Synthesis, Characterization, Cytotoxicity, and Time‐Dependent NMR Spectroscopic Studies of (SP‐4‐3)‐Oxalato[(1R,2R,4R/1S,2S,4S)‐(4‐trifluoromethyl‐cyclohexane‐1,2‐diamine)]platinum(II)

Abstract

The oxaliplatin derivative (SP‐4‐3)‐oxalato[(1R,2R,4R/1S,2S,4S)‐(4‐trifluoromethyl‐cyclohexane‐1,2‐diamine)]platinum(II) hosting a trifluoromethyl group at position 4 of the cyclohexane ring is presented. The ligand was synthesized as an 1R,2R,4R/1S,2S,4S racemic mixture starting from 4‐trifluoromethyl‐cyclohexanol over five steps and coordinated to platinum to yield first the dichlorido and subsequently the oxalato complex. This novel compound and its analogue featuring a (13C2)oxalate ligand were characterized by multinuclear (1H, 13C, 15N, 19F, 195Pt) one‐ and two‐dimensional NMR spectroscopy. Ligand exchange and adduct formation reactions with DMSO, NaCl, CaCl2, l‐methionine, and 5′‐GMP were investigated via time‐dependent measurements by 19F and 13C NMR spectroscopy. The cytotoxicity of the title complex was investigated in three human cancer cell lines; the IC50 values were found in the low micromolar range, attesting moderate to high antiproliferative activity, depending on the cell line.