Substituent Effects in CH Hydrogen Bond Interactions: Linear Free Energy Relationships and Influence of Anions

Aryl
CH hydrogen bonds (HBs) are now commonly recognized as important
factors in a number of fields, including molecular biology, stereoselective
catalysis, and anion supramolecular chemistry. As the utility of CH
HBs has grown, so to has the need to understand the structure–activity
relationship for tuning both their strength and selectivity. Although
there has been significant computational effort in this area, an experimental
study of the substituent effects on CH HBs has not been previously
undertaken. Herein we disclose a systematic study of a single CH HB
by using traditional urea donors as directing groups in a supramolecular
binding cavity. Experimentally determined association constants are
examined by a combination of computational (electrostatic potential)
and empirical (σm and σp) values
for substituent effects. The dominance of electrostatic parameters,
as observed in a computational DFT study, is consistent with current
CH HB theory; however, a novel anion dependence of the substituent
effects is revealed in solution.