The influence of electrostatic and dispersion components of intermolecular interactions on the recognition of carbohydrates by aromatic protein residues is important for many biological processes. Interactions between glucose and galactose and aromatic moieties of tryptophan, phenylalanine and histidine were investigated through 1H nuclear magnetic resonance (NMR) chemical shift perturbation and fully explained by molecular modelling at the density functional theory (DFT) level. According to NMR experiments, aromatic amino acids interact preferably with one face of the carbohydrate and the calculations showed how intermolecular interactions were determinant in explaining the selectivity. Non-covalent interaction surfaces revealed that a CH bond oriented toward the center of the aromatic ring maximized the attractive interaction while minimizing the steric repulsion. Energy decomposition analyses showed that the dispersion component was stronger than the electrostatic component and contributes more when hydrogen bonds are not present in the studied complexes. However, it was the electrostatic component that correlated with the facial preference, especially for the complexes with tryptophan.

The present study describes the synthesis, assessment of the anticholinesterase activity and the inhibition type of novel cis- and trans-3-arylaminocyclohexyl N,N-dimethylcarbamates. In vitro inhibition assay by Ellman's method with human blood samples showed that carbamates were selective for butyrylcholinesterase (BuChE) with compound concentration that inhibits 50% of enzyme activity (IC50) between 0.11 and 0.18 mmol L-1. cis- and trans-3-(4-Methoxyphenylamino)cyclohexyl N,N-dimethylcarbamate hydrochloride were the most active for BuChE, showing that the presence of methoxyl group enhanced the anticholinesterase activity. The enzyme kinetics studies indicate a noncompetitive inhibition against acetylcholinesterase (AChE) and mixed type inhibition for BuChE. Molecular modeling studies confirm the ability of carbamates to bind both the active and peripheral sites of the BuChE.