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Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands

During the past few years increasing attention has been devoted to Mn(II) complexes as possible substitutes for Gd(III) complexes as contrast agents in MRI. Equilibrium (log K(MnL) or pMn value), kinetic parameters (rates and half-lives of dissociation) and relaxivity of the Mn(II) complexes formed...

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Autores principales: Garda, Zoltán, Molnár, Enikő, Kálmán, Ferenc K., Botár, Richárd, Nagy, Viktória, Baranyai, Zsolt, Brücher, Ernő, Kovács, Zoltán, Tóth, Imre, Tircsó, Gyula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099102/
https://www.ncbi.nlm.nih.gov/pubmed/30151358
http://dx.doi.org/10.3389/fchem.2018.00232
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author Garda, Zoltán
Molnár, Enikő
Kálmán, Ferenc K.
Botár, Richárd
Nagy, Viktória
Baranyai, Zsolt
Brücher, Ernő
Kovács, Zoltán
Tóth, Imre
Tircsó, Gyula
author_facet Garda, Zoltán
Molnár, Enikő
Kálmán, Ferenc K.
Botár, Richárd
Nagy, Viktória
Baranyai, Zsolt
Brücher, Ernő
Kovács, Zoltán
Tóth, Imre
Tircsó, Gyula
author_sort Garda, Zoltán
collection PubMed
description During the past few years increasing attention has been devoted to Mn(II) complexes as possible substitutes for Gd(III) complexes as contrast agents in MRI. Equilibrium (log K(MnL) or pMn value), kinetic parameters (rates and half-lives of dissociation) and relaxivity of the Mn(II) complexes formed with 12-membered macrocyclic ligands were studied. The ligands were selected in a way to gain information on how the ligand rigidity, the nature of the donor atoms in the macrocycle (pyridine N, amine N, and etheric O atom), the nature of the pendant arms (carboxylates, phosphonates, primary, secondary and tertiary amides) affect the physicochemical parameters of the Mn(II) complexes. As expected, decreasing the denticity of DOTA (to afford DO3A) resulted in a drop in the stability and inertness of [Mn(DO3A)](−) compared to [Mn(DOTA)](2−). This decrease can be compensated partially by incorporating the fourth nitrogen atom into a pyridine ring (e.g., PCTA) or by replacement with an etheric oxygen atom (ODO3A). Moreover, the substitution of primary amides for acetates resulted in a noticeable drop in the stability constant (PC3AM(H)), but it increased as the primary amides (PC3AM(H)) were replaced by secondary (PC3AM(Gly)) or tertiary amide (PC3AM(Pip)) pendants. The inertness of the Mn(II) complexes behaved alike as the rates of acid catalyzed dissociation increased going from DOTA (k(1) = 0.040 M(−1)s(−1)) to DO3A (k(1) = 0.45 M(−1)s(−1)). However, the rates of acid catalyzed dissociation decreased from 0.112 M(−1)s(−1) observed for the anionic Mn(II) complex of PCTA to 0.0107 M(−1)s(−1) and 0.00458 M(−1)s(−1) for the cationic Mn(II) complexes of PC3AM(H) and PC3AM(Pip) ligands, respectively. In spite of its lower denticity (as compared to DOTA) the sterically more hindered amide complex ([Mn(PC3AM(Pip))](2+)) displays surprisingly high conditional stability (pMn = 8.86 vs. pMn = 9.74 for [Mn(PCTA)](−)) and excellent kinetic inertness. The substitution of phosphonates for the acetate pendant arms (DOTP and DO3P), however, resulted in a noticeable drop in the conditional stability as well as dissociation kinetic parameters of the corresponding Mn(II) complexes ([Mn(DOTP)](6−) and [Mn(DO3P)](4−)) underlining that the phosphonate pedant should not be considered as a suitable building block for further ligand design while the tertiary amide moiety will likely have some implications in this respect in the future.
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spelling pubmed-60991022018-08-27 Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands Garda, Zoltán Molnár, Enikő Kálmán, Ferenc K. Botár, Richárd Nagy, Viktória Baranyai, Zsolt Brücher, Ernő Kovács, Zoltán Tóth, Imre Tircsó, Gyula Front Chem Chemistry During the past few years increasing attention has been devoted to Mn(II) complexes as possible substitutes for Gd(III) complexes as contrast agents in MRI. Equilibrium (log K(MnL) or pMn value), kinetic parameters (rates and half-lives of dissociation) and relaxivity of the Mn(II) complexes formed with 12-membered macrocyclic ligands were studied. The ligands were selected in a way to gain information on how the ligand rigidity, the nature of the donor atoms in the macrocycle (pyridine N, amine N, and etheric O atom), the nature of the pendant arms (carboxylates, phosphonates, primary, secondary and tertiary amides) affect the physicochemical parameters of the Mn(II) complexes. As expected, decreasing the denticity of DOTA (to afford DO3A) resulted in a drop in the stability and inertness of [Mn(DO3A)](−) compared to [Mn(DOTA)](2−). This decrease can be compensated partially by incorporating the fourth nitrogen atom into a pyridine ring (e.g., PCTA) or by replacement with an etheric oxygen atom (ODO3A). Moreover, the substitution of primary amides for acetates resulted in a noticeable drop in the stability constant (PC3AM(H)), but it increased as the primary amides (PC3AM(H)) were replaced by secondary (PC3AM(Gly)) or tertiary amide (PC3AM(Pip)) pendants. The inertness of the Mn(II) complexes behaved alike as the rates of acid catalyzed dissociation increased going from DOTA (k(1) = 0.040 M(−1)s(−1)) to DO3A (k(1) = 0.45 M(−1)s(−1)). However, the rates of acid catalyzed dissociation decreased from 0.112 M(−1)s(−1) observed for the anionic Mn(II) complex of PCTA to 0.0107 M(−1)s(−1) and 0.00458 M(−1)s(−1) for the cationic Mn(II) complexes of PC3AM(H) and PC3AM(Pip) ligands, respectively. In spite of its lower denticity (as compared to DOTA) the sterically more hindered amide complex ([Mn(PC3AM(Pip))](2+)) displays surprisingly high conditional stability (pMn = 8.86 vs. pMn = 9.74 for [Mn(PCTA)](−)) and excellent kinetic inertness. The substitution of phosphonates for the acetate pendant arms (DOTP and DO3P), however, resulted in a noticeable drop in the conditional stability as well as dissociation kinetic parameters of the corresponding Mn(II) complexes ([Mn(DOTP)](6−) and [Mn(DO3P)](4−)) underlining that the phosphonate pedant should not be considered as a suitable building block for further ligand design while the tertiary amide moiety will likely have some implications in this respect in the future. Frontiers Media S.A. 2018-08-13 /pmc/articles/PMC6099102/ /pubmed/30151358 http://dx.doi.org/10.3389/fchem.2018.00232 Text en Copyright © 2018 Garda, Molnár, Kálmán, Botár, Nagy, Baranyai, Brücher, Kovács, Tóth and Tircsó. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Garda, Zoltán
Molnár, Enikő
Kálmán, Ferenc K.
Botár, Richárd
Nagy, Viktória
Baranyai, Zsolt
Brücher, Ernő
Kovács, Zoltán
Tóth, Imre
Tircsó, Gyula
Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands
title Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands
title_full Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands
title_fullStr Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands
title_full_unstemmed Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands
title_short Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands
title_sort effect of the nature of donor atoms on the thermodynamic, kinetic and relaxation properties of mn(ii) complexes formed with some trisubstituted 12-membered macrocyclic ligands
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099102/
https://www.ncbi.nlm.nih.gov/pubmed/30151358
http://dx.doi.org/10.3389/fchem.2018.00232
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