New antitumor-active azole-bridged dinuclear platinum(II) complexes: Synthesis, characterization, crystal structures, and cytotoxic studies

Three new derivatives of the cytotoxic azole-bridged dinuclear platinum(II) complex [{Cis-Pt(NH3)(2)}(2)(mu-OH)-(n mu-pz)][NO3](2) (1) have been prepa red and structurally characterized. Their formulas are [{cis-Pt(NH3)(2)}(mu -OH)-(mu-1,2,3-ta)][NO3](2) (2) (1,2,3-ta = 1,2,3-triazolate), [{Pt(R,R-dac h)}(mu-OH)(mu-pz){Pt(S,S-dach)}][NO3](2) (3) (dach = 1,2-diaminocyclohexane , pz = pyrazolate), and [{Pt(R,R-dach)}(mu-1,2,3-ta)(2){Pt(S,S-dach)}][NO3] (2) (4). The compounds were characterized by H-1, C-13, and Pt-195 NMR spec troscopy,and elemental analysis, and their crystal structures were determin ed. Relevant data for 2: triclinic, space group P (1) over bar, a = 8.5225( 15) Angstrom, b = 9.1977(18) Angstrom, c = 9.9771(7) Angstrom, alpha = 66.9 88(10)degrees, beta = 75.323(9)degrees, gamma = 67.321(13)degrees, Z = 2. 3 : orthorhombic, space group Pca2(1), a = 17.7653(3) Angstrom, b = 12.4076(3 ) Angstrom, c = 10.7091(3) Angstrom, Z = 4. 4: orthorhombic, space group Pb ca, a = 13.8944(1) Angstrom, b = 17.8668(1) Angstrom, c = 20.7647(2) Angstr om, Z = 8, In the crystal structures of 2, and 3, the intramolecular distan ces between the two Pt atoms are 3.4411(6) and 3.4873(5) a, and the dihedra l angles between the platinum coordination planes are 14.1(3) and 9.3(4)deg rees, respectively. In 2, an intramolecular hydrogen bond is observed betwe en N9 of the ammine ligand and the noncoordinated nitrogen atom (N3) of the triazole ring (N9 ... N3: 2.962(10) Angstrom). 4 has a boat-form structure , and the two coordination planes cross at 83.64(10)degrees. A cytotoxicity assay of these dinuclear platinum(II) compounds on human tumor cell lines was performed. in most of the cell lines, 1 and 2 showed much higher cytoto xicity than those of cisplatin. On the other hand, 3 was found to be modera tely active, and 4 was found only marginally cytotoxic. Implications of the se findings are discussed in the context of a structure-activity relationsh ip.