The focus of this work is pointing out the different behavior of two structurally related Pt(II) complexes, the anionic cyclometalated NBu4[(Bzq)Pt(Thio)], 1 and the neutral [(Phen)Pt(Thio)], 2, (Bzq = benzo[h]quinoline, Phen = 1,10-phenantroline, Thio = 1,2-benzenedithiolate), on the interaction with human serum albumin (HSA), a key drug-delivery protein in the bloodstream. Being very limited the number of anionic Pt(II) complexes reported to date, this is a pioneering example of report on a protein-ligand interaction involving a negatively charged platinum compound. The study was carried out by using fluorescence spectroscopy, differential scanning calorimetry and molecular docking simulations. The results revealed a strong binding affinity between the anionic compound and the protein, whereas a weak/moderate binding interaction was highlighted for the neutral one. Comparative studies with site specific ligands (warfarin and ibuprofen), allowed us to identify the protein binding sites of the two compounds. The work aims to shed light on the relevance of the charge in designing new drugs with a favorable binding affinity for HSA, which strongly contributes to influence their pharmacological and toxicological profile.

中文翻译：

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阴离子对中性Pt（II）配合物：电荷与人血清白蛋白结合的相关性。

这项工作的重点是指出两种结构相关的Pt（II）配合物的不同行为，即阴离子环金属化NBu4 [（Bzq）Pt（Thio）]，1和中性[[Phen] Pt（Thio）]，2 （Bzq =苯并[h]喹啉，Phen = 1,10-菲咯啉，Thio = 1,2-苯二硫代硫酸盐），与人血清白蛋白（HSA）相互作用，后者是血液中的关键药物递送蛋白。迄今为止，阴离子Pt（II）络合物的数量非常有限，这是报道涉及带负电荷的铂化合物的蛋白质-配体相互作用的开创性例子。该研究是通过使用荧光光谱，差示扫描量热法和分子对接模拟进行的。结果表明，阴离子化合物与蛋白质之间具有很强的结合亲和力，而对于中性分子则强调了弱/中度的结合相互作用。与位点特异性配体（华法林和布洛芬）的比较研究使我们能够鉴定这两种化合物的蛋白质结合位点。这项工作旨在阐明电荷在设计对HSA具有良好结合亲和力的新药方面的相关性，这对影响其药理和毒理学特性做出了重要贡献。