Exploring C6N6 as an effective drug delivery carrier for anticancer drugs mercaptopurine and thiotepa: A DFT and MD approach.

Conventional chemotherapy often faces challenges related to drug adsorption at the target site, leading to poor drug availability and reduced therapeutic efficacy. Extensive research has been conducted to explore various nanostructures as drug delivery carriers, with the pristine C6N6 surface being explored as a potential drug delivery carrier for the anticancer drugs mercaptopurine (MP) and thiotepa (TP). Density functional theory (DFT) calculations at the ωB97XD/6-31 G(d,p) level of theory, alongside Molecular Dynamics (MD) simulations are employed to investigate the interactions between drugs and the C6N6 surface. The adsorption energies for MP@C6N6 and TP@C6N6 complexes are computed in both gas and solvent phases to evaluate the drug loading properties onto the C6N6 surface. The basis set superposition error is corrected by using counterpoised method. The presence of van der Waals interaction between drug and C6N6 surface is confirmed by non-covalent interaction analysis. According to SAPT0 analysis, dispersion forces are primarily contributing to the stability of both complexes. The region of electron accumulation and depletion of complexes are investigated by EDD isosurfaces. The significant reduction of surface Egap from 7.86 eV to 5.64 eV after complexation with MP, reveals greater conductivity of C6N6 surface towards mercaptopurine. Additionally, the increase in dipole moment from 0.00D to 6.76D for the MP@C6N6 complex further supports its efficiency as a drug delivery system. The structural integrity of MP/TP@C6N6 is confirmed by the RMSD and RMSF values across the 100 ns MD simulation without significant deviations. Through improving the efficacy of chemotherapy and overcoming the drawbacks of conventional drug delivery, this study provides a potential platform for the utilization of the C6N6 surfaceas a targeting drug delivery carrier of different drugs.