Vanadium Complexes with Thioanilide Derivatives of Amino Acids: Inhibition of Human Phosphatases and Specificity in Various Cell Models of Metabolic Disturbances.

In the text, the synthesis and characteristics of the novel ONS-type vanadium (V) complexes with thioanilide derivatives of amino acids are described. They showed the inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1, and SHP2) in the submicromolar range, as well as the inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxidovanadium(IV) (BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, including also glucose utilizatiand ONO Complexes are Inhibitors ofon in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.

A Vanadium-Catalyzed Synthesis of Fully Substituted Pyrroles.

We present a straightforward, fast, inexpensive, and environmentally friendly synthesis of 1,2,3,4,5-pentasubstituted derivatives of pyrrole, which were produced in one-pot reactions of 3-oxoanilides with hydrazides of carboxylic acids, catalyzed by 10 mol % VOSO4·H2O. The reactions were carried out in ethanol in contact with air as the oxidant. The 19 pyrroles obtained were usually crystalline and did not require purification. The reaction tolerates various substituents in both substrates. All products were characterized by infrared, nuclear magnetic resonance, and ultraviolet-visible spectroscopy and elemental analysis. The molecular structures of the products and the intermediates were unambiguously determined by X-ray single-crystal analysis.

In the Search of Glycoside-Based Molecules as Antidiabetic Agents.

This review is an effort to summarize recent developments in synthesis of O-glycosides and N-, C-glycosyl molecules with promising antidiabetic potential. Articles published after 2000 are included. First, the O-glycosides used in the treatment of diabetes are presented, followed by the N-glycosides and finally the C-glycosides constituting the largest group of antidiabetic drugs are described. Within each group of glycosides, we presented how the structure of compounds representing potential drugs changes and when discussing chemical compounds of a similar structure, achievements are presented in the chronological order. C-Glycosyl compounds mimicking O-glycosides structure, exhibit the best features in terms of pharmacodynamics and pharmacokinetics. Therefore, the largest part of the article is concerned with the description of the synthesis and biological studies of various C-glycosides. Also N-glycosides such as N-(ß-D-glucopyranosyl)-amides, N-(ß-D-glucopyranosyl)-ureas, and 1,2,3-triazolyl derivatives belong to the most potent classes of antidiabetic agents. In order to indicate which of the compounds presented in the given sections have the best inhibitory properties, a list of the best inhibitors is presented at the end of each section. In summary, the best inhibitors were selected from each of the summarizing figures and the results of the ranking were placed. In this way, the reader can learn about the structure of the compounds having the best antidiabetic activity. The compounds, whose synthesis was described in the article but did not appear on the figures presenting the structures of the most active inhibitors, did not show proper activity as inhibitors. Thus, the article also presents studies that have not yielded the desired results and show directions of research that should not be followed. In order to show the directions of the latest research, articles from 2018 to 2019 are described in a separate Sect. 5. In Sect. 6, biological mechanisms of action of the glycosides and patents of marketed drugs are described.

On the Structure and Reaction Mechanism of Human Acireductone Dioxygenase.

Acireductone dioxygenase (ARD) is an intriguing enzyme from the methionine salvage pathway that is capable of catalysing two different oxidation reactions with the same substrate depending on the type of the metal ion in the active site. To date, the structural information regarding the ARD-acireductone complex is limited and possible reaction mechanisms are still under debate. The results of joint experimental and computational studies undertaken to advance knowledge about ARD are reported. The crystal structure of an ARD from Homo sapiens was determined with selenomethionine. EPR spectroscopy suggested that binding acireductone triggers one protein residue to dissociate from Fe2+ , which allows NO (and presumably O2 ) to bind directly to the metal. Mössbauer spectroscopic data (interpreted with the aid of DFT calculations) was consistent with bidentate binding of acireductone to Fe2+ and concomitant dissociation of His88 from the metal. Major features of Fe vibrational spectra obtained for the native enzyme and upon addition of acireductone were reproduced by QM/MM calculations for the proposed models. A computational (QM/MM) study of the reaction mechanisms suggests that Fe2+ promotes O-O bond homolysis, which elicits cleavage of the C1-C2 bond of the substrate. Higher M3+ /M2+ redox potentials of other divalent metals do not support this pathway, and instead the reaction proceeds similarly to the key reaction step in the quercetin 2,3-dioxygenase mechanism.

Molecular structure and vibrational spectra of 2,2',4,4',6-pentabromodiphenyl ether (BDE 100).

In this work, FT-IR ATR and Raman (laser line 532nm) spectra of 2,2',4,4',6-pentabromodiphenyl ether (BDE 100) have been recorded in the range of 4000-650 and 4000-100cm-1, respectively. A combined experimental and theoretical approach (DFT/B3LYP/6-311++g** and aug-cc-pVDZ) was used to study molecular structure of BDE 100. Optimization of geometry in the gas phase at these levels of theory indicated that the BDE 100 has skew conformation. The detailed assignment of IR and Raman bands of BDE 100 was done on the basis of calculated results for the most stable conformer. The scaled theoretical frequencies are in good agreement with the experimental ones. Both experimental and theoretical IR and Raman spectra of BDE 100, one of the members of the family of flame retardants, are presented here for the first time.

N-(5-Nitro-pyridin-2-yl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide.

The title compound, C(19)H(13)N(5)O(3), can be obtained from the corresponding α-amido-α-amino-nitrone in a reaction with biphenyl-2,2'-diamine. The amido-amidine core has distinctive geometrical parameters including: an outstandingly long Csp(2)-Csp(2) single bond of 1.5276 (13) Šand an amidine N-C-N angle of 130.55 (9)°. Intra-molecular N-H⋯O, N-H⋯N and C-H⋯O hydrogen bonds occur. In the crystal, mol-ecules form layers parallel to (001) via weak inter-molecular C-H⋯N inter-actions. The layers are linked via N-H⋯O hydrogen bonds and π-π inter-actions along [001] [benzene-pyridine centroid-centroid distance = 3.672 (2) Å].

Preparation of a new Cd(II)-imprinted polymer and its application to determination of cadmium(II) via flow-injection-flame atomic absorption spectrometry.

A new cadmium(II)-imprinted polymer based on cadmium(II) 2,2'-{ethane-1,2-diylbis[nitrilo(E)methylylidene]} diphenolate-4-vinylpyridine complex was obtained via suspension polymerization. The beads were used as a minicolumn packing for flow-injection-flame atomic absorption spectrometry (FI-FAAS) determination of cadmium(II) in water samples. Sorption effectiveness was optimal within pH range of 6.6-7.7. Nitric acid, 0.5% (v/v) was used as eluent. Fast cadmium(II) sorption by the proposed material enabled to apply sample flow rates up to 10mLmin(-1) without loss in sorption effectiveness. Enrichment factor (EF), concentration efficiency (CE) and limit of detection (LOD, 3sigma) found for 120-s sorption time were 117, 39.1min(-1) and 0.11microgL(-1), respectively. Sorbent stability was proved for at least 100 preconcentration cycles (RSD=2.9%). When compared to non-imprinted polymer the new Cd(II)-imprinted polymer exhibited improved selectivity towards cadmium(II) against other heavy metal ions, especially Cu(II) and Pb(II), as well as light metal ions. Accuracy of the method was tested for ground water and waste water certified reference materials and fortified water. The method was applied to Cd(II) determination in natural water samples.

Application of a metal ion-imprinted polymer based on salen-Cu complex to flow injection preconcentration and FAAS determination of copper.

A new Cu(II)-imprinted polymer (Cu-IIP) for preconcentration of copper by liquid-solid extraction via flow injection technique has been proposed. Cu-IIP was obtained by copolymerization of salen-Cu(II) complex with styrene and divinylbenzene using suspension polymerization technique. Granules fraction of 60-80 microm in diameter was used as a microcolumn packing. Cu(II) sorption was proved to be the most effective from solutions of pH 7, whereas similar elution effectiveness was observed when applying as eluents hydrochloric or nitric acid in the concentration range of 0.5-10% (v/v). The system exhibited good long-term stability and acid resistance. Batch sorbent capacity was found to be 0.11 mmol g(-1) of a dry polymer. Enrichment factor (EF) for 30 s loading time was 16. Preconcentration of Cu(II) and potentially interfering metal ions is strongly pH dependent. Examination of Cu(II) sorption in the presence of Pb(II), Cd(II), Zn(II) and Ag(I) showed significant influence of cadmium and zinc ions only and that was for the interferent concentrations above 0.5 mg L(-1) (Cu-IIP mass of ca. 35 mg). The interference effect was reduced with the sorbent mass increase. Fe(III) and Mn(II) ions, present in treated tap water in relatively high concentrations, did not interfere. Effective pH adjusting of the loaded solution in on-line mode, when applying diluted Clark-Lubs buffering solution, allowed accurate copper determination in tap water (compared to graphite furnace atomic absorption spectrometry, GFAAS) using standard addition or combination calibration method.

(2Z)-2-Anilino-2-[oxido(phen-yl)iminio]-N-(2-pyrid-yl)acetamide methanol 0.425-solvate.

The title compound, C(19)H(16)N(4)O(2)·0.425CH(4)O, crystallizes with two formula units per asymmetric unit. Researching its crystal structure constitutes part of a study of the nature of inter-actions between the N(+)-O(-) group and the vicinal NH group. The nitrone group and methanol solvent mol-ecules are linked via four N-H⋯O and one O-H⋯O hydrogen bonds, with donor-acceptor distances of 2.603 (3)-2.730 (3) and 2.770 (3) Å, respectively. The crystal structure also involves two intermolecular N-H⋯N hydrogen bonds.