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(μ-OH)(μ-pz)][NO3]2 (1) have been prepared and structurally characterized. Their formulas are [{cis-Pt(NH3)2}2(μ-OH)(μ-1,2,3-ta)][NO3]2 (2) (1,2,3-ta = 1,2,3-triazolate), [{Pt(R,R-dach)}(μ-OH)(μ-pz){Pt(S,S-dach)}][NO3]2 (3) (dach
= 1,2-diaminocyclohexane, pz = pyrazolate), and [{Pt(R,R-dach)}(μ-1,2,3-ta)2{Pt(S,S-dach)}][NO3]2 (4). The
compounds were characterized by 1H, 13C, and 195Pt NMR spectroscopy, and elemental analysis, and their crystal
structures were determined. Relevant data for 2:  triclinic, space group P1̄, a = 8.5225(15) Å, b = 9.1977(18) Å,
c = 9.9771(7) Å, α = 66.988(10)°, β = 75.423(9)°, γ = 67.321(13)°, Z = 2. 3:  orthorhombic, space group
Pca21, a = 17.7653(3) Å, b = 12.4076(3) Å, c = 10.7091(3) Å, Z = 4. 4:  orthorhombic, space group Pbca, a
= 13.8944(1) Å, b = 17.8668(1) Å, c = 20.7647(2) Å, Z = 8. In the crystal structures of 2, and 3, the intramolecular
distances between the two Pt atoms are 3.4411(6) and 3.4873(5) Å, and the dihedral angles between the platinum
coordination planes are 14.1(3) and 9.3(4)°, respectively. In 2, an intramolecular hydrogen bond is observed
between N9 of the ammine ligand and the noncoordinated nitrogen atom (N3) of the triazole ring (N9···N3: 
2.962(10) Å). 4 has a boat-form structure, and the two coordination planes cross at 83.64(10)°. 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 cytotoxicity than those of cisplatin. On the other hand, 3 was found to be
moderately active, and 4 was found only marginally cytotoxic. Implications of these findings are discussed in the
context of a structure−activity relationship.