Unravelling Guest Dynamics in Crystalline Molecular Organics Using 2 H Solid-State NMR and Molecular Dynamics Simulation

Erastova, Valentina; Evans, Ivana R; Glossop, William N; Guryel, Songül; Hodgkinson, Paul; Kerr, Hannah E; Oganesyan, Vasily S; Softley, Lorna K.; Wickins, Helen M; Wilson, Mark R.

Abstract

2H solid-state NMR and atomistic molecular dynamics (MD) simulations are used to understand the disorder of guest solvent molecules in two cocrystal solvates of the pharmaceutical furosemide. Traditional approaches to interpreting the NMR data fail to provide a coherent model of molecular behavior and indeed give misleading kinetic data. In contrast, the direct prediction of the NMR properties from MD simulation trajectories allows the NMR data to be correctly interpreted in terms of combined jump-type and libration-type motions. Time-independent component analysis of the MD trajectories provides additional insights, particularly for motions that are invisible to NMR. This allows a coherent picture of the dynamics of molecules restricted in molecular-sized cavities to be determined.

Citation

Erastova, V., Evans, I. R., Glossop, W. N., Guryel, S., Hodgkinson, P., Kerr, H. E., Oganesyan, V. S., Softley, L. K., Wickins, H. M., & Wilson, M. R. (2024). Unravelling Guest Dynamics in Crystalline Molecular Organics Using 2 H Solid-State NMR and Molecular Dynamics Simulation. Journal of the American Chemical Society, 146(27), 18360-18369. https://doi.org/10.1021/jacs.4c03246

• Journal Article Type: Article
• Acceptance Date: May 30, 2024
• Online Publication Date: Jun 27, 2024
• Publication Date: Jun 27, 2024
• Deposit Date: Jul 18, 2024
• Publicly Available Date: Jul 18, 2024
• Journal: Journal of the American Chemical Society
• Print ISSN: 0002-7863
• Electronic ISSN: 1520-5126
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 146
• Issue: 27
• Pages: 18360-18369
• DOI: https://doi.org/10.1021/jacs.4c03246
• Public URL: https://durham-repository.worktribe.com/output/2526053