Unravelling the Role of Uncommon Hydrogen Bonds in Cyclodextrin Ferrociphenol Supramolecular Complexes: A Computational Modelling and Experimental Study

• Published in: International journal of molecular sciences Vol. 24; no. 15; p. 12288
• Main Authors: Pigeon, Pascal, Najlaoui, Feten, McGlinchey, Michael James, Sanz García, Juan, Jaouen, Gérard, Gibaud, Stéphane
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.07.2023; MDPI
• Series: Special Issue Cyclodextrins: Properties and Applications
• Subjects: Analysis; atypical hydrogen bond; Chemical Sciences; Computer simulation; Computer software industry; Computer-generated environments; cyclodextrin; Cyclodextrins; Dextrins; ferrocene; Glucose; Hydrogen; Hydrogen bonding; Hydrogen bonds; Methylation; modelling; or physical chemistry; phase solubility; Phenols; Theoretical and; France; United States; database; atypical hydrogen bond; ferrocene; modelling; phase solubility; cyclodextrin; cyclodextrin ferrocene modelling phase solubility database atypical hydrogen bond
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241512288

We sought to determine the cyclodextrins (CDs) best suited to solubilize a patented succinimido-ferrocidiphenol (SuccFerr), a compound from the ferrociphenol family having powerful anticancer activity but low water solubility. Phase solubility experiments and computational modelling were carried out on various CDs. For the latter, several CD-SuccFerr complexes were built starting from combinations of one or two CD(s) where the methylation of CD oxygen atoms was systematically changed to end up with a database of ca. 13 k models. Modelling and phase solubility experiments seem to indicate the predominance of supramolecular assemblies of SuccFerr with two CDs and the superiority of randomly methylated β-cyclodextrins (RAMEβCDs). In addition, modelling shows that there are several competing combinations of inserted moieties of SuccFerr. Furthermore, the models show that ferrocene can contribute to high stabilization by making atypical hydrogen bonds between Fe and the hydroxyl groups of CDs (single bond with one OH or clamp with two OH of the same glucose unit).