title: Physico-chemical properties of MnIIcomplexes formed with cis- and trans-DO2A: thermodynamic, electrochemical and kinetic studies.
abstract: MnIIcomplexes 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 MnIIcomplexes 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 MnIIcomplexes 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 MnIIcomplexes 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 +705mV versus Ag/AgCl, respectively. These values indicate that the MnIIion 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 CuIIor ZnIIions. Kinetic measurements indicate that both MnIIcomplexes 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 MnIIcomplexes as alternatives to Gd-based MRI agents.
authors: Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4010 Debrecen, Hungary.
authors: Zoltán
authors: Z
authors: Garda
authors: Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4010 Debrecen, Hungary.
authors: Attila
authors: A
authors: Forgács
authors: Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
authors: Quyen N
authors: QN
authors: Do
authors: Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4010 Debrecen, Hungary; Centre de Biophysique Moléculaire, CNRS, rue Charles Sadron, 45071 Orléans, Cedex 2, France; Le Studium, Loire Valley Institute for Advanced Studies, 1 Rue Dupanloup, 45000, Orléans, France.
authors: Ferenc K
authors: FK
authors: Kálmán
authors: Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4010 Debrecen, Hungary.
authors: Sarolta
authors: S
authors: Timári
authors: Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4010 Debrecen, Hungary.
authors: Zsolt
authors: Z
authors: Baranyai
authors: Dipartimento di Scienze e Innovazione Tecnologica, Università degli Studi del Piemonte Orientale "A. Avogadro", Viale T. Michel 11, I-15121 Alessandria, Italy.
authors: Lorenzo
authors: L
authors: Tei
authors: Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4010 Debrecen, Hungary.
authors: Imre
authors: I
authors: Tóth
authors: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
authors: Zoltán
authors: Z
authors: Kovács
authors: Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4010 Debrecen, Hungary. Electronic address: gyula.tircso@science.unideb.hu.
authors: Gyula
authors: G
authors: Tircsó
mesh_terms: D002614:Chelating Agents / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry*; D055664:Electrochemical Techniques; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D007700:Kinetics; D008345:Manganese / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: C561329:1,4,7,10-tetraazacyclododecane-1,7-diacetic acid; D002614:Chelating Agents; D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D008345:Manganese
keywords: Contrast agents (CAs); Electrochemistry; Inertness; Magnetic resonance imaging (MRI); Manganese; Thermodynamic stability