טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentTkachenko Elena
SubjectSelective Substitution of Corroles as a Synthetic Tool for
the Preparation of Novel Derivatives
DepartmentDepartment of Chemistry
Supervisor Professor Zeev Gross


Abstract

Corroles may be considered as synthetic analogs of the macrocyclic rings of corrin and porphyrin. The recently introduced methodologies for the synthesis of 5,10,15-triarylcorroles allow for extensive investigations of corroles in biological and biomedical applications where porphyrins are constantly utilized. Amphiphilicity and the absorbtion and emission of long wavelengths are the main requirements for chromophores that are suitable for light-driven damaging and detecting of non-exposed cancer cells. However, practically nothing is known about the synthesis of corrole derivatives that meet the above criteria. One exception is the electrophilic substitution on triarylcorroles, which was shown to proceed with exceptional selectivity on the directly joined pyrrole rings. Consequently, one goal of this research was to explore the reactions of other electrophilic reagents with 5,10,15-tris(pentafluorophenyl)corrole (1) and its metal complexes. It was shown that Vilsmeier formylation of corroles is a feasible and simple method for selective functionalization of corroles. Variations of reaction conditions and the metal ions allowed for the selective synthesis of mono-, bis- and even tris-substituted derivatives. Without exception, substitution occurred exclusively on the directly joined pyrrole rings. Computational methods (DFT) revealed that the enhanced reactivity of these relative to the carbon-bridged pyrrole rings is of electronic origin. Morevore, the theory-based predicted reactivity of C-3 > C-2 > C-8 > C-7 with regard to electrophilic substitution was confirmed by experiments. Finally, the formyl groups in the substitution products were shown to be highly useful for further modifications that lead to novel compounds that met expectations: they were formed in high yields via facile procedures and they displayed highly red-shifted absorbance and emission spectra.