The electrochemistry of 5-halocytosines at carbon based electrodes towards epigenetic sensing

Epigenetic modifications in DNA are strongly linked to the triggering and development of pathophysiological disorders and cancer diseases. The halogenation of DNA via radical species, particularly the formation of 5-chlorocytosine (ClC), has recently emerged as epigenetic modification. This work deals for the first time with the exploration of the electrochemical behaviour of ClC on different carbon electrodes such as glassy carbon and boron-doped diamond using cyclic voltammetry and square wave voltammetry. When comparing both carbon materials, the use of glassy carbon turned out to be the appropriate in terms of a more well-defined anodic wave and higher sensitivity. The electrochemical oxidation potential of ClC resulted to be linearly dependent on the pH with a maximum current intensity in acetic acid buffer solution under the conditions used. Moreover, a linear response between peak current intensity and ClC concentration was obtained within the range of 200 and 1000 μM with a limit of detection of 200 μM. In order to elucidate the reaction mechanism of the process, the main oxidation products after a preparative electrolysis were detected by HPLC-MS. Simultaneous detection of ClC in the presence of the unmodified cytosine and mixtures containing other nucleic bases such as guanine, adenine and thymine was also addressed. Finally, the effect of the halogen atom (X = F, Cl, Br) located at position C-5 of the cytosine entity upon the electrooxidation process was examined by theoretical calculations, too. [Display omitted] •The electrochemical characterisation of chlorocytosine has been performed for the first time on glassy carbon.•Chlorocytosine can be electrochemically detected in the presence of other nucleobases.•A mechanism reaction for the electrooxidation of chlorocytosine has been proposed.•Free and solvation energy theoretical calculations of halocytosines agree with the experimental oxidation potentials.•Feasibility for an electrochemical sensor for the halogenation degree detection in DNA.