Optically Responsive Glutathione-Decorated Gold Nanoclusters for the Detection of Cytosine and 5-Methylcytosine Revealed by Multiscale Simulation

The abnormal concentrations of cytosine (C) and 5-methylcytosine (5-mC) in human plasma and urine have been closely linked to various human diseases, including cancer. Thus, they have become significant biomarkers for the diagnosis and prognosis of these diseases. In this work, we study the signature response between C/5-mC and glutathione-protected gold nanoclusters [Au 25 (GSH) 18 – ]. We have used molecular dynamics (MD) simulation and density functional theory (DFT) calculations to uncover this complicated interaction and acquire insights into complex interactions. Our finding shows that GSH ligand attains the most stable conformation when the values of distance ( d Au-γ-Glu ) and angle (θγ-Glu-Cys-Gly) fall within the range of 0.45–0.54 nm and 85–95°, respectively. Once in stable states, the number of hydrogen bonds between the GSH ligand and water molecules decreased slightly, possibly because the GSH ligands could form hydrogen bonds with each other, potentially competing with the hydrogen bonds between the GSH ligand and water molecules. The C has a higher affinity for the GSH ligand than the 5-mC. The HOMO–LUMO gap of Au 25 (GSH) 18 – can be affected by surface ligands, and it is significantly different when bound with C and 5-mC. It was discovered that both C and 5-mC had an effect on the HOMO–LUMO gap, causing a reduction of 0.13 and 0.44 eV in the gap, respectively. The 5-mC possesses an electron-donating group, a methyl group, which has an increased capability to channel electron density toward the Au core via the S–Au bond through a ligand-to-metal charge transfer mechanism, which leads to effectively enhanced fluorescence intensity. This suggests that the fluorescence of Au 25 (GSH) 18 – can be more effectively enhanced through ligands possessing electron-rich and donating groups. The present study opens the door for the detection of C/5-mC.