Iron-Manganese complexes as mimics of the cofactor in Class I Ribonucleotide Reductases

Sammanfattning: A group of enzymes has recently been reported to have a manganese-iron carboxylate cofactor containing one Mn ion and one Fe ion in the active site. This cofactor is closely related to, and has chemical properties similar to, the well-known diiron-carboxylate cofactor in proteins like the ribonucleotide reductase (RNR) present in pathogens like Mycobacterium T or Chlamydia T.In order to provide a model to the study these mixed metal cofactors three different ligands were synthetized. The first ligand was the very well-known BPMP, the second ligand called DPCPMP had one carboxylate instead of a pyridine and the third ligand, which was a modification of the second one, was called BPCPMP and had two carboxylates in opposite position. From the first and the second ligands it was possible to obtain six complexes: two low-valent homometallic Mn/Mn or Fe/Fe complexes and a heterometallic complex per each ligand. The homometallic complexes were synthetized by addition of the respective metal ions to the ligands. In the case of the heterometallic Mn/Fe complex, instead, the two metal ions were added separately and consecutively to the ligands. For what concerns the third ligand, only the Fe/Fe complex was synthetized.All the seven complexes were characterized by electrochemistry, UV-vis spectroscopy, Mössbauer, and EPR spectroscopy. Our results revealed that the presence of carboxylate in the ligand shifted the redox potential towards negative values, particularly in the case of the homometallic Fe/Fe complex. Next, the behaviour of the complexes in presence of molecular oxygen was assessed and the analysis showed that, even though the metals changed the oxidation state, particularly the iron, no oxygen molecule was trapped inside the complex.In addition, the relative stability of the homometallic dimers versus the heterometallic dimer and the possibility to transform a homometallic complex into a heterometallic complex were investigated. By titrating one metal into a solution containing the other homometallic dimer it was possible to observe that Fe2+ into a Mn/Mn solution led to the replacement of one Mn ion in the complex. In contrast, the titration of the Fe/Fe complex with Mn2+ did not lead to any replacement of iron ions in the complex. In the case of the second ligand, it was also possible to observe that the metal selection of the pocket was not dictated by the asymmetry, and that some complexes showed a disproportionate reaction with oxidants like the hydrogen peroxide.