Hydrogen bonding effects on amine rotation rates in crystalline amino acids

Abstract

Rates of rotation for amines in a variety of crystalline environments are reported, and the trends are explained in terms of the strengths of local hydrogen bonding interactions. Proton spin-lattice relaxation times ( T 1) and deuterium broad-line NMR spectra have been measured for D-, DL- and L- aspartic acid, two polymorphs of glycine, alanine, and leucine in the temperature range from −40 to 110 °C. The energy barriers for amine rotation are 27 ± 2 kJ mol −1 for D- or L-aspartic acid and 22 ± 2 kJ mol −1 for DL-aspartic acid; these energies are slightly lower than the previously reported value for the L form based on direct proton T 1 measurements at 60 MHz. The values for the α and γ forms of glycine were 24 ± 2 and 30 ± 2 kJ mol −1 respectively, that for L-alanine was 40 ± 2 and that for L-leucine was 49 ± 3 kJ mol −1. These are all in rough agreement with previously reported values (although the differences for the polymorphs of glycine and for L- vs. DL-aspartic acid were not reported). Crystal structures of these amino acids indicate differences in hydrogen bonding environments around the R-NH 3 + groups that are probably responsible for the different activation barriers. A molecular mechanics calculation of the rotation energy barriers for L- and DL-aspartic acid based on the crystal structures gave satisfactory agreement with experimental results if a uniform (and arbitrarily chosen) dielectric constant of 2.5 was assumed. Differences between L- and DL-aspartic acids and between two polymorphs of glycine were well represented qualitatively. Including additional neighboring molecules not involved in the hydrogen bonding or including periodic boundary conditions to describe the crystal packing did not significantly affect these results. If vacuum dielectric constants are used, the barriers are uniformly overestimated, and if the experimental macroscopic dielectric constant values are used, the barriers are generally underestimated. Dielectric constants differ substantially from one amino acid to another and significantly affect the estimated barriers; in fact, the bulk dielectric constants appear to be the major difference between the highest and the lowest values. The difficulty of accurately including dielectric relaxation into molecular mechanics calculations resulted in the disagreement between experimental measurements and theoretical calculations.