A green and expedient synthesis of enantiopure diketopiperazines via enzymatic resolution of unnatural amino acids

Dipeptides comprising a d-phenylglycyl moiety coupled to the l-enantiomer of 2-amino butyric acid, norvaline, norleucine, and homocysteine were successfully synthesized from d-phenylglycine amide and the racemate of the corresponding unnatural amino acid. The reaction is catalyzed by an immobilized form of penicillin G acylase in an aqueous medium. The dipeptides were subsequently converted into the corresponding enantiopure diketopiperazines in overall isolated yields of 22–33%.     

Four related benzazepine derivatives in a reaction pathway leading to a benzazepine carboxylic acid: hydrogen‐bonded assembly in zero,one, two and three dimensions

(2R*,4S*)‐Methyl 2,3,4,5‐tetrahydro‐1,4‐epoxy‐1H‐benz[b]azepine‐2‐carboxylate, C₁₂H₁₃NO₃, (I), and its reduction product (2R*,4S*)‐methyl 4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benz[b]azepine‐2‐carboxylate, C₁₂H₁₅NO₃, (II), both crystallize as single enantiomers in the space group P2₁2₁2₁, while the hydrolysis product (2RS,4SR)‐4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benz[b]azepine‐2‐carboxylic acid, C₁₁H₁₃NO₃, (III), and the lactone (2RS,5SR)‐8‐(trifluoromethoxy)‐5,6‐dihydro‐1H‐2,5‐methanobenz[e][1,4]oxazocin‐3(2H)‐one, C₁₂H₁₀F₃NO₃, (IV), both crystallize as racemic mixtures in the space group P2₁/c. The molecules of compound (IV) are linked into centrosymmetric R₂²(10) dimers by N—H...O hydrogen bonds, and those of compound (I) are linked into chains by C—H...π(arene) hydrogen bonds. A combination of O—H...O and O—H...N hydrogen bonds links the molecules of compound (III) into sheets containing equal numbers of R₄⁴(14) and R₄⁴(26) rings, and a combination of C—H...π(arene) hydrogen bonds and three‐centre O—H...(N,O) hydrogen bonds links the molecules of compound (II) into a three‐dimensional framework structure. Comparisons are made with some related compounds.     

Fingerprinting pre-historical symbolic artefacts by a non-destructive methodological approach

Journal of Radioanalytical and Nuclear Chemistry - A contribution to the discussion about Vila Nova de São Pedro (VNSP) as a production centre of symbolic lithic artefacts, the origin of raw...     

Tacrines as Therapeutic Agents for Alzheimer's Disease. V. Recent Developments

Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase inhibitor approved for AD treatment, did not stop the progression of AD, producing only some cognitive improvements, but exhibited secondary effects mainly due to its hepatotoxicity. Thus, the drug was withdrawn from the clinics administration. Since then, many publications have described non‐hepatotoxic tacrines, and in addition, important efforts have been made to design multitarget tacrines by combining their cholinesterase inhibition profile with the modulation of other biological targets involved in AD.     

Gouy wave modes: undistorted pulse focalization in a dispersive medium

Gouy wave modes are linear waves with finite energy that propagate without distortion at any phase and group velocity through a focal region in a dispersive medium. These features make them potentially useful for the onset and control of nonlinear interactions.     

Physicochemical properties of SARS-CoV-2 for drug targeting,virus inactivation and attenuation,vaccine formulation and quality control

The material properties of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its proteins are discussed. We review the viral structure, size, rigidity, lipophilicity, isoelectric point, buoyant density and centrifugation conditions, stability against pH, temperature, UV light, gamma radiation, and susceptibility to various chemical agents including solvents and detergents. Possible inactivation, downstream, and formulation conditions are given including suitable buffers and some first ideas for quality-control methods. This information supports vaccine development and discussion with competent authorities during vaccine approval and is certainly related to drug-targeting strategies and hygienics. Several instructive tables are given, including the pI and grand average of hydropathicity (GRAVY) of SARS-CoV-1 and -2 proteins in comparison. SARS-CoV-1 and SARS-CoV-2 are similar in many regards, so information can often be derived. Both are unusually stable, but sensitive at their lipophilic membranes. However, since seemingly small differences can have strong effects, for example, on immunologically relevant epitope settings, unevaluated knowledge transfer from SARS-CoV-1 to SARS-CoV-2 cannot be advised. Published knowledge regarding downstream processes, formulations and quality assuring methods is, as yet, limited. However, standard approaches employed for other viruses and vaccines seem to be feasible including virus inactivation, centrifugation conditions, and the use of adjuvants.     

Bioactive Properties and Phenolic Compound Profiles of Turnip-Rooted,Plain-Leafed and Curly-Leafed Parsley Cultivars

Petroselinum crispum Mill., Fuss., is a culinary vegetable used as an aromatic herb that garnishes and flavours a great variety of dishes. In the present study, the chemical profiles and bioactivities of leaf samples from 25 cultivars (three types: plain- and curly-leafed and turnip-rooted) from this species were assessed. Seven phenolic compounds were identified in all the varieties, including apigenin and kaempherol derivates. Apigenin-O-pentoside-O-hexoside was the major compound in all the tested parsley types (20, 22 and 13 mg/g of extract, respectively) and responsible for its excellent antioxidant activity, also investigated in this study. Antimicrobial activities were also explored, and the results revealed a good bioactivity against specific tested pathogens, such as bacteria and fungi. In conclusion, the leaves of all the types of P. crispum are a good source of natural bioactive compounds that confer health benefits, and thus, they should be part of a balanced and diversified diet.     

Elemental Chemometrics as Tools to Depict Stalked Barnacle (Pollicipes pollicipes) Harvest Locations and Food Safety

The stalked barnacle Pollicipes pollicipes is an abundant species on the very exposed rocky shore habitats of the Spanish and Portuguese coasts, constituting also an important economical resource, as a seafood item with high commercial value. Twenty-four elements were measured by untargeted total reflection X-ray fluorescence spectroscopy (TXRF) in the edible peduncle of stalked barnacles sampled in six sites along the Portuguese western coast, comprising a total of 90 individuals. The elemental profile of 90 individuals originated from several geographical sites (N = 15 per site), were analysed using several chemometric multivariate approaches (variable in importance partial least square discriminant analysis (VIP-PLS-DA), stepwise linear discriminant analysis (S-LDA), linear discriminant analysis (LDA), random forests (RF) and canonical analysis of principal components (CAP)), to evaluate the ability of each approach to trace the geographical origin of the animals collected. As a suspension feeder, this species introduces a high degree of background noise, leading to a comparatively lower classification of the chemometric approaches based on the complete elemental profile of the peduncle (canonical analysis of principal components and linear discriminant analysis). The application of variable selection approaches such as the VIP-PLS-DA and S-LDA significantly increased the classification accuracy (77.8% and 84.4%, respectively) of the samples according to their harvesting area, while reducing the number of elements needed for this classification, and thus the background noise. Moreover, the selected elements are similar to those selected by other random and non-random approaches, reinforcing the reliability of this selection. This untargeted analytical procedure also allowed to depict the degree of risk, in terms of human consumption of these animals, highlighting the geographical areas where these delicacies presented lower values for critical elements compared to the standard thresholds for human consumption.     

In Vitro Evaluation of the Photoreactivity and Phototoxicity of Natural Polyphenol Antioxidants

Polyphenols are a large family of natural compounds widely used in cosmetic products due to their antioxidant and anti-inflammatory beneficial properties and their ability to prevent UV radiation-induced oxidative stress. Since these compounds present chromophores and are applied directly to the skin, they can react with sunlight and exert phototoxic effects. The available scientific information on the phototoxic potential of these natural compounds is scarce, and thus the aim of this study was to evaluate the photoreactivity and phototoxicity of five phenolic antioxidants with documented use in cosmetic products. A standard ROS assay was validated and applied to screen the photoreactivity of the natural phenolic antioxidants caffeic acid, ferulic acid, p-coumaric acid, 3,4-dihydroxyphenylacetic acid (DOPAC), and rutin. The phototoxicity potential was determined by using a human keratinocyte cell line (HaCaT), based on the 3T3 Neutral Red Uptake phototoxicity test. Although all studied phenolic antioxidants absorbed UV/Vis radiation in the range of 290 to 700 nm, only DOPAC was able to generate singlet oxygen. The generation of reactive oxygen species is an early-stage chemical reaction as part of the phototoxicity mechanism. Yet, none of the studied compounds decreased the viability of keratinocytes after irradiation, leading to the conclusion that they do not have phototoxic potential. The data obtained with this work suggests that these compounds are safe when incorporated in cosmetic products.