DEVELOPMENT OF SECOND GENERATION PHOTOSENSITIZER: NEW FUCHSIN HALOGENATION.

JIMENA VARA; CRISTINA S. ORTIZ

Santa Fe

Congreso; Segunda Reunión Internacional de Ciencias Farmacéuticas; 2012

Introduction: Photodynamic therapy (PDT) is a novel therapeutic modality, which involve the use of a photosensitizer (Ps) activated by light of a specific wavelength in the presence of oxygen. This leads to the formation of toxic oxygen species which produce cell death. Applications of this therapy are growing rapidly because its fundamental specificity and selectivity for the treatment of cancer, bacterial and fungal infections and photodynamic diagnosis.1 Novel Ps have been developed to improve their properties.2 One strategy used is through the heavy atom effect which increases the singlet oxygen generation and produces a red shift of the maximum absorption wavelength.3 For this reason, the aim of the present research was the synthesis, identification and characterization of New Fuchsin di-iodine derivative (NFI2). Materials and methods: Iodination reactions were performed using NaIO4/KI/NaCl in glacial acetic acid/water (9:1v/v).4 The reactions were finished by evaporation, the solid obtained was re-dissolved in dichloromethane and filtered. Methanol/83mM triethylamine phosphate (70:30v/v) was used as mobile phase for HPLC and as a medium for UV-Visible spectrophotometry. Moreover, TLC was carried out using dichloromethane/ethanol (4:1v/v) as eluent and high resolution mass spectrometry (HRMS) was performed in methanol. Results: Different molar ratios of reagents, reaction time and temperature were evaluated and the results obtained are shown in table 1. The retention time (tR) and retention factor (Rf) values, as well as the wavelengths of maximum absorption (max) and the m/z obtained by HRMS are shown in table 2. Discussion and conclusion Optimal conditions selected to synthesize NFI2 were 1:3:3:6 molar ratios of NF:KI:NaIO4:NaCl at 35ºC during 31 hours. Other tested conditions showed similar yields but inorganic salts generated could not be completely eliminated from the crude reaction. The new derivative presented higher tR and Rf values than NF dye as well as the inclusion of the two iodine atoms in the structure produced a bathochromic shift of 14 nm. Finally, NFI2 dye was inequivocally characterized by HRMS. In conclusion, this novel compound was obtained at high purity degree and shown a moderate bathochromic shift improving two requirements of an ideal Ps. For these reasons, we hope to increase the efficiency, safety and reliability of PDT. References1- Veerendra NR, et al. IJDA, 1(1), 2009, 46-50. 2- Robertson CA, et al. Photochem.Photobiol.B, 96, 2009, 1-8. 3- Lacerda SHD, et al. Photochem.Photobiol, 81(6), 2005, 1430-1438. 4- Lourdusamy Emmanuvel, et al. Tetrahedron Lett, 47, 2006, 4793-96.