Preparation, characterization, and antitumor activity of new cisplatin analogs with homopiperazines: crystal structure of [Pt II(1-methylhomopiperazine)(methylmalonato)]·2H 2O

Abstract

A series of new platinum(II) and (IV) complexes with homopiperazine have been synthesized and characterized by elemental analysis, infrared, and 195Pt nuclear magnetic resonance spectroscopic techniques. The complexes are of two types: [Pt IILX] (where L=homopiperazine (hpip), 1-methylhomopiperazine (mhpip), or 1,4-dimethylhomopiperazine (dmhpip), and X=1,1-cyclobutanedicarboxylato (CBDCA), or methylmalonato ligand) and [Pt IV(L-) trans-(Y) 2Cl 2] (where Y=hydroxo, acetato, or chloro ligand). Among the complexes synthesized, the crystal structure of [Pt II(mhpip)(methylmalonato)]·2H 2O was determined by the single crystal X-ray diffraction method. The crystallographic parameters were orthorhombic, P2 12 12 1 (no. 19), a=7.2014(14), b=7.3348(15), c=26.971(5) Å, and Z=4. The structure refinements converged to R1=0.0641 and w R2= 0.1847. In this complex, platinum has a slightly distorted square planar geometry with the two adjacent corners being occupied by two nitrogens of the mhpip ligand, whereas the remaining cis positions are coordinated with two oxygen atoms of the methylmalonato group. The mhpip ligand is in a boat conformation and forms five and six membered chelating rings with platinum. The intricate network of intermolecular hydrogen bonds holds the crystal lattice together. Some of these synthesized cisplatin analogs have good in vitro cytotoxic activity against the cisplatin-sensitive human ovarian A2780 (IC 50=0.083–17.8 μM) and the isogenic cisplatin-resistant 2780CP (IC 50=20.1–118.1 μM) cell lines.