Interaction of cationic meso-porphyrins with liposomes, mitochondria and erythrocytes.

Two series of cationic porphyrins meso-(3N-methylpyridinium)phenylporphyrin (3P1, 3P2c, 3P2t, 3P3 and 3P4) and meso-(4N-methylpyridinium)phenylporphyrin (4P1, 4P2c, 4P2t, 4P3 and 4P4) were studied to obtain a comprehensive understanding of factors that influence the binding of cationic porphyrins to liposomes and mitochondria, as well as their photodynamic efficiencies in erythrocytes. Binding and photodynamic efficiency were found to be inversely proportional to the number of positively charged groups and directly proportional to n-octanol/water partition coefficients (log P(OW)), except for the cis molecules 3P2c and 4P2c. In the cis molecules, binding and photodynamic efficiency were much higher than expected, indicating that specific interactions not accounted by log P(OW) enhance photodynamic efficiency. The effect of mitochondrial transmembrane electrochemical potentials on cationic porphyrin binding constants was estimated to be as large as 15%, and may be useful to selectively target this organelle when promoting photodynamic therapy to induce apoptosis.

Determination of n-octanol/water partition and membrane binding of cationic porphyrins.

Porphyrin and their derivatives are being systematically studied as photosensitizers for photodynamic therapy. The ability to predict their membrane partition properties is of key importance to unveil their in vivo activity and applications. Several n-octanol/water partition coefficients (logP(OW)) of porphyrin derivatives have been reported in the literature but large discrepancies have been observed. Reproducible and reliable logP(OW) data for a series of 20 cationic meso-phenyl(pyridyl)porphyrin derivatives were determined by correlating logP(OW) with the partition coefficients measured in a more adequate n-butanol/water system. Linear correlations as a function of the number of positively charged groups bound to the periphery of the porphyrin rings were found within each series. A significant effect of the stereochemistry and nature of the positively charged substituents was also observed, but diminished steadily converging to a similar value in the mono-substituted derivatives. Binding constants to liposomes were shown to be proportional to logP(OW), except for the cis-isomers of doubly charged porphyrins. The cis-isomer presented smaller logP(OW) and higher membrane affinity. The effect was explained based on the amphiphilic nature of the cis-porphyrin.

Electrospray mass and tandem mass spectrometry of homologous and isomeric singly, doubly, triply and quadruply charged cationic ruthenated meso-(phenyl)m-(meta- and para-pyridyl)n (m + n = 4) macrocyclic porphyrin complexes.

Ten homologous or isomeric singly, doubly, triply and quadruply charged cationic macrocyclic complexes I-Va, bn+ (n = 1-4) formed by the coordination of [Ru(bipy)2Cl]+ to the pyridyl N-atoms of a series of meso-(phenyl)m-(meta or para-pyridyl)n-porphyrins (m + n = 4) were transferred to the gas phase and structurally characterized by electrospray ionization (ESI) mass (MS) and tandem mass (MS/MS) spectrometry. Previously known to be stable in solution and in the solid state, I-Va, bn+ are found to constitute also a new class of stable, long-lived multiply charged gas-phase ions with spatially separated charge sites. Increasing intramolecular electrostatic repulsion from Ia, b+ to IVa, b3+ facilitates in-source and tandem collision-induced dissociation (CID). However, for the quadruply charged ions Va, b4+, electrostatic repulsion is alleviated mainly by ion pairing with the CF3SO3- counterion forming the salt clusters [Va,b/CF3SO3]3+ and [Va,b/(CF3SO3)2]2+ with reduced charge states. Ion-pairing that yields [IVa,b/CF3SO3]2+ is also observed as a minor ESI process for the triply charged ions IVa, b3+. The gaseous ions I-Va, bn+ (n = 2, 3 or 4) dissociate by sequential 'charge partitioning' with the formation of two cationic fragments by the release of [Ru(bipy)2Cl]+. The meta (a) and para (b) isomers and the positional isomers II2+ and III2+ display nearly identical ESI-MS and ESI-MS/MS spectra. ESI-MS/MS of I-Va, bn+ shows that the Ru-py(P) is, intrinsically, the weakest bond since this bond breaks preferentially upon CID.

Photoelectrochemical properties of supramolecular species containing porphyrin and ruthenium complexes on TiO(2) films.

Modification of wide band gap semiconductor surfaces by a new generation of supramolecular sensitizers, combining porphyrin and ruthenium-phenanthroline complexes leads to versatile molecular interfaces, allowing the exploitation of photoinduced charge transfer in dye sensitized photoelectrochemical cells. meso-Tetrapyridylporphyrin coordinated to two ruthenium complexes converts 21% of the incident photons into current after excitation at the Soret band. In this work we discuss the electron/energy transfer mechanisms involved in the TiO(2) sensitization by these supramolecular species, invoking some theoretical calculations.