Study of the ionic equilibriums in aqueous solutions and coordination properties of Adefovir and Cidofovir used as antiviral drugs

摘要

The dissociation constants of Adefovir ({[2-(6-amino-9H-purine-9-l)ethoxi]methyl}phosphoric acid) used in the treatment of hepatitis B and Cidofovir ({[2-(6-amino-9H-purine-9-l)ethoxi]methyl}phosphoric acid), used in the treatment of cytomegalovirus retinitis in AIDS patients, together with the stability constants of its Cu~(2+), Ni~(2+), Zn~(2+), Co~(2+), Ca~(2+), and Mg~(2+) complexes were studied by potentiometric titration. Adefovir and Cidofovir were abbreviated to PMEA and HPMPC. All measurements were obtained under two sets of conditions: at 298K and ionic strength (I) of 0.1moldm~(-3) (NaCl) and at 310K and I of 0.16moldm~(-3) (NaCl), corresponding to the conditions of human blood. Equilibrium constants in aqueous solution were calculated using the program SUPERQUAD. Also, solvent effects on the equilibrium constants of the ligands were examined. Moreover, all coordination studies were carried out with the ligand/metal molar ratios of 1:1. This ligand/metal stoichiometric ratio was spectrometrically determined using Job's method.