We report synthesis and solid-state NMR characterization of two 17O-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). Both 17O 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, the 17O CS and QC tensor orientations were determined in the molecular frame of reference. Significant changes in the 17O CS and QC tensors were observed for the carboxylate oxygen atom upon its coordination to Pt(II). In particular, the 17O 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 the 17O CS tensor components reveals that such a large 17O 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 dyz orbital, 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 the 17O QC tensor of the carboxylate oxygen is also sensitive to Pt(II) coordination, and that 17O CS and QC tensors provide complementary information about the O–Pt bonding.
Solid-State 17O NMR Study of α-D-Glucose: Exploring New Frontiers in Isotopic Labeling, Sensitivity Enhancement, and NMR Crystallography
