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.
Engelmann
Fabio M
FM
Instituto de Química, Universidade de São Paulo, C. Postal 26077, CEP 05513-970, São Paulo, Brazil.
Mayer
Ildemar
I
Gabrielli
Dino S
DS
Toma
Henrique E
HE
Kowaltowski
Alicia J
AJ
Araki
Koiti
K
Baptista
Mauricio S
MS
D020003:1-Octanol / Q000737:chemistry; D000818:Animals; D002412:Cations; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D026082:Singlet Oxygen / Q000378:metabolism; D014867:Water / Q000737:chemistry
D002412:Cations; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D014867:Water; D026082:Singlet Oxygen; D020003:1-Octanol