AZINE DYES: SPECTROSCOPIC AND COMPUTATIONAL STUDIES OF AGGREGATION BEHAVIOR. SINGLET OXYGEN DETERMINATION

URRUTIA MN, ANDRADA DM, PIERINI AB, ORTIZ CS

Congreso; Segunda Reunión Internacional de Ciencias Farmacéuticas. RICiFa.; 2012

AZINE DYES: SPECTROSCOPIC AND COMPUTATIONAL STUDIES OF AGGREGATION BEHAVIOR. SINGLET OXYGEN DETERMINATION Urrutia MN,1 Andrada DM,1,2 Pierini AB,1 Ortiz CS*1 1Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. Haya de La Torre esq. Medina Allende. Córdoba. X5000HUA. Argentina. 2Institut of Physical Chemistry, Georg-August-Universität Göttingen, Tammannstrasse 6, 37077, Germany. Ortiz CS: crisar@fcq.unc.edu.ar Introduction The Photodynamic therapy (PDT) is a promising treatment that involves the administration of a photosensitizer (PS) prior to illumination using an appropriate wavelength.1 Although in the last decade the design of selective and effective novel PS has experimented an exponential growth, a wide scope has not been reached so far. In an attempt to fill this gap several ionic dyes have been used, but it has been pointed out that they tend to aggregate which leading at lowering their capacity to absorb light.2 This context has prompted us to start a project aim at broaden the knowledge on this field. In this work we will present the aggregation behavior of monobrominated Neutral Red (NRBr)3 as well as its singlet oxygen determination. Materials and Methods Experimental Details We have studied UV-visible spectra of Neutral Red (NR) and NRBr using ethanol; N,N-dimethylformamide (DMF) and dimethylsulfoxide (DMSO) as solvents. The experiments were performed with an Evolution 300 spectrophotometer equipment. Photo-oxidation of 9,10-dimethylanthracene (DMA) in DMF was used to determine 1O2 production, whereby the solutions were irradiated with a Parathom® lamp (OSRAM - 5 W). Computational Details Theoretical calculations were performed with the GAUSSIAN 09 B01 suite of programs. All geometry optimizations were computed using B3LYP/6-31+G(d) and B97D/6-31+G* level of theory. The stationary points were located with the Berny algorithm using redundant internal coordinates. To estimate the UVspectra profile of the dyes single point PCM [B3LYP/6-31+G(d)] calculations were used. Results At low concentrations of both NR and NRBr dyes, in all of the solvents evaluated, the UV-visible spectrum profiles display an absorption band assigned to the monomer species, while at higher concentrations a new band appears which was recognized to belong to the aggregate species. Table 1 shows the obtained experimental (λExp) and theoretical (λcalc) spectroscopic data in ethanol, DMSO and DMF solvents and Table 2 gathers the observed rate constant (kobs) and the quantum yield of 1O2 production (Φ) for each dye. Discussion and Conclusions The NR aggregate species was observed in ethanol and DMSO (≥ 14 μM) and in DMF (≥ 69 μM), while the NRBr aggregate species was detected at ≥24 μM in ethanol, ≥65 μM in DMSO and 271 μM in DMF. These results indicate that NRBr forms aggregates in a lower amount than in the case of NR. A possible explanation could be drawn from the ground of the Br atom substituent bulkiness which prevents the aggregation. We have confirmed the monomer assignment due to the fact that the experimental and the theoretical maximum values are close to each other (Table 1). Similar variations between experimental and calculated spectra have been reported elsewhere. 4 NRBr led to a higher Φ value (see Table 2) due to the effect of heavy-atom which increases 1O2 production. In conclusion, the bromine atom derivate of NR has shown striking properties by preventing the aggregation process and also by increasing the Φ values. Those properties are important outcomes for PDT. References 1- Rossetti FC, Lopes LB, Carollo ARH, Thomazini JA, Tedesco AC, Lopes Badra Bentley MV. J. Control. Release. 2011; 155: 400-408. 2- Konan YN, Gurny R, Allémann E. J. Photochem. Photobiol. B. 2002; 66: 89-106. 3- Urrutia MN, Ortiz CS. Chem. Phys. (submitted) 2012. 4- Johnson C, Seth B, Darling SB, You Y. Monatsh. Chem. 2011; 142: 45-52. Table 1: Experimental and theoretical spectroscopic data. Compound EtOH DMSO DMF λcalc (nm) λExp (nm) λcalc (nm) λ Exp (nm) λcalc (nm) λExp (nm) NR 465.8 462 471.1 456 464.9 450 NRBr 470.8 452 478.5 454 470.1 450 Table 2: Kinetic parameters for the photooxidation of DMA and Φ in DMF. Compound k obs Φ a Methylene Blue (166±2) x10-5 1 NR (19±1) x10-4 1.16 NRBr (515±5) x10-5 3.14 a- Relative to the value for Methylene Blue.