Tuning the Reactivity and Bonding Properties of the Pt(II) Complexes by the Substitution(s) on the Trans-Coordinated Non-Aromatic Amine Ligand

Kinetics of the hydration reaction and the bonding properties of the trans-[Pt(NH3)(2)(NH2X)Cl](+) complexes (X=H, CH3, F, Cl, Br, NH2, NO2, OH, dimethylamine (DMA), cyclopropyl (CyP), cyclohexyl (CyH)) were studied theoretically by DFT methodology in the gas phase and the water solution. The electron-donating and electron-withdrawing X substituents lower and increase, respectively, the activation free energy (Delta G(not equal)) and Pt-trans ligand binding energies (BEs) to a similar extent as meta and para substituents of the pyridine ligand studied previously (ACS Omega, 2020, 5, 11768). For the saturated hydrocarbon X substituents (X=H, CH3, CyP, CyH), the Delta G(not equal) values and Pt-trans ligand BEs decrease with the logarithm of the X substituent size being best quantified by the number of electrons. The additivity of the substituent effects was studied on the NF3 ligand and worked well for ligand charges and Pt-trans ligand BEs. The influence of chelation was evaluated by the comparison of the CyH system and the complexes with the cyclohexanediamine (DACH) ligand. Finally, the effect of isomerization was studied on the complexes with the 1,2-bis(aminomethyl)cyclobutane (BAMCB) ligand. Thus, this study also evaluates the influence of the non-leaving ligands present in cisplatin, oxaliplatin, lobaplatin, JM118, and JM11 drugs on the reactivity of the Pt(II) complexes in the same ligand environment.

Automated summary

The kinetics of the hydration reaction and the bonding properties of the trans-[Pt(NH3)(2)(NH2X)Cl](+) complexes were studied theoretically using DFT methodology. It was found that electron-donating and electron-withdrawing X substituents affect the activation free energy and Pt-trans ligand binding energies, with the impact related to the size and number of electrons of the substituents. The study also evaluated the influence of chelation, additivity of the substituent effects, and isomerization on the reactivity of the complexes.