טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentOkun Zoya
SubjectPositively Charged Corroles
DepartmentDepartment of Chemistry
Supervisor Professor Zeev Gross
Full Thesis text - in Hebrew Full thesis text - Hebrew Version


Abstract

The research goal of this study was to enlarge the arsenal of water-soluble corroles and to start a systematic investigation of their properties and applications. The first focus was on developing synthetic methodologies for the preparation of corroles that would be water-soluble due to positively charged substituents.

Three different routes were checked towards this goal, the most successful was synthesis of new corroles bearing meso pyridinium groups, which after N-alkylation led to water-soluble derivatives.

The manganese(III) complex of one of the new corroles (with two pyridinium substituents) was investigated regarding two aspects: interaction with DNA and catalytic decomposition of peroxynitrite. The analogous manganese(III) porphyrin was synthesized and investigated in the same experiments, revealing significant differences regarding the performances of these two macrocycles.

The results suggest that the corrole is capable of intercalation into DNA and the analogous porphyrin only for outside  binding. The differences in binding mode and the apparently stronger binding of the corrole were analyzed in terms of the different coordination properties of manganese(III) residing in corroles vs. porphyrins. A significant aid in these interpretations was the X-ray structure of the new corrole, which was also obtained in this research.

The other field for which the potential of the new corrole was checked was catalytic decomposition of peroxynitrite (HO-ONO) - the cytotoxic agent suspected to play a major role in many pathological conditions. The urgent need to develop therapeutic agents for decomposition of in situ formed peroxynitrite is highlighted by the fact that there is no specific enzyme for decomposition of peroxynitrite into biologically benign products.

Recent research in our laboratory uncovered that manganese complex of negatively-charged corrole was the first manganese complex to display catalytic activity without the aid of sacrificial agents and it did so by a disproportionation process forming only NO2- and O2.

The current examination exposed the high potency of the manganese complex of the bis-positively charged corrole in this application. It appeared to be a ten times faster catalyst for decomposition of peroxynitrite than the negatively charged manganese corrole and 10-100 times faster than natural anti-oxidants.

In summary, this research demonstrates a succesful synthetic route for preparation of pyridyl-substituted corroles whose subsequent N-methylation leads to water-soluble derivatives. The corresponding manganese(III) complex was utilized for DNA binding and as catalyst for peroxynitrite decomposition. These investigations revealed important advantages of the new corrole relative to analogous porphyrin, with regard to both applications.