Abstract
Computational approaches are employed to elucidate the binding mechanism and the SERS phenomenon of 6-mercaptopurine (6MP) adsorbed on the tetrahedral Au20 cluster as a simple model for a nanostructured gold surface. Computations are carried out in both vacuum and aqueous environments using a continuum model. In the gaseous phase and neutral conditions, interaction of 6MP with the gold cluster is mostly dominated by a covalent Au−S bond and partially stabilized by the Au⋅⋅⋅H−N coupling. However, in acidic solution, the nonconventional Au⋅⋅⋅H−S hydrogen-bond becomes the most favorable binding mode. The 6MP affinity for gold clusters decreases in the order of vacuum > neutral solution > acidic medium. During the adsorption, the energy gap of Au20 substantially declines, leading to an increase in its electrical conductivity, which can be converted to an electrical noise. Moreover, such interaction is likely a reversible process and triggered by either the low pH in sick tissues or the presence of cysteine residues in protein matrices. While N−H bending and stretching vibrations play major roles in the SERS phenomenon of 6MP on gold surfaces in neutral solution, the strongest enhancement in acidic environment is mostly due to an Au⋅⋅⋅H−S coupling, rather than an aromatic ring-gold surface π overlap as previously proposed.
Highlights
Sulfur-containing compounds with a C=S functional group often exhibit a variety of biological activities and play vital roles in pharmaceutical applications
According to Equation (6), the electrical conductivity of Au20 will exponentially increase with respect to the drop in energy gap (Eg) that can be converted to an electrical noise, helping to recognize the drug presence
We examined the ability to detach the drug from the gold cluster in target cells, which is considered as the decisive step in a drug delivery process [49,75]
Summary
Sulfur-containing compounds with a C=S functional group often exhibit a variety of biological activities and play vital roles in pharmaceutical applications. Behaving as a nucleobase analogue, the C=S double bond in 6-thiopurine or 6-mercaptopurine (6MP) acts as a surrogate for the natural C=O compounds (Scheme 1) Such a sulfur analogue of adenine is commonly used in the conventional chemotherapy treatment of patients with acute lymphoblastic leukemia, Crohn’s disease, and ulcerative colitis [1,2,3], for its prevention of purine nucleotide biosynthesis [1]. The adsorption of 6MP is rather poor, and its therapeutic intake may cause several adverse reactions such as diarrhea, nausea, vomiting, loss of appetite, hair loss, and inflammation of the mouth [4,5] In this context, it is of great significance to find an appropriate carrier to deliver the drug where it is needed, with the aim of enhancing its therapeutic effects and reducing the unwanted side effects. Development of a simple but powerful method for selective detection of the drug is of great pharmaceutical interest [6]
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