Photosensitizing Properties of 5-(4-Substituted Phenyl) –10,15,20-Tris (2,4,6-Trimethoxyphenyl) Porphyrins in Biometic Systems

M.E.MILANESIO,M.G.ALVAREZ,V.RIVAROLA,J.J.SILVER,E.N.DURANTINI

Viña del Mar, Chile

Congreso; VII ELAFOT , VII Encuentro Latinoamericano de Fotoquímica y Fotobiología,; 2002

  Tetrapyrrolic macrocycles occupy a central place in bioorganic chemistry.[i] On the basis of their photophysical properties, natural and synthetic porphyrin derivatives have recently found specific biomedical applications, particularly in the field of detection and treatment of neoplastic tissues.   A new cationic 5-(4-(trimethylammono)phenyl)-10,15,20-tris(2,4,6-trimethoxy phenyl) porphyrin 2 has been synthesized. The photodynamic effect of the cationic porphyrin 2 was compared with a not charged 5-(4-aminophenyl)-10,15,20-tris(2,4,6-trimethoxylphenyl) porphyrin 1 in media bearing photooxidizable substrates.1 The presence of a cationic charge on the macrocycle peripheral of 2 produce a large increase in the intamolecular polarity respect to 1. Absorption and fluorescence spectroscopic studies in different media show that 2 is mainly not aggregated in these systems. The singlet molecular oxygen, O2(1Dg), production was evaluated using 9,10-dimethylanthracene (DMA) in N,N’-dimethylformamide (DMF) yielding values of FD~0.65 for both porphyrin. The DMA photooxidation is diminished by b-carotene (Car) as O2(1Dg) quencher. The amino acid L-tryptophan (Trp) and guanosine 5’-monophosphate (GMP) were used as biological substrate models to evaluate the photodynamic activity of these sensitizers. The observed rate constants for Trp sensitized photooxidation (kobsTrp) were about 17 times faster for porphyrin 2 than 1. Similar behavior was also observed for the rates of GMP decomposition. Under these conditions, binding of porphyrin 2 with substrates was observed. This association facilitates the substrates decomposition since the highly reactive O2(1Dg) generate at the porphyrin is in close proximity to the amino acid and nucleotide. These results show that the cationic porphyrin 2 could be a promising architecture of phototherapeutic agent with potential applications in tumor cell inactivation by photodynamic therapy (PDT).2 1. M. E. Milanesio, M. G. Alvarez, E. I. Yslas, C. D. Borsarelli, J. J. Silber, V. Rivarola, E. N. Durantini, Photochem. Photobiol. 74, 14, 2001. 2. M. E. Milanesio, F. S. Morán, E. I. Yslas, M. G. Alvarez, V. Rivarola, E. N. Durantini, Bioorg. Medicinal Chem., 9, 1943, 2001. [i] L. R. Milgrom and F. O’Neill, in The Chemistry of Natural Products, Chapter 8: Porphyrins, ed. R. H. Thomson, Blackie Academic & Professional, London, 1993; p. 329-376. Tetrapyrrolic macrocycles occupy a central place in bioorganic chemistry.[i] On the basis of their photophysical properties, natural and synthetic porphyrin derivatives have recently found specific biomedical applications, particularly in the field of detection and treatment of neoplastic tissues.   A new cationic 5-(4-(trimethylammono)phenyl)-10,15,20-tris(2,4,6-trimethoxy phenyl) porphyrin 2 has been synthesized. The photodynamic effect of the cationic porphyrin 2 was compared with a not charged 5-(4-aminophenyl)-10,15,20-tris(2,4,6-trimethoxylphenyl) porphyrin 1 in media bearing photooxidizable substrates.1 The presence of a cationic charge on the macrocycle peripheral of 2 produce a large increase in the intamolecular polarity respect to 1. Absorption and fluorescence spectroscopic studies in different media show that 2 is mainly not aggregated in these systems. The singlet molecular oxygen, O2(1Dg), production was evaluated using 9,10-dimethylanthracene (DMA) in N,N’-dimethylformamide (DMF) yielding values of FD~0.65 for both porphyrin. The DMA photooxidation is diminished by b-carotene (Car) as O2(1Dg) quencher. The amino acid L-tryptophan (Trp) and guanosine 5’-monophosphate (GMP) were used as biological substrate models to evaluate the photodynamic activity of these sensitizers. The observed rate constants for Trp sensitized photooxidation (kobsTrp) were about 17 times faster for porphyrin 2 than 1. Similar behavior was also observed for the rates of GMP decomposition. Under these conditions, binding of porphyrin 2 with substrates was observed. This association facilitates the substrates decomposition since the highly reactive O2(1Dg) generate at the porphyrin is in close proximity to the amino acid and nucleotide. These results show that the cationic porphyrin 2 could be a promising architecture of phototherapeutic agent with potential applications in tumor cell inactivation by photodynamic therapy (PDT).2 1. M. E. Milanesio, M. G. Alvarez, E. I. Yslas, C. D. Borsarelli, J. J. Silber, V. Rivarola, E. N. Durantini, Photochem. Photobiol. 74, 14, 2001. 2. M. E. Milanesio, F. S. Morán, E. I. Yslas, M. G. Alvarez, V. Rivarola, E. N. Durantini, Bioorg. Medicinal Chem., 9, 1943, 2001. [i] L. R. Milgrom and F. O’Neill, in The Chemistry of Natural Products, Chapter 8: Porphyrins, ed. R. H. Thomson, Blackie Academic & Professional, London, 1993; p. 329-376. Tetrapyrrolic macrocycles occupy a central place in bioorganic chemistry.[i] On the basis of their photophysical properties, natural and synthetic porphyrin derivatives have recently found specific biomedical applications, particularly in the field of detection and treatment of neoplastic tissues.   A new cationic 5-(4-(trimethylammono)phenyl)-10,15,20-tris(2,4,6-trimethoxy phenyl) porphyrin 2 has been synthesized. The photodynamic effect of the cationic porphyrin 2 was compared with a not charged 5-(4-aminophenyl)-10,15,20-tris(2,4,6-trimethoxylphenyl) porphyrin 1 in media bearing photooxidizable substrates.1 The presence of a cationic charge on the macrocycle peripheral of 2 produce a large increase in the intamolecular polarity respect to 1. Absorption and fluorescence spectroscopic studies in different media show that 2 is mainly not aggregated in these systems. The singlet molecular oxygen, O2(1Dg), production was evaluated using 9,10-dimethylanthracene (DMA) in N,N’-dimethylformamide (DMF) yielding values of FD~0.65 for both porphyrin. The DMA photooxidation is diminished by b-carotene (Car) as O2(1Dg) quencher. The amino acid L-tryptophan (Trp) and guanosine 5’-monophosphate (GMP) were used as biological substrate models to evaluate the photodynamic activity of these sensitizers. The observed rate constants for Trp sensitized photooxidation (kobsTrp) were about 17 times faster for porphyrin 2 than 1. Similar behavior was also observed for the rates of GMP decomposition. Under these conditions, binding of porphyrin 2 with substrates was observed. This association facilitates the substrates decomposition since the highly reactive O2(1Dg) generate at the porphyrin is in close proximity to the amino acid and nucleotide. These results show that the cationic porphyrin 2 could be a promising architecture of phototherapeutic agent with potential applications in tumor cell inactivation by photodynamic therapy (PDT).2 1. M. E. Milanesio, M. G. Alvarez, E. I. Yslas, C. D. Borsarelli, J. J. Silber, V. Rivarola, E. N. Durantini, Photochem. Photobiol. 74, 14, 2001. 2. M. E. Milanesio, F. S. Morán, E. I. Yslas, M. G. Alvarez, V. Rivarola, E. N. Durantini, Bioorg. Medicinal Chem., 9, 1943, 2001. [i] L. R. Milgrom and F. O’Neill, in The Chemistry of Natural Products, Chapter 8: Porphyrins, ed. R. H. Thomson, Blackie Academic & Professional, London, 1993; p. 329-376. Tetrapyrrolic macrocycles occupy a central place in bioorganic chemistry.[i] On the basis of their photophysical properties, natural and synthetic porphyrin derivatives have recently found specific biomedical applications, particularly in the field of detection and treatment of neoplastic tissues.   A new cationic 5-(4-(trimethylammono)phenyl)-10,15,20-tris(2,4,6-trimethoxy phenyl) porphyrin 2 has been synthesized. The photodynamic effect of the cationic porphyrin 2 was compared with a not charged 5-(4-aminophenyl)-10,15,20-tris(2,4,6-trimethoxylphenyl) porphyrin 1 in media bearing photooxidizable substrates.1 The presence of a cationic charge on the macrocycle peripheral of 2 produce a large increase in the intamolecular polarity respect to 1. Absorption and fluorescence spectroscopic studies in different media show that 2 is mainly not aggregated in these systems. The singlet molecular oxygen, O2(1Dg), production was evaluated using 9,10-dimethylanthracene (DMA) in N,N’-dimethylformamide (DMF) yielding values of FD~0.65 for both porphyrin. The DMA photooxidation is diminished by b-carotene (Car) as O2(1Dg) quencher. The amino acid L-tryptophan (Trp) and guanosine 5’-monophosphate (GMP) were used as biological substrate models to evaluate the photodynamic activity of these sensitizers. The observed rate constants for Trp sensitized photooxidation (kobsTrp) were about 17 times faster for porphyrin 2 than 1. Similar behavior was also observed for the rates of GMP decomposition. Under these conditions, binding of porphyrin 2 with substrates was observed. This association facilitates the substrates decomposition since the highly reactive O2(1Dg) generate at the porphyrin is in close proximity to the amino acid and nucleotide. These results show that the cationic porphyrin 2 could be a promising architecture of phototherapeutic agent with potential applications in tumor cell inactivation by photodynamic therapy (PDT).2 1. M. E. Milanesio, M. G. Alvarez, E. I. Yslas, C. D. Borsarelli, J. J. Silber, V. Rivarola, E. N. Durantini, Photochem. Photobiol. 74, 14, 2001. 2. M. E. Milanesio, F. S. Morán, E. I. Yslas, M. G. Alvarez, V. Rivarola, E. N. Durantini, Bioorg. Medicinal Chem., 9, 1943, 2001. [i] L. R. Milgrom and F. O’Neill, in The Chemistry of Natural Products, Chapter 8: Porphyrins, ed. R. H. Thomson, Blackie Academic & Professional, London, 1993; p. 329-376.