Host-Guest Interactions of Plumbagin with β-Cyclodextrin, Dimethyl-β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin: Semi-Empirical Quantum Mechanical PM6 and PM7 Methods

Abstract

Molecular interactions of plumbagin inclusion complexes with β-cyclodextrin (BCD), dimethyl-β-cyclodextrin (MBCD), and hydroxypropyl-β-cyclodextrin (HPBCD) were investigated by semi-empirical, Parameterization Method 6 and 7 (PM6, and PM7) in the aqueous phase using polarizable continuum calculations. The results revealed two different binding modes of the plumbagin molecule inside the BCD cavity with a negative value of the complexation energy. In conformation-I, the hydroxyl phenolic group of plumbagin was placed in the BCD cavity near the narrow-side of the host molecule. In the other model, conformation-II, the methyl quinone group of plumbagin was placed in the cavity of BCD near the narrow-side of the host molecule. The higher the negative value of the complexation energy, the more favorable is the pathway of inclusion-complex formation.

Current Status of Quantum Chemical Studies of Cyclodextrin Host–Guest Complexes

“…In another study, when compared to the experiment, PM3 provided wrong and at the same time opposite results to those obtained by PM7 [60]. To depict another example, in a study where β-CD, dimethyl-β-CD, and hydroxypropyl-β-CD were analyzed by both PM6 and PM7, in all cases PM7 delivered complexation energies of significantly lower values [58].…”

“…Similarly, as in the case of PM3, FT-IR spectra can be simulated [50,56]. Further, PM6 and PM7 are often combined with the DFT methods in form of the ONIOM approach [42, 52,57,58].…”

Molecular Dynamic Simulation Analysis on the Inclusion Complexation of Plumbagin with β-Cyclodextrin Derivatives in Aqueous Solution

“…We performed molecular dynamics simulations of plumbagin-BCDs inclusion com- Molecular docking and geometry optimization of plumbagin-BCDs inclusion complexes by semi-empirical quantum mechanical PM6 and PM7 methods were performed with a polarizable continuum model in the previous study. Two major stable conformations of inclusion complexes were selected (Figure 8C) [12]. In conformation-I, the methyl group of plumbagin is pointed toward the wider rim of the host molecule.…”

“…Recently researchers have reported that nano-encapsulation of plumbagin with β-cyclodextrin (BCD) can reduce toxicity and enhance pharmaceutical efficacy [9,10]. Our works have also reported the use of BCD and its derivatives to enhance the stability and aqueous solubility of plumbagin [11,12].…”

“…There were two potential binding conformations, socalled conformation-I and conformation-II which have been defined by the position of plumbagin's methyl group inside the bound cavity. The methyl group was located near the wider rim of the truncated cone in conformation-I and near the narrow rim in conformation-II [10,12]. Nevertheless, the intermolecular interactions and dynamics of plumbagin and β-cyclodextrins (BCDs) inclusion complexes were not fully investigated, especially not under an aqueous solution with thermal effects.…”