Estudo teórico da fotofísica do composto 4,5-dibromorodamina metil éster (TH9402) utilizado como fotossensibilizador em terapia fotodinâmica

Abstract

The TH9402 is a photosensitizer (PS) that can be applied to photodynamic therapy. Photophysics studies about this compound as well as the analysis of the thermodynamic reactions involving its first triplet excited state, were carried out. Calculations on TPSSh/def2-TZVP/CPCM(water) level showed that the transition energy related to the main absorption was 2.33 eV. The fluorescence rate calculated employing the Marcus theory combined with Fermi's golden rule was 4.18 x 107 s-1. The total intersystem crossing rate between the first singlet excited state and the triplets excited states T2 and T1 was 27.5 x 107 s-1. Path integral formalism was another approach used in calculating photophysical properties. This method resulted in values of fluorescence rate and intersystem crossing constant of 5.40 x 107 s-1 and 10.1 x 107 s-1, respectively. From the results, the de-excitation pathway S1 → T2 → T1 is the most likely to happen. The thermodynamic study of reactions was carried out in M06-2X/def2-TZVP/SMD(water)//B3LYP/def2-TZVP level. The free energy values of the transfer reactions from the TH9402 triplet excited state to monophosphate guanosine (GMP2-) (G = -24.0 kcal/mol) as well as to molecular oxygen (G = -2.0 kcal/mol) were negative. The charge transfer reactions from GMP-2 and HGMP- to PS also present negative free energy (G = -129.1 kcal/mol and G = -11.1 kcal/mol, respectively), proving to be thermodynamically favorable to happen. Furthermore, the influence of the interaction between TH9402 and the octanucleotide molecule d(AGAGTCT)2 on the absorption spectrum of the photosensitizer was studied. The docking calculation demonstrated that the PS can be intercalated between d(GpC)-d(CpG) base pairs in three different ways. The absorption spectrums showed that the intercalation leads to bathochromic shifts, of the bright state bands. The bands were shifted up to 90 nm. Furthermore, there were decreases greater than 60% in the absorption intensities of the main bands for some of the conformations. The spectrum of the complex in which the photosensitizer interacts as a groove binder showed a bathochromic shift of 52.2 nm and a 56% reduction in the intensity of the maximum absorption band compared to the spectrum of PS isolated. Futures works can use the methodologies applied in the present work to study photophysical properties of unpublished compounds. This work also can be a reference material for the studies about the effects of the interaction between PS and DNA in the spectroscopy properties of PS.