Coordination Dynamics and Coordination Mechanism of a New Type of Anticoagulant Diethyl Citrate with Ca(2+) Ions

Diethyl citrate (Et(2)Cit) is a new potential anticoagulant. The coordination dynamics and coordination mechanism of Et(2)Cit with Ca(2+) ions and the effect of pH on the complex were examined. The result was compared with that for the conventional anticoagulant sodium citrate (Na(3)Cit). The reaction order (n) of Et(2)Cit and Na(3)Cit with Ca(2+) was 2.46 and 2.44, respectively. The reaction rate constant (k) was 120 and 289 L·mol(−1) ·s(−1). The reverse reaction rate constant (k (re)) was 0.52 and 0.15 L·mol(−1) ·s(−1), respectively. It is indicated that the coordination ability of Et(2)Cit with Ca(2+) was weaker than that of Na(3)Cit. However, the dissociation rate of the calcium complex of Et(2)Cit was faster than that of Na(3)Cit. Increased pH accelerated the dissociation rate of the complex and improved its anticoagulant effect. The Et(2)Cit complex with calcium was synthesized and characterized by elemental analysis, XRD, FT-IR, (1)H NMR, and ICP. These characteristics indicated that O in –COOH and C–O–C of Et(2)Cit was coordinated with Ca(2+) in a bidentate manner with 1 : 1 coordination proportion; that is, complex CaEt(2)Cit was formed. Given that CaEt(2)Cit released Ca(2+) more easily than Na(3)Cit, a calcium solution was not needed in intravenous infusions using Et(2)Cit as anticoagulant unlike using Na(3)Cit. Consequently, hypocalcemia and hypercalcemia were avoided.