом потенциметријске методе. Такође, методом
линеарне корелације енергија солватације и применом Catalan-овог моде-
ла испитан је утицај специфичних и неспецифичних међумолекулских
интеракција на померања у UV-Vis апсорпционим спектрима. У циљу
испитивавања потенцијалне биолошке активности 2 - пиридин-(тио) кар-
бохидразона, применом DPPH теста, одређен је њихов антиоксидативни
потенцијал и закључено је да су деривати тиокарбохидразона значајно
активнији у односу на карбохидразоне.
PB  - Бања Лука : Академија наука и умјетности Републике Српске
C3  - Међународни научни скуп Савремени материјали, Бања Лука, 2022.
T1  - Ispitivanje fizičko-hemijskih svojstava i potencijalne biološke aktivnosti derivata 2-piridin-(tio)karbohidrazona
VL  - 46
SP  - 275
EP  - 285
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5968
ER  - 

@conference{
author = "Мрђан, Горана and Ваштаг, Ђенђи and Апостолов, Сузана and Рашета, Милена and Вербић, Татјана and Марковић, Оливера С. and Матијевић, Борко",
year = "2022",
abstract = "Карбохидразони и њихови тио-аналози представљају
једињења добијена кондензацијом карбохидразида, односно тиокарбохи-
дразида са карбонилним једињењима. Захваљујући њиховој структури,
релативно једноставној синтези и великој реактивности, поменути дери-
вати имају широк спектар примене у свим сферама. У оквиру овог рада,
за четири новосинтетисана моно(тио)карбохидразона, одређене су кисе-
линске константе применом потенциметријске методе. Такође, методом
линеарне корелације енергија солватације и применом Catalan-овог моде-
ла испитан је утицај специфичних и неспецифичних међумолекулских
интеракција на померања у UV-Vis апсорпционим спектрима. У циљу
испитивавања потенцијалне биолошке активности 2 - пиридин-(тио) кар-
бохидразона, применом DPPH теста, одређен је њихов антиоксидативни
потенцијал и закључено је да су деривати тиокарбохидразона значајно
активнији у односу на карбохидразоне.",
publisher = "Бања Лука : Академија наука и умјетности Републике Српске",
journal = "Међународни научни скуп Савремени материјали, Бања Лука, 2022.",
title = "Ispitivanje fizičko-hemijskih svojstava i potencijalne biološke aktivnosti derivata 2-piridin-(tio)karbohidrazona",
volume = "46",
pages = "275-285",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5968"
}

Мрђан, Г., Ваштаг, Ђ., Апостолов, С., Рашета, М., Вербић, Т., Марковић, О. С.,& Матијевић, Б.. (2022). Ispitivanje fizičko-hemijskih svojstava i potencijalne biološke aktivnosti derivata 2-piridin-(tio)karbohidrazona. in Међународни научни скуп Савремени материјали, Бања Лука, 2022.
Бања Лука : Академија наука и умјетности Републике Српске., 46, 275-285.
https://hdl.handle.net/21.15107/rcub_cherry_5968

Мрђан Г, Ваштаг Ђ, Апостолов С, Рашета М, Вербић Т, Марковић ОС, Матијевић Б. Ispitivanje fizičko-hemijskih svojstava i potencijalne biološke aktivnosti derivata 2-piridin-(tio)karbohidrazona. in Међународни научни скуп Савремени материјали, Бања Лука, 2022.. 2022;46:275-285.
https://hdl.handle.net/21.15107/rcub_cherry_5968 .

Мрђан, Горана, Ваштаг, Ђенђи, Апостолов, Сузана, Рашета, Милена, Вербић, Татјана, Марковић, Оливера С., Матијевић, Борко, "Ispitivanje fizičko-hemijskih svojstava i potencijalne biološke aktivnosti derivata 2-piridin-(tio)karbohidrazona" in Међународни научни скуп Савремени материјали, Бања Лука, 2022., 46 (2022):275-285,
https://hdl.handle.net/21.15107/rcub_cherry_5968 .

TY  - JOUR
AU  - Mrđan, Gorana S.
AU  - Vastag, Gyöngyi Gy.
AU  - Škorić, Dušan Đ.
AU  - Radanović, Mirjana M.
AU  - Verbić, Tatjana
AU  - Milčić, Miloš K.
AU  - Stojiljković, Ivana N.
AU  - Marković, Olivera S.
AU  - Matijević, Borko M.
PY  - 2021
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4453
AB  - Derivatives of thiocarbohydrazone studied so far have shown great biological activity such as antioxidant, antimicrobial, and anticancer. Most of these compounds are bis-substituted derivatives, while monothiocarbohydrazones are much less investigated. Еighteen monothiocarbohydrazones were synthesized and subjected to physicochemical characterization in order to facilitate the examination of their potential biological activity and application in future studies. The structure of synthesized derivatives was confirmed with NMR and FT–IR spectroscopy, and with elemental analysis. For one of the compounds, single-crystal X-ray diffraction analysis was performed. Specific and non-specific molecular interactions were interpreted by LSER principles, using Catalan’s model. For additional information about the dominance and influence of the interactions presented, correlations with Hansen’s solubility parameters were calculated. Influence of the type and position of the substituent on absorption maxima was determined with LFER (linear free-energy relationship) principles, using Hammett’s equation. Acidity constants of the synthesized compounds were theoretically calculated and experimentally determined. Moreover, the excitation of a molecule by a photon of UV–Vis light was interpreted by time-dependent density functional theory (TD–DFT) calculations of UV absorption bands, and intramolecular charge transfer (ICT) was quantified by calculations of the charge transfer distances (DCT). © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
PB  - Springer Nature
T2  - Structural Chemistry
T2  - Structural Chemistry
T2  - Structural Chemistry
T1  - Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives
VL  - 32
IS  - 3
SP  - 1231
EP  - 1245
DO  - 10.1007/s11224-020-01700-y
ER  - 

@article{
author = "Mrđan, Gorana S. and Vastag, Gyöngyi Gy. and Škorić, Dušan Đ. and Radanović, Mirjana M. and Verbić, Tatjana and Milčić, Miloš K. and Stojiljković, Ivana N. and Marković, Olivera S. and Matijević, Borko M.",
year = "2021",
abstract = "Derivatives of thiocarbohydrazone studied so far have shown great biological activity such as antioxidant, antimicrobial, and anticancer. Most of these compounds are bis-substituted derivatives, while monothiocarbohydrazones are much less investigated. Еighteen monothiocarbohydrazones were synthesized and subjected to physicochemical characterization in order to facilitate the examination of their potential biological activity and application in future studies. The structure of synthesized derivatives was confirmed with NMR and FT–IR spectroscopy, and with elemental analysis. For one of the compounds, single-crystal X-ray diffraction analysis was performed. Specific and non-specific molecular interactions were interpreted by LSER principles, using Catalan’s model. For additional information about the dominance and influence of the interactions presented, correlations with Hansen’s solubility parameters were calculated. Influence of the type and position of the substituent on absorption maxima was determined with LFER (linear free-energy relationship) principles, using Hammett’s equation. Acidity constants of the synthesized compounds were theoretically calculated and experimentally determined. Moreover, the excitation of a molecule by a photon of UV–Vis light was interpreted by time-dependent density functional theory (TD–DFT) calculations of UV absorption bands, and intramolecular charge transfer (ICT) was quantified by calculations of the charge transfer distances (DCT). © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.",
publisher = "Springer Nature",
journal = "Structural Chemistry, Structural Chemistry, Structural Chemistry",
title = "Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives",
volume = "32",
number = "3",
pages = "1231-1245",
doi = "10.1007/s11224-020-01700-y"
}

Mrđan, G. S., Vastag, G. Gy., Škorić, D. Đ., Radanović, M. M., Verbić, T., Milčić, M. K., Stojiljković, I. N., Marković, O. S.,& Matijević, B. M.. (2021). Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives. in Structural Chemistry
Springer Nature., 32(3), 1231-1245.
https://doi.org/10.1007/s11224-020-01700-y

Mrđan GS, Vastag GG, Škorić DĐ, Radanović MM, Verbić T, Milčić MK, Stojiljković IN, Marković OS, Matijević BM. Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives. in Structural Chemistry. 2021;32(3):1231-1245.
doi:10.1007/s11224-020-01700-y .

Mrđan, Gorana S., Vastag, Gyöngyi Gy., Škorić, Dušan Đ., Radanović, Mirjana M., Verbić, Tatjana, Milčić, Miloš K., Stojiljković, Ivana N., Marković, Olivera S., Matijević, Borko M., "Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives" in Structural Chemistry, 32, no. 3 (2021):1231-1245,
https://doi.org/10.1007/s11224-020-01700-y . .

TY  - DATA
AU  - Mrđan, Gorana S.
AU  - Vastag, Gyöngyi Gy.
AU  - Škorić, Dušan Đ.
AU  - Radanović, Mirjana M.
AU  - Verbić, Tatjana
AU  - Milčić, Miloš K.
AU  - Stojiljković, Ivana N.
AU  - Marković, Olivera S.
AU  - Matijević, Borko M.
PY  - 2021
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4454
PB  - Springer Nature
T2  - Structural Chemistry
T1  - Supplementary data for the article: Mrđan, G. S.; Vastag, G. G.; Škorić, D. Đ.; Radanović, M. M.; Verbić, T. Ž.; Milčić, M. K.; Stojiljković, I. N.; Marković, O. S.; Matijević, B. M. Synthesis, Physicochemical Characterization, and TD–DFT Calculations of Monothiocarbohydrazone Derivatives. Structural Chemistry 2021, 32 (3), 1231–1245. https://doi.org/10.1007/s11224-020-01700-y.
UR  - https://hdl.handle.net/21.15107/rcub_cherry_4454
ER  - 

@misc{
author = "Mrđan, Gorana S. and Vastag, Gyöngyi Gy. and Škorić, Dušan Đ. and Radanović, Mirjana M. and Verbić, Tatjana and Milčić, Miloš K. and Stojiljković, Ivana N. and Marković, Olivera S. and Matijević, Borko M.",
year = "2021",
publisher = "Springer Nature",
journal = "Structural Chemistry",
title = "Supplementary data for the article: Mrđan, G. S.; Vastag, G. G.; Škorić, D. Đ.; Radanović, M. M.; Verbić, T. Ž.; Milčić, M. K.; Stojiljković, I. N.; Marković, O. S.; Matijević, B. M. Synthesis, Physicochemical Characterization, and TD–DFT Calculations of Monothiocarbohydrazone Derivatives. Structural Chemistry 2021, 32 (3), 1231–1245. https://doi.org/10.1007/s11224-020-01700-y.",
url = "https://hdl.handle.net/21.15107/rcub_cherry_4454"
}

Mrđan, G. S., Vastag, G. Gy., Škorić, D. Đ., Radanović, M. M., Verbić, T., Milčić, M. K., Stojiljković, I. N., Marković, O. S.,& Matijević, B. M.. (2021). Supplementary data for the article: Mrđan, G. S.; Vastag, G. G.; Škorić, D. Đ.; Radanović, M. M.; Verbić, T. Ž.; Milčić, M. K.; Stojiljković, I. N.; Marković, O. S.; Matijević, B. M. Synthesis, Physicochemical Characterization, and TD–DFT Calculations of Monothiocarbohydrazone Derivatives. Structural Chemistry 2021, 32 (3), 1231–1245. https://doi.org/10.1007/s11224-020-01700-y.. in Structural Chemistry
Springer Nature..
https://hdl.handle.net/21.15107/rcub_cherry_4454

Mrđan GS, Vastag GG, Škorić DĐ, Radanović MM, Verbić T, Milčić MK, Stojiljković IN, Marković OS, Matijević BM. Supplementary data for the article: Mrđan, G. S.; Vastag, G. G.; Škorić, D. Đ.; Radanović, M. M.; Verbić, T. Ž.; Milčić, M. K.; Stojiljković, I. N.; Marković, O. S.; Matijević, B. M. Synthesis, Physicochemical Characterization, and TD–DFT Calculations of Monothiocarbohydrazone Derivatives. Structural Chemistry 2021, 32 (3), 1231–1245. https://doi.org/10.1007/s11224-020-01700-y.. in Structural Chemistry. 2021;.
https://hdl.handle.net/21.15107/rcub_cherry_4454 .

Mrđan, Gorana S., Vastag, Gyöngyi Gy., Škorić, Dušan Đ., Radanović, Mirjana M., Verbić, Tatjana, Milčić, Miloš K., Stojiljković, Ivana N., Marković, Olivera S., Matijević, Borko M., "Supplementary data for the article: Mrđan, G. S.; Vastag, G. G.; Škorić, D. Đ.; Radanović, M. M.; Verbić, T. Ž.; Milčić, M. K.; Stojiljković, I. N.; Marković, O. S.; Matijević, B. M. Synthesis, Physicochemical Characterization, and TD–DFT Calculations of Monothiocarbohydrazone Derivatives. Structural Chemistry 2021, 32 (3), 1231–1245. https://doi.org/10.1007/s11224-020-01700-y." in Structural Chemistry (2021),
https://hdl.handle.net/21.15107/rcub_cherry_4454 .

TY  - CONF
AU  - Marković, Olivera S.
AU  - Marjanović, Nemanja Ž.
AU  - Patel, Nirali
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2021
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5962
AB  - Solubility is important physicochemical parameter and determines drug stability, bioavailability and therapeutic action. The aim of this study was to examine solubility of nortriptyline hydrochloride in a wide pH range, using pH-Ramp Shake-Flask method, already applied to desipramine hydrochloride [1] and based of recently published recommendations [2]. Solubility was measured in phosphate buffer, in chloride-free media and phoshate-free media, using both nortriptyline base and nortriptyline hydrochloride as starting material. Elemental analysis, termogravimetric analysis, differential scaning calorimetric analysis and powder X-ray diffraction analysis were used for solid precipitate analysis.
AB  - Rastvorljivost je značajno fizičko-hemijsko svojstvo biološki aktivnih i potencijalno biološki aktivnih supstancija, koje određuje stabilnost, biodostupnost i terapeutsko dejstvo leka. Cilj ovog rada je ispitivanje rastvorljivosti nortriptilin-hidrohlorida, pomoću pH-Ramp Shake-Flask metode, prethodno primenjene na desipramin-hidrohlorid [1]. Eksperimenti su izvedeni prema novim preporukama iz literature [2]. Rastvorljivost je određena u fosfatnom puferu, u sistemu bez hlorida i sistemu bez fosfata, koristeći nortriptilin bazu i nortriptilin-hidrohlorid. Urađena je i katakterizacija čvrste faze pomoću elementalne analize, termogravimetrije, diferencijalne skenirajuće kalorimetrije i difrakcije X-zraka.
PB  - Belgrade : Serbian Chemical Society
C3  - 57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021
T1  - pH-Dependent solubility profile of nortriptyline hydrochloride
SP  - 32
EP  - 32
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5962
ER  - 

@conference{
author = "Marković, Olivera S. and Marjanović, Nemanja Ž. and Patel, Nirali and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2021",
abstract = "Solubility is important physicochemical parameter and determines drug stability, bioavailability and therapeutic action. The aim of this study was to examine solubility of nortriptyline hydrochloride in a wide pH range, using pH-Ramp Shake-Flask method, already applied to desipramine hydrochloride [1] and based of recently published recommendations [2]. Solubility was measured in phosphate buffer, in chloride-free media and phoshate-free media, using both nortriptyline base and nortriptyline hydrochloride as starting material. Elemental analysis, termogravimetric analysis, differential scaning calorimetric analysis and powder X-ray diffraction analysis were used for solid precipitate analysis., Rastvorljivost je značajno fizičko-hemijsko svojstvo biološki aktivnih i potencijalno biološki aktivnih supstancija, koje određuje stabilnost, biodostupnost i terapeutsko dejstvo leka. Cilj ovog rada je ispitivanje rastvorljivosti nortriptilin-hidrohlorida, pomoću pH-Ramp Shake-Flask metode, prethodno primenjene na desipramin-hidrohlorid [1]. Eksperimenti su izvedeni prema novim preporukama iz literature [2]. Rastvorljivost je određena u fosfatnom puferu, u sistemu bez hlorida i sistemu bez fosfata, koristeći nortriptilin bazu i nortriptilin-hidrohlorid. Urađena je i katakterizacija čvrste faze pomoću elementalne analize, termogravimetrije, diferencijalne skenirajuće kalorimetrije i difrakcije X-zraka.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021",
title = "pH-Dependent solubility profile of nortriptyline hydrochloride",
pages = "32-32",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5962"
}

Marković, O. S., Marjanović, N. Ž., Patel, N., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2021). pH-Dependent solubility profile of nortriptyline hydrochloride. in 57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021
Belgrade : Serbian Chemical Society., 32-32.
https://hdl.handle.net/21.15107/rcub_cherry_5962

Marković OS, Marjanović NŽ, Patel N, Serajuddin ATM, Avdeef A, Verbić T. pH-Dependent solubility profile of nortriptyline hydrochloride. in 57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021. 2021;:32-32.
https://hdl.handle.net/21.15107/rcub_cherry_5962 .

Marković, Olivera S., Marjanović, Nemanja Ž., Patel, Nirali, Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "pH-Dependent solubility profile of nortriptyline hydrochloride" in 57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021 (2021):32-32,
https://hdl.handle.net/21.15107/rcub_cherry_5962 .

TY  - CONF
AU  - Mrđan, Gorana
AU  - Vaštag, Đenđi
AU  - Apostolov, Suzana
AU  - Rašeta, Milena
AU  - Verbić, Tatjana
AU  - Marković, Olivera S.
AU  - Matijević, Borko
PY  - 2021
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5963
AB  - Carbohydrazones and their thio analogs represent compounds obtained
by condensation of carbohydrazide and thiocarbohydrazide with carbonyl
compounds. Due to their structure, relatively simple synthesis, and high reactivity,
mentioned derivatives have a wide range of applications in all fields. In this study,
ionization constants of four newly synthesized mono(thio)carbohydrazones were
determined by applying the potentiometric method. Also, the influence of specific
and nonspecific intermolecular interactions on maxima shifting in UV-Vis absorption
spectra was investigated and quantified using the linear solvation energy relationships
method and Catalan’s model. Finally, by applying the DPPH assay, the
antioxidant potential of the newly synthesized compounds was determined, and thiocarbohydrazone
derivatives proved to be significantly more active when compared
to carbohydrazones.
C3  - XIV International Scientific Conference Contemporary Materials 2021 Programme and the Book of Abstracts, Banja Luka, September 9th to 10th, 2021
T1  - Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives
SP  - 40
EP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5963
ER  - 

@conference{
author = "Mrđan, Gorana and Vaštag, Đenđi and Apostolov, Suzana and Rašeta, Milena and Verbić, Tatjana and Marković, Olivera S. and Matijević, Borko",
year = "2021",
abstract = "Carbohydrazones and their thio analogs represent compounds obtained
by condensation of carbohydrazide and thiocarbohydrazide with carbonyl
compounds. Due to their structure, relatively simple synthesis, and high reactivity,
mentioned derivatives have a wide range of applications in all fields. In this study,
ionization constants of four newly synthesized mono(thio)carbohydrazones were
determined by applying the potentiometric method. Also, the influence of specific
and nonspecific intermolecular interactions on maxima shifting in UV-Vis absorption
spectra was investigated and quantified using the linear solvation energy relationships
method and Catalan’s model. Finally, by applying the DPPH assay, the
antioxidant potential of the newly synthesized compounds was determined, and thiocarbohydrazone
derivatives proved to be significantly more active when compared
to carbohydrazones.",
journal = "XIV International Scientific Conference Contemporary Materials 2021 Programme and the Book of Abstracts, Banja Luka, September 9th to 10th, 2021",
title = "Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives",
pages = "40-40",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5963"
}

Mrđan, G., Vaštag, Đ., Apostolov, S., Rašeta, M., Verbić, T., Marković, O. S.,& Matijević, B.. (2021). Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives. in XIV International Scientific Conference Contemporary Materials 2021 Programme and the Book of Abstracts, Banja Luka, September 9th to 10th, 2021, 40-40.
https://hdl.handle.net/21.15107/rcub_cherry_5963

Mrđan G, Vaštag Đ, Apostolov S, Rašeta M, Verbić T, Marković OS, Matijević B. Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives. in XIV International Scientific Conference Contemporary Materials 2021 Programme and the Book of Abstracts, Banja Luka, September 9th to 10th, 2021. 2021;:40-40.
https://hdl.handle.net/21.15107/rcub_cherry_5963 .

Mrđan, Gorana, Vaštag, Đenđi, Apostolov, Suzana, Rašeta, Milena, Verbić, Tatjana, Marković, Olivera S., Matijević, Borko, "Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives" in XIV International Scientific Conference Contemporary Materials 2021 Programme and the Book of Abstracts, Banja Luka, September 9th to 10th, 2021 (2021):40-40,
https://hdl.handle.net/21.15107/rcub_cherry_5963 .

TY  - JOUR
AU  - Opsenica, Igor
AU  - Selaković, Milica
AU  - Tot, Mikloš
AU  - Verbić, Tatjana
AU  - Srbljanović, Jelena
AU  - Štajner, Tijana
AU  - Đurković-Đaković, Olgica
AU  - Šolaja, Bogdan A.
PY  - 2021
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4389
AB  - Synthesis of novel aminoquinoline derivatives has been accomplished and their activity against malaria strains has been examined. The compounds showed moderate in vitro antimalarial activity against two P. falciparum strains, 3D7 (CQ susceptible clone) and Dd2 (CQ resistant clone). Three aminoquinolines were further examined for antimalarial efficacy in a mouse model using a modified Thompson test. In this model, mice were infected with P. berghei-infected red blood cells, and drugs were administered orally. Antimalarial 3 was found toxic at a dose of 320 (mg/kg)/day in 3/6 mice, however, 2/6 mice of the same group survived through day 31, and one of them was cured. © 2021 Serbian Chemical Society. All rights reserved.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - New 4-aminoquinolines as moderate inhibitors of P. falciparum malaria
VL  - 86
IS  - 2
SP  - 115
EP  - 123
DO  - 10.2298/JSC201225005O
ER  - 

@article{
author = "Opsenica, Igor and Selaković, Milica and Tot, Mikloš and Verbić, Tatjana and Srbljanović, Jelena and Štajner, Tijana and Đurković-Đaković, Olgica and Šolaja, Bogdan A.",
year = "2021",
abstract = "Synthesis of novel aminoquinoline derivatives has been accomplished and their activity against malaria strains has been examined. The compounds showed moderate in vitro antimalarial activity against two P. falciparum strains, 3D7 (CQ susceptible clone) and Dd2 (CQ resistant clone). Three aminoquinolines were further examined for antimalarial efficacy in a mouse model using a modified Thompson test. In this model, mice were infected with P. berghei-infected red blood cells, and drugs were administered orally. Antimalarial 3 was found toxic at a dose of 320 (mg/kg)/day in 3/6 mice, however, 2/6 mice of the same group survived through day 31, and one of them was cured. © 2021 Serbian Chemical Society. All rights reserved.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "New 4-aminoquinolines as moderate inhibitors of P. falciparum malaria",
volume = "86",
number = "2",
pages = "115-123",
doi = "10.2298/JSC201225005O"
}

Opsenica, I., Selaković, M., Tot, M., Verbić, T., Srbljanović, J., Štajner, T., Đurković-Đaković, O.,& Šolaja, B. A.. (2021). New 4-aminoquinolines as moderate inhibitors of P. falciparum malaria. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 86(2), 115-123.
https://doi.org/10.2298/JSC201225005O

Opsenica I, Selaković M, Tot M, Verbić T, Srbljanović J, Štajner T, Đurković-Đaković O, Šolaja BA. New 4-aminoquinolines as moderate inhibitors of P. falciparum malaria. in Journal of the Serbian Chemical Society. 2021;86(2):115-123.
doi:10.2298/JSC201225005O .

Opsenica, Igor, Selaković, Milica, Tot, Mikloš, Verbić, Tatjana, Srbljanović, Jelena, Štajner, Tijana, Đurković-Đaković, Olgica, Šolaja, Bogdan A., "New 4-aminoquinolines as moderate inhibitors of P. falciparum malaria" in Journal of the Serbian Chemical Society, 86, no. 2 (2021):115-123,
https://doi.org/10.2298/JSC201225005O . .

TY  - DATA
AU  - Opsenica, Igor
AU  - Selaković, Milica
AU  - Tot, Mikloš
AU  - Verbić, Tatjana
AU  - Srbljanović, Jelena
AU  - Štajner, Tijana
AU  - Đurković-Đaković, Olgica
AU  - Šolaja, Bogdan A.
PY  - 2021
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4392
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Supplementary data for the article: Opsenica, I.; Selaković, M.; Tot, M.; Verbić, T.; Srbljanović, J.; Štajner, T.; Djaković, O. D.; Šolaja, B. A. New 4-Aminoquinolines as Moderate Inhibitors of P. Falciparum Malaria. J. Serb. Chem. Soc. 2021, 86 (2), 115–123. https://doi.org/10.2298/JSC201225005O
VL  - 86
IS  - 2
UR  - https://hdl.handle.net/21.15107/rcub_cherry_4392
ER  - 

@misc{
author = "Opsenica, Igor and Selaković, Milica and Tot, Mikloš and Verbić, Tatjana and Srbljanović, Jelena and Štajner, Tijana and Đurković-Đaković, Olgica and Šolaja, Bogdan A.",
year = "2021",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Supplementary data for the article: Opsenica, I.; Selaković, M.; Tot, M.; Verbić, T.; Srbljanović, J.; Štajner, T.; Djaković, O. D.; Šolaja, B. A. New 4-Aminoquinolines as Moderate Inhibitors of P. Falciparum Malaria. J. Serb. Chem. Soc. 2021, 86 (2), 115–123. https://doi.org/10.2298/JSC201225005O",
volume = "86",
number = "2",
url = "https://hdl.handle.net/21.15107/rcub_cherry_4392"
}

Opsenica, I., Selaković, M., Tot, M., Verbić, T., Srbljanović, J., Štajner, T., Đurković-Đaković, O.,& Šolaja, B. A.. (2021). Supplementary data for the article: Opsenica, I.; Selaković, M.; Tot, M.; Verbić, T.; Srbljanović, J.; Štajner, T.; Djaković, O. D.; Šolaja, B. A. New 4-Aminoquinolines as Moderate Inhibitors of P. Falciparum Malaria. J. Serb. Chem. Soc. 2021, 86 (2), 115–123. https://doi.org/10.2298/JSC201225005O. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 86(2).
https://hdl.handle.net/21.15107/rcub_cherry_4392

Opsenica I, Selaković M, Tot M, Verbić T, Srbljanović J, Štajner T, Đurković-Đaković O, Šolaja BA. Supplementary data for the article: Opsenica, I.; Selaković, M.; Tot, M.; Verbić, T.; Srbljanović, J.; Štajner, T.; Djaković, O. D.; Šolaja, B. A. New 4-Aminoquinolines as Moderate Inhibitors of P. Falciparum Malaria. J. Serb. Chem. Soc. 2021, 86 (2), 115–123. https://doi.org/10.2298/JSC201225005O. in Journal of the Serbian Chemical Society. 2021;86(2).
https://hdl.handle.net/21.15107/rcub_cherry_4392 .

Opsenica, Igor, Selaković, Milica, Tot, Mikloš, Verbić, Tatjana, Srbljanović, Jelena, Štajner, Tijana, Đurković-Đaković, Olgica, Šolaja, Bogdan A., "Supplementary data for the article: Opsenica, I.; Selaković, M.; Tot, M.; Verbić, T.; Srbljanović, J.; Štajner, T.; Djaković, O. D.; Šolaja, B. A. New 4-Aminoquinolines as Moderate Inhibitors of P. Falciparum Malaria. J. Serb. Chem. Soc. 2021, 86 (2), 115–123. https://doi.org/10.2298/JSC201225005O" in Journal of the Serbian Chemical Society, 86, no. 2 (2021),
https://hdl.handle.net/21.15107/rcub_cherry_4392 .

TY  - CONF
AU  - Мрђан, Горана
AU  - Вербић, Татјана
AU  - Марковић, Оливера С.
AU  - Ваштаг, Ђенђи
AU  - Апостолов, Сузана
AU  - Матијевић, Борко
PY  - 2021
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5965
AB  - Деривати карбохидразона представљају веома значај-
на једињења за проучавање с обзиром да многа од њих показују веома
изражену биолошку активност. Познавање јонизационог стања функци-
оналних група присутних у молекулу је од виталног значаја за разумева-
ње фармакокинетичких и фармакодинамичких особина новосинтетиса-
них једињења. Један од важнијих физичко-хемијских параметара, кисе-
линска константа (pKa), може да послужи као молекулски дескриптор за
повезивање односа стуктуре и активности једињења, што може укази-
вати на даљу потенцијалну примену новосинтетисаних деривата. У
овом раду, применом потенциометријске методе, одређене су киселин-
ске константе за тринаест синтетисаних једињења из серије монокарбо-
хидразона у циљу добијања информација о њиховим јонизационим ста-
њима при одређеним условима.
PB  - Бања Лука : Академија наука и умјетности Републике Српске
C3  - Међународни научни скуп Савремени материјали, Бања Лука, 2021.
T1  - Одређивање јонизационих константи одабраних деривата монокарбохидразона
VL  - 45
SP  - 415
EP  - 422
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5965
ER  - 

@conference{
author = "Мрђан, Горана and Вербић, Татјана and Марковић, Оливера С. and Ваштаг, Ђенђи and Апостолов, Сузана and Матијевић, Борко",
year = "2021",
abstract = "Деривати карбохидразона представљају веома значај-
на једињења за проучавање с обзиром да многа од њих показују веома
изражену биолошку активност. Познавање јонизационог стања функци-
оналних група присутних у молекулу је од виталног значаја за разумева-
ње фармакокинетичких и фармакодинамичких особина новосинтетиса-
них једињења. Један од важнијих физичко-хемијских параметара, кисе-
линска константа (pKa), може да послужи као молекулски дескриптор за
повезивање односа стуктуре и активности једињења, што може укази-
вати на даљу потенцијалну примену новосинтетисаних деривата. У
овом раду, применом потенциометријске методе, одређене су киселин-
ске константе за тринаест синтетисаних једињења из серије монокарбо-
хидразона у циљу добијања информација о њиховим јонизационим ста-
њима при одређеним условима.",
publisher = "Бања Лука : Академија наука и умјетности Републике Српске",
journal = "Међународни научни скуп Савремени материјали, Бања Лука, 2021.",
title = "Одређивање јонизационих константи одабраних деривата монокарбохидразона",
volume = "45",
pages = "415-422",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5965"
}

Мрђан, Г., Вербић, Т., Марковић, О. С., Ваштаг, Ђ., Апостолов, С.,& Матијевић, Б.. (2021). Одређивање јонизационих константи одабраних деривата монокарбохидразона. in Међународни научни скуп Савремени материјали, Бања Лука, 2021.
Бања Лука : Академија наука и умјетности Републике Српске., 45, 415-422.
https://hdl.handle.net/21.15107/rcub_cherry_5965

Мрђан Г, Вербић Т, Марковић ОС, Ваштаг Ђ, Апостолов С, Матијевић Б. Одређивање јонизационих константи одабраних деривата монокарбохидразона. in Међународни научни скуп Савремени материјали, Бања Лука, 2021.. 2021;45:415-422.
https://hdl.handle.net/21.15107/rcub_cherry_5965 .

Мрђан, Горана, Вербић, Татјана, Марковић, Оливера С., Ваштаг, Ђенђи, Апостолов, Сузана, Матијевић, Борко, "Одређивање јонизационих константи одабраних деривата монокарбохидразона" in Међународни научни скуп Савремени материјали, Бања Лука, 2021., 45 (2021):415-422,
https://hdl.handle.net/21.15107/rcub_cherry_5965 .

TY  - CONF
AU  - Mrđan, Gorana
AU  - Verbić, Tatjana
AU  - Marković, Olivera S.
AU  - Matijević, Borko
AU  - Vaštag, Đenđi
AU  - Apostolov, Suzana
PY  - 2020
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5960
AB  - Carbohydrazone derivatives represent a very significant class of compounds due to their wide biological activity. Ionization states of functional groups present in the molecule are of vital importance for understanding of the pharmacokinetic and pharmacodynamic properties of the newly synthesized com-pounds.
One of the physicochemical parameters, the ionization constant (pKa), can be used as a molecular descriptor in order to relate structure and activity of a com-pound, which may indicate further potential application of newly synthesized deri-vatives.
In this work, ionization constants of twenty monocarbohydrazone deriva-tives were determined using potentiometric method, in order to obtain information about their ionization states under certain conditions.
C3  - XIII International Scientific Conference Contemporary Materials 2020  Programme  and the Book of Abstracts, Banja Luka, 11th September, 2020
T1  - Determination of ionization constants of selected monocarbohydrazone derivatives
SP  - 50
EP  - 50
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5960
ER  - 

@conference{
author = "Mrđan, Gorana and Verbić, Tatjana and Marković, Olivera S. and Matijević, Borko and Vaštag, Đenđi and Apostolov, Suzana",
year = "2020",
abstract = "Carbohydrazone derivatives represent a very significant class of compounds due to their wide biological activity. Ionization states of functional groups present in the molecule are of vital importance for understanding of the pharmacokinetic and pharmacodynamic properties of the newly synthesized com-pounds.
One of the physicochemical parameters, the ionization constant (pKa), can be used as a molecular descriptor in order to relate structure and activity of a com-pound, which may indicate further potential application of newly synthesized deri-vatives.
In this work, ionization constants of twenty monocarbohydrazone deriva-tives were determined using potentiometric method, in order to obtain information about their ionization states under certain conditions.",
journal = "XIII International Scientific Conference Contemporary Materials 2020  Programme  and the Book of Abstracts, Banja Luka, 11th September, 2020",
title = "Determination of ionization constants of selected monocarbohydrazone derivatives",
pages = "50-50",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5960"
}

Mrđan, G., Verbić, T., Marković, O. S., Matijević, B., Vaštag, Đ.,& Apostolov, S.. (2020). Determination of ionization constants of selected monocarbohydrazone derivatives. in XIII International Scientific Conference Contemporary Materials 2020  Programme  and the Book of Abstracts, Banja Luka, 11th September, 2020, 50-50.
https://hdl.handle.net/21.15107/rcub_cherry_5960

Mrđan G, Verbić T, Marković OS, Matijević B, Vaštag Đ, Apostolov S. Determination of ionization constants of selected monocarbohydrazone derivatives. in XIII International Scientific Conference Contemporary Materials 2020  Programme  and the Book of Abstracts, Banja Luka, 11th September, 2020. 2020;:50-50.
https://hdl.handle.net/21.15107/rcub_cherry_5960 .

Mrđan, Gorana, Verbić, Tatjana, Marković, Olivera S., Matijević, Borko, Vaštag, Đenđi, Apostolov, Suzana, "Determination of ionization constants of selected monocarbohydrazone derivatives" in XIII International Scientific Conference Contemporary Materials 2020  Programme  and the Book of Abstracts, Banja Luka, 11th September, 2020 (2020):50-50,
https://hdl.handle.net/21.15107/rcub_cherry_5960 .

TY  - JOUR
AU  - Pešić, Miloš P.
AU  - Todorov, Miljana D.
AU  - Becskereki, Gergely
AU  - Horvai, George
AU  - Verbić, Tatjana
AU  - Tóth, Blanka
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3951
AB  - A novel method is successfully tested for non-covalent imprinting. Conditions are used which practically exclude the formation of prepolymerization complexes. The template is cholesterol, and no so-called functional monomer is used. The polymers contain only an acrylic diester crosslinker. The porogen isopropanol prevents even hydrogen bonding between the template and the monomer in the prepolymerization solution. Despite of these apparently very disadvantageous conditions, appreciable imprinting factors for cholesterol and imprinted selectivity against some other steroids are observed, similar to other cholesterol MIPs with proven analytical usefulness.
PB  - Elsevier
T2  - Talanta
T1  - A novel method of molecular imprinting applied to the template cholesterol
VL  - 217
SP  - 121075
DO  - 10.1016/j.talanta.2020.121075
ER  - 

@article{
author = "Pešić, Miloš P. and Todorov, Miljana D. and Becskereki, Gergely and Horvai, George and Verbić, Tatjana and Tóth, Blanka",
year = "2020",
abstract = "A novel method is successfully tested for non-covalent imprinting. Conditions are used which practically exclude the formation of prepolymerization complexes. The template is cholesterol, and no so-called functional monomer is used. The polymers contain only an acrylic diester crosslinker. The porogen isopropanol prevents even hydrogen bonding between the template and the monomer in the prepolymerization solution. Despite of these apparently very disadvantageous conditions, appreciable imprinting factors for cholesterol and imprinted selectivity against some other steroids are observed, similar to other cholesterol MIPs with proven analytical usefulness.",
publisher = "Elsevier",
journal = "Talanta",
title = "A novel method of molecular imprinting applied to the template cholesterol",
volume = "217",
pages = "121075",
doi = "10.1016/j.talanta.2020.121075"
}

Pešić, M. P., Todorov, M. D., Becskereki, G., Horvai, G., Verbić, T.,& Tóth, B.. (2020). A novel method of molecular imprinting applied to the template cholesterol. in Talanta
Elsevier., 217, 121075.
https://doi.org/10.1016/j.talanta.2020.121075

Pešić MP, Todorov MD, Becskereki G, Horvai G, Verbić T, Tóth B. A novel method of molecular imprinting applied to the template cholesterol. in Talanta. 2020;217:121075.
doi:10.1016/j.talanta.2020.121075 .

Pešić, Miloš P., Todorov, Miljana D., Becskereki, Gergely, Horvai, George, Verbić, Tatjana, Tóth, Blanka, "A novel method of molecular imprinting applied to the template cholesterol" in Talanta, 217 (2020):121075,
https://doi.org/10.1016/j.talanta.2020.121075 . .

TY  - JOUR
AU  - Božić, Aleksandra R.
AU  - Filipović, Nenad R.
AU  - Verbić, Tatjana
AU  - Milčić, Miloš K.
AU  - Todorović, Tamara
AU  - Cvijetić, Ilija
AU  - Klisurić, Olivera
AU  - Radišić, Marina
AU  - Marinković, Aleksandar
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/318
AB  - The substituent and solvent effect on intramolecular charge transfer (ICT) of twelve monocarbohydrazones (mCHs) were studied using experimental and theoretical methodology. The effects of specific and non-specific solvent-solute interactions on the UV-Vis absorption maxima shifts were evaluated using linear free energy relationships (LFERs) principles, i.e. using the Kamlet-Taft and Catalán models. Linear free energy relationships in the form of single substituent parameter equation (SSP) was used to analyze substituent effect on UV-Vis, NMR and pK a change. According to crystallographic data and quantum chemical calculations, the trans (E) form was found to be more stable. A photochromism of compounds with 2-hydroxyphenyl and 2-pyridylimino groups substituted at imine carbon atom results in E/Z isomerization due to creation of intermolecular hydrogen bond in E and Z form, respectively. Multiple stage mass spectrometry (MS-MSn) analysis was applied to define main fragmentation pathways. Furthermore, the experimental findings were interpreted with the aid of ab initio MP2/6-311G(d,p) and time-dependent density functional (TD-DFT) methods. TD-DFT calculations were performed to quantify the efficiency of intramolecular charge transfer (ICT) with the aid of the charge-transfer distance (DCT) and the amount of transferred charge (QCT) calculation. It was found that both substituents and solvents influence electron density shift i.e. extent of conjugation, and affect ICT character in the course of excitation. © 2017.
PB  - Elsevier
T2  - Arabian Journal of Chemistry
T1  - A detailed experimental and computational study of monocarbohydrazones
VL  - 13
IS  - 1
SP  - 932
EP  - 953
DO  - 10.1016/j.arabjc.2017.08.010
ER  - 

@article{
author = "Božić, Aleksandra R. and Filipović, Nenad R. and Verbić, Tatjana and Milčić, Miloš K. and Todorović, Tamara and Cvijetić, Ilija and Klisurić, Olivera and Radišić, Marina and Marinković, Aleksandar",
year = "2020",
abstract = "The substituent and solvent effect on intramolecular charge transfer (ICT) of twelve monocarbohydrazones (mCHs) were studied using experimental and theoretical methodology. The effects of specific and non-specific solvent-solute interactions on the UV-Vis absorption maxima shifts were evaluated using linear free energy relationships (LFERs) principles, i.e. using the Kamlet-Taft and Catalán models. Linear free energy relationships in the form of single substituent parameter equation (SSP) was used to analyze substituent effect on UV-Vis, NMR and pK a change. According to crystallographic data and quantum chemical calculations, the trans (E) form was found to be more stable. A photochromism of compounds with 2-hydroxyphenyl and 2-pyridylimino groups substituted at imine carbon atom results in E/Z isomerization due to creation of intermolecular hydrogen bond in E and Z form, respectively. Multiple stage mass spectrometry (MS-MSn) analysis was applied to define main fragmentation pathways. Furthermore, the experimental findings were interpreted with the aid of ab initio MP2/6-311G(d,p) and time-dependent density functional (TD-DFT) methods. TD-DFT calculations were performed to quantify the efficiency of intramolecular charge transfer (ICT) with the aid of the charge-transfer distance (DCT) and the amount of transferred charge (QCT) calculation. It was found that both substituents and solvents influence electron density shift i.e. extent of conjugation, and affect ICT character in the course of excitation. © 2017.",
publisher = "Elsevier",
journal = "Arabian Journal of Chemistry",
title = "A detailed experimental and computational study of monocarbohydrazones",
volume = "13",
number = "1",
pages = "932-953",
doi = "10.1016/j.arabjc.2017.08.010"
}

Božić, A. R., Filipović, N. R., Verbić, T., Milčić, M. K., Todorović, T., Cvijetić, I., Klisurić, O., Radišić, M.,& Marinković, A.. (2020). A detailed experimental and computational study of monocarbohydrazones. in Arabian Journal of Chemistry
Elsevier., 13(1), 932-953.
https://doi.org/10.1016/j.arabjc.2017.08.010

Božić AR, Filipović NR, Verbić T, Milčić MK, Todorović T, Cvijetić I, Klisurić O, Radišić M, Marinković A. A detailed experimental and computational study of monocarbohydrazones. in Arabian Journal of Chemistry. 2020;13(1):932-953.
doi:10.1016/j.arabjc.2017.08.010 .

Božić, Aleksandra R., Filipović, Nenad R., Verbić, Tatjana, Milčić, Miloš K., Todorović, Tamara, Cvijetić, Ilija, Klisurić, Olivera, Radišić, Marina, Marinković, Aleksandar, "A detailed experimental and computational study of monocarbohydrazones" in Arabian Journal of Chemistry, 13, no. 1 (2020):932-953,
https://doi.org/10.1016/j.arabjc.2017.08.010 . .

TY  - JOUR
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Shah, Ankita V.
AU  - Serajuddin, Abu T.M.
AU  - Verbić, Tatjana
AU  - Avdeef, Alex
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2924
AB  - Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H 3 PO 4 , or NaOH to adjust pH) were performed on phosphate-buffered (0.12‑0.15 M) saturated solutions of DsHCl in the pH 1.3–11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (K sp 2:1 = [DsH + ] 2 [HPO 4 2− ]) was determined from data in the pH 4–9 region. The free base of desipramine was prepared and used to determine the K sp 1:1 ([DsH + ][H 2 PO 4 − ]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S 0 , and the 1:1 drug-chloride solubility product, K sp DsH [rad] Cl = [DsH + ][Cl − ]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pH max 8.0. In phosphate-containing solutions, pH max was indicated at higher pH (8.8–9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pH max in saturated phosphate‑containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates
VL  - 133
SP  - 264
EP  - 274
DO  - 10.1016/j.ejps.2019.03.014
ER  - 

@article{
author = "Marković, Olivera S. and Pešić, Miloš P. and Shah, Ankita V. and Serajuddin, Abu T.M. and Verbić, Tatjana and Avdeef, Alex",
year = "2019",
abstract = "Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H 3 PO 4 , or NaOH to adjust pH) were performed on phosphate-buffered (0.12‑0.15 M) saturated solutions of DsHCl in the pH 1.3–11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (K sp 2:1 = [DsH + ] 2 [HPO 4 2− ]) was determined from data in the pH 4–9 region. The free base of desipramine was prepared and used to determine the K sp 1:1 ([DsH + ][H 2 PO 4 − ]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S 0 , and the 1:1 drug-chloride solubility product, K sp DsH [rad] Cl = [DsH + ][Cl − ]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pH max 8.0. In phosphate-containing solutions, pH max was indicated at higher pH (8.8–9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pH max in saturated phosphate‑containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates",
volume = "133",
pages = "264-274",
doi = "10.1016/j.ejps.2019.03.014"
}

Marković, O. S., Pešić, M. P., Shah, A. V., Serajuddin, A. T.M., Verbić, T.,& Avdeef, A.. (2019). Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences
Elsevier., 133, 264-274.
https://doi.org/10.1016/j.ejps.2019.03.014

Marković OS, Pešić MP, Shah AV, Serajuddin AT, Verbić T, Avdeef A. Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences. 2019;133:264-274.
doi:10.1016/j.ejps.2019.03.014 .

Marković, Olivera S., Pešić, Miloš P., Shah, Ankita V., Serajuddin, Abu T.M., Verbić, Tatjana, Avdeef, Alex, "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates" in European Journal of Pharmaceutical Sciences, 133 (2019):264-274,
https://doi.org/10.1016/j.ejps.2019.03.014 . .

TY  - JOUR
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Shah, Ankita V.
AU  - Serajuddin, Abu T.M.
AU  - Verbić, Tatjana
AU  - Avdeef, Alex
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2925
AB  - Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H 3 PO 4 , or NaOH to adjust pH) were performed on phosphate-buffered (0.12‑0.15 M) saturated solutions of DsHCl in the pH 1.3–11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (K sp 2:1 = [DsH + ] 2 [HPO 4 2− ]) was determined from data in the pH 4–9 region. The free base of desipramine was prepared and used to determine the K sp 1:1 ([DsH + ][H 2 PO 4 − ]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S 0 , and the 1:1 drug-chloride solubility product, K sp DsH [rad] Cl = [DsH + ][Cl − ]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pH max 8.0. In phosphate-containing solutions, pH max was indicated at higher pH (8.8–9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pH max in saturated phosphate‑containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates
VL  - 133
SP  - 264
EP  - 274
DO  - 10.1016/j.ejps.2019.03.014
ER  - 

@article{
author = "Marković, Olivera S. and Pešić, Miloš P. and Shah, Ankita V. and Serajuddin, Abu T.M. and Verbić, Tatjana and Avdeef, Alex",
year = "2019",
abstract = "Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H 3 PO 4 , or NaOH to adjust pH) were performed on phosphate-buffered (0.12‑0.15 M) saturated solutions of DsHCl in the pH 1.3–11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (K sp 2:1 = [DsH + ] 2 [HPO 4 2− ]) was determined from data in the pH 4–9 region. The free base of desipramine was prepared and used to determine the K sp 1:1 ([DsH + ][H 2 PO 4 − ]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S 0 , and the 1:1 drug-chloride solubility product, K sp DsH [rad] Cl = [DsH + ][Cl − ]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pH max 8.0. In phosphate-containing solutions, pH max was indicated at higher pH (8.8–9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pH max in saturated phosphate‑containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates",
volume = "133",
pages = "264-274",
doi = "10.1016/j.ejps.2019.03.014"
}

Marković, O. S., Pešić, M. P., Shah, A. V., Serajuddin, A. T.M., Verbić, T.,& Avdeef, A.. (2019). Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences
Elsevier., 133, 264-274.
https://doi.org/10.1016/j.ejps.2019.03.014

Marković OS, Pešić MP, Shah AV, Serajuddin AT, Verbić T, Avdeef A. Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences. 2019;133:264-274.
doi:10.1016/j.ejps.2019.03.014 .

Marković, Olivera S., Pešić, Miloš P., Shah, Ankita V., Serajuddin, Abu T.M., Verbić, Tatjana, Avdeef, Alex, "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates" in European Journal of Pharmaceutical Sciences, 133 (2019):264-274,
https://doi.org/10.1016/j.ejps.2019.03.014 . .