Experimental and theoretical study of the role of CH/π interactions in the aminolysis reaction of acetyl galactoside

Molecular recognition of saccharides is a growing field, which has many implications in cancer therapy, drug discovery, and cellular communication among others. The participation of CH/π interactions in this event is well known. Nevertheless, the intrinsic role of CH/π for modulating chemical reactions is still far from being applicable. In this experimental and computational work we have evaluated the participation of CH/π interactions in the aminolysis reaction of acetyl galactoside promoted with different 6-substituted 2(1H)-pyridones. Two features have been incorporated to the promoter molecular structure, on one end the promoting pyridone group and on the other end the recognition moiety, joined together by an alkyne spacer. The small increment in the observed pseudo-first-order rate constant values (kobs) was related to the stability of the transition state provided by noncovalent interactions, including CH/π interactions. A longer alkyne spacer was necessary to improve the molecular recognition of the galactoside substrate. The trend of the calculated activation energy values (ΔERTS) was in good accordance with the experimental rate constant values. [Display omitted] •2(1H)-Pyridones promoted aminolysis reaction of β-acetyl tetramethoxy galactoside and n-butylamine.•Molecular structure of 2(1H)-pyridones affected the observed pseudo-first-order rate constant values kobs of aminolysis.•Noncovalent interactions, such as CH/π interactions stabilized the transition state increasing the kobs values as a result.