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Photodynamic activity of monocationic and non-charged methoxyphenylporphyrin derivatives in homogeneous and biological media

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Abstract

A novel 5-[4-(trimethylammonium)phenyl]-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin iodide (2) has been synthesized. A positive charge was incorporated at a peripheral position to increase the amphiphilic character of the structure. The photodynamic effect of the cationic porphyrin 2 was compared with that of non-charged 5-(4-aminophenyl)-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin (1), both in a homogeneous medium bearing photooxidizable substrates and in vitro on the Hep-2 human larynx carcinoma cell line. Absorption and fluorescence spectroscopic studies in different media show that 2 is essentially unaggregated in solution, and also in human cells. The singlet molecular oxygen, O2(1Δg), production was evaluated using 9,10-dimethylanthracene in N,N-dimethylformamide, yielding ΦΔ values of ∼0.66 for both porphyrins. The addition of β-carotene suppresses the O2(1Δg)-mediated photooxidation. l-Tryptophan and guanosine 5′-monophosphate were used as biological substrate models. Porphyrin 2 sensitizes the decomposition of both compounds faster than does 1. In the biological medium, no dark cytotoxicity was observed, even though a high porphyrin concentration (10 µM) and a long incubation time (24 h) were employed. Cell treatments were performed with 5 µM of porphyrin for 24 h. Under these conditions, the uptake of porphyrin 2 into Hep-2 was about 3 times higher than that of 1. Cell survival after irradiation with visible light was dependent upon both the light exposure level and intracellular sensitizer concentration. Thus, a higher photocytotoxic effect was found for porphyrin 2 in comparison to 1. These results show that the amphiphilic monocationic porphyrin 2 could be a promising model for phototherapeutic agents with potential applications in tumor cell inactivation by photodynamic therapy.

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  1. Departamento de Química, Universidad Nacional de Río Cuarto, Agencia Postal Nro 3, 5800, Río Cuarto, Córdoba, Argentina

    M. Elisa Milanesio, Juana J. Silber & Edgardo N. Durantini

  2. Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Agencia Postal Nro 3, 5800, Río Cuarto, Córdoba, Argentina

    M. Gabriela Alvarez & Viviana Rivarola

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  1. M. Elisa Milanesio
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  2. M. Gabriela Alvarez
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  3. Juana J. Silber
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  4. Viviana Rivarola
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Correspondence to Edgardo N. Durantini.

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Electronic supplementary information (ESI) available: Fig. S1-S3 and Table S1, discussed in the text. See http://www.rsc.org/suppdata/pp/b2/b212890j/

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Elisa Milanesio, M., Gabriela Alvarez, M., Silber, J.J. et al. Photodynamic activity of monocationic and non-charged methoxyphenylporphyrin derivatives in homogeneous and biological media. Photochem Photobiol Sci 2, 926–933 (2003). https://doi.org/10.1039/b212890j

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