Acta Phys. -Chim. Sin. ›› 2009, Vol. 25 ›› Issue (11): 2350-2356.doi: 10.3866/PKU.WHXB20091123

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Hydrolysis Mechanism of New Anticancer Drug Transplatin Analogues Containing One Nonplanar Heterocyclic Amine Ligand

ZHAO Ya-Hua   

  1. College of Life Science, South China Agricultural University, Guangzhou 510642, P. R. China
  • Received:2009-05-22 Revised:2009-08-09 Published:2009-10-28
  • Contact: ZHAO Ya-Hua


Hydrolysis processes of novel anticancer transplatin analogues, trans-[PtCl2(NH3)(Am)](Am: nonplanar heterocycle piperidine or piperazine), were explored using the B3LYP hybrid functional and isoelectric focusing polarized continuum model (IEF-PCM). Stationary points on the potential energy surfaces for the first and second hydrolysis steps that proceed via a general SN2 pathway were fully optimized and characterized. The most remarkable structural variations in the hydrolysis process were found to occur in the equatorial plane of five-coordinate trigonal-bipyramidal (TBP) like structures of the intermediates and transition states. We obtained lower activation energies for trans-[PtCl2(NH3)(piperazine)] and a slightly higher activation energy for the first step and a slightly lower activation energy for the second step during the hydrolysis of trans-[PtCl2(NH3)(piperidine)] by comparison to previous work on the hydrolysis reactions of cisplatin. Our calculations suggest that this class of non-classical transplatin analogues with one nonplanar heterocyclic amine decreases the equatorial steric effect and the hydrolysis reaction barriers.

Key words: Hydrolysis, Density functional theory, Nonplanar heterocyclic amine ligand, Transition state, Non-classical transplatin