Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IMINES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2004

Imine hydrolysis and role of a rhodium(I)-imine-amine complex in homogeneous H2-hydrogenation of the imine and a rare example of inequivalent NH2 protons.

A Rh-catalyzed, homogeneous hydrogenation of the imine, PhCH(2)N=CHPh, is shown to involve a Rh-imine-amine species that subsequently activates H(2), the amine (benzylamine) being formed via a Rh-catalyzed hydrolysis of the imine by adventitious water. The imine-amine complex, cis-(Rh[P(p-tolyl)(3)](2)(PhCH(2)N=CHPh)(NH(2)CH(2)Ph))PF(6) (2b), is structurally characterized, and the solution (1)H NMR data reveal inequivalent NH(2) protons.

Journal Article↗
PubMedDate not supplied

Copolymers of ethylene imine and N-(2-hydroxyethyl)-ethylene imine as tools to study effects of polymer structure on physicochemical and biological properties of DNA complexes.

A series of five poly[(ethylene imine)-co-N-(2-hydroxyethyl-ethylene imine)] copolymers with similar molecular weights and different degrees of branching was established to study structure-function relationship with regard to physicochemical and biological properties as gene delivery systems. Copolymers were synthesized by acid-catalyzed ring-opening copolymerization of aziridine and N-(2-hydroxyethyl)-aziridine in aqueous solution and characterized by GPC-MALLS, (1)H- and (13)C NMR, IR, potentiometric titration, and ion exchange chromatography. Complexation of DNA was determined by agarose gel electrophoresis, and complex sizes were quantitated by PCS. Cytotoxicity of the copolymers in fibroblasts was assessed by MTT-assay, LDH-assay, and hemolysis. The transfection efficiency was determined using the reporter plasmid pGL3 in 3T3 mouse fibroblasts. The copolymers obtained by solution polymerization had relatively low molecular weights of about 2000 Da, and the degree of branching increased with increasing ethylene imine ratio. The pK(a) as well as the buffer capacity increased proportional to the number of primary and secondary amines. Higher branched polymers showed stronger complexation and condensation of DNA, formed smaller polymer/DNA complexes, and induced the expression of plasmids to a higher extent than less branched polymers. In vitro cytotoxic effects and the hemolysis of erythrocytes decreased with decreased branching. Our results indicate that the basicity and degree of protonation of the polymers depending on their amount of primary and secondary amines seem to be important factors both for their transfection efficiency and for their cytotoxicity in gene transfer.

3T3 Cells↗
PubMed2003

Design and synthesis of orally bioavailable inhibitors of inducible nitric oxide synthase. synthesis and biological evaluation of dihydropyridin-2(1H)-imines and 1,5,6,7-tetrahydro-2H-azepin-2-imines.

The process of discovery and biological evaluation of alpha,beta-unsaturated cyclic amidines, as selective inhibitors of inducible nitric oxide synthase (iNOS), is reported. Dihydropyridin-2(1H)-imines and 1,5,6,7-tetrahydro-2H-azepin-2-imines were synthesized and biologically evaluated both in vitro and in vivo using a nitric oxide synthase inhibition assay. Compounds 1, 5, 6, 8-12 and 16 exhibited potent inhibition of iNOS. Among these, compounds 6, 7, 10, 11 and 16 showed 5- to 19-fold isoform selectivity. Compounds 1, 6, 10, 11 and 16 also showed potent inhibitory activity in the NOx accumulation assay in mice. Compounds 1 and 6 showed excellent bioavailability (BA) in rats when administered orally. Full details are presented here, including the structure-activity relationship (SAR) studies, the chemistry of these compounds, and the pharmacokinetic data and the computer-aided docking study of 10 with hiNOS.

Animals↗
PubMed2001

Reduction of (imine)Pt(IV) to (imine)Pt(II) complexes with carbonyl-stabilized phosphorus ylides.

A novel method is reported for generation of the difficult-to-obtain (imine)Pt(II) compounds that involves reduction of the corresponding readily available Pt(IV)-based imines by carbonyl-stabilized phosphorus ylides, Ph3P=CHCO2R, in nonaqueous media. The reaction between neutral (imino)Pt(IV) compounds [PtCl4[NH=C(Me)ON=CR1R2]2] [R1R2 = Me2, (CH2)4, (CH2)5, (Me)C(Me)=NOH], [PtCl4[NH=C(Me)ONR2]2] (R = Me, Et, CH2Ph), (R1 = H; R2 = Ph or C6H4Me; R3 = Me) as well as anionic-type platinum(IV) complexes (Ph3PCH2Ph)[PtCl5[NH=C(Me)ON=CR2]] [R2 = Me2, (CH2)4, (CH2)5] and 1 equiv of Ph3P=CHCO2R (R = Me, Et) proceeds under mild conditions (ca. 4 h, room temperature) to give selectively the platinum(II) products (in good to excellent isolated yields) without further reduction of the platinum center. All thus prepared compounds (excluding previously described Delta4-1,2,4-oxadiazoline complexes) were characterized by elemental analyses, FAB mass spectrometry, IR and 1H, 13C[1H], 31P[1H] and 195Pt NMR spectroscopies, and X-ray single-crystal diffractometry, the latter for [PtCl2[NH=C(Me)ON=CMe2]2] [crystal system tetragonal, space group P4(2)/n (No. 86), a = b = 10.5050(10) A, c = 15.916(3) A] and (Ph3PCH2CO2Me)[PtCl3(NCMe)] [crystal system orthorhombic, space group Pna2(1) (No. 33), a = 19.661(7) A, b = 12.486(4) A, c = 10.149(3) A]. The reaction is also extended to a variety of other Pt(II)/Pt(IV) couples, and the ylides Ph3P=CHCO2R are introduced as mild and selective reducing agents of wide applicability for the conversion of Pt(IV) to Pt(II) species in nonaqueous media, a route that is especially useful in the case of compounds that cannot be prepared directly from Pt(II) precursors, and for the generation of systematic series of Pt(II)/Pt(IV) complexes for biological studies.

Journal Article↗
PubMed2000

Keto<==>enol, imine<==>enamine, and nitro<==>aci-nitro tautomerism and their interrelationship in substituted nitroethylenes. Keto, imine, nitro, and vinyl substituent effects and the importance of H-bonding

Tautomeric isomers and conformers of 2-nitrovinyl alcohol (1), 2-nitrovinylamine (2), and 1-nitro-propene (3) are reported at the MP2 and B3LYP levels of theory, using the 6-31G* basis set, with energy evaluation at B3LYP/6-311+G** and G2MP2. The nitroalkenes are the global minima on their respective potential energy surfaces. The barriers for the concerted 1,5-H transfer to the corresponding nitronic acids amount to only 5.0 kcal/mol for 1, 13.2 kcal/mol for 2, and a sizable 37.8 kcal/mol for 3. Whereas the aci-nitro tautomer of 2-nitrovinyl alcohol is easily accessible, beta-iminonitronic acid has little kinetic stability. H-bonding is a strong stabilizing factor in these nitroalkenes, estimated at 7.0 and 3.7 kcal/mol for the OH and NH2 derivatives, respectively, while its stabilization in their nitronic acids amounts to as much as 13 kcal/mol. The H-bonds are evident from the very short O...H and N...H distances and are characterized by bond critical points. The NO2 substituent effect of about 11.4 kcal/mol at G2MP2 on both the classical keto <==> enol and imine <==> enamine tautomeric processes stabilizes the nitroethylene derivatives. The keto, imine, and vinyl substituent effects at G2MP2 on the nitro <==> aci-nitro tautomeric process are also determined as are their pi-resonance components. The substituents have a large influence on the ionization energies of the nitroethylene derivatives.

Journal Article↗
PubMed1984

Enzymatic and non-enzymatic reduction of N-acetyl-p-benzoquinone imine and some properties of the N-acetyl-p-benzosemiquinone imine radical.

N-Acetyl-p-benzoquinone imine (NAPQI) is the postulated hepatotoxic intermediate in acetaminophen overdosage. NAPQI was rapidly metabolized by NADPH-cytochrome P-450 reductase, with an apparent Km of 1.8 to 4.0 microM and an apparent Vmax of 29.4 mumoles per min per mg, and exhibited substrate inhibition of metabolism at NAPQI concentrations above 10 microM. NADPH was oxidized by NAPQI at a slower rate in the absence of enzyme. NAPQI did not appear to undergo redox cycling at an appreciable rate to form superoxide, and it did not stimulate oxygen utilization or superoxide release by rat isolated hepatocytes. Electron spin resonance studies failed to show formation of a free radical by chemical or enzymatic reduction of NAPQI under anaerobic conditions in aqueous media.

Animals↗
PubMed2000

Comparative study of the diastereoselective addition of allenyl zinc reagents to alpha-alkoxy (or silyloxy) aldehydes and imines. A straightforward synthesis of amino alcohols from imines

The addition of allenylzinc bromides to alpha-chiral imines proceeds with very high diastereoselectivity. This result is in contrast with the addition to the corresponding aldehydes, leading to poor diastereoselectivity. The anti/anti adducts are explained by Felkin-Ahn and Gaudemar-Yamamoto models of the transition state.

Journal Article↗
PubMed2003

Asymmetric synthesis of allyl- and alpha-allenylamines from chiral imines and alkynes via (eta(2)-imine)Ti(O-i-Pr)2 complexes.

[reaction: see text] The reaction of a divalent titanium reagent Ti(O-i-Pr)(4)/2i-PrMgX with optically active arylaldimines derived from arylaldehydes and O-methylphenylglycinol provided, in a highly diastereoselective manner, chiral (eta(2)-imine)Ti(O-i-Pr)(2) complexes, which in turn reacted with 1-alkynes or propargyl compounds to give optically active allyl- and alpha-allenylamines, respectively.

Journal Article↗
PubMed2002

Direct observation of eta 2-imine formation through beta-H abstraction between amide ligands. Neutron and X-ray diffraction structure of a dihydride imine ditantalum complex.

Reactions of Ta(NMe2)5 with D2SiR'Ph (R' = Me, Ph) were found to give a dideuteride eta 2-imine complex (Me2N)3Ta(mu-D)2(mu-N-eta 2-N,C-CH2NMe)Ta(NMe2)3(1-d2) through C-H activation of an amide ligand via beta-H abstraction, and the structure of 1 was confirmed by single crystal neutron and X-ray diffraction.

Journal Article↗
PubMed2003

Catalytic asymmetric Mannich reactions of glycine derivatives with imines. A new approach to optically active alpha,beta-diamino acid derivatives.

Imines of glycine alkyl esters react with imines in a diastereo- and highly enantioselective Mannich reaction in the presence of chiral copper(I) complexes as the catalyst to give optically active alpha,beta-diamino acid derivatives. A series of imines of glycine esters derived from glycine and aromatic carbonyl compounds has been screened as substrates for the Mannich reaction with different imines in the presence of various combinations of metal salts and chiral ligands. The benzophenone imine of glycine esters was found to react with N-protected imines in a diastereoselective fashion giving functionalized alpha,beta-diamino acid esters with excellent enantioselectivities. The most effective chiral catalysts are chiral copper(I) complexes having phosphino-oxazoline (P,N)-ligands, and among these ligands, those derived from (1R,2S)-dihydroxy-1,2,3,4-tetrahydronaphthalene gave the best results. The scope of this new catalytic asymmetric reaction of the benzophenone imine glycine esters is demonstrated for the reaction with different N-protected-C-aryl and C-alkyl imines giving the Mannich adducts with excellent optical purity. Furthermore, the synthetic aspects of the reaction are presented by converting the Mannich adducts into alpha,beta-diamino acid derivatives. The relative and absolute configuration of the Mannich adduct have been determined and based on the stereochemical outcome of the reaction a tetrahedral chiral-copper(I)-imino glycine alkyl ester intermediate is proposed. In this intermediate the Re-face of the benzophenone imine glycine ester is shielded by the chiral ligand leaving the Si-face available for approach of the Si-face of the imine. A series of semiempirical calculations has been performed to support the structure of the tetrahedral chiral-copper(I) complex and to account for the influence of the substituents in the chiral phosphino-oxazoline ligands.

Amino Acids↗
PubMed1988

Comparative cytotoxic effects of N-acetyl-p-benzoquinone imine and two dimethylated analogues.

N-acetyl-p-benzoquinone imine (NAPQI), a reactive metabolite of acetaminophen, has previously been shown to be toxic to hepatocytes freshly isolated from rat liver [Mol. Pharmacol. 28:306-311 (1985)] NAPQI arylates and oxidizes cellular thiols, and either one or both reactions may be important in the pathogenesis of cytotoxicity. Two dimethylated analogues of NAPQI, N-acetyl-3,5-dimethyl-p-benzoquinone imine (3,5-diMeNAPQI) and N-acetyl-2,6-dimethyl-p-benzoquinone imine (2,6-diMeNAPQI), were prepared to determine whether one reaction might be more damaging to cells than the other. Of the three quinone imines, the least potent cytotoxin to rat hepatocytes was 3,5-diMeNAPQI. However, the cytotoxicity of 3,5-diMeNAPQI was markedly enhanced by pretreatment of cells with 1,3-bis-(2-chloroethyl)-N-nitrosourea, which inhibits glutathione reductase. Reactions of 3,5-diMeNAPQI with GSH, both chemically and in hepatocytes, indicated that this quinone imine primarily oxidized thiols. These findings were corroborated by results of covalent binding experiments, which showed that radiolabeled 3,5-diMeNAPQI bound only to a small extent to hepatocyte proteins. On the other hand, 2,6-diMeNAPQI, the most potent cytotoxin of the three quinone imines that was investigated bound extensively to hepatocyte proteins. In addition, 2,6-diMeNAPQI reacted with GSH, both chemically and in hepatocytes, to form significant amounts of GSSG. Reduction products of NAPQI and its dimethylated analogues were not important contributors to cytotoxicity or GSSG formation based on the following results: 1) the quinone imines did not increase oxygen consumption by hepatocytes nor did they lead to oxygen uptake in solution; 2) dicoumarol, an inhibitor of the reductase, DT-diaphorase, had no effect on cytotoxicity caused by the quinone imines. Evidence for the involvement of ipso-adducts of the quinone imines in their reactions with cellular thiols is provided by results of investigations on the effects of DTT on the metabolism, covalent protein binding, and cytotoxic effects of the quinone imines.

Acetaminophen↗
PubMed1984

Reduction and glutathione conjugation reactions of N-acetyl-p-benzoquinone imine and two dimethylated analogues.

N-Acetyl-3,5-dimethyl-p-benzoquinone imine, N-acetyl-2,6-dimethyl-p-benzoquinone imine, and N-acetyl-p-benzoquinone imine were synthesized via the oxidation of 3,5-dimethylacetaminophen, 2,6-dimethylacetaminophen, and acetaminophen, respectively. All three quinone imines were rapidly reduced to their corresponding semiquinone imines by NADPH-cytochrome P-450 reductase. All three benzoquinone imines underwent comproportionation with their respective phenols to yield the corresponding semiquinone imines, which in the presence of oxygen gave superoxide. Identification of this latter free radical was based on spin-trapping techniques. Reduced GSH was found to be an excellent nucleophile toward N-acetyl-2,6-dimethyl-p-benzoquinone imine, whereas this thiol behaved as a one-electron reductant toward N-acetyl-3,5-dimethyl-p-benzoquinone imine. Finally, GSH was determined to act as both a nucleophile and a reductant toward N-acetyl-p-benzoquinone imine.

Animals↗
PubMed2003

m-Phenylene ethynylene sequences joined by imine linkages: dynamic covalent oligomers.

Imine metathesis between m-phenylene ethynylene oligomers of various lengths was performed in acetonitrile, a solvent in which oligomers containing eight or more repeat units adopt a compact helical conformation. The equilibrium constants and corresponding free energy change for the imine metathesis reactions were estimated. The results showed that the magnitude of equilibrium shifting measured by the free energy change for the formation of imine-containing oligomers increases linearly below a critical product chain length and grows asymptotically above it. The linear region is ascribed to the constant increase in contact area between monomer units of adjacent helical turns as the product chain grows to the 12-mer. Once the ligation product is 12 units in length, full contact is made between adjacent helical turns. On the other hand, for imine metathesis between oligomers leading to products having more than 12 units, the driving force is the difference between the folding energy of products and that of reactants. The additional stabilizing energy is roughly constant, regardless of the chain length, since the contact area between adjacent helical turns is unchanged. Consistent with the notion that the imine bond only minimally destabilizes the helical conformation, the position of the imine bond in the ligation product has been observed to have no significant effect on the folding stability. The magnitudes of equilibrium shifting are similar for ligation products of the same length but having the imine at various positions along the sequence. This suggests that the imine bond is compatible with the m-phenylene ethynylene backbone, regardless of the position in the sequence. Imine metathesis of m-phenylene ethynylene oligomers could allow a quick access to an unbiased, dynamic library of oligomer sequences joined by imine linkages.

Journal Article↗
PubMed1992

N-acetyl-p-benzoquinone imine-induced protein thiol modification in isolated rat hepatocytes.

Incubation of isolated rat hepatocytes with N-acetyl-p-benzoquinone imine (NAPQI) or 3,5-dimethyl-N-acetyl-p-benzoquinone imine (3,5-Me2-NAPQI) resulted in a concentration-dependent decrease in the protein thiol content of the mitochondrial, cytosolic and microsomal fractions. On a concentration basis, 3,5-Me2-NAPQI induced a more marked depletion of protein thiols than did NAPQI. Sodium dodecyl sulphate-polyacrylamide gel electrophoretic separation of the proteins of each fraction showed that different proteins had different susceptibilities to modification of their cysteine residues by the quinone imines. A few protein bands showed a decreased protein thiol content following incubation with non-toxic concentrations of quinone imines, whereas other proteins were affected by higher concentrations. Concentrations of quinone imines that were highly cytotoxic induced a general loss of protein thiols. NAPQI-induced protein thiol depletion occurred within 5 min and remained essentially unchanged for at least 30 min. In contrast, protein thiol depletion induced by 3,5-Me2-NAPQI increased over the 30-min time course of the experiment. Toxic concentrations of 3,5-Me2-NAPQI caused the formation of high molecular mass aggregates in all three subcellular fractions after 30 min of incubation. The observed crosslinking was not due to protein disulfide formation. However, no aggregate formation was observed after exposure of hepatocytes to NAPQI. One of the major target proteins of quinone imine-induced protein thiol depletion was a 17 kDa microsomal protein that was identified as the microsomal glutathione S-transferase. Exposure of hepatocytes and isolated liver microsomes to the quinone imines resulted in an up to four-fold increase in the specific activity of the microsomal glutathione S-transferase. In conclusion, our results are consistent with the suggestion of a critical role of protein thiol depletion in quinone imine-induced cytotoxicity.

Animals↗
PubMed1990

Quinone imine-induced Ca2+ release from isolated rat liver mitochondria.

Incubation of Ca2(+)-loaded rat liver mitochondria with N-acetyl-p-benzoquinone imine (NAPQI) or its two dimethylated analogues resulted in a concentration dependent Ca2+ release, with the following order of potency: 2,6-(Me)2-NAPQI greater than NAPQI greater than 3,5-(Me)2-NAPQI. The quinone imine-induced Ca2+ release was associated with NAD(P)H oxidation and was prevented when NAD(P)+ reduction was stimulated by the addition of 3-hydroxybutyrate. Mitochondrial glutathione was completely depleted within 0.5 min by all three quinone imines, even at low concentrations that did not result in Ca2+ release. Depletion of mitochondrial GSH by pretreatment with 1-chloro-2,4-dinitrobenzene enhanced quinone imine-induced NAD(P)H oxidation and Ca2+ release. However, 3-hydroxybutyrate protected from quinone imine-induced Ca2+ release in GSH-depleted mitochondria. Mitochondrial membrane potential was lost after the addition of quinone imines at concentrations that caused rapid Ca2+ release; however, subsequent addition of EGTA led to the complete recovery of the transmembrane potential. In the absence of Ca2+, the quinone imines caused only a small and transient loss of the transmembrane potential. Taken together, our results suggests that the quinone imine-induced Ca2+ release from mitochondria is a consequence of NAD(P)H oxidation rather than GSH depletion, GSSG formation, or mitochondrial inner membrane damage.

Animals↗
PubMed1986

Reactions of N-acetyl-p-benzoquinone imine with reduced glutathione, acetaminophen, and NADPH.

Synthetic N-acetyl-p-benzoquinone imine reacted with reduced glutathione (GSH), [14C]acetaminophen, and NADPH. It reacted rapidly with GSH to yield acetaminophen (33%) and 3-(glutathion-S-yl)acetaminophen (67%), and with acetaminophen or NADPH to yield acetaminophen polymers. The data suggested that N-acetyl-p-benzoquinone imine was reduced by GSH to form acetaminophen but primarily reacted with GSH to form 3-(glutathion-S-yl)acetaminophen. The evidence further suggested that N-acetyl-p-benzoquinone imine comproportionated with [14C]acetaminophen to yield a mixture of radioactive and nonradioactive N-acetyl-p-benzosemiquinone imine which subsequently formed acetaminophen polymers by a radical coupling reaction. [14C]Acetaminophen was incorporated into the acetaminophen polymers. The amount of 14C incorporation was dependent on the initial concentration of [14C]acetaminophen and N-acetyl-p-benzoquinone imine. An increase in the ratio of [14C]acetaminophen to N-acetyl-p-benzoquinone imine resulted in an increase in [14C] acetaminophen incorporation into the acetaminophen polymers. NADPH reduced N-acetyl-p-benzoquinone imine to acetaminophen and acetaminophen polymers were formed. When [14C]N-acetyl-p-benzoquinone imine was incubated without acetaminophen, only minor amounts of acetaminophen polymerization were observed.

Acetaminophen↗