Syntheses, electrochemistry and spectroscopic studies of metallocene-containing porphyrin complexes with biomedical applications

[摘要] In this study, a series of carboxylic acid functionalised pyrrole derivatives and ferrocene- andruthenocene-containing dipyrromethanes were synthesised. Porphyrin complexes bearing amono-carboxylic acid functional group in the β-position as well as ferrocene or ruthenocene inthe -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 acidfunctional groups on the para position of one of the phenyl rings were synthesised from pyrroleand a substituted benzaldehyde. In addition, a series of metal-free porphyrins containing anelectron-withdrawing CF3 group in the ortho, meta or para positions of a phenyl group in one ortwo of the four meso porphyrin position as well as three or two electron-donating ferrocenyl orruthenocenyl group in the other meso porphyrin positions were synthesised though a modifiedstatistical condensation procedure of a substituted dipyrromethane and an appropriatelyfunctionalised benzaldehyde. Copper and nickel were also inserted into the cavities of theseporphyrins. Techniques to synthesise water-soluble polymers bearing a porphyrin side chainwere also developed. All complexes were fully characterised inter alia with 1H NMR, IR andUV/vis spectroscopic methods and by electrochemical studies.The new porphyrins described in this study may enhance cancer therapy by synergistic effectsbetween the chemotherapeutically active metallocene groups and the photodynamically activeporphyrin macrocycle. The availability of water-soluble porphyrins via the water-solublepolymeric drug delivery systems synthesised in this study may enhance clinical administration ofthese new antineoplastic drugs to patients.Electrochemical studies revealed that all ferrocene-containing porphyrins exhibited chemicallyand electrochemically reversible one-electron transfer steps for the Fc/Fc+ couple. Because of theuse of [NBu4][B(C6F5)4] as supporting electrolyte, an electrochemical reversible Rc/Rc+ couplecould be identified, rather than the usual irreversible Cp2RuII/Cp2RuIV couple. The metallocenefreeporphyrins exhibited two one-electron oxidation waves as well as two one-electronreduction waves. The metallocene-containing porphyrins exhibited only one one-electronoxidation 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-peripherallysubstituted phthalocyanines to optimise gas phase structures and to generate theoreticallypredicted UV/vis spectra. The result indicated that DFT calculations could be utilised to design aphthalocyanine that possesses Q-band λmax values in its electronic spectra that is red-shiftedenough to render the phthalocyanine appropriate for application in photodynamic therapy of cancer.

[发布机构] University of the Free State