Quantitative Structure–Activity Relationship Analysis of the Effect of Metoclopramide and Related Compounds on the Surface Ionization of Fumed Silica

Abstract

Potentiometric titration curves were generated for fumed silica with various concentrations of dissolved metoclopramide. The effects of various benzamide analogs of metoclopramide, which are positively charged in the titration medium and differ solely by their aromatic substituents, as well as lidocaine, which is also structurally analogous but is mainly in the unionized form, were also studied. At sufficiently high pH, pH 7.0 and above, the silica surface charge was independent of the metoclopramide concentration. A reasonable linear relationship with a positive slope was found between the logarithmic octanol–water partition coefficient (log P) values of the compounds and the negative surface charge determined at pH 7.0 and 7.2. These results can be attributed to specific adsorbate–surface interactions rather than concentration effects. The carbonyl oxygens of the benzamide structures most likely form hydrogen bonds with the neutral silanols. The use of positively charged triethylamine and ephedrine resulted in surface charge values that were the least negative in the aforementioned quantitative structure–activity relationship analyses. These results are consistent with ionic interactions between the positively charged aliphatic amine groups and the negatively charged surface silanols occurring simultaneously with the nonionic interactions.