The electrochemistry of phenothiazine derivatives

Abstract

Methylene blue derivatives (MBDs) such as methylene blue (MB -), 1-methyl methylene blue (1MMB) and 1,9-dimethyl-methylene blue (DMMB) have potential use as drugs within photodynamic therapy (PDT). Knowing the redox properties of MBDs will help in understanding the way in which MBDs interact with a range of biological systems.
In this work, the electrochemical behaviour of MBDs at various solution pHs have been studied for the first time on gold microdisc electrodes using steady state and non-steady state cyclic voltammetric methods.
Steady-state studies
The reduction of MBDs is an ECE(CC) process where the C steps are protonation reactions. The number (m) of W participating in the overall electrode process increases from 1 to 2 or 3 with decreasing pH although the profile is different among MBDs.
The half-wave potential (E 112) of each methylene blue derivative (MBD) shifts to more negative potential with increasing pH values. The E 112 of MBD at the same pH shifts to more cathodic potentials with an increasing number of -CH 3 substituent, indicating that the thermodynamic facility of MB, lMMB and DMMB reduction decreases with increasing the number of -CH3 substituents.
The reduction products of MBDs depend strongly on pH, sweep rate, and sweep potential limit, as well as number of -CH 3 substituents.
Non-steady state studies
The redox behaviour of MBDs under non-steady-state conditions is complicated. Their common characteristics are that (i) the initial reduction of MBD is a diffusion controlled process; (ii) the onset potentials for MBD reduction shift to more negative
potentials with increasing pH and number of CH 3 substituents; (iii) the facility of observation of the charge transfer complex increases with increasing pH; (vi) the charge transfer complex can be further reduced at more cathodic potentials; and (v) the amounts of charge transfer complex and leuco form depend on sweep rate and sweep potential window. They also have some differences among the electrochemical behaviour of the three drugs, such as, some anodic and cathodic processes may occur in one of MBDs, and some may not.
Possible mechanisms for the electroreduction of MBDs are suggested and discussed in the light of the effect of pH and potential sweep rate on the reaction products.