Abstract
Chloroquine and its derivative hydroxychloroquine are primarily known as antimalaria drugs. Here, we investigate the influence of hydration water on the molecular dynamics in hydroxychloroquine sulfate, a commonly used solubilized drug form. When hydration, even at a low level, results in a disordered structure, as opposed to the highly ordered structure of dry hydroxychloroquine sulfate, the activation barriers for the rotation of methyl groups in the drug molecules become randomized and, on average, significantly reduced. The facilitated stochastic motions of the methyl groups may benefit the biomolecular activity due to the more efficient sampling of the energy landscape in the disordered hydration environment experienced by the drug molecules in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 21231-21240 |
| Number of pages | 10 |
| Journal | ACS Omega |
| Volume | 5 |
| Issue number | 33 |
| DOIs | |
| State | Published - Aug 25 2020 |
Funding
The neutron scattering experiments at Oak Ridge National Laboratory’s (ORNL’s) Spallation Neutron Source (SNS) were supported by the Scientific User Facilities Division, Office of Science (Basic Energy Sciences), US Department of Energy (DOE). This research project also benefited from the capabilities provided by the user program at the Center for Nanophase Materials Sciences (CNMS), a DOE Office of Science User Facility operated by ORNL. The authors acknowledge the US Department of Energy (DOE) Office of Science (Basic Energy Sciences) for research funding. M.R.R. acknowledges the National Energy Research Scientific Computing Center (NERSC), a US Department of Energy (DOE) Office of Science User Facility, operated under Contract No. DE-AC02–05CH11231, for access to supercomputing resources. Computing resources were also made available through the VirtuES and the ICEMAN projects, funded by Laboratory Directed Research and Development program at ORNL. We thank R. Moody for the dedication to obtaining sample materials. The authors also thank Dr. Jessica V. Lamb for assistance with the structural representations and Dr. Mark D. Lumsden for valuable discussion. This manuscript has been authored by UT-Battelle, LLC, under contract DE-AC05–00OR22725 with the US Department of Energy (DOE). The US Government retains and the publisher, by accepting the article for publication, acknowledges that the US government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript or allow others to do so, for US government purposes. DOE will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan ( http://energy.gov/downloads/doe-public-access-plan ).
