Modelagem Molecular (TD-DFT) aplicada na predição do fator de proteção solar de compostos naturais / Molecular Modeling (TD-DFT) applied to predict the sun protection factor of natural compounds

Na área da saúde pública, as doenças provocadas pela radiação solar têm ganho grande destaque, por serem cada vez mais comuns. Dentre as principais formas de prevenção a utilização de filtros solares são as mais comuns e de fácil acesso. Os filtros utilizados atuam por sua capacidade de refletir, absorver ou dispersar os raios solares ultravioletas (UV). A aplicação de métodos teóricos tornou-se indispensável no auxílio do planejamento de novos compostos com função terapêutica, em estudos de suas diferentes propriedades, buscando gerar, manipular e analisar representações realistas de estruturas moleculares obtidas a partir de cálculos de propriedades físico-químicas por meio da química computacional. Neste estudo, foram selecionados compostos naturais de origem vegetal (3-O-metilquercetina, ácido gálico, aloína, catequina, quercetina e resveratrol), os quais são descritos com propriedades fotoprotetoras, para os quais se aplicou métodos computacionais para predição dos espectros de absorção, por meio do método TD-DFT (Teoria funcional da densidade dependente do tempo). Foram avaliadas as principais transições eletrônicas dos compostos estudados e se as diferenças de energia HOMO e LUMO para os compostos que absorvem na faixa UV compreendem na UVA (320400 nm, 3.103.87 eV), UVB (290320 nm, 3.874.27 eV) ou na UVC (100290 nm, 4.2712.4 eV). Realizou-se a validação experimental para o método aplicado para o EMC, quercetina e resveratrol, demonstrando a eficácia. Após os estudos realizados concluímos que o resveratrol, teoricamente é um ótimo candidato a fotoprotetor. O estudo ofereceu informações relevantes sobre o poder de predição in silico para fotoprotetores, e se utilizado pode contribuir diminuindo de tempo e custos em pesquisas para desenvolver fármacos

In the area of public health, diseases caused by solar radiation have gained great prominence, as they are increasingly common. Among the main ways to prevent the use of sunscreens are the most common and easily accessible. The filters used act by their ability to reflect, absorb or scatter the sun's ultraviolet (UV) rays. The application of theoretical methods has become indispensable in helping to plan new compounds with therapeutic function, in studies of their different properties, seeking to generate, manipulate and analyze realistic representations of molecular structures obtained from calculations of physicochemical properties through computational chemistry. In this study, natural compounds of plant origin (3-O-methylquercetin, gallic acid, aloin, catechin, quercetin, and resveratrol) were selected, which are described with photoprotective properties, for which computational methods were applied to predict the absorption spectra, using the TD-DFT (Time-Dependent Density Functional Theory) method. The main electronic transitions of the studied compounds were evaluated and whether the differences in HOMO and LUMO energy for compounds that absorb in the UV range comprise UVA (320400 nm, 3.103.87 eV), UVB (290 320 nm, 3.87 4.27 eV) or UVC (100290 nm, 4.2712.4 eV). Experimental validation was carried out for the method applied for CME, quercetin, and resveratrol, demonstrating its effectiveness. After the studies carried out, we concluded that resveratrol, theoretically, is an excellent candidate for sunscreen. The study provided relevant information about the in silico predictive power for photoprotectors, and if used, it can contribute to reducing time and costs in research to develop drugs

New noninvasive approach assessing in vivo sun protection factor (SPF) using diffuse reflectance spectroscopy (DRS) and in vitro transmission.

BACKGROUND/PURPOSE: In the past 56 years, many different in vitro methodologies have been developed and published to assess the sun protection factor (SPF) of products, but there is no method that has 1:1 correlation with in vivo measurements. Spectroscopic techniques have been used to noninvasively assess the UVA protection factor with good correlation to in vivo UVA-PF methodologies. To assess the SPF of sunscreen product by diffuse reflectance spectroscopy (DRS) technique, it is necessary to also determine the absorbance spectrum of the test material in the UVB portion of the spectrum (290-320 nm). However, because of the high absorbance characteristics of the stratum corneum and epidermis, the human skin does not remit enough UVB radiation to be used to measure the absorption spectrum of the applied product on skin. In this work, we present a new method combining the evaluation of the absolute UVA absorption spectrum, as measured by DRS with the spectral absorbance 'shape' of the UVB absorbance of the test material as determined with current in vitro thin film spectroscopy. METHODS: The measurement of the in vivo UVA absorption spectrum involves the assessment of the remitted intensity of monochromatic UVA radiation (320-400 nm) before and after a sunscreen product was applied on skin using a spectrofluorimeter Fluorolog 3, FL3-22 (Yvon Horiba, Edison, NJ, USA). The probe geometry assures that light scattering products as well as colored products may be correctly assessed. This methodology has been extensively tested, validated, and reported in the literature. The in vitro absorption spectrum of the sunscreen samples and polyvinyl chloride (PVC) films 'surrogate' sunscreen standards were measured using Labsphere® UV-2000S (Labsphere, North Sutton, NH, USA). Sunscreens samples were tested using PMMA Helioplates (Helioscience, Marseille, France) as substrates. The UVB absorbance spectrum (Labsphere) is 'attached' to the UVA absorbance spectrum (diffuse reflectance) with the UVB absorbance matched to the UVA absorbance at 340 nm to complete the full spectral absorbance from which an estimate the SPF of the product can be calculated. RESULTS: Seventeen test materials with known in vivo SPF values were tested. Two of the tested products were PVC sunscreen thin films with 10-15 micrometers thickness and were used to investigate the absorption spectrum of these films when applied on different reflectance surfaces. Similar to the human in vivo SPF test, the developed methodology suggests limiting the use on Fitzpatrick skin phototypes I to III. The correlation of this new method with in vivo clinical SPF values was 0.98 (r2) with a slope of 1.007. CONCLUSION: This new methodology provides a new approach to determine SPF values without the extensive UV irradiation procedures (and biological responses) currently used to establish sunscreen efficacy. Further work will be conducted to establish methods for evaluation of products that are not photostable.