%0 Journal Article
%T Coordination Dynamics and Coordination Mechanism of a New Type of Anticoagulant Diethyl Citrate with Ca2+ Ions
%A Jin Han
%A Jun-Fa Xue
%A Meng Xu
%A Bao-Song Gui
%A Li Kuang
%A Jian-Ming Ouyang
%J Bioinorganic Chemistry and Applications
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/354736
%X Diethyl citrate (Et2Cit) is a new potential anticoagulant. The coordination dynamics and coordination mechanism of Et2Cit with Ca2+ ions and the effect of pH on the complex were examined. The result was compared with that for the conventional anticoagulant sodium citrate (Na3Cit). The reaction order (n) of Et2Cit and Na3Cit with Ca2+ 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 ( ) was 0.52 and 0.15£¿L¡¤mol£¿1¡¤s£¿1, respectively. It is indicated that the coordination ability of Et2Cit with Ca2+ was weaker than that of Na3Cit. However, the dissociation rate of the calcium complex of Et2Cit was faster than that of Na3Cit. Increased pH accelerated the dissociation rate of the complex and improved its anticoagulant effect. The Et2Cit complex with calcium was synthesized and characterized by elemental analysis, XRD, FT-IR, 1H NMR, and ICP. These characteristics indicated that O in ¨CCOOH and C¨CO¨CC of Et2Cit was coordinated with Ca2+ in a bidentate manner with 1£¿:£¿1 coordination proportion; that is, complex CaEt2Cit was formed. Given that CaEt2Cit released Ca2+ more easily than Na3Cit, a calcium solution was not needed in intravenous infusions using Et2Cit as anticoagulant unlike using Na3Cit. Consequently, hypocalcemia and hypercalcemia were avoided. 1. Introduction An anticoagulant must be added to dialysates to prevent blood solidification in vitro (in a dialysis machine). Sodium citrate (Na3Cit) is an important anticoagulant used in clinical settings [1¨C3]. However, using Na3Cit as an anticoagulant easily causes hypocalcemia and hypercalcemia [4, 5] because of the strong chelating ability of Na3Cit with Ca2+ ions. Given this ability, the dissociation metabolism of the formed chelate CaCit in vivo takes 30£¿min. Using Na3Cit also negatively affects the maintenance of coagulation stability of high-risk hemorrhage patients in vivo, which easily causes complications such as hypocalcemia during or after dialysis. Our group has previously synthesized a new anticoagulant [6], namely, diethyl citrate (Et2Cit). The anticoagulant mechanism of Et2Cit is based on the formation of Ca2+ with Et2Cit. This formation decreases the Ca2+ concentration in blood and inhibits prothrombin conversion into thrombin, thereby influencing the anticoagulant effect. The large steric effect of Et2Cit weakens the coordination of Ca2+ ion compared with that of Na3Cit. Therefore, hypocalcemia and hypercalcemia can be avoided using Et2Cit as anticoagulant [7]. The frequency of blood gas analyses can also be
%U http://www.hindawi.com/journals/bca/2013/354736/