Silver is widely used for its antimicrobial properties, but microbial resistance to heavy metals is increasing. Silver(II) compounds are more oxidizing and therefore have the potential to overcome resistance via extensive attack on cellular components, but have traditionally been hard to stabilize for biological applications. Here, the high oxidation state cation was stabilised using pyridinecarboxylate ligands, of which the 2,6-dicarboxypyridine Ag(II) complex (Ag2,6P) was found to have the best tractability. This complex was found to be more stable in phosphate buffer than DMSO, allowing studies of its interaction with water soluble antioxidants and biological macromolecules, with the aim of demonstrating its potential to oxidize them, as well as determining the reaction products. Spectrophotometric analysis showed that Ag2,6P was rapidly reduced by the antioxidants glutathione, ascorbic acid and vitamin E; the unsaturated lipids arachidonic and linoleic acids, model carbohydrate β-cyclodextrin, and protein cytochrome c also reacted readily. Analysis of the reaction with glutathione by NMR and electrospray mass spectrometry confirmed that the glutathione was oxidized to the disulfide form. Mass spectrometry also clearly showed the addition of multiple oxygen atoms to the unsaturated fatty acids, suggesting a radical mechanism, and cross-linking of linoleic acid was observed. The seven hydroxyl groups of β-cyclodextrin were found to be completely oxidized to the corresponding carboxylates. Treatment of cytochrome c with Ag2,6P led to protein aggregation and fragmentation, and dose-dependent oxidative damage was demonstrated by oxyblotting. Thus Ag2,6P was found to be highly oxidizing to a wide variety of polar and nonpolar biological molecules.

中文翻译：

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银（II）配合物与生物大分子和抗氧化剂的相互作用。

银因其抗菌特性而被广泛使用，但微生物对重金属的抵抗力正在增强。银(II)化合物的氧化性更强，因此有可能通过对细胞成分的广泛攻击来克服耐药性，但传统上很难在生物应用中保持稳定。在这里，使用吡啶羧酸盐配体来稳定高氧化态阳离子，其中 2,6-二羧基吡啶 Ag(II) 配合物 (Ag2,6P) 被发现具有最佳的易处理性。人们发现该复合物在磷酸盐缓冲液中比 DMSO 更稳定，因此可以研究其与水溶性抗氧化剂和生物大分子的相互作用，目的是证明其氧化它们的潜力，并确定反应产物。分光光度分析表明Ag2,6P被抗氧化剂谷胱甘肽、抗坏血酸和维生素E迅速还原；不饱和脂质花生四烯酸和亚油酸、模型碳水化合物β-环糊精和蛋白质细胞色素c也很容易发生反应。通过核磁共振和电喷雾质谱分析与谷胱甘肽的反应证实谷胱甘肽被氧化成二硫化物形式。质谱分析还清楚地表明不饱和脂肪酸中添加了多个氧原子，表明存在自由基机制，并且观察到亚油酸的交联。发现β-环糊精的七个羟基被完全氧化成相应的羧酸盐。用 Ag2,6P 处理细胞色素 c 会导致蛋白质聚集和断裂，并且通过氧印迹法证明了剂量依赖性氧化损伤。因此，Ag2,6P被发现对多种极性和非极性生物分子具有高度氧化性。