New oxazine and oxazone derivatives: Evaluation of physicochemical and photochemical properties.

URRUTIA M, ORTIZ C

Congreso; Cuarta Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2016); 2016

New oxazine and oxazone derivatives: Evaluation of physicochemical and photochemical propertiesUrrutia, M.1,2; Ortiz, C.2,3*1 Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA ? CONICET). Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata.2 Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba.3 Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA ? CONICET).*E-mail: crisar@fcq.unc.edu.arKeywords: Cresyl Violet, Cresyl Red, Log PHPLC, singlet oxygenOxazines and Oxazones are important groups of fluorescent stains in modern biology and histology with interesting properties.1 Tribrominated Cresyl Violet (CVBr3 - Oxazine) and tribrominated Cresyl Red (CRBr3 - Oxazone) are new compounds synthesized in our laboratory derivated from Cresyl Violet (CV) and Cresyl Red (CR), respectively. The aim of this research was to determine octanol-water partition coefficient and singlet oxygen (1O2) production, one of the main species responsible for the death cell.CV was purchased from Sigma Chemical Co. and purified by column chromatography, obtaining highly pure CV and CR. Reversed-phase high-performance liquid chromatography (RP-HPLC) was carried out using an Agilent 1100 Series HPLC system and a reversed-phase C18 (Supelco®) column. Methanol-buffer pH 7.4 mixtures were used as mobile phases and seven compounds were evaluated as references. Solutions of the dyes were irradiated with a Parathom® lamp, with 9,10-dimethylanthracene (DMA) in N,N-Dimethylformamide. The kinetics of DMA photooxidation were studied by following the decrease of the absorbance at λmax=378 nm as a function of irradiation time. The values were calculated relative to methylene blue.The log PHPLC obtained for CV, CVBr3, CR and CRBr3 were (2.9±0.1); (4.5±0.1); (3.7±0.1) and (5.5±0.4), respectively. The lipophilicity was increased for the novel brominated derivatives. This result is important because a rise in lipophilicity is usually correlated with increasing biological activity.2A higher 1O2 production was determined for CVBr3 (Φ Δ=0.11) and CRBr3 (Φ Δ=0.65) in comparison with the corresponding starting reagents (CV Φ Δ=0.04 and CR ΦΔ=0.17). This could be explained in terms of heavy-atom effect. In addition, the value of CRBr3 was higher than that of the CVBr3 due to the carbonyl group.3In conclusion, the novel derivatives CVBr3 and CRBr3 have shown striking properties due to their better photochemical properties and lipophilicity, thus, could be promising photosensitizers in photodynamic therapeutic applications.References[1]- R.J. Nieckarz, J. Oomens, G. Berden, P. Sagulenko, R. Zenobi. Infrared multiple photon dissociation (IRMPD) spectroscopy of oxazine dyes. Phys Chem Chem Phys. 2013; 15: 5049-5056.[2]- E. G. Friberg, B. Cunderlíkova, E.O. Pettersen, J. Moan. pH effects on the cellular uptake of four photosensitizing drugs evaluated for use in photodynamic therapy of cancer. Cancer Lett. 2003; 195 (1): 73-80.[3]- C. B. Nielsen, M. Johnsen, J. Arnbjerg, M. Pittelkow, S. P. McIlroy, P. R. Ogilby, M. Jørgensen. Synthesis and Characterization of Water-Soluble Phenylene−Vinylene-Based Singlet Oxygen Sensitizers for Two-Photon Excitation. J. Org. Chem. 2005; 70 (18): 7065-7079.