Silyl modifications of biologically active compounds 6. Organosilicon complexes of rhenium(V) with mixed ligands

Neutral organosilicon complexes of rhenium with mixed ligands of general formula ReO(SSS)(S-Q-OSiRR'₂) have been synthesized. An X-ray crystallographic investigation of (2-triphenylsiloxyethanethiolato)(3-thiapentan-1,5-dithiolato)oxorhenium has been carried out and its neurotropic properties have been studied.For part 5, see [1].Latvian Institute of Organic Synthesis, Riga, LV-1006. e-mail: aez@osi.lanet.lv, and Forschungszentrum Rossendorf, Dresden, Germany. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, 116–125, January 1999.     

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds—A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes

The synthesis of inhibitors for oxidative stress-associated destructive processes based on 2H-imidazole-derived phenolic compounds affording the bifunctional 2H-imidazole-derived phenolic compounds in good-to-excellent yields was reported. In particular, a series of bifunctional organic molecules of the 5-aryl-2H-imidazole family of various architectures bearing both electron-donating and electron-withdrawing substituents in the aryl fragment along with the different arrangements of the hydroxy groups in the polyphenol moiety, namely derivatives of phloroglucinol, pyrogallol, hydroxyquinol, including previously unknown water-soluble molecules, were studied. The structural and antioxidant properties of these bifunctional 5-aryl-2H-imidazoles were comprehensively studied. The redox transformations of the synthesized compounds were carried out. The integrated approach based on single and mixed mechanisms of antioxidant action, namely the AOC, ARC, Folin, and DPPH assays, were applied to estimate antioxidant activities. The relationship “structure-antioxidant properties” was established for each of the antioxidant action mechanisms. The conjugation effect was shown to result in a decrease in the mobility of the hydrogen atom, thus complicating the process of electron transfer in nearly all cases. On the contrary, the conjugation in imidazolyl substituted phloroglucinols was found to enhance their activity through the hydrogen transfer mechanism. Imidazole-derived polyphenolic compounds bearing the most electron-withdrawing functionality, namely the nitro group, were established to possess the higher values for both antioxidant and antiradical capacities. It was demonstrated that in the case of phloroglucinol derivatives, the conjugation effect resulted in a significant increase in the antiradical capacity (ARC) for a whole family of the considered 2H-imidazole-derived phenolic compounds in comparison with the corresponding unsubstituted phenols. Particularly, conjugation of the polyphenolic subunit with 2,2-dimethyl-5-(4-nitrophenyl)-2H-imidazol-4-yl fragment was shown to increase ARC from 2.26 to 5.16 (10⁴ mol-eq/L). This means that the considered family of compounds is capable of exhibiting an antioxidant activity via transferring a hydrogen atom, exceeding the activity of known natural polyphenolic compounds.     

Synthesis of dimeric 1,3,2λ5-benzoxazaphospholes from phosphinic acid derivatives by silylation/desiloxylation

The reaction of N,N,O-tris(trimethylsilyl)-o-aminophenol with two equivalents of phosphinic chloride yielded dimeric 2,2-disubstituted 1,3,2λ⁵-benzoxazaphospholes and trimethylsilyl phosphinate. The chlorides having the bulk substituents (o-chlorophenyl or tert-butyl) at phosphorus or containing P N and P O bonds (instead of a P C bond) either didn't react at all or reacted to retain the phosphoryl group. Being stable in solution at 20°C, the individual diastereoisomers of dimeric 1,3,2-benzoxazaphospholes were converted upon warming to an equilibrium mixture of isomers. When reacted with another dimer each gave a mixed dimeric compound having two different phosphorus atoms in the molecule.     

Ionization equilibrium in salt‐containing aqueous solutions of synthetic polyampholytes

The peculiarities of ionic equilibrium in salt‐containing aqueous solutions of polyampholytes (acrylic acid–2‐methyl‐5‐vinylpyridine copolymers) of various compositions and molecular weights were studied. The protonation degree of base groups (β_iep), the dissociation degree of acid groups (α_iep), and the ionization constant of methylvinylpyridine groups (pK_b) for the isoelectric points of the studied polyampholytes under various ionic strength values (I) were assessed spectrophotometrically. The dependencies of α_iep and pK_b versus the copolymer composition in the absence of low molecular weight electrolyte are described by the following equations: pK_b = 6.2–0.037z and lg α_iep = 0.27–0.0215z, where z is the molar content of the acrylic acid units. The basicity of methylvinylpyridine groups increases in proportion to the content of acid groups at a constant ionic strength and is independent of the molecular weight and molecular weight distribution of the copolymer. The relationship between pK_b and the ionic strength of the solution for acrylic acid–methylvinylpyridine copolymers was established: pK_b(I) = pK + B · I^1/2, where pK is the thermodynamic ionization constant of base groups and B is 0.21 + 0.0065z. A good agreement between the experimental and theoretical (calculated from the given equation) values of the ionization constant, pK_b, of methylvinylpyridine groups for other polyampholytes (copolymers of methacrylic acid with 2‐methyl‐5‐vinylpyridine) demonstrated that the ionic state of polyampholytes is determined by the basicity of methylvinylpyridine groups, which depends on the copolymer composition and solution ionic strength. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 1824–1831, 2000     

Structural Effects of Disease-Related Mutations in Actin-Binding Period 3 of Tropomyosin

Tropomyosin (Tpm) is an actin-binding coiled-coil protein. In muscle, it regulates contractions in a troponin/Ca²⁺-dependent manner and controls the thin filament lengths at the pointed end. Due to its size and periodic structure, it is difficult to observe small local structural changes in the coiled coil caused by disease-related mutations. In this study, we designed 97-residue peptides, Tpm1.1_64–154 and Tpm3.12_65–155, focusing on the actin-binding period 3 of two muscle isoforms. Using these peptides, we evaluated the effects of cardiomyopathy mutations: I92T and V95A in Tpm1.1, and congenital myopathy mutations R91P and R91C in Tpm3.12. We introduced a cysteine at the N-terminus of each fragment to promote the formation of the coiled-coil structure by disulfide bonds. Dimerization of the designed peptides was confirmed by gel electrophoresis in the presence and absence of dithiothreitol. Using circular dichroism, we showed that all mutations decreased coiled coil stability, with Tpm3.12_65–155R91P and Tpm1.1_64–154I92T having the most drastic effects. Our experiments also indicated that adding the N-terminal cysteine increased coiled coil stability demonstrating that our design can serve as an effective tool in studying the coiled-coil fragments of various proteins.     

Lithium Ascorbate as a Promising Neuroprotector: Fundamental and Experimental Studies of an Organic Lithium Salt

Given the observable toxicity of lithium carbonate, neuropharmacology requires effective and non-toxic lithium salts. In particular, these salts can be employed as neuroprotective agents since lithium ions demonstrate neuroprotective properties through inhibition of glycogen synthetase kinase-3β and other target proteins, increasing concentrations of endogenous neurotrofic factors. The results of theoretical and experimental studies of organic lithium salts presented here indicate their potential as neuroprotectors. Chemoreactomic modeling of lithium salts made it possible to select lithium ascorbate as a suitable candidate for further research. A neurocytological study on cerebellar granular neurons in culture under conditions of moderate glutamate stress showed that lithium ascorbate was more effective in supporting neuronal survival than chloride or carbonate, i.e., inorganic lithium salts. Biodistribution studies indicated accumulation of lithium ions in a sort of “depot”, potentially consisting of the brain, aorta, and femur. Lithium ascorbate is characterized by extremely low acute and chronic toxicity (LD50 > 5000 mg/kg) and also shows a moderate antitumor effect when used in doses studied (5 or 10 mg/kg). Studies on the model of alcohol intoxication in rats have shown that intake of lithium ascorbate in doses either 5, 10 or 30 mg/kg did not only reduced brain damage due to ischemia, but also improved the preservation of myelin sheaths of neurons.     

机械化学法制备的Al/Ce复合氧化物负载NiMo催化剂的加氢脱硫活性(英文)

将Al和/或Ce的硝酸盐与NH_4HCO_3球磨混合,采用机械化学法制备了Al_2O_3-CeO_2载体(其中Ce含量为1-10 wt%),再以杂多钼酸盐(NH_4)_4NiMo_6O_(24)为活性金属Ni和Mo的前驱体,通过浸渍法制备NiMo_6/Al_2O_3-CeO_2催化剂,并将其用于1-苯并噻吩(BT)的加氢脱硫(HDS)反应中.运用化学分析、X射线衍射、N_2吸附-脱附法、H_2程序升温还原、NH_3程序升温脱附和X射线光电子能谱对催化剂的物化性质进行了表征.结果表明,催化剂的酸性随着载体中Ce含量的增加而下降.Ce修饰的Al_2O_3载体表面的NiS/MoS原子比下降了2倍.NiMo_6/Al_2O_3催化剂表现出最高的HDS活性(以单位重量催化剂计),其酸性和表面MoO_xS_y物种的浓度(Mo~(5+)浓度)也最高;当催化剂中Ce含量逐渐增加到10 wt%以上时,其活性逐渐将为0.与浸渍法制得的参比催化剂相比,前驱体和催化剂组成相同的情况下,采用机械化学法制得的所有催化剂活性明显提高.     

Soft nanosystems based on hydroxypiperidinium surfactants as adjuvants and micellar catalysts

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The self-organizing vector of atom-pairs proportions: use to develop models for melting points

Structural Chemistry - Atom-pairs proportions are the transparent quality of a molecule: if a molecule has two atoms of oxygen and three atoms of nitrogen, the atom-pair atom1-atom2 can be...     

4-Methylamino antipyrine determination in human plasma by high-performance liquid chromatography tandem mass spectrometry

In the present study, a simple and rapid method for metamizole metabolite 4-methylamino antipyrine (MAA) determination in human plasma was developed, validated and successfully applied to a clinical trial. Chromatographic separation was achieved in HILIC mode on a YMC-Pack SIL column (100 × 2.0 mm; S-5 μm, 30 nm), with a mobile phase consisting of acetonitrile, water and formic acid. Protein precipitation of a small plasma volume using acetonitrile was selected for sample preparation. The multiple reaction monitoring transitions in the positive ionization mode were m/z 218.2 → 56.2 for MAA and m/z 221.2 → 56.2 for MAA-d3 (IS, internal standard). Concentration levels of MAA calibration standards were in the range of 0.100–20 μg/ml. Metamizole conversion into MAA in both water and organic media was investigated, and the level of the conversion in commercially available injection solutions was estimated.