Comparative analysis of complex formation of magnesium and calcium ions with low-molecular-weight and unfractionated heparin

The acid-base and complexing properties of Logiparin (a low-molecular-weight variety (LMH) of heparin (H₄L) with magnesium and calcium ions were studied using mathematical modeling of chemical equilibria in aqueous solutions of Logiparin and its solutions with magnesium and calcium ions and pH titration. The heparin concentration was set equal to the concentration of its disaccharide units. The protonated heparin form HL^3? and the most significant heparin complexes of Mg²⁺ and Ca²⁺ were identified; relevant formation constants were estimated. Comparative analysis of the results is carried out against available data on ion complexing with unfractionated (high-molecular-weight) heparin (HMH). The Logiparin complexes of calcium and magnesium ions are inferior to the HMH complexes in both their formation constants in solution and their effect on the decrease in the equilibrium concentration of free calcium ions, a participant of all blood coagulation processes. This distinction creates prerequisites for the lower blood-coagulating activity of Logiparin compared to that of HMH, which is for the first time confirmed in biological experiments with the in vitro administration of the same concentration of HMH or LMH into the blood plasma of laboratory rats.