Cristais/moléculas de fármacos: Uma descrição via teoria do funcional da densidade

Abstract

Molecular crystals have several applications in science and technology and have attracted considerable attention in recent years to study the properties of these materials by both theoretical and experimental research. With the advancement of theories describing the electronic structure of materials of various types, it became possible to describe in detail the electronic behavior as well as its influence on the properties of these materials. The most successful theory applied today is the theory of functional density (DFT). Based on this, the structural, electronic and optical properties of various drug crystals related to sickle cell anemia (hydroxyurea) and multiple sclerosis (Dimethyl Fumarate), as well as the crystals, polymorphs and hydrates, of the aminoacid glycine. The present work presents the results obtained for the hydroxyurea crystal as a model, for the system bonded by hydrogen bonds; Dimethyl Fumarate as a model of systems bonded by van der Waals forces; and Glycine, which serve as model for describing the influence of polymorphism/hydration in the properties of molecular crystals. The same methodology was applied to the others systems. The studies were made on the basis of the density functional theory, in which were applied the LDA and GGA, with and without dispersion forces correction. In general, it has been observed that the functional that best describes this type of system, i.e. a molecular crystal, is GGA. The results are improved by adding dispersion corrections to the functional one. The deviations found for this functional were smaller than 2%, with maximum deviation -0.12 Å (-1.72%) for the a lattice parameter of the hydroxyurea crystal; -0.07 Å (-1.26%) for the b lattice parameter of the dimethyl fumarate crystal; and 0.047 (0.75%) for the b lattice parameter of the glycine crystal (β-form). The other crystals of the glycine had lower maximum deviation, relative to the maximum deviation of βform. A study of the influence of the size of the base used was also performed, where it was verified that the convergence was reached even in the lowest base used, in the present work the lowest base was of 830 eV, for the hydroxyurea and dimethyl fumarate crystals. For the glycine crystal, the convergence was achieved with 850 eV basis set. After the convergence study, the electronic and optical properties of the crystals under study were calculated. In general, the errors of the estimated gaps, relative to those obtained experimentally, were below 300 meV, after making the gap energy corrections. This result corroborates with errors in the estimation of gaps by DFT, which are between 30 - 100%. The gaps of the crystals were also calculated by the Δ-sol method. The gap difference predicted by the Δ-sol method was lower than that predicted by DFT calculations.