Deciphering the degree of proton-transfer in pyrido-cyclophanes by chiroptical outcomes in non-aqueous solvents

Abstract

Proton transfer equilibria are of pivotal importance due to the role they play in a plethora of biological and phamaceutical processes. With the aim of explaining the relative position of the hydrogen to be transferred, we investigated the behavior of chiral pyrido-cyclophanes with different morphologies using circular dichroism in the presence of different acids in acetonitrile. The results showed that all three compounds underwent double protonation and formation of cascade ion-pairs, leading to the appearance of diagnostic signals in their ECD spectra. The presence of water fosters the crystallization of several intermediates that do not correspond to those in solution. By using Brønsted correlations, it was found that proton transfer from the acid to the pyridine occurred regardless of the acid's pK_a.