Syntheses, electrochemistry and spectroscopic studies of metallocene-containing porphyrin complexes with biomedical applications
Shago, Rebotsamang Florence
MetadataShow full item record
In this study, a series of carboxylic acid functionalised pyrrole derivatives and ferrocene- and ruthenocene-containing dipyrromethanes were synthesised. Porphyrin complexes bearing a mono-carboxylic acid functional group in the β-position as well as ferrocene or ruthenocene in the -5-, or -5,10-, or -5,15- meso positions have been prepared from these pyrrole derivatives. A series of metal-free tetraphenylporphyrins containing nitro, amino or carboxylic acid functional groups on the para position of one of the phenyl rings were synthesised from pyrrole and a substituted benzaldehyde. In addition, a series of metal-free porphyrins containing an electron-withdrawing CF3 group in the ortho, meta or para positions of a phenyl group in one or two of the four meso porphyrin position as well as three or two electron-donating ferrocenyl or ruthenocenyl group in the other meso porphyrin positions were synthesised though a modified statistical condensation procedure of a substituted dipyrromethane and an appropriately functionalised benzaldehyde. Copper and nickel were also inserted into the cavities of these porphyrins. Techniques to synthesise water-soluble polymers bearing a porphyrin side chain were also developed. All complexes were fully characterised inter alia with 1H NMR, IR and UV/vis spectroscopic methods and by electrochemical studies. The new porphyrins described in this study may enhance cancer therapy by synergistic effects between the chemotherapeutically active metallocene groups and the photodynamically active porphyrin macrocycle. The availability of water-soluble porphyrins via the water-soluble polymeric drug delivery systems synthesised in this study may enhance clinical administration of these new antineoplastic drugs to patients. Electrochemical studies revealed that all ferrocene-containing porphyrins exhibited chemically and electrochemically reversible one-electron transfer steps for the Fc/Fc+ couple. Because of the use of [NBu4][B(C6F5)4] as supporting electrolyte, an electrochemical reversible Rc/Rc+ couple could be identified, rather than the usual irreversible Cp2RuII/Cp2RuIV couple. The metallocenefree porphyrins exhibited two one-electron oxidation waves as well as two one-electron reduction waves. The metallocene-containing porphyrins exhibited only one one-electron oxidation wave; the second went-off scale in the potential window that CH2Cl2 as solvent allows. ADF quantum chemical computations were performed on peripherally and non-peripherally substituted phthalocyanines to optimise gas phase structures and to generate theoretically predicted UV/vis spectra. The result indicated that DFT calculations could be utilised to design a phthalocyanine that possesses Q-band λmax values in its electronic spectra that is red-shifted enough to render the phthalocyanine appropriate for application in photodynamic therapy of cancer.