Evaluating intramolecular hydrogen bond strengths in (1-4) linked disaccharides from electron density relationships

The binding energy of intermolecular hydrogen bonds can be readily and accurately assessed using model pairs of functional groups; however, the energy of intramolecular hydrogen bonds as found in carbohydrates and folded proteins has not been computationally and experimentally accessible. We present a procedure to evaluate the intramolecular hydrogen bond strength from a set of correlation curves based on the electron density within the hydrogen bond. B3LYP 6-31G(d), 6-31+G(d,p), and 6-311++G(d,p) were used to optimize all combinations of functional group OH, NH2, and NHCOCH3 pairs. The intermolecular hydrogen bonds and the electron density in the hydrogen bond were measured using Bader's atoms in molecules method. A linear relationship between the binding energy/hydrogen bond strength (ΔEHB) and a modified Grabowski complex parameter (Δel+lap) for the entire set of functional group pairs was established. Correlation curves (ΔEHB vs Δel+lap) for each individual pair of functional groups were then construc...