title: The Crystal Structure of Oxaliplatin: A Case of Overlooked Pseudo Symmetry.
abstract: The crystal structure of the anticancer drug oxaliplatin, [Pt(R,R-DACH)(oxalate)] (DACH = diaminocyclohexane), was first reported in the non-centrosymmetric space group P21, confirming the sole presence of theR,Renantiomer of the DACH ligand [M. A. Brucket al.,Inorg. Chim. Acta, 92 (1984) 279-284]. It was later proposed that the crystal structure is better described in the centrosymmetric space group P21/m, signifying the presence of the compound as a racemic mixture [A. S. Abu-Surrahet al.,Polyhedron, 22 (2003) 1529-1534]. Herein is presented a reinvestigation of this crystal structure, which shows that the discrepancy between the two proposed space group assignments arises from overlooked pseudo symmetry. The crystal structures of the synthetic precursor to oxaliplatin, Pt(R,R-DACH)I2, and a platinum(IV) derivative,trans-[Pt(R,R-DACH)(oxalate)(OH)2], were also determined, and the absolute configuration of the DACH ligand in each was confirmed to beR,R. A spectroscopic investigation of the optical rotatory dispersion (ORD) of the oxaliplatin crystals was carried out to further confirm the lack of the true crystallographic mirror plane required for a P21/m solution. The ORD was theoretically simulated, in one instance, by applying the Kramers-Kronig transform to the computed circular dichroism spectrum and was found to corroborate the spectroscopic and crystallographic findings. Finally, a brief discussion is given of the importance of discussing the details of nuanced crystal structures and of providing evidence in addition to X-ray structure determination if chemically unexpected results are obtained.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Johnstone
keywords: Kramers-Kronig transform; Oxaliplatin; X-ray crystallography; absolute structure; optical rotatory dispersion; pseudo symmetry