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Complexation in the systems Pd(II)-Cl-HA-HGlu (HA is the l- or d-conformer of 2-methylamino-1-phenylpropanol; HGlu is glutamic acid) was studied using pH-metric titration, electronic absorption spectroscopy, and quantum-chemical modeling. It was found that the ratio of the complex species largely depends on pH and the amine, the crucial factor being stabilization of the structures by hydrogen bonding. This provides explanation to the previous data on the different radioprotective activities of the complexes (HA)[PdCl] containing the l- and d-conformers of the ligand HA. [ABSTRACT FROM AUTHOR]

A new method for the computer simulation of chemical equilibria in multicomponent biological liquids has been developed on the basis of a consistent analysis of the databank on equilibria in solutions, combined with the AUTOEQUIL program for the calculation of such equilibria. This method has been applied to the search for new low-molecular-weight endogenous blood anticoagulants with a mechanism of action based on reduction of the equilibrium concentration of biologically active Ca2+ ions by means of complex formation. Using the results of simulation of the metal-ion equilibria in blood plasma with a databank including over 800 units, an adequate model is created, which is capable of describing 64 equilibria in a basis set of 29 components. An analysis of these equilibria revealed four endogenous ligands capable of forming stable complexes with Ca2+, including glutamate (GLU), lactate (LAC), citrate (CIT) and adenosinetriphosphate (ATP). Their anticoagulant properties have been confirmed by universal biological assays in rats in terms of the plasma recalcification time ( RCT) and the activated partial thromboplastin time ( APTT). It has been found that the anticoagulant activities of components are as follows: LAC, 500%; ATP, 240%; GLU, 176%; CIT, 154%(relative to the substrate plasma activity of 100%). [ABSTRACT FROM AUTHOR]