Theoretical, Solid-State, and Solution Quantification of the Hydrogen Bond-Enhanced Halogen Bond

Proximal noncovalent forces are commonplace in natural systems and understanding the consequences of their juxtaposition is critical. This paper experimentally quantifies for the first time a Hydrogen Bond-Enhanced Halogen Bond (HBeXB) without the complexities of protein structure or preorganization. An HBeXB is a halogen bond that has been strengthened when the halogen donor simultaneously accepts a hydrogen bond. Our theoretical studies suggest that electron-rich halogen bond donors are strengthened most by an adjacent hydrogen bond. Furthermore, stronger hydrogen bond donors enhance the halogen bond the most. X-ray crystal structures of halide complexes (X⁻=Br⁻, I⁻) reveal that HBeXBs produce shorter halogen bonds than non-hydrogen bond analogues. ¹⁹F NMR titrations with chloride highlight that the HBeXB analogue exhibits stronger binding. Together, these results form the foundation for future studies concerning hydrogen bonds and halogen bonds in close proximity.