New Antitumor-Active Azole-Bridged Dinuclear Platinum(II) Complexes:  Synthesis, Characterization, Crystal Structures, and Cytotoxic Studies

• Published in: Inorganic chemistry Vol. 39; no. 19; pp. 4230 - 4236
• Main Authors: Komeda, Seiji, Lutz, Martin, Spek, Anthony L, Chikuma, Masahiko, Reedijk, Jan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.09.2000
• Subjects: Antineoplastic Agents - chemical synthesis; Azoles - chemical synthesis; Azoles - chemistry; Azoles - toxicity; Bridged-Ring Compounds - chemical synthesis; Bridged-Ring Compounds - chemistry; Bridged-Ring Compounds - toxicity; Humans; Magnetic Resonance Spectroscopy; Molecular Structure; Platinum Compounds - chemical synthesis; Platinum Compounds - chemistry; Platinum Compounds - toxicity; Stereoisomerism; Structure-Activity Relationship; Tumor Cells, Cultured; X-Ray Diffraction
• DOI: 10.1021/ic000273v
• ISSN: 0020-1669

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.