New paper in Angewandte Chemie: Improper hydrogen bonding in RCH\u2082F and RCHF\u2082 motifs<\/p>\n\n\n\n
Congratulations to Bruno A. Piscelli for his new paper published in Angewandte Chemie! This paper was done in collaboration with David O\u2019Hagan and Michael B\u00fchl from the University of St Andrews. Our results show that the key player is not the hydrogen but the carbon<\/em> atom attached to fluorine. Fluorination makes this carbon strongly electropositive, and the anion or water molecule preferentially interacts with the CF carbon center. Charge is redistributed from hydrogen toward carbon and fluorine as the acceptor approaches, and the interaction is dominated by electrostatics rather than classical n \u2192 \u03c3*(C\u2013H) donation alone. The study also rationalizes when C\u2013H stretching bands show blue shifts (bond shortening) or red shifts (bond elongation) in these systems.<\/p>\n\n\n\n We then extend this analysis to C\u2083\u2013C\u2086 rings bearing all-cis CH\u2082F or CHF\u2082 substituents and show that they can form surprisingly strong complexes with chloride. Some of these fluorinated alicycles bind anions in solution with strengths comparable to typical urea-based anion receptors, suggesting a new design platform for anion-binding molecules and organocatalysts.<\/p>\n\n\n\n
In this work, we use high-level quantum-chemical calculations to understand how partially fluorinated methyl groups (CH\u2082F and CHF\u2082) interact through so-called \u201cimproper\u201d or \u201cnon-classical\u201d hydrogen bonds. These groups are increasingly used in medicinal and agrochemical design because they lower LogP and tune polarity, but their hydrogen bonding behavior is not intuitive. As fluorines are added, the geminal C\u2013H hydrogens actually become less<\/em> positively charged, which would normally suggest weaker hydrogen bonding. Yet, the interaction with hydrogen-bond acceptors such as chloride or water becomes stronger.<\/p>\n\n\n\n