Role of the magnesium cation on antihypertensive molecule-human serum albumin binding: affinity chromatography approach

摘要

The role of the Mg~(2+) cation on antihypertensive molecule binding on human serum albumin (HSA) was studied by affinity chromatography. The thermodynamic data corresponding to this binding were determined for a wide range of Mg~(2+) concentrations (c). For the nifedipine molecule, an increase in the Mg~(2+) concentration produced a decrease in binding due to a decrease in the electrostatic interactions. For verapamil and diltiazem, which have the highest solvent accessible surface area, the solute binding on HSA was divided into two Mg~(2+) concentration regions. For a low c value below c_c (≈1.6 mmol/l), the binding dependence with c was similar to that of nifedipine. For c above c_c the hydrophobic effect created in the bulk solvent associated with a decrease in the van der Waals interactions between the solute molecule and the HSA implied a decrease in its binding. These results showed that for patients with hypertension, an Mg~(2+) supplementation during treatment with these antihypertensive molecules can increase the active pharmacological molecule concentration.