Elucidating the binding mechanism of thione‐containing mercaptopurine and thioguanine drugs to small gold clusters,Journal of Computational Chemistry

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Elucidating the binding mechanism of thione‐containing mercaptopurine and thioguanine drugs to small gold clusters
Journal of Computational Chemistry ( IF 3.4 ) Pub Date : 2020-05-01 , DOI: 10.1002/jcc.26216
Pham Vu Nhat ₁ , Nguyen Thanh Si _{1,

2} , Nguyen Thi Thu Tram ₃ , Long Van Duong ₄ , Minh Tho Nguyen _{2,

5}

Affiliation

Density functional theory methods were employed to clarify the adsorption/desorption behaviors of the thione‐containing mercaptopurine and thioguanine drugs on the gold surface using both small Au6 and Au8 clusters as model reactants. Structural features, thermodynamic parameters, bonding characteristics, and electronic properties of the resulting complexes were investigated using the Perdew–Burke–Ernzerhof (PBE) and LC‐BLYP functionals along with correlation‐consistent basis sets, namely cc‐pVDZ‐PP for gold and cc‐pVTZ for non‐metals. Computed results show that the drug molecules tend to anchor on the gold cluster at the S atom with binding energies around −34 to −40 kcal/mol (in vacuum) and − 28 to −32 kcal/mol (in aqueous solution). As compared to Au8, Au6 undergoes a shorter recovery time and a larger change of energy gap that could be converted to an electrical signal for selective detection of the drugs. Furthermore, interactions between the drugs and gold clusters are reversible processes and a drug release mechanism was also proposed. Accordingly, the drugs are able to separate from the gold surface due to either a slight change of pH in tumor cells or the presence of cysteine residues in protein matrices.

中文翻译：

阐明含硫酮的巯基嘌呤和硫鸟嘌呤药物与小金簇的结合机制

采用密度泛函理论方法，使用小的 Au6 和 Au8 簇作为模型反应物，阐明了含硫酮的巯基嘌呤和硫鸟嘌呤药物在金表面的吸附/解吸行为。使用 Perdew-Burke-Ernzerhof (PBE) 和 LC-BLYP 泛函以及相关一致的基组，即 cc-pVDZ-PP 用于金和cc-pVTZ 用于非金属。计算结果表明，药物分子倾向于锚定在 S 原子处的金簇上，结合能约为 -34 至 -40 kcal/mol（真空中）和 -28 至 -32 kcal/mol（水溶液中）。与 Au8 相比，Au6 经历较短的恢复时间和较大的能隙变化，可以将其转换为电信号以选择性检测药物。此外，药物与金簇之间的相互作用是可逆过程，并提出了药物释放机制。因此，由于肿瘤细胞中 pH 值的轻微变化或蛋白质基质中半胱氨酸残基的存在，药物能够从金表面分离。

更新日期：2020-05-01

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