Electrochemical and mARC-catalyzed enzymatic reduction of para-substituted benzamidoximes: consequences for the prodrug concept "amidoximes instead of amidines".

The mitochondrial amidoxime reducing component (mARC) activates amidoxime prodrugs by reduction to the corresponding amidine drugs. This study analyzes relationships between the chemical structure of the prodrug and its metabolic activation and compares its enzyme-mediated vs. electrochemical reduction. The enzyme kinetic parameters KM and Vmax for the N-reduction of ten para-substituted derivatives of the model compound benzamidoxime were determined by incubation with recombinant proteins and subcellular fractions from pig liver followed by quantification of the metabolites by HPLC. A clear influence of the substituents at position 4 on the chemical properties of the amidoxime function was confirmed by correlation analyses of (1) H NMR chemical shifts and the redox potentials of the 4-substituted benzamidoximes with Hammett's σ. However, no clear relationship between the kinetic parameters for the enzymatic reduction and Hammett's σ or the lipophilicity could be found. It is thus concluded that these properties as well as the redox potential of the amidoxime can be largely ignored during the development of new amidoxime prodrugs, at least regarding prodrug activation.

A water-soluble tin(IV) porphyrin as a bioinspired photosensitiser for light-driven proton-reduction.

The water-soluble tin(IV) porphyrin dichlorido-5,10,15,20-tetrakis(p-carboxyphenyl)-porphyrinato-tin(IV) (SnTPPC, 1) was synthesised as a mimic of biological chlorophyll photosensitisers. In natural photosynthesis, chlorophyll pigments start the multi-electron transfer processes resulting in water-oxidation and NADP(+)-reduction. The photochemical properties of compound 1 were characterised by measuring absorption and fluorescence spectra. Electrochemical measurements in water revealed well-suited redox potentials of 1 for both proton-reduction to H2 as well as water-oxidation to O2. The tin(IV) porphyrin was then used as a photosensitiser in model systems for light-induced proton-reduction in aqueous solution, where an optimization of the experimental conditions was carried out to achieve reaction rates comparable to those found for [Ru(bipy)3](2+), a standard dye in artificial photosynthesis. By employing UV/Vis-spectroelectrochemistry, we found that the porphyrin ligand of 1 is redox non-innocent in water. A complex set of reduction reactions of the porphyrin macrocycle occurs during photocatalytic experiments involving the ligand's chlorin form as a key intermediate. On the basis of these results, a potential reaction sequence for light-driven H2-formation is formulated, where the reductive quenching of 1 forms the initial reaction step and reduced forms of 1 serve as hydride transfer agents to the H2 evolution catalyst. The spectroscopic, electrochemical and catalytic properties of SnTPPC make this compound class an attractive, affordable and easily accessible choice for photosensitisers in artificial photosynthetic systems. Finally, the detected complicated redox reactions of the porphyrin ring in water offer a possible explanation of why the chlorophylls of P680 or P700 are carefully wrapped in a water-free part of the PSII and PSI proteins.

A manganese oxido complex bearing facially coordinating trispyridyl ligands--is coordination geometry crucial for water oxidation catalysis?

In this work the synthesis of the novel manganese complex [Mn(2)(III,III)(tpdm)(2)(µ-O)(µ-OAc)(2)](2+) (1) is reported, containing two manganese centres ligated to the unusual, facially coordinating, all-pyridine ligand tpdm (tris(2-pyridyl)methane). The geometric and electronic properties of complex 1 were characterised by X-ray crystallography, vibrational (IR and Raman) and optical spectroscopy (UV/Vis and MCD). Cyclic voltammograms of 1 showed a quasi-reversible oxidation event at 950 mV and an irreversible reduction wave at -250 mV vs. Ag/Ag(+). The redox behaviour of the compound was investigated in detail by UV/Vis- and X-band EPR-spectroelectrochemistry. Both electrochemical (+1200 mV) and chemical (tBuOOH) oxidations transform 1 into the singly oxidized di-µ-oxido species [Mn(2)(III,IV)(tpdm)(2)(µ-O)(2)(µ-OAc)](2+). Further electrochemical oxidation at the same potential results in the removal of a second electron to obtain a Mn(2)(IV,IV)-species. The ability of compound 1 to evolve O(2) was studied using different reaction agents. While reactions with both hydrogen peroxide and peroxomonosulfate yield O(2), homogeneous water-oxidation using Ce(IV) was not observed. Nevertheless, the oxidation reactions of 1 are very interesting model processes for oxidation state (S-state) transitions of the natural manganese water-oxidation catalyst in photosynthesis. However, despite its favourable coordination geometry and multielectron redox chemistry, complex 1 fails to be a catalytically active model for natural water-oxidation.