Electron transfer reduction of biologically relevant endoperoxides

The electron transfer (ET) reduction of several endoperoxides, molecules with a cyclic structure containing an oxygen-oxygen (O-O) bond, were studied in aprotic media using homogeneous and heterogeneous electrochemical methods. Compounds examined include two simple endoperoxides that serve as analogs of the more complex class of biological endoperoxides, ascaridole ( ASC) and dihydroascaridole (DASC). The 1,2,4-trioxane artemisinin (ART), a potent antimalarial agent, was also investigated since ET to its O-O bond is known to be the initiation step in its bioactivity. ET to the endoperoxides of 9,10-diphenyl anthracene (DPA-O2) and 9,10-dimethyl anthracene (DMA-O2), well known thermal and photochemical generators of singlet oxygen, were investigated to add to the general knowledge of ET chemistry of O-O bonds and as an extension of the earlier studies to systems that contain aryl groups.; Voltammetric characteristics for the reduction of the endoperoxides studied are consistent with a dissociative ET mechanism that involves a rate determining ET fragmentation of the O-O bond to form a distonic radical anion product in a single step, a so-called concerted dissociative ET. The kinetics of this process was determined using heterogeneous voltammetric methods for each of the endoperoxides. For ASC and DASC, determining the rate constants for ET from homogeneous solution electron donors extended the available kinetic range. The ET kinetic data collected then used to construct activation-driving force plots that were analysed according to the current ET theories to determine standard reduction potentials &parl0;EoROOR/˙ORRO-&parr0; for the ET-bond fragmentation. These values were previously unavailable using conventional voltammetric methods. Similar approaches used with the other systems provided were used to estimate standard dissociative reduction potentials for the endoperoxides. The values are in parentheses are in volts and referenced to SCE: ASC (-1.20), DASC (-1.10), ART (-0.82), DPA-O2 (-0.56) and DMA-O2 (-0.57).; The activation-driving force relationships were applied to a model of concerted dissociative ET by Saveant to determine accurate values of the intrinsic free energy barrier &parl0;DG≠o&parr0; for this process. In order to accurately use this model, nonadiabatic effects related to the inefficiency in the dissociative ET mechanism had to be taken to account. Nonadiabatic effects on the ET were verified by low preexponential factors determined from the temperature dependence of the homogeneous kinetics of ASC and DASC. The nonadiabatic nature was also verified by applying the homogeneous kinetic data for ASC and DASC to a quantum mechanical model for nonadiabatic dissociative ET. (Abstract shortened by UMI.)...