Controlling Antibacterial Activity Exclusively with Visible Light: Introducing a Tetra-ortho-Chloro-Azobenzene Amino Acid

The introduction of a novel tetra-ortho-chloroazobenzene amino acid (CEBA) has enabled photoswitching of the antimicrobial activity of tyrocidine A analogues by using exclusively visible light, granting spatiotemporal control under benign conditions. Compounds bearing this photoswitchable amino acid become active upon irradiation with red light, but quickly turn-off upon exposure to other visible light wavelengths. Critically, sunlight quickly triggers isomerisation of the red light-activated compounds into their original trans form, offering an ideal platform for self-deactivation upon release into the environment. Linear analogues of tyrocidine A were found to provide the best photocontrol of their antimicrobial activity, leading to compounds active against Acinetobacter baumannii upon isomerisation. Exploration of their N- and C-termini has provided insights into key elements of their structure and has allowed obtaining new antimicrobials displaying excellent strain selectivity and photocontrol.     

Evaluation of the Storage Conditions and Type of Cork Stopper on the Quality of Bottled White Wines

The effects of different storage conditions, light exposure, temperature and different commercially available cork stoppers on the phenolic, volatile and sensorial profile of Verdejo wines were studied. Two natural corks of different visual quality and a microgranulated cork stopper were investigated over one year at two different storage conditions. One simulating light exposure and temperature in retail outlets and the other simulating optimal cellar conditions (darkness and 12 °C). The wines stored under commercial conditions showed greater losses of total and free SO₂ and higher levels of brown-yellowish tones, related to the oxidation of flavan-3-ols. Although these wines underwent a decrease in the total content of stilbenes, a significant increase in trans-piceid was observed. In addition, these wines suffered important changes in their volatile and sensory profile. Volatile compounds with fruity and floral aromas decreased significantly, while volatile compounds related to aged-type characters, as linalool oxides, vitispirane, TDN or furan derivatives increased. Wines stored in darkness at 12 °C underwent minor changes and their sensory profiles were similar to wine before bottling. The high-quality natural corks and microgranulated corks better preserved the quality of the white wines from a sensory point of view. These results showed that temperature and light exposure conditions (diffuse white LEDs and 24 ± 2 °C) in retail outlets considerably decrease the quality of bottled white wines and, consequently, their shelf life, due to the premature development of aged-type characters.     

Melatonin in Wine and Beer: Beneficial Effects

Melatonin is a hormone secreted in the pineal gland with several functions, especially regulation of circadian sleep cycle and the biological processes related to it. This review evaluates the bioavailability of melatonin and resulting metabolites, the presence of melatonin in wine and beer and factors that influence it, and finally the different benefits related to treatment with melatonin. When administered orally, melatonin is mainly absorbed in the rectum and the ileum; it has a half-life of about 0.45–1 h and is extensively inactivated in the liver by phase 2 enzymes. Melatonin (MEL) concentration varies from picograms to ng/mL in fermented beverages such as wine and beer, depending on the fermentation process. These low quantities, within a dietary intake, are enough to reach significant plasma concentrations of melatonin, and are thus able to exert beneficial effects. Melatonin has demonstrated antioxidant, anticarcinogenic, immunomodulatory and neuroprotective actions. These benefits are related to its free radical scavenging properties as well and the direct interaction with melatonin receptors, which are involved in complex intracellular signaling pathways, including inhibition of angiogenesis and cell proliferation, among others. In the present review, the current evidence on the effects of melatonin on different pathophysiological conditions is also discussed.     

An Integrative Approach of an In Vitro Measurement of the Digestibility of Triacylglycerols of Human Milk

Several studies have been published regarding the effect of different factors on the digestion of milk lipids, considering their natural structural arrangement as milk fat globules and the efficiency of the digestive enzymes in the lipolysis of such complex structures. During digestion, the lipolytic products are dispersed in vesicles and micelles, which are the source for absorption of digested lipids. Therefore, it is necessary to consider the isolation of the micellar phase from the digesta to appropriately determine the amounts and classes of lipids which are bioaccessible. This study presents an integrative approach that included an isolation procedure to separate the micellar fraction from undigested and non-micellar parts, and the distribution of digested milk lipids in micelles determined directly through chromatographic techniques. Four groups of five full term mothers donated colostrum or mature milk. Two sets of samples were analyzed directly (raw), and two sets were pasteurized and then analyzed. Our data revealed that the profile of digested milk lipids is different depending on the lactation period and processing stage, while the carbon atom number distribution of the digested triacylglycerols in the micellar fraction provides a substantial information regarding the acylglycerols species that are less available for absorption.     

Suitability of density functional methods for calculation of electrostatic properties

A systematic analysis was performed on the suitability of the molecular electrostatic potential (MEP) and MEP-derived properties determined by means of density functional (DFT) methods. Attention was paid to the electrostatic potential (ESP) derived charges, the ESP and exact quantum mechanical dipole moments, the depth of MEP minima, and the MEP distribution in layers around the molecule for a large series of molecules. The electrostatic properties were determined at either local or nonlocal DFT levels using different functionals. The results were compared with the values estimated from quantum mechanical calculations performed at Hartree–Fock, Møller–Plesset up to fourth order, and CIPSI levels. The suitability of the MEP-derived properties estimated from DFT methods is discussed for application in different areas of chemical interest. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 980–991, 1997     

Dithiolane quartets: thiol-mediated uptake enables cytosolic delivery in deep tissue

The cytosolic delivery of various substrates in 3D multicellular spheroids by thiol-mediated uptake is reported. This is important because most orthodox systems, including polycationic cell-penetrating peptides, fail to deliver efficiently into deep tissue. The grand principles of supramolecular chemistry, that is the pH dependence of dynamic covalent disulfide exchange with known thiols on the transferrin receptor, are proposed to account for transcytosis into deep tissue, while the known but elusive exchange cascades along the same or other partners assure cytosolic delivery in kinetic competition. For quantitative detection in the cytosol, the 2D chloroalkane penetration assay (CAPA) is translated to 3D deep tissue. The targeted delivery of quantum dots, otherwise already troublesome in 2D culture, and the controlled release of mechanophores are realized to exemplify the power of thiol-mediated uptake into spheroids. As transporters, dithiolane quartets on streptavidin templates are introduced as modular motifs. Built from two amino acids only, the varied stereochemistry and peptide sequence are shown to cover maximal functional space with minimal structural change, i.e., constitutional isomers. Reviving a classic in peptide chemistry, this templated assembly of β quartets promises to expand streptavidin biotechnology in new directions, while the discovery of general cytosolic delivery in deep tissue as an intrinsic advantage further enhances the significance and usefulness of thiol-mediated uptake.

Cytosolic delivery in multicellular 3D spheroids is shown to be an intrinsic advantage of thiol-mediated uptake, which is compatible with proteins and QDs, achieving targeting and controlled release.     

Comparative Study of Antioxidant and Pro-Oxidant Properties of Homoleptic and Heteroleptic Copper Complexes with Amino Acids,Dipeptides and 1,10-Phenanthroline: The Quest for Antitumor Compounds

In a search for new antitumoral agents, a series of homoleptic copper(II) complexes with amino acids and dipeptides, as well as heteroleptic complexes containing both dipeptides and 1,10-phenanthroline, were studied. Furthermore, a single-crystal structure containing alanyl-leucinato ([Cu₃(AlaLeu)₃(H₂O)₃(CO₃)]·PF₆·H₂O), which is the first homotrinuclear carbonato-bridged copper(II) complex with a dipeptide moiety, is presented. To assess possible antitumor action mechanisms, we focused on the comparative analysis of pro- and antioxidant behaviors. Pro-oxidant activity, in which the reactive oxygen species (ROS) formed by the reaction of the complexes with H₂O₂ produce oxidative damage to 2-deoxy-d-ribose, was evaluated using the TBARS method. Additionally, the antioxidant action was quantified through the superoxide dismutase (SOD)-like activity, using a protocol based on the inhibitory effect of SOD on the reduction of nitrobluetetrazolium (NBT) by the superoxide anion generated by the xanthine/xanthine oxidase system. Our findings show that Cu–amino acid complexes are strong ROS producers and moderate SOD mimics. Conversely, Cu–dipeptide–phen complexes are good SOD mimics but poor ROS producers. The activity of Cu–dipeptide complexes was strongly dependent on the dipeptide. A DFT computational analysis revealed that complexes with high SOD-like activity tend to display a large dipole moment and condensed-to-copper charge, softness and LUMO contribution. Moreover, good ROS producers have higher global hardness and copper electrophilicity, lower copper softness and flexible and freely accessible coordination polyhedra.     

Combining Coagulation and Electrocoagulation with UVA-LED Photo-Fenton to Improve the Efficiency and Reduce the Cost of Mature Landfill Leachate Treatment

This study focused on the reduction of the treatment cost of mature landfill leachate (LL) by enhancing the coagulation pre-treatment before a UVA-LED photo-Fenton process. A more efficient advanced coagulation pretreatment was designed by combining conventional coagulation (CC) and electro-coagulation (EC). Regardless of the order in which the two coagulations were applied, the combination achieved more than 73% color removal, 80% COD removal, and 27% SUVA removal. However, the coagulation order had a great influence on both final pH and total dissolved iron, which were key parameters for the UVA-LED photo-Fenton post-treatment. CC (pH = 5; 2 g L⁻¹ of FeCl₃6H₂O) followed by EC (pH = 5; 10 mA cm⁻²) resulted in a pH of 6.4 and 100 mg L⁻¹ of dissolved iron, whereas EC (pH = 4; 10 mA cm⁻²) followed by CC (pH = 6; 1 g L⁻¹ FeCl₃6H₂O) led to a final pH of 3.4 and 210 mg L⁻¹ dissolved iron. This last combination was therefore considered better for the posterior photo-Fenton treatment. Results at the best cost-efficient [H₂O₂]:COD ratio of 1.063 showed a high treatment efficiency, namely the removal of 99% of the color, 89% of the COD, and 60% of the SUVA. Conductivity was reduced by 17%, and biodegradability increased to BOD₅:COD = 0.40. With this proposed treatment, a final COD of only 453 mg O₂ L⁻¹ was obtained at a treatment cost of EUR 3.42 kg COD⁻¹.     

Porphyrin–Schiff Base Conjugates Bearing Basic Amino Groups as Antimicrobial Phototherapeutic Agents

New porphyrin–Schiff base conjugates bearing one (6) and two (7) basic amino groups were synthesized by condensation between tetrapyrrolic macrocycle-containing amine functions and 4-(3-(N,N-dimethylamino)propoxy)benzaldehyde. This approach allowed us to easily obtain porphyrins substituted by positive charge precursor groups in aqueous media. These compounds showed the typical Soret and four Q absorption bands with red fluorescence emission (Φ_F ~ 0.12) in N,N-dimethylformamide. Porphyrins 6 and 7 photosensitized the generation of O₂(¹Δ_g) (Φ_Δ ~ 0.44) and the photo-oxidation of L-tryptophan. The decomposition of this amino acid was mainly mediated by a type II photoprocess. Moreover, the addition of KI strongly quenched the photodynamic action through a reaction with O₂(¹Δ_g) to produce iodine. The photodynamic inactivation capacity induced by porphyrins 6 and 7 was evaluated in Staphylococcus aureus, Escherichia coli, and Candida albicans. Furthermore, the photoinactivation of these microorganisms was improved using potentiation with iodide anions. These porphyrins containing basic aliphatic amino groups can be protonated in biological systems, which provides an amphiphilic character to the tetrapyrrolic macrocycle. This effect allows one to increase the interaction with the cell wall, thus improving photocytotoxic activity against microorganisms.