Hydration-Induced Disorder and Methyl Rotation in Potential COVID-19 Treatment Drug Molecules
April 5, 2021
Using neutrons, ORNL researchers analyzed the molecular dynamics of previously proposed COVID-19 drug candidates remdesivir (left), hydroxychloroquine (center), and dexamethasone (right) in hydrated environments. Their results offer insights into how these molecules might behave in human cells. Credit: ORNL/Jill Hemman
Scientific Achievement
For several drug molecules it is shown that activation energies for methyl rotations are lower in hydration-induced disordered states than in the ordered or dry material.
Significance and Impact
The energy landscape governing side group dynamics in drug molecules must be determined using explicitly disordered samples rather than isolated molecules or crystalline material.
Research Details
- Relaxation and vibrational dynamics of several drug molecules were studied using quasi-elastic (QENS) and inelastic (INS) neutron scattering.
- Study compared hydration states of COVID-19 drugs hydroxychloroquine and its sulfate (HCQS), dexamethasone and its sodium diphosphate, and remdesivir.
- Analysis of the QENS spectra yielded the energy barriers for methyl rotations.
- Density functional theory calculations were used to interpret the INS spectra.
“Hydration-Induced Disorder Lowers the Energy Barriers for Methyl Rotation in Drug Molecules”
Eugene Mamontov, Yongqiang Cheng, Luke L. Daemen, Alexander I. Kolesnikov, Anibal J. Ramirez-Cuesta, Matthew R. Ryder, and Matthew B. Stone
Journal of Physical Chemistry Letters 11, 10256 (2020).
