A solid-state17O NMR study of platinum-carboxylate complexes: carboplatin and oxaliplatin

Abstract

We report synthesis and solid-state NMR characterization of two17O-labeled platinum anticancer drugs: cis-diammine(1,1-cyclobutane-[17O4]dicarboxylato)platinum(II) (carboplatin) and ([17O4]oxalato)[(1R, 2R)-(−)-1,2-cyclohexanediamine)]platinum(II) (oxaliplatin). Both17O chemical shift (CS) and quadrupolar coupling (QC) tensors were measured for the carboxylate groups in these two compounds. With the aid of plane wave DFT computations, the17O CS and QC tensor orientations were determined in the molecular frame of reference. Significant changes in the17O CS and QC tensors were observed for the carboxylate oxygen atom upon its coordination to Pt(II). In particular, the17O isotropic chemical shifts for the oxygen atoms directly bonded to Pt(II) are found to be smaller (more shielded) by 200 ppm than those for the non-Pt-coordinated oxygen atoms within the same carboxylate group. Examination of the17O CS tensor components reveals that such a large17O coordination shift is primarily due to the shielding increase along the direction that is within the O=C–O–Pt plane and perpendicular to the O–Pt bond. This result is interpreted as due to the σ donation from the oxygen nonbonding orbital (electron lone pair) to the Pt(II) empty dyzorbital, which results in large energy gaps between σ(Pt–O) and unoccupied molecular orbitals, thus reducing the paramagnetic shielding contribution along the direction perpendicular to the O–Pt bond. We found that the17O QC tensor of the carboxylate oxygen is also sensitive to Pt(II) coordination, and that17O CS and QC tensors provide complementary information about the O–Pt bonding.