Unveiling the molecular mechanism of acyclovir interaction with carbon dots: a DFT approach

This study investigates the interaction between carbon dots (CD) and acyclovir (ACV), an antiviral drug, using experimental and theoretical approaches, supported by density functional theory (DFT). CD have gained attention for enhancing drug solubility and stability, making them promising candidates for drug delivery. ACV, while effective against various herpes viruses, faces challenges such as poor solubility, limited membrane permeability, and potential side effects from high-dose or long-term use. To address these issues, the research explores CD-ACV (ADA) complex formation. CDs are chosen for their unique properties including low cytotoxicity, good water solubility, biocompatibility, and potential to enhance cellular uptake. Fourier-transform infrared (FT-IR) and UV spectroscopy provide experimental validation of the ADA complex formation. DFT calculations offer insights into the binding mechanisms and electronic interactions within the ADA complex, allowing for predictive modeling of drug-carrier combinations. Docking studies with 2KI5 Thymidine Kinase further validated the inhibitory effect of CD and ADMET predictions suggested that CD possess drug-like properties. By integrating experimental and computational approaches, this study aims to enhance the understanding of molecular stability in ADA complexes and contribute to the development of more effective CD-based drug delivery systems for improved antiviral efficacy.

The structures of CD, ACV, and ADA were optimized using r $_{}^2$ SCAN-3c level of theory with CPCM in water, implemented in the ORCA 5.0.4 software. The theoretical UV-Vis spectra and electronic transitions were investigated using time-dependent density functional theory (TD-DFT). CAM-B3LYP functional in combination with the Def2-TZVP basis set was applied to perform these computations. The HFLD method was employed for interaction energy calculations, utilizing the aug-cc-pVDZ basis set along with the auxiliary basis sets aug-cc-pVDZ/C and aug-cc-pVTZ/JK within the RIJK approximation. Energy decomposition analysis (EDA) and interaction energy assessments were carried out using symmetry-adapted perturbation theory (SAPT0) calculations performed with the jun-cc-pVDZ basis set in the Psi4 software. AIMALL 19.10.12 software was used to calculate bond topological properties. Multiwfn 3.8 software package was used to generate a deformation density contour map. Intrinsic bond strength index (IBSI) analysis was performed using the independent gradient model (IGM) with IGMplot (Rev. 3.08) software, utilizing the wave function from the M06-2X method with a 6-31 G** basis set. NBO 7.0 was used to conduct natural bond orbital (NBO) analysis, while the Chemcraft package and VMD were employed for visualizations.