B3LYP/6-31G*, RHF/6-31G*and MM3 heats of formation of disaccharide analogs

DeltaH(f) values were calculated with the bond- and group-enthalpy method for analogs of 13 disaccharides to learn the relative stabilities for various configurations about the carbon atoms connected to the linkage oxygen atom. The analogs were based on tetrahydropyran and, in the case of the sucrose analogs, tetrahydrofuran. The molecular mechanics program MM3 calculates these values as an option. The method was also used with RHF/6-31G* and B3LYP/6-31G* quantum mechanics (QM) theory. DeltaH(f) values had ranges of 15-17 kcal tall energies herein are molar) by the different methods, with the analogs of the three trehaloses and sucrose having the lowest values. DeltaH(f) values for the isomeric analogs of non-reducing sugars with two anomeric centers are about - 150 kcal, about 8 kcal lower than for the analogs of the reducing dimers (nigerose, maltose, laminarabiose. cellobiose and galabiose (alpha -D-galactosyl-D-galactose)) by all three types of calculation. The analogs of the di-axial, axial-equatorial and di-equatorial, non-glycosidic pseudo-disaccharides had DeltaH(f) values within 1.0 kcal by each of the three methods. They were about 8 kcal higher than for the molecules that contain one glycosidic sequence. The relative DeltaH(i) values by QM were within 1.0 kcal of their corresponding relative electronic energies, except for the methylated sucrose analog, for which the discrepancy was about 1.85 kcal at both QM levels. Compared to our B3LYP results, the RHF-based calculations overestimated the stability of all molecules by about 2.85 kcal. The MM3 values were close to the B3LYP numbers, with the largest discrepancy for the cellobiose analog, 1.76 kcal. The stabilization embodied in the group enthalpy increment for anomeric centers is another manifestation of the anomeric effect. (C) 2000 Elsevier Science B,V. All rights reserved.