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Abstract: Here, we used circular dichroism (CD) and fluorescence microscopy (FM) to examine the interactions of a series of antitumor-active tetrazolato-bridged dinuclear platinum(II) complexes, [{cis-Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)]n+ (R=CH3 (1), C6H5 (2), CH2COOCH2CH3 (3), CH2COO− (4), n=2 (1–3) or 1 (4)), which are derivatives of [{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)]2+ (5-H-Y), with DNA to elucidate the influence of these interactions on the secondary or higher-order structure of DNA and reveal the mechanism of action. The CD study showed that three derivatives, 1–3, with a double-positive charge altered the secondary structures of calf thymus DNA but that 4, the only complex with a single positive charge, induced almost no change, implying that the B- to C-form conformational change is influenced by ionic attraction. Unexpectedly, single-molecule observations with FM revealed that 4 changed the higher-order structure of T4 DNA into the compact-globule state most efficiently, at the lowest concentration, which was nearly equal to that of 5-H-Y. These contradictory results suggest that secondary structural changes are not necessarily linked to higher-order ones, and that the non-coordinative interaction could be divided into two distinct interactions: (1) ionic attraction and (2) hydrogen bonding and/or van der Waals contact. The relationship between diffusion-controlled non-coordinative DNA interactions and cytotoxicities is also discussed. [Copyright &y& Elsevier]

• Unusual intraligand substitution of N3 for N2 of 1,2,3-triazolate. • Pt(II) migration related to the mechanism of action of the dinuclear Pt(II) compounds. • Dimerization reaction to yield a unique tetranuclear Pt(II) compound. • Presented importance of 1,2,3-triazolate derivatives as a tridentate building block. The reaction of the anticancer azolato-bridged dinuclear platinum(II) compound [{ cis -Pt(NH 3) 2 } 2 (µ-OH)(µ-1,2,3-triazolato- N1 , N2)](NO 3) 2 (AMTA) in 0.2 M DCl-D 2 O solution was monitored at 298 K using 1H NMR spectroscopy. Acid hydrolysis of AMTA first provided a dinuclear Pt(II) cationic species [{ cis -Pt(NH 3) 2 Cl} 2 (µ-1,2,3-triazolato- N1 , N2)]+ (intermediate A) which then turned into [{ cis -Pt(NH 3) 2 Cl} 2 (µ-1,2,3-triazolato- N1 , N3)]+ (intermediate B) by migration of a Pt(II) ion, initially bound to N2, to N3. Hence, intramolecular ligand substitution of N3 for N2 occurred after substitution of two chloride ligands for the hydroxido bridge. Under the reaction conditions, the intermediate A and B were unambiguously detected, and both or either of the intermediate species then dimerized by a substitution of the chlorido ligand by N3 or N2 of a partner molecule to yield an unprecedented tetranuclear Pt(II) compound [{ cis -Pt(NH 3) 2 Cl}µ-{ cis -Pt(NH 3) 2 } 2 (µ-1,2,3-triazolato- N2 , N3) 2 - N1 , N1′ ]Cl 2 (NO 3) 2 (compound 1), whose 3D structure has been determined by X-ray crystal analysis. The fact that all triazolate nitrogen atoms coordinated to 3 different Pt(II) ions indicates that 1,2,3-triazolate derivatives could be important as a unique tridentate building block for metal-organic framework. [ABSTRACT FROM AUTHOR]