New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators

A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length of the aliphatic chain was varied. For the most interesting compounds some modifications on the terminal amino group were also performed. The most sensitive isoform to activation was hCA I (KA values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives (1, 3a and 22) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII.

Unveiling the Chemical Diversity of the Deep-Sea Sponge Characella pachastrelloides

Sponges are at the forefront of marine natural product research. In the deep sea, extreme conditions have driven secondary metabolite pathway evolution such that we might expect deep-sea sponges to yield a broad range of unique natural products. Here, we investigate the chemodiversity of a deep-sea tetractinellid sponge, Characella pachastrelloides, collected from ~800 m depth in Irish waters. First, we analyzed the MS/MS data obtained from fractions of this sponge on the GNPS public online platform to guide our exploration of its chemodiversity. Novel glycolipopeptides named characellides were previously isolated from the sponge and herein cyanocobalamin, a manufactured form of vitamin B12, not previously found in nature, was isolated in a large amount. We also identified several poecillastrins from the molecular network, a class of polyketide known to exhibit cytotoxicity. Light sensitivity prevented the isolation and characterization of these polyketides, but their presence was confirmed by characteristic NMR and MS signals. Finally, we isolated the new betaine 6-methylhercynine, which contains a unique methylation at C-2 of the imidazole ring. This compound showed potent cytotoxicity towards against HeLa (cervical cancer) cells.

SYNTHESIS AND SPECTROSCOPIC STUDY OF COMPLEX COMPOUNDS MN (II), CO (II), CU (II) AND ZN WITH 5-AMINO-2-MERCAPTOBENZIMIDAZOLE

The aim of this work is to study the effect of the nature of electron-donor and electron-withdrawing substituents in the molecules of heterocyclic ligands, the nature of acidoligands and transition metal ions on the properties of the synthesized coordination compounds. A method for the synthesis of new complex compounds of Mn (II), Cо (II), Cu (II) and Zn with 5-amino-2-mercaptobenzimidazole has been developed and the composition and structure of the synthesized complex compounds have been studied using modern physicochemical methods, such as elemental, thermogravimetric, X-ray phase analysis and IR spectroscopy. Coordination competing donor centers, electronic and geometric structures of the ligand molecule were studied using quantum-chemical calculations in the Gaussian09 LanL2DZ software package. It was shown that during the formation of a metal complex, the ligand 5-amino-2-mercaptobenzimidazole is coordinated through the localized nitrogen atom of the imidazole ring.

Determination of Histidine Protonation States in Proteins by Fast Magic Angle Spinning NMR

Histidine residues play important structural and functional roles in proteins, such as serving as metal-binding ligands, mediating enzyme catalysis, and modulating proton channel activity. Many of these activities are modulated by the ionization state of the imidazole ring. Here we present a fast MAS NMR approach for the determination of protonation and tautomeric states of His at frequencies of 40–62 kHz. The experiments combine 1H detection with selective magnetization inversion techniques and transferred echo double resonance (TEDOR)–based filters, in 2D heteronuclear correlation experiments. We illustrate this approach using microcrystalline assemblies of HIV-1 CACTD-SP1 protein.

Ovothiol-A Isolated from Sea Urchin Eggs Suppress Oxidative Stress, Inflammation, and Dyslipidemia Resulted in Restoration of Liver Activity in Cholestatic Rats

Cholestasis is dropping in bile flow, leading to the intrahepatic bulk of bile acids and other poisonous compounds with the progression of liver pathology, including hepatocellular injury and fibrosis. Ovothiols extracted from sea urchin display unusual antioxidant properties due to the peculiar position of the thiol group on the imidazole ring of histidine. The present study aims to evaluate the anti-fibrotic effect of Ovothiol-A in rats. 28 rats were allocated randomly into 4 groups: Sham, BDL, and BDL + Ovothiol A (500 mg/kg). All rats were treated for 7 days. Oxidative stress biomarkers, liver functions, lipid profile, and histology were all examined. The results revealed that BDL operation induced oxidative stress in rats, which negatively impacted liver functions, as confirmed by the histopathological examination. Ovothiol-A has been shown to lower oxidative stress and enhance lipid profile, resulting in considerable improvements in most biochemical markers. Also, histopathological examination showed an improvement in the liver architecture of the treated group compared to the BDL group. Ovothiol-A protects the liver against toxicity results from cholestasis in rats.

A Convenient and Label-Free Colorimetric Detection for L-Histidine Based on Inhibition of Oxidation of 3,3′,5,5′-Tetramethylbenzidine-H2O2 System Triggered by Copper Ions

L-Histidine (L-His) is an essential amino acid, which is used to synthesize proteins and enzymes. The concentration of L-His in the body is controlled to regulate tissue growth and repair of tissues. In this study, a rapid and sensitive method was developed for colorimetric L-his detection using Cu2+ ions to inhibit the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB)–H2O2 system. H2O2 can oxidize TMB to oxTMB in the presence of copper, and the change in color from colorless (TMB) to blue (oxTMB) is similar to that observed in the presence of peroxidase. However, because the imidazole ring and carboxyl group of L-His can coordinate with Cu2+ ions to form stable L-His–Cu2+ complexes, the color of the TMB–H2O2 solution remains unchanged after the addition of L-His. Therefore, because L-His effectively hinders the colorimetric reaction of TMB with H2O2, this assay can be used to quantitatively determine the concentration of L-His in samples. Under optimized conditions, our colorimetric sensor exhibited two linear ranges of 60 nM to 1 μM and 1 μM to 1 mM for L-His detection and a detection limit of 50 nM (S/N = 3); furthermore, the assay can be performed within 20 min. Moreover, the proposed assay was used to determine the concentration of L-His in urine samples, suggesting that this convenient and label-free colorimetric method presents promising applications in bioanalytical chemistry and clinical diagnosis.

Anion Exchange Membranes Based on Imidazoline Quaternized Polystyrene Copolymers for Fuel Cell Applications

Imidazoline is a five-membered heterocycle derived by the partial reduction of one double bond of the imidazole ring. This work prepared new anion exchange membranes (AEMs) based on imidazoline quaternized polystyrene copolymers bearing N-b-hydroxyethyl oleyl imidazolinium pendent groups to evaluate the application potential for anion exchange membrane fuel cells (AEMFCs). For comparison, an imidazole quaternized polystyrene copolymer was also synthesized. The polymer chemical structure was confirmed by FTIR, NMR, and TGA. In addition, the essential properties of membranes, including ion exchange capacity (IEC), water uptake, and hydroxide conductivity, were measured. The alkaline stabilities of imidazolium-based and imidazolinium-based AEMs were compared by means of the changes in the TGA thermograms, FTIR spectra, and hydroxide conductivity during the alkaline treatment in 1 M KOH at 60 °C for 144 h. The results showed that the imidazolinium-based AEMs exhibited relatively lower hydroxide conductivity (5.77 mS/cm at 70 °C) but much better alkaline stability compared with the imidazolium-based AEM. The imidazolinium-based AEM (PSVBImn-50) retained 92% of its hydroxide conductivity after the alkaline treatment. Besides, the fuel cell performance of the imidazolium-based and imidazolinium-based AEMs was examined by single-cell tests.

Elimination of Interionic Hydrogen Bonding in The Imidazolium-Based Ionic Liquids

Hydrogen bonding is a phenomenon of paramount importance in room-temperature ionic liquids. The presence or absence of the hydrogen bond drastically alternates self-diffusion, shear viscosity, phase transition points, and other key properties of a pure substance. For certain applications, the presence of cation-anion hydrogen bonding is undesirable. In the present paper, we investigate perspectives of removing the hydrogen...fluorine interionic attraction in the imidazolium borates, the strongest non-covalent interaction in this type of system. Chemical modification of the tetrafluoroborate anion not only eliminates hydrogen bonding but also changes the most thermodynamically preferable orientation of the cation in the vicinity of the anion. Although the most acidic hydrogen atom of the imidazole ring remains the paramount electrophilic center of the cation, it does not engender a strong electrostatically driven coordination pattern with the properly modified anions. The reported new physical insights help compose more robust ionic liquids and tune solvation properties of the imidazolium-based RTILs.

Removal performance and mechanism of typical amino acids in water by the peroxymonosulfate/Fe3O4 nanoparticles

Dissolved organic nitrogen (DON) as precursors of nitrogenous disinfection byproducts (N-DBPs) has become a serious issue for drinking water treatment. Here, Fe3O4/peroxymonosulfate (PMS) system was used to examine the amino acid removal and formation of N-DBPs in the system and the corresponding mechanisms. Results showed a remarked variation in removal efficiency of three typical amino acids, i.e., glutamate (78%), histidine (53%) and phenylalanine (27%) in Fe3O4/PMS system at optimum conditions (0.1 g/L Fe3O4, 1.5 mM PMS, 1 h). Notably, Fe3O4/PMS treatment led to dichloroacetonitrile (DCAN) formation caused by the chlorination of glutamate, phenylalanine and histidine being reduced by 53.3%, 9.7% and 41.9%, respectively. The degradation and subsequent N-DBPs formation in the Fe3O4/PMS system mainly depended on the types and properties of the amino acids. The formation of dichloroacetamide (DCAcAm) exhibited different trends, which may be due to the different R group structure of the three amino acids and the special aromaticity of imidazole ring in the histidine side chain that facilitates its quick electrophilic substitution and ring-opening reaction. This study highlights that the Fe3O4/PMS system is a promising strategy to remove DON and efficiently eliminate N-DBPs formation in the drinking water treatment process depending on the amino acid type.