The series of tetrazolato-bridged complexes with the formula [{cis‑Pt(NH₃)₂}₂(μ-OH)(μ-5-H-tetrazolato-N1,N2)]^2 + (5-H-X) or [{cis‑Pt(NH₃)₂}₂(μ-OH)(μ-5-R-tetrazolato-N2,N3)]^n + (R = H (5-H-Y), CH₃ (1), CH₂COOCH₂CH₃ (2), CH₂COO^– (3), n = 2 (5-H-Y, 1, 2) or 1 (3)) are promising candidate complexes for formulation as next-generation platinum-based anticancer drugs that form multimodal bindings with DNA molecules. These multimodal bindings involve both non-covalent and covalent interactions, the latter of which are acknowledged to be essential for platinum-based drugs to exert their anticancer activity. In the present study, the tetrazolato-bridged complexes reacted with two molar equivalents of guanosine-5′-monophosphate (GMP) to yield the 1:2 reaction products [{cis‑Pt(NH₃)₂(GMP-N7)}₂(μ-5-R-tetrazolato-N1,N3)]^{2 − or 1 −}. This reaction was accompanied by an intramolecular Pt(II) migration that contributed to the formation of diverse DNA crosslinking, such as interhelical crosslinks. The second-order reaction rate constants for the reactions performed in phosphate-buffered D₂O solution showed that the reactivity of the complexes decreased in the order 5-H-X ≳ 5-H-Y > 2 ≳ 1 > 3 and that reactivity was correlated with the cytotoxicity of the complexes. A similar result was obtained for the reaction of the complexes with calf thymus DNA in which the formation of covalent DNA adducts was quantified by means of inductively coupled plasma mass spectrometry. These results suggest that overall charge affects the kinetics of the reactions of platinum complexes with GMP and calf thymus DNA. Thus, the positive charge of the complexes affects not only the non-covalent but also the covalent interactions between the complexes and nucleotides and DNA, which are negatively charged molecules.

具有式[{顺式-Pt（NH ₃）₂ } ₂（μ -OH）（μ -5-H-四唑-N1，N2）] ^{2 +}（5-HX）的四唑桥连络合物系列{顺式-Pt（NH ₃）₂ } ₂（μ -OH）（μ -5-R-四唑-N2，N3）] ^{n +}（R = H（5-HY），CH ₃（1），CH ₂ COOCH ₂频道₃（2），CH ₂ COO ^- （3）中，n = 2（5-HY，1，2）或1（3））是有希望的候选物为制剂作为下一代基于铂的形成多峰绑定抗癌药物DNA分子。这些多峰结合涉及非共价和共价相互作用，公认后者对于铂基药物发挥其抗癌活性至关重要。在本研究中，四唑桥连络合物与2摩尔当量的鸟苷5'-单磷酸酯（GMP）反应生成1：2反应产物[{ cis ‑Pt（NH ₃）₂（GMP- N7）} ₂（μ -5-R-四唑-N1，N3）] ^2-或1-。该反应伴随着分子内Pt（II）迁移，这有助于形成各种DNA交联，例如螺旋间交联。二阶反应速率常数反应在磷酸盐缓冲d进行₂ O解决方案表明，复合物的反应性的顺序降低5-HX  ≳  5-HY  >  2  ≳  1  >  3反应性与复合物的细胞毒性有关。对于络合物与小牛胸腺DNA的反应获得了相似的结果，其中通过电感耦合等离子体质谱法定量了共价DNA加合物的形成。这些结果表明总电荷影响铂配合物与GMP和小牛胸腺DNA反应的动力学。因此，复合物的正电荷不仅影响非共价，而且影响复合物与核苷酸和DNA之间的共价相互作用，而核苷酸和DNA是带负电荷的分子。