Journal article
Crystalline Forms of Tomatidine: Mechanochemistry Facilitates a Solvent-Reduced Isolation of the Free Base
Crystal growth & design
02/24/2026
DOI: 10.1021/acs.cgd.5c01499
Abstract
Tomatidine (TO) is a steroid with potential as a therapeutic agent against persistent infections caused by methicillin-resistant small-colony variants (SCVs) of Staphylococcus aureus, with low minimal inhibitory concentrations. The antibacterial activity of TO arises from inhibition of bacterial ATP synthase, a key enzyme in energy metabolism, thereby impairing bacterial growth and survival under stress conditions. Recent studies have demonstrated that the optimization of the TO scaffold through simple chemical modifications has successfully broadened the antibacterial spectrum to include both Gram-positive, including non-SCV S. aureus, and Gram-negative bacteria. Despite emerging pharmaceutical significance, the solid-state properties of TO and its crystalline forms remain underexplored. We report the first single-crystal X-ray structures of the free base of TO, its hydrochloride salt (TO·HCl), and a novel crystalline dihydrate form (TO·2H2O). Neutralization of the salt form of TO was achieved using mechanochemistry, highlighting mechanochemistry as an efficient and cleaner neutralization pathway that reduces solvent consumption compared to conventional extraction methods. The results reveal insights into the intermolecular interactions and phase stability of solid forms of TO, contributing to the understanding of crystallization behavior and stability in the solid state.
Details
- Title: Subtitle
- Crystalline Forms of Tomatidine: Mechanochemistry Facilitates a Solvent-Reduced Isolation of the Free Base
- Creators
- Vishal A. Lohar - Université de SherbrookeBharathkumar Yasam - Université de SherbrookeFrançois Malouin - Université de SherbrookePierre-Luc BoudreaultLeonard R. MacGillivray - Université de Sherbrooke
- Resource Type
- Journal article
- Publication Details
- Crystal growth & design
- DOI
- 10.1021/acs.cgd.5c01499
- ISSN
- 1528-7483
- eISSN
- 1528-7505
- Publisher
- American Chemical Society
- Grant note
- Canada Excellence Research Chairs, Government of Canada: NA Centre in Green Chemistry and Catalysis: NA
L.R.M. acknowledges financial support from the Canada Excellence Research Chairs (CERC) Program. We also acknowledge support of the Centre for Green Chemistry and Catalysis (CCVC) of Quebec. Nous remercions le Centre pour la catalyse et la chimie verte (CCVC) du Quebec de son soutien.
- Language
- English
- Electronic publication date
- 02/24/2026
- Academic Unit
- Chemistry
- Record Identifier
- 9985141874302771
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