Synthesis, structure, and antitumor activity of novel platinum(II) complexes involving asymmetric chiral diamines as carrier ligands

Abstract

New platinum(II) complexes with asymmetrically substituted chiral diamine ligands A(2)PtX(2), (A(2) = NH2CH (CH3)CH2NH(c-C5H9) (apcpa), NH2CH(CH3)CH2NH(c-C6H11) (apcha); X-2 = 2Cl, isopropylidenmalonate (IPM), 1,1'-cyclobutandicarboxylate (CBDCA)) have been synthesized and characterized by means of elemental analyses, infrared and NMR spectroscopies, and X-ray crystallography. The crystal structures of (S- apcha)Pt[CBDCA] . 3H(2)O (orthorhombic, P2(1)2(1)2(No. 18), a = 6.926(3), b = 15.243(3), c = 19.319(4) Angstrom, V = 2039.5(10) Angstrom(3), Z = 3, R = 0.072) and (S-apcha)Pt[IPM] . 2.5H(2)O (monoclinic, P2/c(No. 13), a = 9.882(1), b = 18.502(1), c = 22.056(1) Angstrom, V = 4032.8(5) Angstrom(3), Z = 8, R=0.093) exhibit that the platinum atoms achieve a typical square planar arrangement with two nitrogen atoms in cis position and with the chiral center retained. The spectroscopic data disclose that these platinum complexes are stable and their molecular structures are retained in aqueous solution. Among these platinum complexes, the asymmetric diamine-Pt(II) complexes with chloride leaving group exhibit high in vivo activity comparable to cisplatin against leukemia L1210 cell line.