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
N1 - Funding Information:
The authors thank the Hungarian Scientific Research Fund (OTKA K-109029 and K-120224 ) and TÁMOP 4.2.4. A/2-11-1-2012-0001 ‘National Excellence Program’ (grant no.: A2-MZPD-12-0038 ) (Zs. B.) supported by the European Union and the State of Hungary , co-financed by the European Social Fund . This paper was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (K. F. K. and Gy. T.). This work has been carried out in the frame of the COST TD1004 Action “Theragnostics Imaging and Therapy: An Action to Develop Novel Nanosized Systems for Imaging-Guided Drug Delivery”. Norbert Lihi (Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen) is thanked for his help with the preparation of Figs. S1 and S2.
Publisher Copyright:
© 2016 Elsevier Inc.
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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U2 - 10.1016/j.jinorgbio.2016.07.018
DO - 10.1016/j.jinorgbio.2016.07.018
M3 - Article
C2 - 27567150
AN - SCOPUS:84993990174
SN - 0162-0134
VL - 163
SP - 206
EP - 213
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
ER -