Unveiling the relevance of the redox character of nitroaromatic and nitroheteroaromatic compounds as potential medicines

This review discusses the state of the art, challenges, and perspectives in recent applications of nitroaromatics and nitroheteroaromatics, which are redox-bio-activated drugs or leads, in Medicinal Chemistry. It deals mainly with the electrochemical approach toward the electron transfer-based molecular mechanisms of drug action, drug design, estimation and measurement of redox potentials, correlation of physicochemical and pharmacological data, and electrochemical studies of the main representatives of nitro-containing prodrugs, along with approaches to combat their toxicity issues, aiming at a better therapeutic profile. Electrochemical investigation plays essential roles, being strategic in the design and discovery of potential medicines.     

Calorimetric study of spinodal decomposition in β-Cu–Al–Mn

Journal of Thermal Analysis and Calorimetry - We report data obtained from the spinodal decomposition in samples of two compositions of intermetallic Cu–Al–Mn shape memory alloys....     

Enhancement of Antibiotic Activity by 1,8-Naphthyridine Derivatives against Multi-Resistant Bacterial Strains

The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure–activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.     

Quantitative characterization of the global electrophilicity pattern of some reagents involved in 1,3-dipolar cycloaddition reactions

The global electrophilicity power, ω, of a series of dipoles and dipolarophiles commonly used in 1,3-dipolar cycloadditions may be conveniently classified within a unique relative scale. The effects of chemical substitution on the electrophilicity of molecules have been evaluated using a representative set of electron-withdrawing and electron-releasing groups for a series of dipoles including nitrone, nitrile oxide and azide derivatives. The absolute scale of electrophilicity is used to rationalize the chemical reactivity of these species as compared to the static reactivity pattern of the reagents involved in the Diels-Alder reactions.     

Two hydrates of 2,6‐bis­(1H‐benzimidazol‐2‐yl)­pyridine

The structures of the mono‐ and sesquihydrates of 2,6‐bis(1H‐benz­imi­da­zol‐2‐yl)­pyridine (bbip) are reported. Phase (I), C₁₉H₁₃N₅·H₂O, has one water and one bbip mol­ecule in the asymmetric unit, while phase (II), C₁₉H₁₃N₅·1.5H₂O, has three water mol­ecules and two bbip mol­ecules in the asymmetric unit. The compounds exhibit very similar molecular geom­etries but different packing organizations, which result from intricate hydrogen‐bonding schemes.     

[2,6‐Bis(1H‐benzimidazol‐2‐yl‐κN3)­pyridine‐κN](di­methyl­form­amide‐κO)­(thio­sulfato‐κ2O,S)­nickel(II) mono­hydrate

The structure of the title compound, [Ni(ths)(bbip)(dmf)]·­H₂O [ths is thio­sulfate, S₂O₃; bbip is 2,6‐bis(1H‐benz­imidazol‐2‐yl)­pyridine, C₂₁H₁₃N₅; and dmf is di­methyl­form­amide, C₃H₇NO], is monomeric, with the nickel ion octahe­drally surrounded by an N,N′,N′′‐tridentate bbip mol­ecule, an S,O‐bidentate ths mol­ecule and an O‐monodentate dmf mol­ecule. The H atoms of the hydration water mol­ecule and the amino groups of bbip are involved in hydrogen bonding and determine a spatial organization of broad layers parallel to (001), which are connected by weak interactions.     

Preparative mass‐spectrometry profiling of minor concentrated metabolites in Salicornia gaudichaudiana Moq by high‐speed countercurrent chromatography and off‐line electrospray mass‐spectrometry injection

Salicornia species have just been introduced to the European market as a vegetable named ‘samphire’, ‘green asparagus’, or ‘sea asparagus’. Due to its increasing attention, and associated value, minor compounds of Salicornia gaudichaudiana Moq were investigated. The use of countercurrent chromatography and mass spectrometry enabled the search for known, as well as potentially novel natural products. Their identification was achieved based on molecular weights and mass‐spectrometric fragmentation data. Low detection limits enabled the visualization of all compounds with their identification in almost real time close to the preparative countercurrent chromatography experiment. A list of known natural products from Salicornia genus guided the identification process of compounds occurring in Salicornia gaudichaudiana Moq by tandem mass spectrometry fragment comparison. The natural product classes were divided into four groups: chlorogenic acid derivatives; flavonoid derivatives; pentacyclic triterpenoid saponins; and other compounds.     

Development of a synthetic route towards N4,N9-disubstituted 4,9-diaminoacridines: On the way to multi-stage antimalarials

A multi-step synthetic route towards N⁴,N⁹-disubstituted 4,9-diaminoacridines that, to the best of our knowledge, has no precedence in the literature, has been developed. The target structures are likely to reveal interesting biological activities in the near future, not only due to their mepacrine-like core, but also because they embed simultaneously the pharmacophores of chloroquine and primaquine, antimalarial drugs that act at different stages of malaria infection.     

Introducing the Petasis Reaction for Late‐Stage Multicomponent Diversification,Labeling, and Stapling of Peptides

For the first time, the Petasis (borono‐Mannich) reaction is employed for the multicomponent labeling and stapling of peptides. The report includes the solid‐phase derivatization of peptides at the N‐terminus, Lys, and N^?‐MeLys side‐chains by an on‐resin Petasis reaction with variation of the carbonyl and boronic acid components. Peptides were simultaneously functionalized with aryl/vinyl substituents bearing fluorescent/affinity tags and oxo components such as dihydroxyacetone, glyceraldehyde, glyoxylic acid, and aldoses, thus encompassing a powerful complexity‐generating approach without changing the charge of the peptides. The multicomponent stapling was conducted in solution by linking N^?‐MeLys or Orn side‐chains, positioned at i, i+7 and i, i+4, with aryl tethers, while hydroxy carbonyl moieties were introduced as exocyclic fragments. The good efficiency and diversity oriented character of these methods show prospects for peptide drug discovery and chemical biology.