Prediction of q-values and conformations of gadolinium chelates for magnetic resonance imaging

For gadolinium chelates, we determined that there is a linear correlation b etween calculated solvent-accessible surface area and q-value, the number o f rapidly exchanging water molecules directly bound to the gadolinium ion. A calibration curve was developed to predict q-value based on the solvent-a ccessible surface area of gadolinium. This predictive method was validated with the following gadolinium crystal structures: (ethylenediaminetetraacet ic acid)-gadolinium(III) [Gd(EDTA)] [Templeton, L. K., Templeton, D. H., Za lkin, A., and Ruben, H. W. (1982) Anomalous Scattering by Praseodymium, Sam arium, and Gadolinium and Structures of their Thylenediaminetetraacetate (E DTA) Salts. Acta Crystallogr., Sect. B 38, 2155], (1,4,7,10-tetraazacyclodo decane-N,N',N ",N'''-tetraacetic acid)-gadolinium(III) [Gd(DOTA)] [Dubost, J.-P., Leger, J.-M., Langlois, M.-H., Meyer, D., and Schaefer, M. (1991) St ructure of a Magnetic Resonance Imaging Agent - The Gadolinium-DOTA Complex C16H24N4O8NaGd, 5H2O. C. R. Acad. Sci., Ser. 2 312, 349], (diethylenetriam inepentaacetic acid)-gadolinium(III) [Gd(DTPA)] [Stezowski, J. J., and Hoar d, J. L. (1984) Heavy Metal Ionophores - Correlations Among Structural Para meters of Complexed Nonpeptide Polyamino Acids. Isr. J. Chem. 24, 323], (di ethylenepenta-acetato)-gadolinium(III) [Gd(DTPA-BEA)] [Smith, P. H., Braina rd, J. R., Morris, D. E., Jarvinen, G. D., and Ryan, R. R. (1989) Solution and Solid-State Characterization of Europium and Gadolinium Schiff-Base Com plexes and Assessment of their Potential as Contrast Agents in Magnetic Res onance Imaging. J. Am. Chem. Soc. 111, 7437], and (1,7,13-triaza-4,10,16-tr ioxacyclo-octadecane-N,N',N "-triacetato)-gadolinium(III) [Gd(TTTA)] [Chen, D., Squattrito, P. J., Martell, A. E., and Clearfield, A. (1990) Synthesis and Crystal Structure of a 9-Coordinate Gadolinium(III) Complex of 1,7,13- Triaza-4,10,16-Trioxacyclooctadecane-N,N',N "-Trioxaacyclooctadecane-N,N',N "-Tri-Acetic Acid. Inorg. Chem. 29, 4366]. Predicted q-values were in comp lete agreement with experimentally determined q-values. A genetic algorithm -based conformational search method was developed to generate valid 3D mode ls for gadolinium chelates. The method was successfully tested on the follo wing gadolinium chelates: Gd(EDTA) (Templeton et al., 1982), Gd(DOTA) (Dubo st et al., 1991), Gd(DTPA-BEA) (Smith et al., 1989), Gd(TTTA) (Chen et al., 1990), Gd(triethylene glycol) [Rogers, R. D., Voss, E. J., and Etzenhouser , R. D. (1988) F-Element Crown Ether Complexes. 17. Synthetic and Structura l Survey of Lanthanide Chloride Tiethylene Glycol Complexes. Inorg. Chem. 2 7, 533], and Gd(tetraethylene glycol) [Rogers, R. D., Etzenhouser, R. D., M urdoch, J. S., and Reyes, E. (1991) Macrocycle Complexation Chemistry. 35. Survey of the Complexation of the Open-Chain 15-Crown-5 Analogue tetraethyl ene Glycol with the Lanthanide Chlorides. Inorg. Chem. 30, 1445].