Methyl Group Dynamics and Conformational Flexibility in Methacetin Revealed by Neutron Spectroscopy | Sciact - CRIS-system of Boreskov Institute of Catalysis

Methyl Group Dynamics and Conformational Flexibility in Methacetin Revealed by Neutron Spectroscopy Full article

Journal

Journal of Molecular Structure
ISSN: 0022-2860

Output data

Year: 2026, Article number : 145589, Pages count : DOI: 10.1016/j.molstruc.2026.145589

Tags

Methacetin; Acetamide group; Hydrogen bond; Methyl group dynamics; Conformational flexibility; Neutron spectroscopy; Density functional theory; Pharmaceutical compounds

Authors

Pereira Jose E.M. ¹ , Boldyreva Elena ² , Zakharov Boris A. ² , Mitsutake Hery ³ , Rudić Svemir ⁴ , Koza Michael M. ⁵ , Seydel Tilo ⁵ , Eckert Juergen ⁶ , Bordallo Heloisa N. ³

Affiliations

1	ESS Bilbao, Technological Park, Building 201, Zamudio 48170, Spain
2	Novosibirsk State University, Pirogova Str. 2, 630090 Novosibirsk, Russia
3	Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark
4	ISIS Facility, STFC, Rutherford Appleton Laboratory, Chilton, Oxfordshire OX11 0QX, UK
5	Institut Laue-Langevin, BP 156 - 38042 Grenoble, Cedex 9 – France
6	Department of Chemistry and Biochemistry, Texas Tech, Lubbock, Texas 79409-1061, United States

The dynamics of functional groups within drug molecules influences their medicinal or toxicological effects, with methyl groups‟ conformational changes affecting binding to active sites. Here, we combine inelastic neutron scattering spectroscopy with density functional theory to investigate molecular dynamics and conformational flexibility of methacetin (C9H11NO2), a member of the acetamide family that includes paracetamol (C8H9NO2) and phenacetin (C10H13NO2). Our results reveal that subtle variations in its crystal packing and hydrogen bonding lead to multiple conformations, with methyl group reorientations contributing significantly to the molecule‟s dynamics. This study stresses the importance of integrating experimental and computational methods to understand the structural dynamics of pharmaceutical compounds and their implications for drug design.

Pereira J.E.M. , Boldyreva E. , Zakharov B.A. , Mitsutake H. , Rudić S. , Koza M.M. , Seydel T. , Eckert J. , Bordallo H.N.
Methyl Group Dynamics and Conformational Flexibility in Methacetin Revealed by Neutron Spectroscopy
Journal of Molecular Structure. 2026. 145589 . DOI: 10.1016/j.molstruc.2026.145589 OpenAlex

Submitted:	Dec 16, 2025
Accepted:	Feb 4, 2026

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W7127947540

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Сбор данных от 15.02.2026