Structural and energetic analysis of cyclic peptide-gold nano-drug delivery system: a DFT study

By applying cyclooctaglycine model for cyclic peptide (CP) and cluster Au6 model for gold nanoparticles (GN), seven different configurations of cyclic peptide-gold nanoparticles (CPGN) with 5-fluorouracil (FU) were investigated. Binding energies, quantum molecular descriptors, and solvation energies in the aqueous solution and gas phase were studied at the density functional level of M06-2X/6-31g(d, p). Solvation energies indicate that the solubility of FU increases in CPGN/FU1-7. This subject is considered a key factor for drug transfer, so CPGNs can be used as an appropriate drug delivery system. The large negative values of calculated binding energies show the stability of CPGN/FU1-7 structures, and quantum molecular descriptors, such as electrophilicity ($\omega$) and global hardness ($\eta$) indicate that the reactivity of FU in CPGN/FU1-7 structures increases. AIM calculations for all structures also show that intermolecular hydrogen bonding and Au-drug interactions play an important role for this drug delivery system.