Complexation of chromium (III) with the antifibrinolytic drug tranexamic acid: Formation, kinetics, and molecular modeling studies

Tranexamic acid (TXA) is widely used as an antifibrinolytic drug, inhibits fibrinolysis by blocking lysine-binding sites on plasminogen, limiting the activation of plasmin; and therefore, prevents excessive blood loss from trauma, surgery (e.g., cardiac, orthopedic, liver transplantation), postpartum bleeding, nosebleeds, and heavy menstruation. Tranexamic acid complexes of some metal ions have shown significant microbiological and anticancer activities. Here, the formation of tranexamate-chromium (III) complex in aqueous solution has been spectrophotometrically and potentiometrically studied. Kinetics of formation of tranexamate-chromium(III) complex has been spectrophotometrically studied under pseudo order conditions over the 303-323 K range, pH (3.20-4.56) range, and ionic strength of 0.30 M for a set of TXA concentrations. The formation of this complex was studied potentiometrically at (298.2 +/- 0.1) K, in which the overall stability constant and TXA protonation constants were calculated. The UV-visible spectroscopic measurements were carried out to confirm the formation of the Cr(III)-TXA complex. The density functional theory (DFT) and molecular dynamics (MD) simulation were used to illustrate the geometries of the Cr(III)-TXA complex in gas and water phases, as well as the interactions among the involved species. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

Tranexamic acid, widely used as an antifibrinolytic drug, blocks fibrinolysis by inhibiting plasminogen activation, thus preventing excessive blood loss. The formation of a tranexamate-chromium (III) complex in aqueous solution was studied through spectrophotometry and potentiometry. The interaction and geometries of the Cr(III)-TXA complex were illustrated using density functional theory and molecular dynamics simulation.