Kinetics of the acid hydrolysis of heparin from its Cu (II) complex and its relation to biological activity

Abstract

The acid‐catalyzed hydrolysis of heparin from Cu(II) complex was studied as a function of time and temperature. Four independent calculations showed that the hydrolysis, during the 5‐hr period examined, obeys the first‐order kinetic law. Specific rate constants, calculated at 50°C, 57°C, 65°C, 71°C, and 80°C, were 3.3 × 10⁻⁵ sec⁻¹, 6.5 × 10⁻⁵ sec⁻¹, 10.4 × 10⁻⁵ sec⁻¹, 15.1 × 10⁻⁵ sec⁻¹, and 26.6 × 10⁻⁵ sec⁻¹, respectively. Arrhenius plots of the data yielded 14.7 kcal as the energy of activation. An independent run of the self‐hydrolysis of heparin at 57°C also obeyed first‐order kinetics and its specific rate constant of 6.4 × 10⁻⁵ sec⁻¹ is in excellent agreement with that of the hydrolysis of Cu(II)‐heparin at 57°C. The anticoagulant activity of heparin and of the Cu(II)‐heparin are not appreciably different. Further, the inactivation of heparin closely parallels Cu(II) release from the Cu(II) complex which in turn parallels desulfation.