A theoretical investigation on the hydrolysis of gold(III) 1,10-phenanthroline complexes and their interaction with amino acids and DNA purine bases

IF 4.2 Q2 CHEMISTRY, MULTIDISCIPLINARY

Results in Chemistry Pub Date : 2025-09-18 DOI:10.1016/j.rechem.2025.102723

Asitbaran Barik, Paritosh Mondal

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Abstract

This study explores the hydrolysis mechanism and biomolecular interaction of gold(III) phenanthroline-based anticancer complexes, such as [Au^III(1,10-phenanthroline)Cl₂][PF₆] (R1), [Au^III(4,7-diphenyl-1,10-phenanthroline)Cl₂][PF₆] (R2), [Au^III(5-chloro-1,10-phenanthroline)Cl₂][PF₆] (R3), and [Au^III(5-nitro-1,10-phenanthroline)Cl₂][PF₆] (R4), using the density functional theory (DFT) method incorporating solvation by a conductor-like polarizable continuum model (CPCM). The detailed structural characteristics and thermodynamics for the hydrolysis of all selected gold complexes have been evaluated. Hydrolysis mechanism proceeds via two sequential steps: (i) first chloride substitution to form mono-aquated intermediates and (ii) remaining chloride substitution yielding di-aquated products. Thermodynamics and kinetic analysis suggest that the first hydrolysis step is rate-determining, with higher activation free energies (∆G: P1-I = 21.6 kcal/mol, P2-I = 21.3 kcal/mol, P3-I = 21.7 kcal/mol, and P4-I = 22.0 kcal/mol) compared to the second hydrolysis step (∆G: P1-II = 20.5 kcal/mol, P2-II = 20.1 kcal/mol, P3-II = 20.8 kcal/mol and P4-II = 21.1 kcal/mol). DFT evaluated, rate constant (k) values for the second hydrolysis of R1, R2, R3 and R4 are 2.32 × 10⁻², 4.43× 10⁻², 1.42 × 10⁻², and 8.78 × 10⁻² s ⁻¹, respectively, indicating faster second hydrolysis of the gold complexes. The di-aquated complexes exhibits enhanced electrophilicity, enabling stronger interactions with biomolecules. Binding interaction with DNA bases (adenine and guanine) and amino acids (cysteine and selenocysteine) demonstrates preferential affinity for the N7 site of guanine and selenium in selenocysteine. Kinetic study and activation free energies indicate that these interactions are stabilized by hydrogen bonding in all stationary points i.e. RA(reactant adduct), TS(transition state), and PA(product adduct) obtained during ligand exchange processes.

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金（III） 1,10-邻菲罗啉配合物的水解及其与氨基酸和DNA嘌呤碱基相互作用的理论研究

本研究采用密度泛函理论（DFT）方法，通过类导体极化连续体模型（CPCM）结合溶剂化，探讨了金（III）菲罗啉类抗癌配合物[AuIII（1,10-菲罗啉）Cl2][PF6] （R1）、[AuIII（4,7-二苯基-1,10-菲罗啉）Cl2][PF6] （R2）、[AuIII（5-氯-1,10-菲罗啉）Cl2][PF6] （R3）和[AuIII（5-硝基-1,10-菲罗啉）Cl2][PF6] （R4）的水解机理和生物分子相互作用。对所选金配合物的详细结构特征和水解热力学进行了评价。水解机制通过两个连续的步骤进行：(i)第一个氯取代形成单水的中间体；（ii）剩余的氯取代产生双水的产物。热力学和动力学分析表明，与第二水解步骤（∆G: P1-II = 20.5 kcal/mol, P2-II = 20.1 kcal/mol, P3-II = 20.8 kcal/mol, P2-I = 21.3 kcal/mol, P3-I = 21.7 kcal/mol, P4-I = 22.0 kcal/mol）相比，第一水解步骤具有较高的活化能（∆G: P1-II = 21.6 kcal/mol, P2-I = 21.3 kcal/mol, P3-I = 21.7 kcal/mol, P4-II = 21.1 kcal/mol）。经DFT计算，R1、R2、R3和R4的二次水解速率常数(k)分别为2.32 × 10−2、4.43× 10−2、1.42 × 10−2和8.78 × 10−2 s−1，表明金配合物的二次水解速度更快。双水配合物表现出增强的亲电性，使其与生物分子的相互作用更强。与DNA碱基（腺嘌呤和鸟嘌呤）和氨基酸（半胱氨酸和硒代半胱氨酸）的结合相互作用表明对硒代半胱氨酸中鸟嘌呤和硒的N7位点具有优先亲和力。动力学研究和激活自由能表明，这些相互作用在配体交换过程中得到的RA（反应物加合物）、TS（过渡态）和PA（生成物加合物）的所有固定点上都被氢键稳定。

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