The amphiphilic gadolinium complex MS-325 ((trisodium-{(2-(R)-[(4,4-diphenylcyclohexyl) phosphonooxymethyl] diethylenetriaminepentaacetato) (aquo)gadolinium(III)}) is a contrast agent for magnetic resonance angiography (MRA). MS-325 comprises a GdDTPA core with an appended phosphodiester moiety linked to a diphenylcyclohexyl group to facilitate noncovalent binding to serum albumin and extension of the plasma half-life in vivo. The chiral DTPA ligand (R) was derived from l-serine, and upon complexation with gadolinium, forms two interconvertible diastereomers, denoted herein as isomers A and B. X-ray crystallography of the tris(ethylenediamine)cobalt(III) salt derivative of isomer A revealed a structure in the polar acentric space group P3(2). The structure consisted of three independent molecules of the gadolinium complex in the asymmetric unit along with three Delta-[Co(en)(3)](3+) cations, and it represents an unusual example of spontaneous Pasteur resolution of the cobalt cation. The geometry of the coordination core was best described as a distorted trigonal prism, and the final R factor was 5.6%. The configuration of the chiral central nitrogen of the DTPA core was S. The Gd-water (2.47-2.48 angstrom), the Gd-acetate oxygens (2.34-2.42 angstrom), and the Gd-N bond distances (central N, 2.59-2.63 angstrom; terminal N, 2.74-2.80 angstrom) were similar to other reported GdDTPA structures. The structurally characterized single crystal was one of two interconvertable diastereomers (isomers A and B) that equilibrated to a ratio of 1.81 to 1 at pH 7.4 and were separable at elevated pH by ion-exchange chromatography. The rate of isomerization was highly pH dependent: k(1) = (1.45 +/- 0.08) x 10(2)[H+] + (4.16 +/- 0.30) x 10(5)[H+](2); k(-1) = (2.57 +/- 0.17) x 10(2)[H+] + (7.54 +/- 0.60) x 10(5)[H+](2).