Molecular Dynamics Study of Conformations of Beta-Cyclodextrin and its Eight Derivatives in Four Different Solvents
Abstract
Understanding the atomic level interactions and the resulting structural characteristics is required for developing beta-cyclodextrin (CD) derivatives for pharmaceutical and other applications. The effect of four different solvents on the structures of the native CD and its hydrophilic (methylated CD; MECD and hydroxypropyl CD; HPCD) and hydrophobic derivatives (ethylated CD; ETCD) were explored using molecular dynamics (MD) simulations and solvation free energy calculations. The native CD, 2-MECD, 6-MECD, 2,6-DMCD, 2,3,6-TMCD, 6-HPCD, 2,6-HPCD and 2,6-ETCD in non-polar solvents (cyclohexane; CHX and octane; OCT) were stably formed in symmetric cyclic cavity shape through their intramolecular hydrogen bonds. In contrast, CDs in polar solvents (methanol; MeOH and water; WAT) exhibited large structural changes and fluctuations leading to significant deformations of their cavities. Hydrogen bonding with polar solvents was found to be one of the major contributors to this behavior: solvent-\b{eta}CD hydrogen bonding strongly competes with intramolecular bonding leading to significant changes in structural stability of CDs. The exception to this is the hydrophobic 2,6-ETCD which retained its spherical cavity in all solvents. Based on this, it is proposed that 2,6-ETCD can act as a sustained release drug carrier.
Keywords
Cite
@article{arxiv.1708.00714,
title = {Molecular Dynamics Study of Conformations of Beta-Cyclodextrin and its Eight Derivatives in Four Different Solvents},
author = {Wasinee Khuntawee and Mikko Karttunen and Jirasak Wong-ekkabut},
journal= {arXiv preprint arXiv:1708.00714},
year = {2017}
}