Theoretical study on the interaction of flutamide anticancer drug with cucurbit[n]uril (n = 5–8) as a drug delivery system

Abstract

The supramolecular complexation of flutamide, an anti-androgen drug with cucurbit[n]uril was studies using density functional theory (DFT). The structural and electronic analysis of the complexes was performed. The negative binding energy of the complexes show that complexation process is exothermic. The thermodynamic results reveal that the process of inclusion complex formation is spontaneous. To gain insightful knowledge about the nature of interactions present between the hostguest molecules of the complexes, molecular electrostatic potential, non-covalent interaction-reduced density gradient, and natural bond orbital analysis was done.These results suggest that electrostatic interactions and intermolecular hydrogen bond formation contribute to the stability of these complexes. The coupled-cluster theory with single, double and perturbatively connected triple excitations calculations for the complexes support the DFT results. The quantitative decomposition of the interaction energies of the complexes was acquired by the local energy decomposition analysis. The atom-centered density matrix propagation molecular dynamic analysis confirms the stability of the examined complexes.

Theoretical Analysis of the Role of Water in Ligand Binding to Cucurbit[n]uril of Different Sizes

“…Molecular recognition (MR) is one of the most fundamental processes in biological systems and has attracted much attention in the field of physics, chemistry, biochemistry, and drug/material design. , It is regarded as a process in which a ligand molecule binds within the cavity of a host molecule through noncovalent chemical bonds between host and ligand molecules, such as electrostatic interactions, hydrogen bonding, and van der Waals forces. Basically, this process is a fundamental mechanism of drug delivery systems. − MR also includes molecular aggregation and self-assembly, and it is the subject of research in a wide range of scientific fields. − MR is known as a stochastic process, governed by free energy change of the system. Therefore, it is important to consider not only the direct interaction between the host and ligand molecules but also the influence of surrounding environments in the MR process.…”

“…CB–ligand binding systems have attracted much attention due to the various intrinsic properties of CB structures. , Their cavities can be varied, resulting in changes in the portal size, which can then lead to the formation of larger ligands of interest or involve more molecules inside the cavity. , Moreover, CB n has low toxicity and is biocompatible; its medicinal and pharmaceutical use has been suggested. − …”

“…To date, many authors have utilized the continuum solvent model , and explicit solvent water in molecular dynamics (MD) simulations − to computationally study the behavior of CB–ligand binding systems in aqueous solution. In those studies, the essential role of solvent water has been pointed out.…”

“…1,2 Their cavities can be varied, resulting in changes in the portal size, which can then lead to the formation of larger ligands of interest or involve more molecules inside the cavity. 1,4 Moreover, CBn has low toxicity and is biocompatible; its medicinal and pharmaceutical use has been suggested. 11−16 In an aqueous solution, the CB pocket will be occupied by water molecules when no ligand molecule binds with the CB host.…”