title: Prediction of q-values and conformations of gadolinium chelates for magnetic resonance imaging.
abstract: For gadolinium chelates, we determined that there is a linear correlation between calculated solvent-accessible surface area and q-value, the number of rapidly exchanging water molecules directly bound to the gadolinium ion. A calibration curve was developed to predict q-value based on the solvent-accessible surface area of gadolinium. This predictive method was validated with the following gadolinium crystal structures: (ethylenediaminetetraacetic acid)-gadolinium(III) [Gd(EDTA)] [Templeton, L. K., Templeton, D. H., Zalkin, A., and Ruben, H. W. (1982) Anomalous Scattering by Praseodymium, Samarium, and Gadolinium and Structures of their Thylenediaminetetraacetate (EDTA) Salts. Acta Crystallogr., Sect. B 38, 2155], (1,4,7,10-tetraazacyclododecane-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) Structure of a Magnetic Resonance Imaging Agent - The Gadolinium-DOTA Complex C(16)H(24)N(4)O(8)NaGd, 5H(2)O. C. R. Acad. Sci., Ser. 2 312, 349], (diethylenetriaminepentaacetic acid)-gadolinium(III) [Gd(DTPA)] [Stezowski, J. J., and Hoard, J. L. (1984) Heavy Metal Ionophores - Correlations Among Structural Parameters of Complexed Nonpeptide Polyamino Acids. Isr. J. Chem. 24, 323], (diethylenepenta-acetato)-gadolinium(III) [Gd(DTPA-BEA)] [Smith, P. H., Brainard, J. R., Morris, D. E., Jarvinen, G. D., and Ryan, R. R. (1989) Solution and Solid-State Characterization of Europium and Gadolinium Schiff-Base Complexes and Assessment of their Potential as Contrast Agents in Magnetic Resonance Imaging. J. Am. Chem. Soc. 111, 7437], and (1,7,13-triaza-4,10, 16-trioxacyclo-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' '-Tri-Acetic Acid. Inorg. Chem. 29, 4366]. Predicted q-values were in complete agreement with experimentally determined q-values. A genetic algorithm-based conformational search method was developed to generate valid 3D models for gadolinium chelates. The method was successfully tested on the following gadolinium chelates: Gd(EDTA) (Templeton et al., 1982), Gd(DOTA) (Dubost 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 Structural Survey of Lanthanide Chloride Tiethylene Glycol Complexes. Inorg. Chem. 27, 533], and Gd(tetraethylene glycol) [Rogers, R. D., Etzenhouser, R. D., Murdoch, J. S., and Reyes, E. (1991) Macrocycle Complexation Chemistry. 35. Survey of the Complexation of the Open-Chain 15-Crown-5 Analogue tetraethylene Glycol with the Lanthanide Chlorides. Inorg. Chem. 30, 1445].
authors.affiliation: Departments of Biophysics and Computational Chemistry, Medicinal, and Analytical Chemistry, Sterling Winthrop Pharmaceutical Research Division, Collegeville, PA 19426-0900, USA. castong@merck.com
authors.forename: L A
authors.initials: LA
authors.lastname: Castonguay
authors.forename: A M
authors.initials: AM
authors.lastname: Treasurywala
authors.forename: T J
authors.initials: TJ
authors.lastname: Caulfield
authors.forename: E P
authors.initials: EP
authors.lastname: Jaeger
authors.forename: K E
authors.initials: KE
authors.lastname: Kellar
mesh_terms: D000465:Algorithms; D002614:Chelating Agents / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003287:Contrast Media / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D004492:Edetic Acid / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D019786:Gadolinium DTPA / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry; D012984:Software; D012997:Solvents; D013329:Structure-Activity Relationship
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D012997:Solvents; C041365:gadolinium EDTA; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D004492:Edetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA