Synthesis and characterisation of bismacrocyclic DO3A-amide derivatives - an approach towards metal-responsive PARACEST agents
Апстракт
Three new bismacrocyclic Ln(3+) chelates consisting of triamide derivatives of cyclen with glycine, methyl and tert-butyl substituents (L1-3, respectively) linked to an acyclic EGTA-derived calcium chelator were synthesised as potential MRI contrast agents (EGTA -ethylene glycol-bis(2-aminoethylether)-N, N, N', N'-tetraacetic acid). Eu3+ and Yb3+ complexes of L1-3 were investigated as chemical exchange saturation transfer (CEST) agents. Moderate to minor CEST effects were observed for Eu2L1, Eu2L2 and Yb2L2 complexes in the absence of Ca2+, with negligible changes upon addition of this metal ion. Luminescence steady-state emission and lifetime experiments did not reveal any changes in the coordination environment of the complexes, while the number of inner-sphere water molecules remained constant in the absence and presence of Ca2+. The protonation constants of Eu2L1 and Eu2L2 and stability constants of their complexes with Ca2+, Mg2+ and Zn2+ were determined by means of potentiometric... titrations. The results show that the charge of the complex dramatically affects the protonation constants of the EGTA-binding unit. The stability constants of the complexes formed with Ca2+, Mg2+ and Zn2+ are several orders of magnitude lower than those of EGTA. These findings indicate that the nature of Ln(3+) chelates and their charge are the main reasons for the observed results and weaker response of these EGTA-derived triamide derivatives compared to their tricarboxylate analogues.
Извор:
Dalton Transactions, 2016, 45, 15, 6555-6565Издавач:
- Royal Soc Chemistry, Cambridge
Финансирање / пројекти:
- European COST Action [CM1006]
- Max-Planck Society
Напомена:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3623
DOI: 10.1039/c5dt04625d
ISSN: 1477-9226
PubMed: 26956151
WoS: 000373994800028
Scopus: 2-s2.0-84964614019
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Cakić, Nevenka AU - Verbić, Tatjana AU - Jelić, Ratomir AU - Platas-Iglesias, Carlos AU - Angelovski, Goran PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1911 AB - Three new bismacrocyclic Ln(3+) chelates consisting of triamide derivatives of cyclen with glycine, methyl and tert-butyl substituents (L1-3, respectively) linked to an acyclic EGTA-derived calcium chelator were synthesised as potential MRI contrast agents (EGTA -ethylene glycol-bis(2-aminoethylether)-N, N, N', N'-tetraacetic acid). Eu3+ and Yb3+ complexes of L1-3 were investigated as chemical exchange saturation transfer (CEST) agents. Moderate to minor CEST effects were observed for Eu2L1, Eu2L2 and Yb2L2 complexes in the absence of Ca2+, with negligible changes upon addition of this metal ion. Luminescence steady-state emission and lifetime experiments did not reveal any changes in the coordination environment of the complexes, while the number of inner-sphere water molecules remained constant in the absence and presence of Ca2+. The protonation constants of Eu2L1 and Eu2L2 and stability constants of their complexes with Ca2+, Mg2+ and Zn2+ were determined by means of potentiometric titrations. The results show that the charge of the complex dramatically affects the protonation constants of the EGTA-binding unit. The stability constants of the complexes formed with Ca2+, Mg2+ and Zn2+ are several orders of magnitude lower than those of EGTA. These findings indicate that the nature of Ln(3+) chelates and their charge are the main reasons for the observed results and weaker response of these EGTA-derived triamide derivatives compared to their tricarboxylate analogues. PB - Royal Soc Chemistry, Cambridge T2 - Dalton Transactions T1 - Synthesis and characterisation of bismacrocyclic DO3A-amide derivatives - an approach towards metal-responsive PARACEST agents VL - 45 IS - 15 SP - 6555 EP - 6565 DO - 10.1039/c5dt04625d ER -
@article{ author = "Cakić, Nevenka and Verbić, Tatjana and Jelić, Ratomir and Platas-Iglesias, Carlos and Angelovski, Goran", year = "2016", abstract = "Three new bismacrocyclic Ln(3+) chelates consisting of triamide derivatives of cyclen with glycine, methyl and tert-butyl substituents (L1-3, respectively) linked to an acyclic EGTA-derived calcium chelator were synthesised as potential MRI contrast agents (EGTA -ethylene glycol-bis(2-aminoethylether)-N, N, N', N'-tetraacetic acid). Eu3+ and Yb3+ complexes of L1-3 were investigated as chemical exchange saturation transfer (CEST) agents. Moderate to minor CEST effects were observed for Eu2L1, Eu2L2 and Yb2L2 complexes in the absence of Ca2+, with negligible changes upon addition of this metal ion. Luminescence steady-state emission and lifetime experiments did not reveal any changes in the coordination environment of the complexes, while the number of inner-sphere water molecules remained constant in the absence and presence of Ca2+. The protonation constants of Eu2L1 and Eu2L2 and stability constants of their complexes with Ca2+, Mg2+ and Zn2+ were determined by means of potentiometric titrations. The results show that the charge of the complex dramatically affects the protonation constants of the EGTA-binding unit. The stability constants of the complexes formed with Ca2+, Mg2+ and Zn2+ are several orders of magnitude lower than those of EGTA. These findings indicate that the nature of Ln(3+) chelates and their charge are the main reasons for the observed results and weaker response of these EGTA-derived triamide derivatives compared to their tricarboxylate analogues.", publisher = "Royal Soc Chemistry, Cambridge", journal = "Dalton Transactions", title = "Synthesis and characterisation of bismacrocyclic DO3A-amide derivatives - an approach towards metal-responsive PARACEST agents", volume = "45", number = "15", pages = "6555-6565", doi = "10.1039/c5dt04625d" }
Cakić, N., Verbić, T., Jelić, R., Platas-Iglesias, C.,& Angelovski, G.. (2016). Synthesis and characterisation of bismacrocyclic DO3A-amide derivatives - an approach towards metal-responsive PARACEST agents. in Dalton Transactions Royal Soc Chemistry, Cambridge., 45(15), 6555-6565. https://doi.org/10.1039/c5dt04625d
Cakić N, Verbić T, Jelić R, Platas-Iglesias C, Angelovski G. Synthesis and characterisation of bismacrocyclic DO3A-amide derivatives - an approach towards metal-responsive PARACEST agents. in Dalton Transactions. 2016;45(15):6555-6565. doi:10.1039/c5dt04625d .
Cakić, Nevenka, Verbić, Tatjana, Jelić, Ratomir, Platas-Iglesias, Carlos, Angelovski, Goran, "Synthesis and characterisation of bismacrocyclic DO3A-amide derivatives - an approach towards metal-responsive PARACEST agents" in Dalton Transactions, 45, no. 15 (2016):6555-6565, https://doi.org/10.1039/c5dt04625d . .