Physico-chemical properties of MnII complexes formed with cis- and trans-DO2A: thermodynamic, electrochemical and kinetic studies

Zoltán Garda, Attila Forgács, Quyen N. Do, Ferenc K. Kálmán, Sarolta Timári, Zsolt Baranyai, Lorenzo Tei, Imre Tóth, Zoltán Kovács, Gyula Tircsó

Research output: Contribution to journalArticle

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Abstract

Synopsis: MnII complexes formed with cis- and trans-DO2A (DO2A = 1,4,7,10-tetraazacyclododecane-1,4 (or 1,7) -diacetic acid) chelators were investigated by pH-potentiometry, 1H relaxometry, UV-vis spectrophotometry and cyclic voltammetry. The physico-chemical characteristics of MnII complexes of these structure isomers do not differ dramatically, however the cis-DO2A platform has better potential for further development. Manganese (MnII) is a promising alternative to gadolinium (GdIII) as a magnetic resonance imaging (MRI) agent. Unlike gadolinium, this biogenic metal might be better tolerated by the body, reducing the risk of toxicity associated with dissociation of the complex. Herein we report detailed equilibrium and kinetic studies performed with MnII complexes of 1,4,7,10-tetraazacyclododecane-1,4-diacetic acid (1,4-DO2A or cis-DO2A) and 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (1,7-DO2A or trans-DO2A). The protonation constants of the ligands as well as stability constants of their MnII complexes have been determined by pH-potentiometry. The stability constants of [Mn(cis-DO2A)] are slightly higher than those of [Mn(trans-DO2A)] (log KMnL = 15.68 and 15.22, respectively). Cyclic voltammetric (CV) experiments performed on [Mn(cis-DO2A)] and [Mn(trans-DO2A)] revealed quasireversible systems with a half-wave potential of + 636 and + 705 mV versus Ag/AgCl, respectively. These values indicate that the MnII ion in these complexes is more stabilized against the oxidation than in [Mn(EDTA)]2 −. The kinetic inertness of the complexes has been studied in transmetallation reactions with CuII or ZnII ions. Kinetic measurements indicate that both MnII complexes primarily undergo acid catalyzed dissociation and positions of the acetate pendant arms do not influence kinetic inertness. The inertness of these complexes is comparable to that of [Mn(NOTA)] (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid) and about twenty times lower than that of [Mn(DOTA)]2 − (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). In conclusion, [Mn(cis-DO2A)] displays some very interesting features (thermodynamic and redox stability as well as kinetic inertness) which makes this complex a promising platform for the development of more efficient MnII complexes as alternatives to Gd-based MRI agents.

Original languageEnglish (US)
Pages (from-to)206-213
Number of pages8
JournalJournal of Inorganic Biochemistry
Volume163
DOIs
StatePublished - Oct 1 2016

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Thermodynamics
Chemical properties
Kinetics
Potentiometry
Acids
Gadolinium
Magnetic resonance
Magnetic Resonance Imaging
Ions
Imaging techniques
Spectrophotometry
Protonation
Chelating Agents
Manganese
Edetic Acid
Isomers
Cyclic voltammetry
Oxidation-Reduction
Toxicity
Acetates

Keywords

  • Contrast agents (CAs)
  • Electrochemistry
  • Inertness
  • Magnetic resonance imaging (MRI)
  • Manganese
  • Thermodynamic stability

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

Physico-chemical properties of MnII complexes formed with cis- and trans-DO2A : thermodynamic, electrochemical and kinetic studies. / Garda, Zoltán; Forgács, Attila; Do, Quyen N.; Kálmán, Ferenc K.; Timári, Sarolta; Baranyai, Zsolt; Tei, Lorenzo; Tóth, Imre; Kovács, Zoltán; Tircsó, Gyula.

In: Journal of Inorganic Biochemistry, Vol. 163, 01.10.2016, p. 206-213.

Research output: Contribution to journalArticle

Garda, Zoltán ; Forgács, Attila ; Do, Quyen N. ; Kálmán, Ferenc K. ; Timári, Sarolta ; Baranyai, Zsolt ; Tei, Lorenzo ; Tóth, Imre ; Kovács, Zoltán ; Tircsó, Gyula. / Physico-chemical properties of MnII complexes formed with cis- and trans-DO2A : thermodynamic, electrochemical and kinetic studies. In: Journal of Inorganic Biochemistry. 2016 ; Vol. 163. pp. 206-213.
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abstract = "Synopsis: MnII complexes formed with cis- and trans-DO2A (DO2A = 1,4,7,10-tetraazacyclododecane-1,4 (or 1,7) -diacetic acid) chelators were investigated by pH-potentiometry, 1H relaxometry, UV-vis spectrophotometry and cyclic voltammetry. The physico-chemical characteristics of MnII complexes of these structure isomers do not differ dramatically, however the cis-DO2A platform has better potential for further development. Manganese (MnII) is a promising alternative to gadolinium (GdIII) as a magnetic resonance imaging (MRI) agent. Unlike gadolinium, this biogenic metal might be better tolerated by the body, reducing the risk of toxicity associated with dissociation of the complex. Herein we report detailed equilibrium and kinetic studies performed with MnII complexes of 1,4,7,10-tetraazacyclododecane-1,4-diacetic acid (1,4-DO2A or cis-DO2A) and 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (1,7-DO2A or trans-DO2A). The protonation constants of the ligands as well as stability constants of their MnII complexes have been determined by pH-potentiometry. The stability constants of [Mn(cis-DO2A)] are slightly higher than those of [Mn(trans-DO2A)] (log KMnL = 15.68 and 15.22, respectively). Cyclic voltammetric (CV) experiments performed on [Mn(cis-DO2A)] and [Mn(trans-DO2A)] revealed quasireversible systems with a half-wave potential of + 636 and + 705 mV versus Ag/AgCl, respectively. These values indicate that the MnII ion in these complexes is more stabilized against the oxidation than in [Mn(EDTA)]2 −. The kinetic inertness of the complexes has been studied in transmetallation reactions with CuII or ZnII ions. Kinetic measurements indicate that both MnII complexes primarily undergo acid catalyzed dissociation and positions of the acetate pendant arms do not influence kinetic inertness. The inertness of these complexes is comparable to that of [Mn(NOTA)]− (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid) and about twenty times lower than that of [Mn(DOTA)]2 − (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). In conclusion, [Mn(cis-DO2A)] displays some very interesting features (thermodynamic and redox stability as well as kinetic inertness) which makes this complex a promising platform for the development of more efficient MnII complexes as alternatives to Gd-based MRI agents.",
keywords = "Contrast agents (CAs), Electrochemistry, Inertness, Magnetic resonance imaging (MRI), Manganese, Thermodynamic stability",
author = "Zolt{\'a}n Garda and Attila Forg{\'a}cs and Do, {Quyen N.} and K{\'a}lm{\'a}n, {Ferenc K.} and Sarolta Tim{\'a}ri and Zsolt Baranyai and Lorenzo Tei and Imre T{\'o}th and Zolt{\'a}n Kov{\'a}cs and Gyula Tircs{\'o}",
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TY - JOUR

T1 - Physico-chemical properties of MnII complexes formed with cis- and trans-DO2A

T2 - thermodynamic, electrochemical and kinetic studies

AU - Garda, Zoltán

AU - Forgács, Attila

AU - Do, Quyen N.

AU - Kálmán, Ferenc K.

AU - Timári, Sarolta

AU - Baranyai, Zsolt

AU - Tei, Lorenzo

AU - Tóth, Imre

AU - Kovács, Zoltán

AU - Tircsó, Gyula

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Synopsis: MnII complexes formed with cis- and trans-DO2A (DO2A = 1,4,7,10-tetraazacyclododecane-1,4 (or 1,7) -diacetic acid) chelators were investigated by pH-potentiometry, 1H relaxometry, UV-vis spectrophotometry and cyclic voltammetry. The physico-chemical characteristics of MnII complexes of these structure isomers do not differ dramatically, however the cis-DO2A platform has better potential for further development. Manganese (MnII) is a promising alternative to gadolinium (GdIII) as a magnetic resonance imaging (MRI) agent. Unlike gadolinium, this biogenic metal might be better tolerated by the body, reducing the risk of toxicity associated with dissociation of the complex. Herein we report detailed equilibrium and kinetic studies performed with MnII complexes of 1,4,7,10-tetraazacyclododecane-1,4-diacetic acid (1,4-DO2A or cis-DO2A) and 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (1,7-DO2A or trans-DO2A). The protonation constants of the ligands as well as stability constants of their MnII complexes have been determined by pH-potentiometry. The stability constants of [Mn(cis-DO2A)] are slightly higher than those of [Mn(trans-DO2A)] (log KMnL = 15.68 and 15.22, respectively). Cyclic voltammetric (CV) experiments performed on [Mn(cis-DO2A)] and [Mn(trans-DO2A)] revealed quasireversible systems with a half-wave potential of + 636 and + 705 mV versus Ag/AgCl, respectively. These values indicate that the MnII ion in these complexes is more stabilized against the oxidation than in [Mn(EDTA)]2 −. The kinetic inertness of the complexes has been studied in transmetallation reactions with CuII or ZnII ions. Kinetic measurements indicate that both MnII complexes primarily undergo acid catalyzed dissociation and positions of the acetate pendant arms do not influence kinetic inertness. The inertness of these complexes is comparable to that of [Mn(NOTA)]− (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid) and about twenty times lower than that of [Mn(DOTA)]2 − (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). In conclusion, [Mn(cis-DO2A)] displays some very interesting features (thermodynamic and redox stability as well as kinetic inertness) which makes this complex a promising platform for the development of more efficient MnII complexes as alternatives to Gd-based MRI agents.

AB - Synopsis: MnII complexes formed with cis- and trans-DO2A (DO2A = 1,4,7,10-tetraazacyclododecane-1,4 (or 1,7) -diacetic acid) chelators were investigated by pH-potentiometry, 1H relaxometry, UV-vis spectrophotometry and cyclic voltammetry. The physico-chemical characteristics of MnII complexes of these structure isomers do not differ dramatically, however the cis-DO2A platform has better potential for further development. Manganese (MnII) is a promising alternative to gadolinium (GdIII) as a magnetic resonance imaging (MRI) agent. Unlike gadolinium, this biogenic metal might be better tolerated by the body, reducing the risk of toxicity associated with dissociation of the complex. Herein we report detailed equilibrium and kinetic studies performed with MnII complexes of 1,4,7,10-tetraazacyclododecane-1,4-diacetic acid (1,4-DO2A or cis-DO2A) and 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (1,7-DO2A or trans-DO2A). The protonation constants of the ligands as well as stability constants of their MnII complexes have been determined by pH-potentiometry. The stability constants of [Mn(cis-DO2A)] are slightly higher than those of [Mn(trans-DO2A)] (log KMnL = 15.68 and 15.22, respectively). Cyclic voltammetric (CV) experiments performed on [Mn(cis-DO2A)] and [Mn(trans-DO2A)] revealed quasireversible systems with a half-wave potential of + 636 and + 705 mV versus Ag/AgCl, respectively. These values indicate that the MnII ion in these complexes is more stabilized against the oxidation than in [Mn(EDTA)]2 −. The kinetic inertness of the complexes has been studied in transmetallation reactions with CuII or ZnII ions. Kinetic measurements indicate that both MnII complexes primarily undergo acid catalyzed dissociation and positions of the acetate pendant arms do not influence kinetic inertness. The inertness of these complexes is comparable to that of [Mn(NOTA)]− (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid) and about twenty times lower than that of [Mn(DOTA)]2 − (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). In conclusion, [Mn(cis-DO2A)] displays some very interesting features (thermodynamic and redox stability as well as kinetic inertness) which makes this complex a promising platform for the development of more efficient MnII complexes as alternatives to Gd-based MRI agents.

KW - Contrast agents (CAs)

KW - Electrochemistry

KW - Inertness

KW - Magnetic resonance imaging (MRI)

KW - Manganese

KW - Thermodynamic stability

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