Complexation of Calix[4]arene bis-Hydroxymethylenediphosphonic Acid with Amino acids. Binding Constants Determination by RP HPLC Method

Abstract

Host-Guest complexation of calixarene-bis-hydroxymethylenediphosphonic acid with 17 amino acids in water solution had been studied by the RP HPLC and molecular modelling methods. It had been shown the binding constants of the complexes are depended on the nature of the amino acid residue, log P and pKa of the acids. The complexation is mainly determined by the electrostatic interactions between the positively charged nitrogen atom of the amino acid and the negatively charged oxygen atom of phosphonic acid residue of the calixarene, the Host-Guest p-p, СН-p and solvophobic interactions.

Haemostasis modulation by calix[4]arene methylenebisphosphonic acid C-145 and its sulfur-containing analogue

“…The effect of C-145S was more prominent. In conclusion, calix [4]arene C-145S proved to be the more potent inhibitor of fibrin polymerization in comparison to C-145, which suggested earlier as anticoagulant agent. C-145S proved to have much more outlined inhibitory action on Ca 2+ -signaling in platelets and stimulatory effect on endothelial cells proliferation.…”

“…C-145 (octasodium salt of calix [4]arene-tetra-methylenebisphosphonic acid) was previously considered as specific anti-сoagulant agent that affects fibrin polymerization and does not notably influence other parameters of coagulation system. C-145S (octasodium salt of thiacalix [4]arene-tetra-methylenebisphosphonic acid) possessing wider hydrophobic hole was expected to be more effective antithrombotic agent than C-145. The aim of present work was to compare the action of both organic compounds on fibrin polymerization, fibrinolysis, platelets and endothelial cells.…”

“…The change of turbidity during fibrin clot formation induced by aPtt-reagent and digestion induced by tPa was estimated. turbidity study was used for the estimation of polymeric fibrin hydrolysis by plasmin in the presence of thiacalix [4]arene C-145S and calix [4]arene C-145. Effects of thiacalix [4]arene C-145S and calix [4]arene C-145 on the activation of Glu-plasminogen by streptokinase were studied using chromogenic substrate S2251.…”

“…Thus C-145 remained the most prospective molecular platform for the development of antithrombotic agent. [4]arene, haemostasis, fibrinolysis, endothelial cells, platelets, blood coagulation, antithrombotic drugs.…”

“…alix [4]arenes and thiacalix [4]arenes are macrocyclic compounds composed of hydrophobic 'cup' that is modified on the edge by fragments of methylenebisphosphonic acid [1]. They can effectively bind amino acids, namely Ar-ginine and Arginine-containing peptides as well as proteins and supramolecular complexes in solution [2,3].…”