Gold electrode was functionalized with glutathione (GSH) by adsorption and analyzed by cyclic voltammetry and electrochemical impedance techniques. The structure and properties of the surface film are strongly dependent on the modification procedure, pH value and supporting electrolyte. The blocking properties and the electron transfer through the GSH film and the "ion gating" effect of Ca2+ ions was analyzed in the frame of the model of a disk type electrode surface with active sites. The interaction of two antitumoral drugs, doxorubicin (+1) and mitoxantrone (+2) with the modified electrode was investigated using the same model. Both drugs exert an "ion gating" effect similar to Ca2+ ions due to the electrostatic interaction of the positively charged drug with the ionized COO- groups of the GSH film. The results also show that doxorubicin interacts in a first step with the negatively charged surface of the film leading to a deprotonated species, which may penetrate the GSH film and undergo electron transfer at the electrode surface. Therefore it may be used as positively charged electroactive probe, in the potential range 0/-800 mV vs. SCE. The possible involvement of redox process of molecular oxygen in the reduction of doxorubicin at electrodes modified by SAM's terminated by hydrophilic groups is also suggested. The PM3 semiempirical MO-modeling accounts reasonably for the experimental features outlined by cyclic voltammetry and impedance results. (C) 2011 Elsevier B.V. All rights reserved.