We present a theoretical study of the reactivity of some substituted porphyrins and phthalocyanines toward the electroxidation of 2-mercaptoethanol. The donor-acceptor intermolecular hardness and the electrophilicity index have been chosen indicators in order to discriminate the relative reactivity of the different species, Ail the calculations have been carried out using a recent hybrid Hartree-Fock/density functional approach (PBE0). and solvent effects have been introduced using a recent version of the polarizable continuum model (C-PCM). Our results show that azaporphyrin molecules are less reactive than the corresponding porphyrins in the gas phase. In contrast, solvation significantly affects the reactivity of the considered species, reversing the general trend. Our theoretical results are in agreement with the electrochemical experiments, carried out to further validate the computational predictions.