Substituent effects on the electrochemistry and photostability of model compounds of calcium channel antagonist drugs

Abstract

We have synthesized three nitrocompounds in order to mimic the model structure of some relevant drugs such as nifedipine, nitrendipine, nisoldipine, nimodipine, and related ones, in order to investigate the effect of structural change on its electrochemical and photodegradation properties. We have found that ortho substitution with a nitro group produces a distortion of the coplanar arrangement, thus decreasing the resonance interaction between the nitro group and the aromatic system. A consequence of this fact is the observed cathodic peak potential shift toward negative values in the ortho-substituted isomer. It is observed that the position of the nitro substitution also produced differences in the photostability of the studied compounds, Stability studies of the compounds in buffered solutions (pH 7) stored in room light conditions show that only the ortho derivative was unstable in the time scale of the experiment (2 h). The instability of the ortho derivative may be explained if we consider that in this isomer, the photoexcited state of the nitro group is not stabilized by resonance as a consequence of the loss of coplanarity between the nitro group and the aromatic ring. Using molecular modeling, we have found that the configuration of minimal energy shows torsion angles of 70, 7.5, and 2.2 degrees for ortho- meta- and para-derivatives, respectively, confirming the lost of coplanarity between the nitro group and the aromatic ring in the ortho derivative.