A combined experimental and computational study of metronidazole and P-hydroxybenzoic acid cocrystal: QTAIM hydrogen-bond analysis, polymorphism screening and molecular docking
Pure and Applied Chemistry, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1515/pac-2025-0701
- Dergi Adı: Pure and Applied Chemistry
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, DIALNET, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO), Health Research Premium Collection (ProQuest), Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
- Anahtar Kelimeler: Cocrystal, metronidazole, molecular docking, polymorph, QTAIM analysis
- Ondokuz Mayıs Üniversitesi Adresli: Evet
Özet
In this work, a new cocrystal composed of metronidazole (MTZ) and P-hydroxybenzoic acid (PHBA) was synthesized using the slow evaporation method. Characterization by PXRD, DSC, FTIR, and SEM confirmed the formation of a new crystalline phase distinct from the starting materials. Computational analysis based on QTAIM revealed two possible forms stabilized by different hydrogen-bonding patterns: in form I, two hydrogen bonds link the carboxyl group of PHBA to the hydroxyl group of MTZ, whereas in form II, a single hydrogen bond forms between the hydroxyl groups of MTZ and PHBA. This suggests potential polymorphism, further supported by recrystallization experiments and PXRD diffractograms indicating a phase transformation. Molecular docking studies showed that cocrystallization enhanced the antibacterial activity of Metronidazole against Clostridium difficile, and that the two polymorphs exhibited distinct binding affinities, suggesting that polymorphism can influence the biological performance of the cocrystal.