Nicotine N-oxides

Nicotine-1-N-oxide, trans and cis isomers of nicotine-1′-N-oxide and of nicotine-1,1′-di-N-oxide have been prepared and characterised by NMR, MS and reduction to nicotine. The trans and cis isomers of nicotine-1′-N-oxide have been identified in leaves, stems and roots of Nicotiana tabacum, N. affinis and N. sylvestris.     

Magnetic, spectroscopic, structural and biological properties of mixed-ligand complexes of copper(II) with N,N,N,N″,N″-pentamethyldiethylenetriamine and polypyridine ligands

Two new mixed ligand complexes of copper(II) with N,N,N^′,N″,N″-pentamethyldiethylenetriamine and polypyridine ligands have been prepared and characterized by means of spectroscopic, magnetic and single-crystal X-ray diffraction methods. These two complexes are isomorph and isostructure in which the coordination polyhedron about the copper(II) ion is distorted square pyramidal. [Cu(PMDT)(bipy)]²⁺ and [Cu(PMDT)(phen)]²⁺ show an absorption wavelength maximum at 625 and 678 nm, respectively, assigned to the d-d transition. Antibacterial, antifungal and superoxide dismutase activities of these complexes have also been measured. It was observed that [Cu(PMDT)(bipy)](ClO₄)₂ was more effective against P. Pyocyanea and Klebsiella sp. than S. aureus. Similarly, Fusarium sp. was highly susceptible against [Cu(PMDT)(bipy)](ClO₄)₂ but less susceptible against [Cu(PMDT)(phen)](ClO₄)₂.     

Alkylation of isolated chromatin with N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea

When isolated chromatin is incubated with the carcinogens N-methyl-N-nitrosourea (MeNU) and N-ethyl-N-nitrosourea (EtNU), DNA and chromosomal proteins become alkylated to increasingly greater extents as the carcinogen concentrations increase. With either MeNU or EtNU, the core and linker DNA of chromatin are alkylated to essentially identical extents. Alkylation of chromatin DNA as well as free DNA is drastically reduced at physiological ionic strengths (e.g. 0.15 M NaCl). The presence of 0.15 M NaCl, on the other hand, enhances alkylation of chromosomal proteins. While EtNU is much less reactive to DNA than MeNU, alkylation of chromosomal proteins relative to that of chromatin DNA has been found to be markedly greater with EtNU than with MeNU. Such a difference in their relative reactivities toward DNA and proteins may be related to the known difference of carcinogenic potency between these N-nitroso compounds.     

Facile synthesis of N-glycosyl amides using a N-glycosyl-2,4-dinitrobenzenesulfonamide and thioacids

N-Glucosyl-2,4-dinitrobenzenesulfonamide was prepared from N-acetyl-d-glucosamine and 2,4-dinitrobenzenesulfonyl chloride. Amidation of several thioacids using the N-glucosylsulfonamide donor proceeded smoothly to give the desired N-glucosylamides in good to high yields. The amidation reactions were carried out at room temperature, under mild conditions, and were completed in a very short time.     

Synthesis, spectroscopic, thermal and X-ray structure characterization of 1,3-propanediammonium tetrathiomolybdate and N,N,N′,N′-tetramethylethylenediammonium tetrathiomolybdate

The title compounds 1,3-propanediammonium tetrathiomolybdate, (1,3-pnH₂)[MoS₄], 1 and, N,N,N′,N′-tetramethylethylenediammonium tetrathiomolybdate, (tmenH₂)[MoS₄], 2, were prepared by reacting the ammonium salt of [MoS₄]²⁻ with the corresponding organic diamine. In 1 and 2 the organic diamines 1,3-propanediamine (1,3-pn) and N,N,N′,N′-tetramethylethylenediamine (tmen) are present in their diprotonated form. The reaction of 1 or 2 with [Ni(en)₃]Cl₂ · 2H₂O (en is ethylenediamine) results in the formation of the highly insoluble complex tris(ethylenediamine)Ni(II) tetrathiomolybdate, [Ni(en)₃][MoS₄], in quantitative yields. 1 and 2 have been characterized by chemical analysis, vibrational, UV-Vis and NMR spectroscopy, TG-DTA-MS and single crystal X-ray crystallography. Compound 1 is thermally more stable compared to 2. Both complexes decompose in a single step forming amorphous molybdenum sulfide. The structure of the title complexes can be described as consisting of tetrahedral [MoS₄]²⁻ dianions which accept a complex series of H-bonds from the organic dications. The strength and number of these hydrogen bonds affect the Mo-S bond lengths.     

A structural study of the hydrated and the dimethylsulfoxide, N,N′-dimethylpropyleneurea, and N,N-dimethylthioformamide solvated iron(II) and iron(III) ions in solution and solid state

The structures of the solvated iron(II) and iron(III) ions have been studied in solution and solid state by extended X-ray absorption fine structure (EXAFS) in three oxygen donor solvents, water, dimethylsulfoxide (Me₂SO), N,N′-dimethylpropyleneurea (DMPU), and one sulfur donor solvent, N,N-dimethylthioformamide (DMTF); these solvents have different coordination and solvation properties. In addition, the structure of hexakis(dimethylsulfoxide)iron(III) perchlorate has been determined crystallographically to support the determination of the corresponding solvate in solution. The hydrated, the dimethylsulfoxide and N,N-dimethylthioformamide solvated iron(II) ions show regular octahedral coordination in both solution and solid state with mean Fe-O, Fe-O, and Fe-S bond distances of 2.10, 2.10, and 2.52 Å, respectively, whereas the N,N′-dimethylpropyleneurea iron(II) solvate is five-coordinated, d(Fe-O) = 2.06 Å. The compounds vary in color from light green (hydrate) to dark orange or red (DMPU). The hydrated iron(III) ion in aqueous solution and the dimethylsulfoxide solvated iron(III) ions in solution and solid state show the expected octahedral coordination, the Fe-O bond distances are 2.00 Å for both, whereas the N,N′-dimethylpropyleneurea iron(III) solvate is found to be five-coordinated with a mean Fe-O bond distance of 1.99 Å. The N,N-dimethylthioformamide solvated iron(III) ion in the solid perchlorate salt is tetrahedrally four-coordinated, the mean Fe-S bond distance is 2.20 Å. Iron(III) is reduced with time to iron(II) in N,N-dimethylthioformamide solution. The compounds vary in color from pale yellow (hydrate) to blackish red (DMPU).     

Amdxidation and demethylation of N,N-dimethylaniline by rabbit liver and lung microsomes effects of age and metals

Lung N-oxidase enzyme activity was about three times higher than liver N-oxidase at the pH optimum, about pH 8.9, whereas the activities were nearly the same at more physiological ranges of pH. The lung N-oxidase was also stimulated about 2-fold by 100 mM Mg²⁺ and by 0.1 mM Hg²⁺, whereas liver N-oxidase activity was inhibited by these concentrations of ions. The difference in response of liver and lung enzymes to Mg²⁺ and Hg²⁺ was not altered by preparing the microsomes in the presence of 50 mM ethylenediamine tetraacetic acid (EDTA) in 0.1 M Tris (hydroxymethyl) amino methane (Tris) buffer or 50 mM EDTA in 0.1 M KPO₄ buffer, both at pH 7.6, indicating that the differences are probably not due to the presence of endogenous metals. The difference between the liver and lung N-oxidase systems may be due to the tissue environment rather than to the enzyme itself since mercury stimulation of lung N-oxidation began to disappear upon partial purification of the N-oxidase enzymes. In contrast to the effects of Hg²⁺ and Mg²⁺, 1 mM Ni²⁺ enhanced liver N-oxidase activity about 30% and 5 mM Ni²⁺ stimulated lung enzyme activity about 30% whereas concentrations above 10 mM were inhibitory to both N-oxidases. Both liver and lung demethylase activities were inhibited by these concentrations of Mg²⁺, Hg²⁺ and Ni²⁺.Various suifhydryl reagents were also tested for their effects on these enzymes. The mercurials, para-chloromercurybenzoate (pCMB) and phenylmercuryacetate (PMA) at concentrations of 0.1 mM had the same effect as HgCl₂ inhibiting both demethylases and liver N-oxidase, but stimulating lung N-oxidase activity. However, 0.1 mM to 1 mMN-ethylmaleimide (NEM) and iodoacetamide had little if any effect on either liver or lung N-oxidase. It was also shown that Hg²⁺ effects on N-oxidase activity could be overcome by dilution.Changes in N,N-dimethyl aniline (DMA) metabolism with age were followed in rabbits from 4 days old to adult. There was a steady increase in lung demethylase activity and N-oxidase activity in the liver and lung to adult levels. However, the liver demethylase had a sharp increase in activity between 2 weeks and 1 month much like that seen with benzphetamine demethylase in rabbit liver.Activities of N-demethylase in liver and lung, and N-oxidr.se in liver from new-born rabbits were from 10 to 20 % of adult levels. However, in lung, N-oxidase activities in the newborn were about 50 % of adult levels. Microsomal N-oxidation in lungs from 2-day-old rabbits was stimulated by 0.1 mM mercury just as in the adult.     

Identification of N, O-diacetyl-, N-acetyl- and N-glycolylneuraminyl-(2 → 3)-lactose in rat urine

The structure of three neuraminyl-oligosaccharides isolated from rat urine-have been studied by chromatographic and mass spectrometric analyses of different hydrolysis and methylation products. The structures of the oligosaccharides were identifies as O-α-N-acetyl(O-acetyl)neuraminyl-(2 → 3)-O-β-galactopyranosyl-(1 → 4)-glucopyranose, O-α-N-acetylneuraminyl-(2 → 3)-O-β-galactopyranosyl-(1 → 4)-glucopyranose and O-α-N-glycolylneuraminyl-(2 → 3)-O-β-galactopyranosyl-(1 → 4)-glucopyranose.     

Solvent effect on the stereoselective addition reaction of optically active amines to N-methylphenylalanine N-carboxyanhydride

The effect of solvent on stereoselectivity in the nucleophilic addition reaction of various optically active amines to N-methylphenylalanine N-carboxyanhydride has been investigated. In m-dimethoxybenzene as solvent, (S)-valine, (S)-leucine, and (S)-phenylalanine ethyl esters reacted preferentially with (R)-N-methylphenylalanine N-carboxyanhydride, but the stereoselectivity decreased considerably in nitrobenzene and dimethylacetamide as solvents. In the latter solvents, the dipolar interactions between an amine and an N-carboxyanhydride and the orientation of the substituent of N-carboxyanhydride were seriously affected, hence the stereoselectivity decreased. As a consequence, the enantiomer selection by the terminal amine of a growing chain in the nucleophilic addition-type polymerization of α-amino acid N-carboxyanhydride can be controlled by the choice of solvent. (S)-Proline ethyl ester and (S)-α-phenylethylamine reacted preferentially with (S)-N-methylphenylalanine N-carboxyanhydride in m-dimethoxybenzene, and this type of selectivity did not change in nitrobenzene. But in dimethylacetamide the stereoselectivity decreased. In the transition state of the reaction of these amines and N-methylphenylalanine N-carboxyanhydride dipolar interactions are operating, which should be destroyed by dimethylacetamide but may not be affected by nitrobenzene.     

N-acetylneuraminic acid and sialoglycoconjugate metabolism in fibroblasts from a patient with generalized N-acetylneuraminic acid storage disease

Cultured skin fibroblasts from a patient suffering from generalized N-acetylneuraminic acid storage disease were found to accumulate large amounts (approx. 4.0 μmol/g fresh weight) of free N-acetylneuraminic acid in a lysosome-enriched subcellular fraction. However, there were no detectable deficiencies in lysosomal hydrolase activities (including neuraminidase), and the activities of CMP-N-acetylneuraminic acid synthetase and N-acetylneuraminic acid aldolase were within normal limits. The cellular glycoconjugate composition was normal, and pathologic fibroblasts labeled with either [³H]glucosamine-HCl or $\text{N-[}{}^3\text{H]acetylmannosamine}$ showed a marked accumulation of labeled free N-acetylneuraminic acid, along with elevated incorporation into sialoglycoconjugates. Neither normal nor pathologic fibroblasts secreted labeled free N-acetylneuraminic acid into the culture medium. These results are consistent with an inherited defect in N-acetylneuraminic acid reutilization, resulting in the lysosomal accumulation of the free monosaccharide in generalized N-acetylneuraminic acid storage disease.     

The N-permethylation of chitosan and the preparation of N-trimethyl chitosan iodide

Chitosan was N-permethylated by reaction with formaldehyde and sodium borohydride under controlled conditions (pH 4·0, 15°C, reaction times 12 and 8 h, respectively). The N-permethylated chitosan was reacted with methyl iodide at 35°C and N-trimethyl chitosan iodide with a quaternary nitrogen degree of 60% was obtained. This material may have uses as an antibiotic and an ion exchange material.     

Characterization of heparan sulfate N-deacetylase/N-sulfotransferase isoform 4 using synthetic oligosaccharide substrates

Background

The final structure of heparan sulfate chains is strictly regulated in vivo, though the biosynthesis is not guided by a template process. N-deacetylase/N-sulfotransferase (NDST) is the first modification enzyme in the HS biosynthetic pathway. The N-sulfo groups introduced by NDST are reportedly involved in determination of the susceptibility to subsequent processes catalyzed by C₅-epimerse and 3-O-sulfotransferases. Understanding the substrate specificities of the four human NDST isoforms has become central to uncovering the regulatory mechanism of HS biosynthesis.

N,N-Dialkylcarbamato derivatives of niobium and tantalum as precursors to metal-functionalized silica surfaces

Chemical implantation of Group 5 cations [Nb(III), Nb(V), and Ta(V)] has been carried out under mild conditions by the reaction of N,N-dialkylcarbamato derivatives M(O₂CNR₂)_n (M = Nb, Ta) with silanol groups of amorphous silica, carbon dioxide, and secondary amine being released in the process. The amount of supported cations depends on the metal and on the initial number of N,N-dialkylcarbamato ligands on M; partial reduction to the +4 oxidation state occurs in the case of Nb(O₂CNR₂)₅.     

Synthesis and characterization of gallium complexes bearing N-arylmethylenethiobenzahydrazone ligands; crystal structure of diethyl[N-(4-N,N-dimethylamino)benzylidene thiobenzahydrazonato]gallium

Five diethylgallium complexes of type Et₂GaL [(L = N-(4-methoxy) benzylidenethiobenzahydrazonato (1), N-(3,4-dimethoxy)benzylidenethio benzahydrazonato (2), N-(4-N,N-dimethylamino)benzylidenethiobenza hydrazonato (3), N-(2-naphthyl)methylenethiobenzahydrazonato (4), N-(9-anthryl)methylenethiobenzahydrazonato (5)] have been synthesized by the reaction of triethylgallium with appropriate N-arylmethylene thiobenzahydrazones. The compounds obtained have been characterized by elemental analysis, ¹H NMR, IR and mass spectroscopies, respectively. The solid structure of 3 has been determined by X-ray single crystal analysis, in which Ga atom is four coordinate. The photoluminescent property of complex 1 was studied. The maximum emission wavelength is 475 nm upon radiation by UV light.     

Rotundifoline N-oxides

The N-oxides of rotundifoline are prepared for comparison with a new alkaloid from Mitragyna rubrostipulata.     

Hyoscyamine N-oxide in Atropa belladonna

Separated organs of Atropa belladonna have been examined for their total alkaloid, hyoscyamine and hyoscyamine N-oxide contents during ontogenesis. Marked fluctuations in N-oxide content were observed, the highest being found in the ripe fruit. [G-³H]-atropine was fed to A. belladonna fruits and radioactively labelled hyoscyamine N-oxide isolated.     

N-oxides of hyoscyamine and hyoscine in the solanaceae

The N-oxides of (−)-hyoscyamine and (−)-hyoscine have been prepared and characterized. Two N-oxides of hyoscyamine have been isolated from species of Atropa,Datura,Hyoscyamus,Scopolia andMandragora,andoneN-oxideofhyoscinehasbeenisolatedfromspeciesofthefirstfourgenera.     

An N-acylamino acid acylase from Nicotiana tabacum leaves

An N-acylamino acid acylase was partially purified from tobacco (Nicotiana tabacum) leaves and some of its properties are described. It hydrolyses N-acetylarginine, N-acetylmethionine, N-acetylcysteine and to a lesser extent N-formylmethionine. It does not appreciably hydrolyse N-formyl peptides and is therefore unlikely to be involved in protein synthesis.     

Phosphatidylserine-stimulated production of N-acyl-phosphatidylethanolamines by Ca2+-dependent N-acyltransferase

N-acyl-phosphatidylethanolamine (NAPE) is known to be a precursor for various bioactive N-acylethanolamines including the endocannabinoid anandamide. NAPE is produced in mammals through the transfer of an acyl chain from certain glycerophospholipids to phosphatidylethanolamine (PE) by Ca²⁺-dependent or -independent N-acyltransferases. The ε isoform of mouse cytosolic phospholipase A₂ (cPLA₂ε) was recently identified as a Ca²⁺-dependent N-acyltransferase (Ca-NAT). In the present study, we first showed that two isoforms of human cPLA₂ε function as Ca-NAT. We next purified both mouse recombinant cPLA₂ε and its two human orthologues to examine their catalytic properties. The enzyme absolutely required Ca²⁺ for its activity and the activity was enhanced by phosphatidylserine (PS). PS enhanced the activity 25-fold in the presence of 1?mM CaCl₂ and lowered the EC₅₀ value of Ca²⁺ >8-fold. Using a PS probe, we showed that cPLA₂ε largely co-localizes with PS in plasma membrane and organelles involved in the endocytic pathway, further supporting the interaction of cPLA₂ε with PS in living cells. Finally, we found that the Ca²⁺-ionophore ionomycin increased [¹⁴C]NAPE levels >10-fold in [¹⁴C]ethanolamine-labeled cPLA₂ε-expressing cells while phospholipase A/acyltransferase-1, acting as a Ca²⁺-independent N-acyltransferase, was insensitive to ionomycin for full activity. In conclusion, PS potently stimulated the Ca²⁺-dependent activity and human cPLA₂ε isoforms also functioned as Ca-NAT.