Dispersion-corrected DFT calculations and umbrella sampling simulations to investigate stability of Chrysin-cyclodextrin inclusion complexes

The study of inclusion complexes of Chrysin (ChR) with three forms of cyclodextrins (CDs) alpha-, beta-, and gamma-CD was accomplished to examine the stability of ChR inside the central cavities of CDs. The aim of study was to identify the most suitable form of CD to improve the hydro-solubility of poorly soluble ChR bioactive molecule. Microsecond timescale molecular dynamics (MD) simulations were performed on four inclusion complexes (alpha-CD/ChR, beta-CD/ChR, and two conformations of gamma-CD/ChR) to examine the dynamics of ChR inside the cavity of CDs. The first conformation of gamma-CD/ChR inclusion complex (gamma-CD1/ChR) was identified to possess the highest affinity between host and guest molecule on the basis of binding energy calculated by employing Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) and umbrella sampling simulations. To further strengthen the claims of classical and biased MD studies, Our own N-layered Integrated molecular Orbital and Molecular mechanics (ONIOM) (wB97XD/6-311+g(d,p):pm7) calculations were performed on the selected inclusion complexes. The ONIOM based complexation energy reaffirmed that ChR had highest affinity for the gamma-CD1 host molecule. Further, the non-covalent interaction analysis was conducted using Multiwfn software on QM-optimized inclusion complexes with wB97XD/6-311+G(d,p) model chemistry, revealing non-covalent interactions between ChR and CDs. This atomic level information helped us to gain better insights into critical atoms of ChR and CD that participated in intermolecular interactions and identify gamma-CD as a suitable host molecule for improving the hydro-solubulity of ChR. The structural insights would help to derive new derivatives of gamma-CD with better host capacity.

Automated summary

This study examined the stability of Chrysin (ChR) inside cyclodextrins (CDs) by forming inclusion complexes with three forms of CDs (alpha-, beta-, and gamma-CD). The aim was to find the most suitable CD form to improve the hydro-solubility of ChR. Molecular dynamics simulations were performed on the complexes to study the dynamics of ChR inside the cavity of CDs. The results showed that the gamma-CD1/ChR complex had the highest affinity, making gamma-CD a suitable host molecule for improving the hydro-solubility of ChR.