Coordination dynamics and coordination mechanism of a new type of anticoagulant diethyl citrate with ca(2+) ions

Abstract

Diethyl citrate (Et2Cit) is a new potential anticoagulant. The coordination dynamics and coordination mechanism of Et2Cit 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 (Na3Cit). The reaction order (n) of Et2Cit and Na3Cit 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 Et2Cit with Ca(2+) 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, (1)H NMR, and ICP. These characteristics indicated that O in -COOH and C-O-C of Et2Cit was coordinated with Ca(2+) in a bidentate manner with 1 : 1 coordination proportion; that is, complex CaEt2Cit was formed. Given that CaEt2Cit released Ca(2+) 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.

Figure 1

Changes in Ca²⁺ concentration with reaction time in different systems: (a) Et₂Cit-Ca²⁺ system and (b) Na₃Cit-Ca²⁺ system.

Figure 2

Plots of log⁡⁡r-log⁡⁡c(Ca²⁺) in different systems: (a) Et₂Cit-Ca²⁺ system and (b) Na₃Cit-Ca²⁺ system.

Figure 3

Plots of concentration change of free Ca²⁺ ions with reaction time under different pH conditions: (a) Et₂Cit and (b) Na₃Cit.

Figure 4

XRD patterns of CaEt₂Cit and CaCl₂: (a) CaEt₂Cit and (b) CaCl₂.

Figure 5

FT-IR spectra of Et₂Cit and its complex CaEt₂Cit: (a) Et₂Cit and (b) CaEt₂Cit.

Figure 6

¹H NMR spectra of Et₂Cit and its complex CaEt₂Cit. (a₁, b₁, and c₁) are Et₂Cit; (a₂, b₂, and c₂) are CaEt₂Cit. (a) Total spectra, (b) δ = 2.70–3.00 section, (c) δ = 4.10–4.21 section.

Figure 7

Schematic of the coordination of Ca²⁺ ion with two isomers of anticoagulant Et₂Cit. The asterisk ∗ shows the center C atom of Et₂Cit.