טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentShlomit Avidan-Shlomovich
SubjectCorroles as Catalysts for the Decomposition of Peroxynitrite
DepartmentDepartment of Chemistry
Supervisors Professor Gandelman Mark
Full Professor Gross Zeev
Full Thesis text - in Hebrew Full thesis text - Hebrew Version


Abstract

Peroxynitrite is a very important precursor to strongly oxidizing and nitrating species that damage a large variety of biomolecules. It is formed in vivo by the diffusion-controlled reaction between nitrogen monoxide and superoxide-anion, the two less harmful radicals that are formed by normal metabolic processes. The oxidative/nitrosative damage caused by peroxynitrite is mainly due to the .OH and .NO2 radicals that are formed via homolytic cleavage of the O-O bond of the acid form of peroxynitrite. Unlike other reactive oxygen and nitrogen species, there is no specific enzymatic system for the decomposition of peroxynitrite. Synthetic corrole and porphyrin metal complexes are most efficient for the catalytic decomposition of peroxynitrite to non-reactive products.

The research goal of this thesis was to elucidate the mechanism by which iron corroles decompose peroxynitrite. For that purpose, the reactions of peroxynitrite with phenolic compounds were examined in the presence and absence of catalyst.  The experimental results revealed that the iron corrole actually accelerates the phenolic nitrating products, while the ortho/para isomeric ratio was identical to solution without catalyst. This finding led to the conclusions that: a) the nitrating species produced during catalysis is .NO2 and b) the mechanism also involves phenoxyl radical intermediates.

A complementary methodology was the tracking of very fast (msec-sec) spectral changes during catalysis. The results revealed that the initial reaction of the iron corrole with peroxynitrite leads to a new complex within 4 msec, which decays relatively slowly into the final products of catalysis. A large variety of kinetic measurements at different reaction conditions revealed a mechanism that is consistent with ultrafast formation of .NO2 and (corrole)iron(IV)-hydroxo. The decay of the latter is the rate limiting step in catalysis, which involves several pathways: return to the Fe(III) state by the formation a N-O bond leading to formation of nitrate (NO3-), nitration of the corrole macrocyclic, and formation of the Fe(IV)- µ oxo dimer. This hypothesis is also consistent with the observations acquired by the non-kinetic investigations. A most important discovery is that the co-presence of ascorbate (Vitamin C) accelerates the decomposition rate constant by orders of magnitude and eliminates nitration as well. This suggests that the beneficial effects of iron corroles under the reducing conditions present in most tissues/organs/cells might be even larger than those in purely chemical systems.