RESUMO
Epoxide of oestradiol is one of the main risk factors for the genesis and evolution of breast cancer; hence, in recent years there has been considerable interest in the investigation of new inhibitors capable of reducing its carcinogenic activity. The aim of this article is to study the [2 + 2] cycloaddition reaction of epoxide of oestradiol in different pristine (C76 and D5h-C80) and endohedral metallofullerene (C72@Sc2C2, C76@Sc2 and C80@Sc2) by means of molecular electrostatic potential (MEP) topological analysis. Different from other molecular scalar fields, MEP topology enables to find minima related to lone pairs and π electrons, therefore, this molecular scalar field is appropriate to identify the most reactive sites. In consonance with our results, it was found that C80 was the best candidate to carry out the epoxide of oestradiol cycloaddition since more stable adducts were obtained. Furthermore, it is expected that more than one oestradiol epoxide molecule will be added to C80, forasmuch as C80 reactivity is enhanced once the adduct is formed. The study was carried through DFT framework included in the Gaussian 09 package (MPWB95/6-31G(d,p)).
Assuntos
Antineoplásicos/química , Antineoplásicos/síntese química , Fulerenos/química , Animais , Antineoplásicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológicoRESUMO
DNA is one of the most important biomolecules since it contains all the genetic information about an organism. The tridimensional structure of DNA is a determinant factor that influences the physiological and biochemical mechanisms by which this molecule carries out its biological functions. It is believed that hydrogen bonds and π-π stacking are the most relevant non-covalent interactions regarding DNA stability. Due to its importance, several theoretical works have been made to describe these interactions, however, most of them often consider only the presence of two nitrogenous bases, having a limited overview of the participation of these in B-DNA stabilization. Furthermore, due to the complexity of the system, there are discrepancies between which involved interaction is more important in duplex stability. Therefore, in this project we describe these interactions considering the effect of chain length on the energy related to both hydrogen bonds and π-π stacking, using as model TATA-box-like chains with n base pairs (n=1 to 14) and taking into consideration two different models: ideal and optimized B-DNA. We have found that there is a cooperative effect on hydrogen bond and π-π stacking mean energies when the presence of other base pairs is considered. In addition, it was found that hydrogen bonds contribute more importantly than π-π stacking to B-DNA stability; nevertheless, the participation of π-π stacking is not negligible: when B-DNA looks for a conformation of lower energy, π-π stacking interaction are the first to be optimized. All work was realized under the framework of DFT using the DMol3 code (M06-L/DNP).