Silver(I) complexes with proline and hydroxyproline were synthesized and structurally characterized and crystal structure analysis shows that the formulas of the compounds are {[Ag₂(Pro)₂(NO₃)]NO₃}_n (AgPro) (Pro = L-proline) and {[Ag₂(Hyp)₂(NO₃)]NO₃}_n (AgHyp) (Hyp = trans-4-hydroxy-L-proline). Both complexes crystallize in the monoclinic lattice with space group P2₁ with a carboxylate bidentate-bridging coordination mode of the organic ligands Pro and Hyp (with NH₂⁺ and COO⁻ groups in zwitterionic form). Both complexes have a distorted seesaw (C_2v) geometry around one silver(I) ion with τ₄ values of 58% (AgPro) and 51% (AgHyp). Moreover, the results of spectral and thermal analyses correlate with the structural ones. ¹H and ¹³C NMR spectra confirm the complexes species’ presence in the DMSO biological testing medium and their stability in the time range of the bioassays. In addition, molar conductivity measurements indicate complexes’ behaviour like 1 : 1 electrolytes. Both complexes showed higher or the same antibacterial activity against Bacillus cereus, Pseudomonas aeruginosa and Staphylococcus aureus as AgNO₃ (MIC = 0.063 mM) and higher than silver(I) sulfadiazine (AgSD) (MIC > 0.5 mM) against Pseudomonas aeruginosa. In addition, complex AgPro exerted a strong cytotoxic effect against the tested MDA-MB-231 and Jurkat cancer cell lines (IC₅₀ values equal to 3.7 and 3.0 μM, respectively) compared with AgNO₃ (IC₅₀ = 6.1 (5.7) μM) and even significantly higher selectivity than cisplatin (cisPt) against MDA-MB-231 cancer cell lines (SI = 3.05 (AgPro); 1.16 (cisPt), SI – selectivity index). The binding constants and the number of binding sites (n) of AgPro and AgHyp complexes with bovine serum albumin (BSA) were determined at four different temperatures, and the zeta potential of BSA in the presence of silver(I) complexes was also measured. The in ovo method shows the safety of the topical and intravenous application of AgPro and AgHyp. Moreover, the complexes’ bioavailability was verified by lipophilicity evaluation from the experimental and theoretical points of view.

中文翻译：

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脯氨酸和羟脯氨酸作为抗菌和抗癌肽成分对银 (I) 离子活性的影响：采用新的理论和实验 SAR 方法进行结构和生物学评估

合成了银( I )与脯氨酸和羟脯氨酸的配合物并进行了结构表征，晶体结构分析表明该化合物的分子式为{[Ag ₂ (Pro) ₂ (NO ₃ )]NO ₃ } _n (AgPro) (Pro = L -脯氨酸）和{[Ag ₂ (Hyp) ₂ (NO ₃ )]NO ₃ } _n (AgHyp)（Hyp=反式-4-羟基-L-脯氨酸）。两种配合物均在具有空间群P 2 ₁的单斜晶格中结晶，具有有机配体 Pro 和 Hyp 的羧酸酯二齿桥配模式（具有两性离子形式的 NH ₂ ⁺和 COO ^-基团）。两种配合物都围绕一个银 ( I ) 离子具有扭曲的跷跷板 (C _2v ) 几何形状， τ ₄值为 58% (AgPro) 和 51% (AgHyp)。此外，光谱和热分析的结果与结构分析的结果相关。¹ H 和¹³ C NMR 谱证实了复合物种类在 DMSO 生物测试介质中的存在及其在生物测定时间范围内的稳定性。此外，摩尔电导率测量表明复合物的行为类似于 1:1 电解质。两种复合物对蜡样芽胞杆菌、铜绿假单胞菌和金黄色葡萄球菌的抗菌活性均高于或与 AgNO ₃ (MIC = 0.063 mM) 相同，并且高于磺胺嘧啶银( AgSD) (MIC > 0.5 mM) 对铜绿假单胞菌的抗菌活性。此外，与 AgNO ₃ (IC ₅₀ = 6.1 (5.7) μM)相比，复合 AgPro 对测试的 MDA-MB-231 和 Jurkat 癌细胞系 (IC ₅₀值分别等于 3.7 和 3.0 μM)产生了强烈的细胞毒性作用对 MDA-MB-231 癌细胞系的选择性甚至显着高于顺铂 (cisPt)（SI = 3.05 (AgPro)；1.16 (cisPt)，SI – 选择性指数）。在四种不同温度下测定了 AgPro 和 AgHyp 复合物与牛血清白蛋白 (BSA) 的结合常数和结合位点 ( n )数量，并测量了银 ( I ) 复合物存在下 BSA 的 zeta 电位。卵内方法显示了 AgPro 和 AgHyp 局部和静脉应用的安全性。此外，通过亲脂性评价从实验和理论角度验证了复合物的生物利用度。