The authors thank the National Institutes of Health (EB-011687), Oregon Nanoscience and Microtechnologies Institute (N00014-11-1-0193), the Regione Piemonte (Italy) through the Nano-IGT and PIIMDMT projects; a János Bolyai Research Scholarship of the Hungarian Academy of Sciences, the Hungarian Scientific Research Found (OTKA K84291) and the TÁMOP 4.2.1./B-09/1/KONV-2010-0007 project implemented through the New Hungary Development Plan, cofinanced by the European Social Fund and the European Regional Development Fund (G.T.); M.J. Murdock Charitable Trust, Portland State University, and the Oregon Opportunity for financial support of this work.
Ligands (Biochemistry), Carboxylates, Chelates -- Synthesis, Contrast media (Diagnostic imaging), Magnetic resonance imaging, Isomerism
The chemistry of polyamino carboxylates and their use as ligands for Ln(3+) ions is of considerable interest from the point of view of the development of new imaging agents. Of particular interest is the chemistry of the macrocyclic ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and its derivatives. Herein we report that the tetramethylated DOTA derivative, DOTMA, possess several properties that, from an imaging agent development point of view, are more advantageous than those of the parent DOTA. In particular, the Ln(3+) chelates of DOTMA exhibit a marked preference for the monocapped twisted square antiprismatic coordination isomer which imparts more rapid water exchange kinetics on the chelates; τ(M)(298) was determined to be 85 ns for GdDOTMA. Differential analysis of the (17)O R(2ρ) temperature profiles of both GdDOTA and GdDOTMA afforded the τ(M)(298) values for the square (SAP) and twisted square antiprismatic (TSAP) isomers of each chelate that were almost identical: 365 ns (SAP) and 52 ns (TSAP). The origin of this accelerated water exchange in the TSAP isomer appears to be the slightly longer Gd-OH(2) bond distance (2.50 Å) that is observed in the crystal structure of GdDOTMA which crystallizes in the P(2) space group as a TSAP isomer. The Ln(3+) chelates of DOTMA also exhibit high thermodynamic stabilities ranging from log K(ML) = 20.5 for CeDOTMA, 23.5 for EuDOTMA and YbDOTMA comparable to, but a shade lower than, those of DOTA.
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Pubished as: Aime, S., Botta, M., Garda, Z., Kucera, B. E., Tircso, G., Young, V. G., & Woods, M. (2011). Properties, Solution State Behavior, and Crystal Structures of Chelates of DOTMA. Inorganic Chemistry, 50(17), 7955–7965.