Manganese complexes with biomimetic antioxidant activity

Several seven-coordinate manganese complexes have been synthesised, characterised and tested for both superoxide dismutase and catalase activity. Macrocyclic ring contractions have led to a series of new seven coordinate mononuclear manganese(II) macrocycles that have potential for their use as working superoxide dismutase mimics. Numerous polynuclear seven coordinate manganese(II) macrocycles have been synthesised via Schiff base condensation. Subsequent reduction of the imine bonds has led to a variety of reduced amine analogues with varying axial ligands. The geometry has been compared about the manganese centres where possible. From the results of each complex tested for superoxide dismutase activity, the µ-chloro bridged tetranuclear complex [Mn2(C24H29N6O2)(Cl)2]2(ClO4)2 has proved to be the most efficient mimic with a calculated KMcCF value of 7.7 x 106 [M-1 s-1]. A method for measuring catalase activity has been developed, and the most efficient catalase active compound was found to be [Mn5(C24H29N6O2)2(OAc)2(ClO4)2](ClO4)2 with one molecule of complex breaking down approximately 59000 molecules of hydrogen peroxide after one minute. Catalase testing showed that a reduction of the imine bonds produced an increase in activity overall for the complexes of H2L1 (C24H29N6O2), but a decrease was observed for the reduced tripodal complexes. An increase in the number of manganese centres resulted in a rise in catalase activity. Many of the complexes tested for catalase activity showed an induction period prior to the activity being observed. This may suggest that the complexes undergo a change in structure, or that there is a rearrangement occurring before catalase activity may be observed. The results that are presented indicate that the axial ligands have an effect on the rate of catalase activity and the observed induction period. Of the molecules that were tested for both superoxide dismutase and catalase activity, the pentanuclear complex [Mn5(C24H29N6O2)2(OAc)2(ClO4)2](ClO4)2 showed high activity for both analyses. This may be due to the extra manganese centre within the complex and the axial ligands that are present when compared with other tetranuclear complexes. The complex [Mn5(HL1)(OAc)2(ClO4)2](ClO4)2 may prove to be a good candidate for a working superoxide dismutase mimic. Ring contracted complexes show high rates of superoxide dismutase activity but possess limited catalase activity. Attempts have been made to produce a direct method of measuring superoxide dismutase activity using a stop-flow technique to complement the results using the indirect NBT (Nitro blue Tetrazoleum) method. This was carried out by analysing low concentration solutions of both complex and superoxide on a millisecond timescale. Progress has been made for this method with preliminary results being obtained.