The formation of the calcium and zinc salts from CaCl2, ZnCl2 and six monomeric structural units of heparin (1-OMe Delta UA-2S, 1-OMe GlcN-S6S, 1,4-DiOMe GlcA, 1,4-DiOMe GlcN-S3S6S, 1,4-DiOMe IdoA-2S, and 1,4-DiOMe GlcN-S6S) have been studied in gas phase and aqueous solution as model reactions for formation of heparin-Ca2+ and heparin-Zn2+ complexes. Gibbs reaction energies computed at the B3LYP/6-311++G(d,p) level of theory for the reactions studied in aqueous solution are positive and range from 20 to 250 kJ/mol. (C) 2014 Elsevier B.V. All rights reserved.