Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography
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2022
Authors
Šegan, Sandra B.Jevtić, Ivana I.
Tosti, Tomislav
Penjišević, Jelena
Šukalović, Vladimir
Kostić-Rajačić, Slađana
Milojković-Opsenica, Dušanka
Article (Published version)
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Show full item recordAbstract
Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin-
layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the
piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diaste-
reomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant
of fentanyl were also determined by the same method, as a reference. The physicochemical property, lip-
ophilicity, expressed as retention indices RM
0 , b, and C0, as well as PC1, was determined and correlated with in
silico values. Ionization constants were determined on the basis of the relationships between analyte’s retention
expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were
subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to p...rovide
basic insights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation
was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and mo-
lecular weight. In general, results of the present research corroborate well with previously determined anti-
nociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another
set of important parameters should be taken into account when designing new derivatives of C-3 substituted
fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC
can be considered as a valuable asset in the ligand-based drug design
Keywords:
reverse-phased thin-layer chromatography / lipophilicity / ionization constants / fentanyl / chemometric analysisSource:
Journal of Chromatography B, 2022, 1211, 123481-Publisher:
- Elsevier
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200026 (University of Belgrade, Institute of Chemistry, Technology and Metallurgy - IChTM) (RS-MESTD-inst-2020-200026)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200168 (University of Belgrade, Faculty of Chemistry) (RS-MESTD-inst-2020-200168)
Note:
- Supplementary material: https://cherry.chem.bg.ac.rs/handle/123456789/5650
Related info:
- Referenced by
https://cherry.chem.bg.ac.rs/handle/123456789/5650
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Šegan, Sandra B. AU - Jevtić, Ivana I. AU - Tosti, Tomislav AU - Penjišević, Jelena AU - Šukalović, Vladimir AU - Kostić-Rajačić, Slađana AU - Milojković-Opsenica, Dušanka PY - 2022 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5649 AB - Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin- layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diaste- reomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant of fentanyl were also determined by the same method, as a reference. The physicochemical property, lip- ophilicity, expressed as retention indices RM 0 , b, and C0, as well as PC1, was determined and correlated with in silico values. Ionization constants were determined on the basis of the relationships between analyte’s retention expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to provide basic insights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and mo- lecular weight. In general, results of the present research corroborate well with previously determined anti- nociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another set of important parameters should be taken into account when designing new derivatives of C-3 substituted fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC can be considered as a valuable asset in the ligand-based drug design PB - Elsevier T2 - Journal of Chromatography B T1 - Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography VL - 1211 SP - 123481 DO - 10.1016/j.jchromb.2022.123481 ER -
@article{ author = "Šegan, Sandra B. and Jevtić, Ivana I. and Tosti, Tomislav and Penjišević, Jelena and Šukalović, Vladimir and Kostić-Rajačić, Slađana and Milojković-Opsenica, Dušanka", year = "2022", abstract = "Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin- layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diaste- reomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant of fentanyl were also determined by the same method, as a reference. The physicochemical property, lip- ophilicity, expressed as retention indices RM 0 , b, and C0, as well as PC1, was determined and correlated with in silico values. Ionization constants were determined on the basis of the relationships between analyte’s retention expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to provide basic insights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and mo- lecular weight. In general, results of the present research corroborate well with previously determined anti- nociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another set of important parameters should be taken into account when designing new derivatives of C-3 substituted fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC can be considered as a valuable asset in the ligand-based drug design", publisher = "Elsevier", journal = "Journal of Chromatography B", title = "Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography", volume = "1211", pages = "123481", doi = "10.1016/j.jchromb.2022.123481" }
Šegan, S. B., Jevtić, I. I., Tosti, T., Penjišević, J., Šukalović, V., Kostić-Rajačić, S.,& Milojković-Opsenica, D.. (2022). Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography. in Journal of Chromatography B Elsevier., 1211, 123481. https://doi.org/10.1016/j.jchromb.2022.123481
Šegan SB, Jevtić II, Tosti T, Penjišević J, Šukalović V, Kostić-Rajačić S, Milojković-Opsenica D. Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography. in Journal of Chromatography B. 2022;1211:123481. doi:10.1016/j.jchromb.2022.123481 .
Šegan, Sandra B., Jevtić, Ivana I., Tosti, Tomislav, Penjišević, Jelena, Šukalović, Vladimir, Kostić-Rajačić, Slađana, Milojković-Opsenica, Dušanka, "Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography" in Journal of Chromatography B, 1211 (2022):123481, https://doi.org/10.1016/j.jchromb.2022.123481 . .