Thermodynamic Features of Diethyl Citrate Calcium Complexes and Factors Affecting the Complex Stability

Abstract

Diethyl citrate (Et₂Cit) is a promising new anticoagulant. In this study, the stoichiometry of the Et₂Cit complex with Ca²⁺ ions and the stability constant (K_s) were determined. The effect of pH and temperature on K_s were then discussed. Thermodynamic functions (DG, DH, DS) of the complex were also calculated. These results were compared with those of sodium citrate (Na₃Cit), a current clinical anticoagulant. Both Et₂Cit and Na₃Cit formed complexes with Ca²⁺ ion at 1:1 ratio. The K_s measured for calcium diethyl citrate (CaEt₂Cit) and calcium citrate (CaCit) was 231 and 1988, respectively, at pH 7.4, 37 ºC. It is indicated that CaCit was more stable than CaEt₂Cit. Increasing pH or solution temperature favoured the formation of both complexes. Increasing temperature from 15 to 40 ºC led to a shift of K_s from 58 up to 327 for CaEt₂Cit and 327 up to 2327 for CaCit, as a result of their endothermic reactions. Animal testing results on rabbits showed that the recovery speed of blood calcium concentration with Et₂Cit as anticoagulant was more rapid than that with Na₃Cit. Et₂Cit is expected to circumvent the problems of hypocalcemia and hypercalcemia which are usually encountered when using Na₃Cit for anticoagulation. Therefore, Et₂Cit has shown great potential as a new anticoagulant.