Manganese complexes as catalase and superoxide dismutase mimics: structure and reactivity relationships

Macrocycle (H2L1) was prepared by a Schiff base condensation reaction of 2,6-diformylpyridine and 1,3-diamino-2-propanol in the presence of Ba(II) as template ion. Seven-coordinate Mn(II) complexes were prepared by transmetallation reactions of the initial [Ba(H2L1)(μ1,2-ClO4)]2(ClO4)2 complex. Two mononuclear, ring-contracted complexes were obtained when methanol or ethanol were used as solvents in transmetallation reactions. For both complexes, X-ray analysis showed that the H2L1 macrocycle undergoes a ring-contraction via addition of methanol or ethanol across one imine bond, followed by a nucleophilic addition of the secondary amine across an adjacent imine bond resulting in a six-membered, hexahydropyrimidine ring sitting in a chair conformation. The ring-contraction process reduces the size of the cavity in the macrocycle to accommodate one Mn(II) ion in the macrocycle. The macrocyclic tetraimine ligand (H2L1) gave access to the polynuclear, ring-expanded assemblies, [Mn4(H2L*)Cl4][MnCl4] and [Mn4(H2L*)(N3)4](ClO4)2, when acetonitrile was used as a solvent. The macrocycle (H2L1) undergoes rearrangement from a 20-membered to a 40-membered tetranuclear Mn(II) complex. Manganese complexes of acyclic ligands, derived from 2,6-diformylpyridine and several aminoalcohols and aminophenols, were prepared and structurally characterised by X-ray crystallography. Most of the complexes are seven-coordinate with approximate pentagonal bipyramidal geometry, however, some five, six and seven-coordinate complexes were identified. Asymmetric and symmetric tripodal Schiff base ligands and their manganese complexes were also prepared and characterised. Additionally, N-alkylated benzimidazole 2,6-bis(1-butyl-1H-benzo[d]imidazol-2-yl)pyridine and its Mn(II) complexes were prepared and characterised. The potential application of the complexes has been tested in two main areas: (a) as new catalase mimics and (b) as new superoxide dismutase (SOD) mimics. The trinuclear, acyclic complex, [Mn3(L9)2(OAc)2(MeOH)2] 2MeOH, derived from 2,6-diformylpyridine and 2-aminophenol, was found to be the most efficient catalase mimic of the tested complexes with approximately 500 molecules of H2O2 broken down per second for each complex during the fastest rate of activity. Catalase testing showed that an increase of the arm size of the tripodal complexes produced an increase in activity overall for the complexes. Most of the complexes tested for catalase activity showed an induction period prior to the activity being observed. This may be due to a rearrangement occurring before catalase activity is observed. The tripodal complex, [Mn(L18)](ClO4)2 is the only complex to show a catalase activity without added base, but with a long induction period. The results that are presented indicate that the axial ligands have an effect on both the rate of catalase activity and the observed induction period. The SOD results indicated that the complex, [Mn(H2L6)Cl(H2O)]Cl H2O, derived from 2,6-diformylpyridine and 1 aminopropan-2-ol, shows the highest SOD activity amongst the complexes prepared, with a rate of 2.05x106 M-1s-1 and the IC50 value of 0.78 μM. Most of the complexes showed SOD activity with a rate around 105-106 M-1s-1. The SOD results showed that the axial ligands have an effect on SOD activity; strongly bound ligands such as thiocyanate and azide generally result in lower SOD activity. Most of the complexes showed both SOD and catalase activity. Ring-contracted complexes, [Mn(H3L2)(NCS)2] and [Mn(H3L3)(NCS)2], show high rates of superoxide dismutase activity but possess limited catalase activity.