Albérico B. F. da Silva

Bio: Albérico B. F. da Silva is an academic researcher from University of São Paulo. The author has contributed to research in topics: Density functional theory & Gaussian. The author has an hindex of 19, co-authored 114 publications receiving 1441 citations.

Infrared Spectroscopy of Anionic, Cationic, and Zwitterionic Surfactants

Abstract: This paper describes the ordering degree of anionic, cationic, and zwitterionic surfactants with the increase of their packing density on Ge substrate by using Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy. This work shows new insights on the conformational order of sodium dodecyl sulfate (SDS), N-hexadecyl-N-N-dimethyl-3-ammonio-1-propane-sulfonate (HPS), hexadecyl-trimethylammonium bromide (CTAB), and dodecyl trimethylammonium bromide (DTAB). DFT and semiempirical calculations are also performed in order to evaluate the effect of headgroup hydration and counterion. The CH2 asymmetric and symmetric stretching bands for the SDS molecule show a shift of 1.7 and 0.9 cm−1 to higher frequencies as the packing density increases, while it is observed a shift of 2.6 and 2.7 cm−1 for the HPS molecule, respectively. The DTAB molecule shows a shift of 4.5 cm−1 to lower frequencies for both CH2 asymmetric and symmetric stretching bands as the packing density increases, indicating the decrease of gauche conformations and the increase of all-trans conformations over the aliphatic chain.

Understanding the Molecular Aspects of Tetrahydrocannabinol and Cannabidiol as Antioxidants

Abstract: An antioxidant mechanism of tetrahydrocannabinol (THC) and cannabidiol (CBD) were compared with a simplified model of α-tocopherol, butylhydroxytoluene and hydroxytoluene in order to understand the antioxidant nature of THC and CBD molecules using DFT. The following electronic properties were evaluated: frontier orbitals nature, ionization potential, O-H bond dissociation energy (BDEOH), stabilization energy, and spin density distribution. An important factor that shows an influence in the antioxidant property of THC is the electron abstraction at the phenol position. Our data indicate that the decrease of the HOMO values and the highest ionization potential values are related to phenol, ether, and alkyl moieties. On the other hand, BDEOH in molecules with the cyclohexenyl group at ortho position of phenol are formed from lower energies than the molecules with an ether group at the meta position. In the light of our results, the properties calculated here predict that THC has a sightly higher antioxidant potential than CBD.

Non-peptidic Cruzain Inhibitors with Trypanocidal Activity Discovered by Virtual Screening and In Vitro Assay

Abstract: A multi-step cascade strategy using integrated ligand- and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (Ki) in the low micromolar range (3–60 µM) acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies. Cruzain, a validated therapeutic target for new chemotherapy for Chagas disease, also shares high similarity with the mammalian homolog cathepsin L. Because increased activity of cathepsin L is related to invasive properties and has been linked to metastatic cancer cells, cruzain inhibitors from the same library were assayed against it. Affinity values were in a similar range (4–80 µM), yielding poor selectivity towards cruzain but raising the possibility of investigating such inhibitors for their effect on cell proliferation. In order to select the most promising enzyme inhibitors retaining trypanocidal activity for structure-activity relationship (SAR) studies, the most potent cruzain inhibitors were assayed against T. cruzi-infected cells. Two compounds were found to have trypanocidal activity. Using compound Nequimed42 as precursor, an SAR was established in which the 2-acetamidothiophene-3-carboxamide group was identified as essential for enzyme and parasite inhibition activities. The IC50 value for compound Nequimed42 acting against the trypomastigote form of the Tulahuen lacZ strain was found to be 10.6±0.1 µM, tenfold lower than that obtained for benznidazole, which was taken as positive control. In addition, by employing the strategy of molecular simplification, a smaller compound derived from Nequimed42 with a ligand efficiency (LE) of 0.33 kcal mol−1 atom−1 (compound Nequimed176) is highlighted as a novel non-peptidic, non-covalent cruzain inhibitor as a trypanocidal agent candidate for optimization.

Advances and Perspectives in Applying Deep Learning for Drug Design and Discovery

Abstract: Discovering (or planning) a new drug candidate involves many parameters, which makes this process slow, costly and leading to failures at the end in some cases. In the last decades, we have witnessed a revolution in the computational area (hardware, software, large-scale computing, etc.), as well as an explosion in data generation (big data), which raises the need for more sophisticated algorithms to analyze this myriad of data. In this scenario, we can highlight the potentialities of artificial intelligence (AI) or computational intelligence (CI) as a powerful tool to analyze medicinal chemistry data. According to IEEE, computational intelligence involves the theory, the design, the application and the development of biologically and linguistically motivated computational paradigms. In addition, CI encompasses three main methodologies: neural networks (NN), fuzzy systems and evolutionary computation. In particular, artificial neural networks have been successfully applied in medicinal chemistry studies. A branch of the NN area that has attracted a lot of attention refers to deep learning (DL) due to its generalization power and ability to extract features from data. Therefore, in this mini-review we will briefly outline the present scope, advances and challenges related to the use of DL in drug design and discovery, describing successful studies involving quantitative structure-activity relationships (QSAR) and virtual screening (VS) of databases containing thousands of compounds.

Complexation of the anti-Trypanosoma cruzi Drug Benznidazole Improves Solubility and Efficacy

Abstract: The ruthenium complex, trans-[Ru(Bz)(NH3)4SO2](CF3SO3)2 1, Bz = benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide), is more hydrosoluble and more active (IC50try/1 h = 79 ± 3 μM) than free benznidazole 2 (IC50try/1 h > 1 mM). 1 also exhibits low acute toxicity in vitro (IC50macrophages > 1 mM) and in vivo (400 μmol/kg < LD50 < 600 μmol/kg) and the formation of hydroxylamine is more favorable in 1 than in 2 by 9.6 kcal/mol. In murine acute models of Chagas’ disease, 1 was more active than 2 even when only one dose was administrated. Moreover, 1 at a thousand-fold smaller concentration than the considered optimal dose for 2 (385 μmol/kg/day = 100 mg/kg/day), proved to be sufficient to protect all infected mice, eliminating the amastigotes in their hearts and skeletal muscles as observed in H&E micrographics.

Methods in Enzymology.

Abstract: I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Abstract: : The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Density functional theory for transition metals and transition metal chemistry

Abstract: We introduce density functional theory and review recent progress in its application to transition metal chemistry. Topics covered include local, meta, hybrid, hybrid meta, and range-separated functionals, band theory, software, validation tests, and applications to spin states, magnetic exchange coupling, spectra, structure, reactivity, and catalysis, including molecules, clusters, nanoparticles, surfaces, and solids.