Premium
Elucidating the binding mechanism of thione‐containing mercaptopurine and thioguanine drugs to small gold clusters
Author(s) -
Nhat Pham Vu,
Si Nguyen Thanh,
Tram Nguyen Thi Thu,
Duong Long Van,
Nguyen Minh Tho
Publication year - 2020
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.26216
Subject(s) - chemistry , adsorption , desorption , molecule , binding energy , density functional theory , gold cluster , aqueous solution , cluster (spacecraft) , atom (system on chip) , computational chemistry , organic chemistry , physics , computer science , nuclear physics , embedded system , programming language
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 Au 6 and Au 8 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 Au 8 , Au 6 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.