Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/74634 |
Resumo: | The thermodynamic, kinetic, and structural properties of Ln<sup>3+</sup> complexes with the bifunctional DO3A-ACE<sup>4−</sup> ligand and its amide derivative DO3A-BACE<sup>4−</sup> (modelling the case where DO3A-ACE<sup>4−</sup> ligand binds to vector molecules) have been studied in order to confirm the usefulness of the corresponding Gd<sup>3+</sup> complexes as relaxation labels of targeted MRI contrast agents. The stability constants of the Mg<sup>2+</sup> and Ca<sup>2+</sup> complexes of DO3A-ACE<sup>4−</sup> and DO3A-BACE<sup>4−</sup> complexes are lower than for DOTA<sup>4−</sup> and DO3A<sup>3−</sup>, while the Zn<sup>2+</sup> and Cu<sup>2+</sup> complexes have similar and higher stability than for DOTA<sup>4−</sup> and DO3A<sup>3−</sup> complexes. The stability constants of the Ln(DO3A-BACE)<sup>−</sup> complexes increase from Ce<sup>3+</sup> to Gd<sup>3+</sup> but remain practically constant for the late Ln<sup>3+</sup> ions (represented by Yb<sup>3+</sup>). The stability constants of the Ln(DO3A-ACE)<sup>4−</sup> and Ln(DO3A-BACE)<sup>4−</sup> complexes are several orders of magnitude lower than those of the corresponding DOTA<sup>4−</sup> and DO3A<sup>3−</sup> complexes. The formation rate of Eu(DO3A-ACE)<sup>−</sup> is one order of magnitude slower than for Eu(DOTA)<sup>−</sup>, due to the presence of the protonated amine group, which destabilizes the protonated intermediate complex. This protonated group causes the Ln(DO3A-ACE)<sup>−</sup> complexes to dissociate several orders of magnitude faster than Ln(DOTA)<sup>−</sup> and its absence in the Ln(DO3A-BACE)<sup>−</sup> complexes results in inertness similar to Ln(DOTA)<sup>−</sup> (as judged by the rate constants of acid assisted dissociation). The <sup>1</sup>H NMR spectra of the diamagnetic Y(DO3A-ACE)<sup>−</sup> and Y(DO3A-BACE)<sup>−</sup> reflect the slow dynamics at low temperatures of the intramolecular isomerization process between the SA pair of enantiomers, R-<i>Λ</i>(<i>λλλλ</i>) and S-<i>Δ</i>(<i>δδδδ</i>). The conformation of the C<sub>α</sub>-substituted pendant arm is different in the two complexes, where the bulky substituent is further away from the macrocyclic ring in Y(DO3A-BACE)<sup>−</sup> than the amino group in Y(DO3A-ACE)<sup>−</sup> to minimize steric hindrance. The temperature dependence of the spectra reflects slower ring motions than pendant arms rearrangements in both complexes. Although losing some thermodynamic stability relative to Gd(DOTA)<sup>−</sup>, Gd(DO3A-BACE)<sup>−</sup> is still quite inert, indicating the usefulness of the bifunctional DO3A-ACE<sup>4−</sup> in the design of GBCAs and Ln<sup>3+</sup>-based tags for protein structural NMR analysis. |
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Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studiesBifunctional ligands (BFCs)ComplexesEquilibriumFormation and dissociation kineticsDynamic NMRScience & TechnologyThe thermodynamic, kinetic, and structural properties of Ln<sup>3+</sup> complexes with the bifunctional DO3A-ACE<sup>4−</sup> ligand and its amide derivative DO3A-BACE<sup>4−</sup> (modelling the case where DO3A-ACE<sup>4−</sup> ligand binds to vector molecules) have been studied in order to confirm the usefulness of the corresponding Gd<sup>3+</sup> complexes as relaxation labels of targeted MRI contrast agents. The stability constants of the Mg<sup>2+</sup> and Ca<sup>2+</sup> complexes of DO3A-ACE<sup>4−</sup> and DO3A-BACE<sup>4−</sup> complexes are lower than for DOTA<sup>4−</sup> and DO3A<sup>3−</sup>, while the Zn<sup>2+</sup> and Cu<sup>2+</sup> complexes have similar and higher stability than for DOTA<sup>4−</sup> and DO3A<sup>3−</sup> complexes. The stability constants of the Ln(DO3A-BACE)<sup>−</sup> complexes increase from Ce<sup>3+</sup> to Gd<sup>3+</sup> but remain practically constant for the late Ln<sup>3+</sup> ions (represented by Yb<sup>3+</sup>). The stability constants of the Ln(DO3A-ACE)<sup>4−</sup> and Ln(DO3A-BACE)<sup>4−</sup> complexes are several orders of magnitude lower than those of the corresponding DOTA<sup>4−</sup> and DO3A<sup>3−</sup> complexes. The formation rate of Eu(DO3A-ACE)<sup>−</sup> is one order of magnitude slower than for Eu(DOTA)<sup>−</sup>, due to the presence of the protonated amine group, which destabilizes the protonated intermediate complex. This protonated group causes the Ln(DO3A-ACE)<sup>−</sup> complexes to dissociate several orders of magnitude faster than Ln(DOTA)<sup>−</sup> and its absence in the Ln(DO3A-BACE)<sup>−</sup> complexes results in inertness similar to Ln(DOTA)<sup>−</sup> (as judged by the rate constants of acid assisted dissociation). The <sup>1</sup>H NMR spectra of the diamagnetic Y(DO3A-ACE)<sup>−</sup> and Y(DO3A-BACE)<sup>−</sup> reflect the slow dynamics at low temperatures of the intramolecular isomerization process between the SA pair of enantiomers, R-<i>Λ</i>(<i>λλλλ</i>) and S-<i>Δ</i>(<i>δδδδ</i>). The conformation of the C<sub>α</sub>-substituted pendant arm is different in the two complexes, where the bulky substituent is further away from the macrocyclic ring in Y(DO3A-BACE)<sup>−</sup> than the amino group in Y(DO3A-ACE)<sup>−</sup> to minimize steric hindrance. The temperature dependence of the spectra reflects slower ring motions than pendant arms rearrangements in both complexes. Although losing some thermodynamic stability relative to Gd(DOTA)<sup>−</sup>, Gd(DO3A-BACE)<sup>−</sup> is still quite inert, indicating the usefulness of the bifunctional DO3A-ACE<sup>4−</sup> in the design of GBCAs and Ln<sup>3+</sup>-based tags for protein structural NMR analysis.This research was funded by the Hungarian National Research, Development and Innovation Office (Projects NKFIH K-128201, K-134694, and FK-134551).Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoGarda, ZoltánKócs, TamaraBányai, IstvánMartins, J. A. R.Kálmán, Ferenc KrisztiánTóth, ImreGeraldes, Carlos F. G. C.Tircsó, Gyula2021-08-162021-08-16T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/74634engGarda, Z.; Kócs, T.; Bányai, I.; Martins, J.A.; Kálmán, F.K.; Tóth, I.; Geraldes, C.F.G.C.; Tircsó, G. Complexes of Bifunctional DO3A-N-(α-amino)propinate Ligands with Mg(II), Ca(II), Cu(II), Zn(II), and Lanthanide(III) Ions: Thermodynamic Stability, Formation and Dissociation Kinetics, and Solution Dynamic NMR Studies. Molecules 2021, 26, 4956. https://doi.org/10.3390/molecules261649561420-304910.3390/molecules2616495634443543https://www.mdpi.com/1420-3049/26/16/4956info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:39:04Zoai:repositorium.sdum.uminho.pt:1822/74634Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:35:37.927340Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies |
title |
Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies |
spellingShingle |
Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies Garda, Zoltán Bifunctional ligands (BFCs) Complexes Equilibrium Formation and dissociation kinetics Dynamic NMR Science & Technology |
title_short |
Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies |
title_full |
Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies |
title_fullStr |
Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies |
title_full_unstemmed |
Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies |
title_sort |
Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies |
author |
Garda, Zoltán |
author_facet |
Garda, Zoltán Kócs, Tamara Bányai, István Martins, J. A. R. Kálmán, Ferenc Krisztián Tóth, Imre Geraldes, Carlos F. G. C. Tircsó, Gyula |
author_role |
author |
author2 |
Kócs, Tamara Bányai, István Martins, J. A. R. Kálmán, Ferenc Krisztián Tóth, Imre Geraldes, Carlos F. G. C. Tircsó, Gyula |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Garda, Zoltán Kócs, Tamara Bányai, István Martins, J. A. R. Kálmán, Ferenc Krisztián Tóth, Imre Geraldes, Carlos F. G. C. Tircsó, Gyula |
dc.subject.por.fl_str_mv |
Bifunctional ligands (BFCs) Complexes Equilibrium Formation and dissociation kinetics Dynamic NMR Science & Technology |
topic |
Bifunctional ligands (BFCs) Complexes Equilibrium Formation and dissociation kinetics Dynamic NMR Science & Technology |
description |
The thermodynamic, kinetic, and structural properties of Ln<sup>3+</sup> complexes with the bifunctional DO3A-ACE<sup>4−</sup> ligand and its amide derivative DO3A-BACE<sup>4−</sup> (modelling the case where DO3A-ACE<sup>4−</sup> ligand binds to vector molecules) have been studied in order to confirm the usefulness of the corresponding Gd<sup>3+</sup> complexes as relaxation labels of targeted MRI contrast agents. The stability constants of the Mg<sup>2+</sup> and Ca<sup>2+</sup> complexes of DO3A-ACE<sup>4−</sup> and DO3A-BACE<sup>4−</sup> complexes are lower than for DOTA<sup>4−</sup> and DO3A<sup>3−</sup>, while the Zn<sup>2+</sup> and Cu<sup>2+</sup> complexes have similar and higher stability than for DOTA<sup>4−</sup> and DO3A<sup>3−</sup> complexes. The stability constants of the Ln(DO3A-BACE)<sup>−</sup> complexes increase from Ce<sup>3+</sup> to Gd<sup>3+</sup> but remain practically constant for the late Ln<sup>3+</sup> ions (represented by Yb<sup>3+</sup>). The stability constants of the Ln(DO3A-ACE)<sup>4−</sup> and Ln(DO3A-BACE)<sup>4−</sup> complexes are several orders of magnitude lower than those of the corresponding DOTA<sup>4−</sup> and DO3A<sup>3−</sup> complexes. The formation rate of Eu(DO3A-ACE)<sup>−</sup> is one order of magnitude slower than for Eu(DOTA)<sup>−</sup>, due to the presence of the protonated amine group, which destabilizes the protonated intermediate complex. This protonated group causes the Ln(DO3A-ACE)<sup>−</sup> complexes to dissociate several orders of magnitude faster than Ln(DOTA)<sup>−</sup> and its absence in the Ln(DO3A-BACE)<sup>−</sup> complexes results in inertness similar to Ln(DOTA)<sup>−</sup> (as judged by the rate constants of acid assisted dissociation). The <sup>1</sup>H NMR spectra of the diamagnetic Y(DO3A-ACE)<sup>−</sup> and Y(DO3A-BACE)<sup>−</sup> reflect the slow dynamics at low temperatures of the intramolecular isomerization process between the SA pair of enantiomers, R-<i>Λ</i>(<i>λλλλ</i>) and S-<i>Δ</i>(<i>δδδδ</i>). The conformation of the C<sub>α</sub>-substituted pendant arm is different in the two complexes, where the bulky substituent is further away from the macrocyclic ring in Y(DO3A-BACE)<sup>−</sup> than the amino group in Y(DO3A-ACE)<sup>−</sup> to minimize steric hindrance. The temperature dependence of the spectra reflects slower ring motions than pendant arms rearrangements in both complexes. Although losing some thermodynamic stability relative to Gd(DOTA)<sup>−</sup>, Gd(DO3A-BACE)<sup>−</sup> is still quite inert, indicating the usefulness of the bifunctional DO3A-ACE<sup>4−</sup> in the design of GBCAs and Ln<sup>3+</sup>-based tags for protein structural NMR analysis. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-08-16 2021-08-16T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/74634 |
url |
http://hdl.handle.net/1822/74634 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Garda, Z.; Kócs, T.; Bányai, I.; Martins, J.A.; Kálmán, F.K.; Tóth, I.; Geraldes, C.F.G.C.; Tircsó, G. Complexes of Bifunctional DO3A-N-(α-amino)propinate Ligands with Mg(II), Ca(II), Cu(II), Zn(II), and Lanthanide(III) Ions: Thermodynamic Stability, Formation and Dissociation Kinetics, and Solution Dynamic NMR Studies. Molecules 2021, 26, 4956. https://doi.org/10.3390/molecules26164956 1420-3049 10.3390/molecules26164956 34443543 https://www.mdpi.com/1420-3049/26/16/4956 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132882705317888 |