Reactivity of amino acids and short peptide sequences: identifying bioactive compounds via DFT calculations.

Bioactive peptides are short amino acid sequences that play important roles in various physiological processes, including antioxidant and protective effects. These compounds can be obtained through protein hydrolysis and have a wide range of potential applications in a variety of areas. However, despite the potential of these compounds, more in-depth knowledge is still necessary to better understand details regarding their chemical reactivity and electronic properties. In this study, we used molecular modeling techniques to investigate the electronic structure of isolated amino acids (AA) and short peptide sequences. Details on the relative alignments between the frontier electronic levels, local chemical reactivity and donor-acceptor properties of the 20 primary amino acids and some di- and tripeptides were evaluated in the framework of the density functional theory (DFT). Our results suggest that the electronic properties of isolated amino acids can be used to interpret the reactivity of short sequences. We found that aromatic and charged amino acids, as well as Methionine, play a key role in determining the local reactivity of peptides, in agreement with experimental data. Our analyses also allowed us to identify the influence of the relative position of AA and terminations on the local reactivity of the sequences, which can guide experimental studies and help to propose/evaluate possible mechanisms of action. In summary, our data indicate that the position of active sites of polypeptides can be predicted from short sequences, providing a promising strategy for the synthesis and bioprospection of new optimized compounds.

Polythiophene derivatives as chemical sensors: a DFT study on the influence of side groups.

Conjugated polymers have been considered promising candidates for applications in chemical sensors, mainly due to their high versatility of synthesis, low cost, light weight, and suitable optoelectronic properties. In this context, polythiophene (PT) derivatives have been successfully employed. However, at the same time that the versatility of the synthesis allows the production of varied derivatives, the complexity of interactions with analytes hinders an efficient design of compounds with improved sensing properties. In the present report, electronic structure calculations were employed to identify promising PT derivatives for chemical sensor applications. Structural, optoelectronic, and reactivity properties of a set of branched PT derivatives were evaluated. Adsorption studies considering different gaseous compounds were conducted for selected systems. The results suggest that an appropriate choice of the side groups can lead to derivatives with improved sensorial properties. In particular, PT-CN derivative was identified as the most promising compound for high sensitive chemical sensors towards SO2 and NH3 analytes.

Reactivity of eumelanin building blocks: A DFT study of monomers and dimers.

Melanins are natural pigments with important biological properties and have been considered promising materials for several bio-electronic applications. In spite of it, until now there is no satisfactory understanding of the macromolecular structure of these compounds. In this work, we have employed electronic structure calculations to evaluate the local reactivity on monomeric building blocks of eumelanin and on a varied combination of these units (dimers). The reactivity studies were accomplished by Condensed-to-Atoms Fukui Indexes in a DFT approach. The results have evidenced a dominance order in the reactivity of the building units that guides the polymerization process of melanin. In addition, from the differences of the local reactivities it was possible to better understand the reactions that can take place during eumelanin synthesis and estimate how they could be influenced by experimental conditions.

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study.

Regioselective glycosylations allow planning simpler strategies for the synthesis of oligosaccharides, and thus reducing the need of using protecting groups. With the idea of gaining further understanding of such regioselectivity, we analyzed the relative reactivity of the OH-3 and OH-4 groups of 2,6-diprotected methyl α- and ß-galactopyranoside derivatives in glycosylation reactions. The glycosyl acceptors were efficiently prepared by simple methodologies, and glycosyl donors with different reactivities were assessed. High regioselectivities were achieved in favor of the 1→3 products due to the equatorial orientation of the OH-3 group. A molecular modeling approach endorsed this general trend of favoring O-3 substitution, although it showed some failures to explain subtler factors governing the difference in regioselectivity between some of the acceptors. However, the Galp-(ß1→3)-Galp linkage could be regioselectively installed by using some of the acceptors assayed herein.