Binding of Heparin to Metals

Heparin is a major prophylactic and treatment agent for thrombosis. Structurally, this anticoagulant is a polydisperse, highly negatively charged polysaccharide mixture that contains a variable density of sulfate group substituents per molecule. Previous study has shown that heparin molecules have a high affinity for a wide range of metal ions with varying oxidation states. However, reports in literature on binding of heparin to metals have investigated only a small sampling of heparin–metal ion interactions. Since interaction of heparin with fluid phase and cell surface macromolecules in vivo is dependent on the heparin structure when bound in a metal ion complex, a survey of the physical parameters for heparin binding to metals is imperative. Atomic absorption and spectrophotometry experiments were performed for metal quantification, and in this study, the relative values for affinity constants and number of binding sites for heparin binding to several alkaline, alkaline earth, main group, and transition metals in their most common oxidation states are reported. We found an overall trend for heparin–metal affinity to be Mn2+ > Cu2+ > Ca2+ > Zn2+ > Co2+ > Na+ > Mg2+ > Fe3+ > Ni2+ > Al3+> Sr2+, with the trend in Nb being opposite compared with the Ka.