橙皮素与苯甲酰肼(HHSB或L1H3)缩合形成的三种席夫碱与小牛胸腺DNA(CT-DNA)的相互作用,异烟肼(HIN或L2H3),或氨基硫脲(HTSC或L3H3)及其CuII复合物(CuHHSB,库欣,和通式为[CuLnH2(AcO)])的CuHTSC在水溶液中进行了实验和理论评估。UV-Vis研究表明,配体和配合物表现出低色度,这表明DNA螺旋中的螺旋排序。Cu化合物与CT-DNA的固有结合常数(Kb),范围为(2.3-9.2)×106,从CuHTSC到CuHHSB,高于其他铜基潜在药物,这表明,由于芳香环的存在,π-π堆叠相互作用有利于结合。噻唑橙(TO)测定证实,配体和Cu络合物从DNA结合位点取代TO,猝灭荧光发射。DFT计算允许评估[Cu(LnH2)(AcO)]和[Cu(LnH2)(H2O)]之间的平衡,结合CuII的互变异构体,amido(am)而不是imido(im),以及HTSC的协调模式(O-,N,S),而不是(O-,N,NH2)。对接研究表明,与小沟结合CT-DNA相比,插层更可取,顺序为[Cu(L1H2am)(AcO)]>[Cu(L2H2am)(AcO)]≈TO≈L1H3>[Cu(L3H2am)(AcO)],与实验Kb常数一致,从紫外可见光谱获得。此外,对接预测[Cu(L1H2am)(AcO)]的结合强度大于[Cu(L1H2am)(H2O)]+。总的来说,结果表明,当不同的对映异构体,互变异构体,和供体组可能用于金属络合物,应该推荐一种计算方法来预测与DNA结合的类型和强度,总的来说,大分子。
The interactions with calf thymus DNA (CT-DNA) of three Schiff bases formed by the condensation of hesperetin with benzohydrazide (HHSB or L1H3), isoniazid (HIN or L2H3), or thiosemicarbazide (HTSC or L3H3) and their CuII complexes (CuHHSB, CuHIN, and CuHTSC with the general formula [CuLnH2(AcO)]) were evaluated in aqueous solution both experimentally and theoretically. UV-Vis studies indicate that the ligands and complexes exhibit hypochromism, which suggests helical ordering in the DNA helix. The intrinsic binding constants (Kb) of the Cu compounds with CT-DNA, in the range (2.3-9.2) × 106, from CuHTSC to CuHHSB, were higher than other copper-based potential drugs, suggesting that π-π stacking interaction due to the presence of the aromatic rings favors the binding. Thiazole orange (TO) assays confirmed that ligands and Cu complexes displace TO from the DNA binding site, quenching the fluorescence emission. DFT calculations allow for an assessment of the equilibrium between [Cu(LnH2)(AcO)] and [Cu(LnH2)(H2O)]+, the tautomer that binds CuII, amido (am) and not imido (im), and the coordination mode of HTSC (O-, N, S), instead of (O-, N, NH2). The docking studies indicate that the intercalative is preferred over the minor groove binding to CT-DNA with the order [Cu(L1H2am)(AcO)] > [Cu(L2H2am)(AcO)] ≈ TO ≈ L1H3 > [Cu(L3H2am)(AcO)], in line with the experimental Kb constants, obtained from the UV-Vis spectroscopy. Moreover, dockings predict that the binding strength of [Cu(L1H2am)(AcO)] is larger than [Cu(L1H2am)(H2O)]+. Overall, the results suggest that when different enantiomers, tautomers, and donor sets are possible for a metal complex, a computational approach should be recommended to predict the type and strength of binding to DNA and, in general, to macromolecules.