Medicinal Electrochemistry: the case of the first BODIPYBased Fluorescent Naphthoquinone

In this study, the electrochemical behavior of a new BODIPY based fluorescent naphthoquinone with potent antitumour activity [1] was investigated by cyclic voltammetry (CV). The characterization of the reduction mechanism is fundamental to the understanding of the cytotoxic effects and mechanism of action of this novel hybrid compound. This new compound behaves as a fluorescent probe in subcellular localization studies [1]. CV experiments were performed in a conventional threeelectrode cell. The working electrode was a glassy carbon (GC) BAS (d = 3 mm), the counter electrode was a Pt wire and the reference electrode, an Ag|AgCl, Cl− (saturated). Compound 1 was composed of two non-conjugated main reducible systems, the orthodihydrofuran- naphthoquinone (nor-beta-lapachone) and the boron-dipyrromethene, (BODIPY) separated by a methylene spacer. The electrochemical profile of the compound is presented in figure 1A. The first reduction is represented by two redox systems, the first, well-defined, diffusional and quasi-reversible (Ic/Ia), at potentials of -0.535 V and -0.407 V and the second, ill-defined, better visualized at higher scan rates (1 V s-1) (IIc/IIa). This behavior is representative of the quinone system, where disproportionation occurs, at slow scan rates, leading to the hydroquinone dianion (Fig. 1A and 1C , marked in red). The other reduction wave (IIIc), at -1.901 V (Fig. 1A and 1C, in blue), is related to the reduction of the heterocyclic system and leads to an aromatic ring and a very stabilized radical, which is oxidized at the potential IIIa (-0.009 V), as shown by inversion potentials (Fig.1A). This is a very interesting and complex redox system, represented by the scheme in figure 1C. The proposed mechanism is proved in figure 1B through combined CVs of nor-β-lapachone and BODIPY.This molecule constitutes a promising prototype owing to its potential biological activities and imaging capability aimed to performing mechanistic investigations in cells and in vivo, and opens up an interesting avenue of research.