Enantioselective Henry (nitroaldol) reaction catalyzed by axially chiral guanidines

The enantioselective activation of nitroalkanes was attempted on the basis of the complexation between chiral guanidinium and nitronate through two hydrogen bonds. The proposed enantioselective activation was applied to the diastereo- and enantioselective Henry (nitroaldol) reaction of nitroalkanes with aldehydes using axially chiral guanidine bases as the catalyst. Optically active nitroaldol products were obtained in acceptable yields with fairly good enantio- and diastereoselectivities at low temperature.     

1,3-Bis[N-sulfonyl-(1R,2S)-1,3-diphenyl-2-aminopropanol]benzene: an excellent ligand for titanium-catalyzed asymmetric AlPh3(THF) additions to aldehydes

Asymmetric AlPh(3) (THF) additions to a wide variety of aldehydes catalyzed by a titanium catalyst of 20 mol % 1,3-bis[N-sulfonyl-(1R,2S)-1,3-diphenyl-2-aminopropanol]benzene (1) are reported. The catalytic system works excellently for aromatic aldehydes bearing either an electron-donating or an electron-withdrawing substituent on the aromatic ring to afford secondary diaryl alcohols in excellent isolated yields of >or=95% and excellent enantioselectivities of >or=94% ee. The phenyl addition to cinnamaldehyde or 2-furylaldehyde gave corresponding secondary alcohols in 85% and 95% ee, respectively. For aliphatic aldehydes, increasing enantioselectivities of the addition products in terms of increasing steric sizes of aldehydes are observed, and this trend goes from the linear 1-pentanal (87% ee), the secondary cyclohexylaldehyde (95% ee) or the 2-methylpropanal (97% ee), to the tertiary 2,2-dimethylpropanal (99% ee).     

Microsomal metabolism of hydroxyl radical scavenging agents: Relationship to the microsomal oxidation of alcohols

Previous studies provided indirect evidence that hydroxyl radicals are involved in the oxidation of primary aliphatic alcohols by rat liver microsomes. In the current study, three ·OH scavengers were used as chemical probes to evaluate ·OH production by microsomes. The scavengers and their products were 3-thiomethylpropanal (methional) and 2-keto-4-thiomethylbutyric acid, which yield ethylene gas, and dimethylsulfoxide, which yields methane gas. We observed that microsomes actively generate the appropriate hydrocarbon gas from each scavenger when electron transport is initiated with NADPH. Hydrocarbon gas production is augmented by 0.5 mm azide, an agent which inhibits catalase and, thereby, permits H₂O₂ to accumulate. However, no metabolism of scavengers occurs when H₂O₂ is added in the absence of microsomes. These results are consistent with a presumed role for H₂O₂ as a precursor of hydroxyl radicals. In addition, no metabolism of scavengers occurs when azide and H₂O₂ are added either to boiled microsomes or to intact microsomes in the absence of electron transport (NADPH-generating system omitted). Therefore, both H₂O₂ and simultaneous electron transport are required. Ethanol inhibits the metabolism of the scavengers. Similarly, the scavengers inhibit the oxidation of ethanol to acetaldehyde; inhibition in the presence of azide is competitive. These latter results indicate a competition between the scavengers and ethanol for metabolically generated ·OH in microsomes. The specificity of this interaction is evident from the observation that the scavengers do not affect the activities of microsomal aminopyrine demethylase or aniline hydroxylase. Two model ·OH-generating systems (Fenton's reagent and iron-EDTA-ascorbate) were also studied and they produced acetaldehyde from ethanol and hydrocarbon gases from the scavengers. These results, as a whole, tend to verify a role for ·OH in the microsomal oxidation of alcohols.     

Effects of B group vitamins on reactions of various alpha-hydroxyl-containing organic radicals

Effects of vitamins B1, B2, B6, and pyridoxal phosphate (PPh) on final product formation in radiolysis of aqueous solutions of ethanol, ethylene glycol, alpha-methylglycoside, and maltose were studied. It has been found that vitamin B2 and PPh effectively oxidize R*CHOH species, while suppressing their recombination and fragmentation reactions, thereby increasing the yields of the respective oxidation products. Vitamins B1 and B2 are capable of reducing alcohol radicals to the respective initial molecules, decreasing the yields of the radical transformation products.     

Breaking the light and heavy chain linkage of human immunoglobulin G1 (IgG1) by radical reactions

We report that the production of hydrogen peroxide by radical chain reductions of molecular oxygen into water in buffers leads to hinge degradation of a human IgG1 under thermal incubation conditions. The production of the hydrogen peroxide can be accelerated by superoxide dismutase or redox active metal ions or inhibited by free radical scavengers. The hydrogen peroxide production rate correlates well with the hinge cleavage. In addition to radical reaction mechanisms described previously, new degradation pathways and products were observed. These products were determined to be generated via radical reactions initiated by electron transfer and addition to the interchain disulfide bond between Cys(215) of the light chain and Cys(225) of the heavy chain. Decomposition of the resulting disulfide bond radical anion breaks the C-S bond at the side chain of Cys, converting it into dehydroalanine and generating a sulfur radical adduct at its counterpart. The hydrolysis of the unsaturated dehydropeptides removes Cys and yields an amide at the C terminus of the new fragment. Meanwhile, the competition between the carbonyl (-C(α)ONH-) and the side chain of Cys allows an electron transfer to the α carbon, forming a new intermediate radical species (-(·)C(α)(O(-))NH-) at Cys(225). Dissociative deamidation occurs along the N-C(α) bond, resulting in backbone cleavage. Given that hydrogen peroxide is a commonly observed product of thermal stress and plays a role in mediating the unique degradation of an IgG1, strategies for improving stability of human antibody therapeutics are discussed.     

Damage to the DNA bases in mammalian chromatin by hydrogen peroxide in the presence of ferric and cupric ions.

Modification of DNA bases in mammalian chromatin upon treatment with hydrogen peroxide in the presence of ferric and cupric ions was studied. Ten DNA base products in mammalian chromatin were identified and quantitated by the use of gas chromatography-mass spectrometry with selected-ion monitoring after hydrolysis of chromatin and trimethylsilylation of hydrolysates. This technique permitted the analysis of modified DNA bases in chromatin without the necessity of isolation of DNA from chromatin first. Modified bases identified were typical hydroxyl radical-induced products of DNA, indicating the involvement of hydroxyl radical in their formation. This was also confirmed by inhibition of product formation by typical scavengers of hydroxyl radical. The inhibition of product formation was much more prominent in the presence of chelated ions than unchelated ions, indicating a possible site-specific formation of hydroxyl radical when metal ions are bound to chromatin. Hydrogen peroxide in the presence of cupric ions caused more DNA damage than in the presence of ferric ions. Chelation of cupric ions caused a marked inhibition in product formation. By contrast, DNA was damaged more extensively in the presence of chelated ferric ions than in the presence of unchelated ferric ions. The presence of ascorbic acid generally increased the yields of the products, indicating increased production of hydroxyl radical by reduction of metal ions by ascorbic acid. Superoxide dismutase afforded partial inhibition of product formation only in the case of chelated iron ions. The yields of the modified bases in chromatin were lower than those observed with calf thymus DNA under the same conditions.     

Bilirubin chemiluminescence induced by the attack of active oxygen species

Ultraweak chemiluminescence (CL) from bilirubin occurs in the presence of triplet oxygen and is stimulated by the addition of aldehydes. Active oxygen species also enhance bilirubin CL, in the absence of aldehydes. An inhibitory effect of active oxygen scavengers on the CL indicated that active oxygens generated from the decomposition of added hydrogen peroxide or from the xanthine-xanthine oxidase reaction contributed to the CL from bilirubin molecules. However, the contribution of singlet oxygen to the CL disappeared in the presence of formaldehyde. This suggested that the scission of tetrapyrrole bonds via a dioxetane intermediate or the production of triplet carbonyls from the oxidation of aldehydes by singlet oxygen was not involved in the CL, at least in the presence of formaldehyde. The spectrum of CL induced by the generation of active oxygen was the same as that from the aldehyde-enhanced CL reaction. We propose that the formation of a hydroperoxide (and/or hydroxide) bilirubin intermediate, but not a dioxetane, may be involved in the excitation of bilirubin molecules for CL.     

Facile solid-phase synthesis of C-terminal peptide aldehydes and hydroxamates from a common Backbone Amide-Linked (BAL) intermediate.

C-Terminal peptide aldehydes and hydroxamates comprise two separate classes of effective inhibitors of a number of serine, aspartate, cysteine, and metalloproteases. Presented here is a method for preparation of both classes of peptide derivatives from the same resin-bound Weinreb amide precursor. Thus, 5-[(2 or 4)-formyl-3,5-dimethoxyphenoxy]butyramido-polyethylene glycol-polystyrene (BAL-PEG-PS) was treated with methoxylamine hydrochloride in the presence of sodium cyanoborohydride to provide a resin-bound methoxylamine, which was efficiently acylated by different Fmoc-amino acids upon bromo-tris-pyrrolidone-phosphonium hexafluorophosphate (PyBrOP) activation. Solid-phase chain elongation gave backbone amide-linked (BAL) peptide Weinreb amides, which were cleaved either by trifluoroacetic acid (TFA) in the presence of scavengers to provide the corresponding peptide hydroxamates, or by lithium aluminum hydride in tetrahydrofuran (THF) to provide the corresponding C-terminal peptide aldehydes. With several model sequences, peptide hydroxamates were obtained in crude yields of 68-83% and initial purities of at least 85%, whereas peptide aldehydes were obtained in crude yields of 16-53% and initial purities in the range of 30-40%. Under the LiAlH4 cleavage conditions used, those model peptides containing t-Bu-protected aspartate residues underwent partial side chain reduction to the corresponding homoserine-containing peptides. Similar results were obtained when working with high-load aminomethyl-polystyrene, suggesting that this chemistry will be generally applicable to a range of supporting materials.     

An expeditious regioselective synthesis of novel bioactive indole-substituted chromene derivatives via one-pot three-component reaction

Novel fused 1H-benzo[f]chromen-indole derivatives were synthesized regioselectivly in good to high yields by triethyl amine catalyzed condensation of 3-cyanoacetylindoles, β-naphthol and aryl aldehydes in methanol under ultrasounic irradiations and conventional conditions. The easy work-up of the products, rapidity, and mild reaction conditions are notable features of this protocol. The antibacterial activity of the selected products was examined. Some products showed promising activities.     

Chemiluminescence in the crude extracts of soybean seedlings. Postulated mechanism on the formation of hydroperoxide intermediates.

It has been reported that weak chemiluminescence (CL) from crude extracts of soybean seedlings is remarkably enhanced with the addition of various aldehydes (Biochim. Biophys. Acta 1058, 209-216). The reactivity of certain emitter(s) with oxygen species was examined in the autoclaved extracts of seedlings. When samples were reduced by the addition of hydrosulfite, two different types of reactivities in CL were defined. One type showed an initial rapid increase and a subsequent fast decay in CL upon mixing with oxygen. This rapid increase in CL intensity was independent of the presence of aldehydes, and was significantly suppressed by SOD. However, the subsequent slow decay phase in CL was dependent on the presence of aldehydes. In the sample reduced more moderately by borohydride, the same slow decay of CL appeared upon mixing with acetaldehyde and oxygen. This second type of CL was not inhibited by active oxygen scavengers. Hydrogen peroxide added to unreduced (oxidized) samples also elicited CL. Three types of primary emitters may be oxidized to form transient hydroperoxide, and excited for light emission by slightly different ways: two of them are excited by abstraction of one atomic oxygen from the hydroperoxy intermediate with aldehyde or hydrogen peroxide, leading to formation of an excited hydroxide intermediate. The third is excited directly on the binding of superoxide anion to the reduced primary emitter.     

Synthesis of prebiotic molecules — Role of some carbonyl compounds in prebiotic chemistry

Methyleneaminoacetonitrile(MAAN) resulting from the interaction of formaldehyde, ammonia and hydrogen cyanide on hydrolysis under mildly alkaline conditions gives a number of amino acids and peptides. Various aldehydes react with glycine to give corresponding hydroxyalkyl amino acids, which on reduction with formic acid are converted to reduced amino acids. Formaldehyde reacts with uracil to give 5-hydroxymethyl uracil which on reduction with formic acid yields thymine. Pyrrole formed by heating serine reacts with aldehydes to form porphyrins. Clays do not seem to influence most of these reactions, except the uracil-formaldehyde — formic acid reaction which results in enhanced yield of thymine.     

Abiotic Condensation Synthesis of Glyceride Lipids and Wax Esters Under Simulated Hydrothermal Conditions

Precursor compounds for abiotic proto cellular membranes are necessary for the origin of life. Amphipathic compounds such as fatty acids and acyl glycerols are important candidates for micelle/bilayer/vesicle formation. Two sets of experiments were conducted to study dehydration reactions of model lipid precursors in aqueous media to form acyl polyols and wax esters, and to evaluate the stability and reactions of the products at elevated temperatures. In the first set, mixtures of n-nonadecanoic acid and ethylene glycol in water, with and without oxalic acid, were heated at discrete temperatures from 150 ^∘C to 300 ^∘C for 72 h. The products were typically alkyl alkanoates, ethylene glycolyl alkanoates, ethylene glycolyl bis-alkanoates and alkanols. The condensation products had maximum yields between 150 ^∘C and 250 ^∘C, and were detectable and thus stable under hydrothermal conditions to temperatures < 300 ^∘C. In the second set of experiments, mixtures of n-heptanoic acid and glycerol were heated using the same experimental conditions, with and without oxalic acid, between 100 ^∘C and 250 ^∘C. The main condensation products were two isomers each of monoacylglycerols and diacylglycerols at all temperatures, as well as minor amounts of the fatty acid anhydride and methyl ester. The yield of glyceryl monoheptanoates generally increased with increasing temperature and glyceryl diheptanoates decreased noticeably with increasing temperature. The results indicate that condensation reactions and abiotic synthesis of organic lipid compounds under hydrothermal conditions occur easily, provided precursor concentrations are sufficiently high.     

Free radical and free radical scavenger effects on indole-3-acetic acid levels and ethylene production

Stable free radicals, together with horseradish peroxidase, promoted degradation of indole-3-acetic acid (IAA). These reactions were retarded by the free radical scavengers Bromoxynil, Na-benzoate and kinetin. Certain free radicals promoted, but the free radical scavenger Bromoxynil retarded ethylene production in apple slices and mung bean stem tissues. The interdependency of free radicals and free radical scavengers in systems controlling IAA levels and ethylene production is discussed.     

Microbiological and engineering aspects of biohydrogen production

Dramatically rising oil prices and increasing awareness of the dire environmental consequences of fossil fuel use, including startling effects of climate change, are refocusing attention worldwide on the search for alternative fuels. Hydrogen is poised to become an important future energy carrier. Renewable hydrogen production is pivotal in making it a truly sustainable replacement for fossil fuels, and for realizing its full potential in reducing greenhouse gas emissions. One attractive option is to produce hydrogen through microbial fermentation. This process would use readily available wastes as well as presently unutilized bioresources, including enormous supplies of agricultural and forestry wastes. These potential energy sources are currently not well exploited, and in addition, pose environmental problems. However, fuels are relatively low value products, placing severe constraints on any production process. Therefore, means must be sought to maximize yields and rates of hydrogen production while at the same time minimizing energy and capital inputs to the bioprocess. Here we review the various attributes of the characterized hydrogen producing bacteria as well as the preparation and properties of mixed microflora that have been shown to convert various substrates to hydrogen. Factors affecting yields and rates are highlighted and some avenues for increasing these parameters are explored. On the engineering side, we review the potential waste pre-treatment technologies and discuss the relevant bioprocess parameters, possible reactor configurations, including emerging technologies, and how engineering design-directed research might provide insight into the exploitation of the significant energy potential of biomass resources.     

Thioureas react with superoxide radicals to yield a sulfhydryl compound. Explanation for protective effect against paraquat

Thiourea and superoxide dismutase were effective antidotes to paraquat toxicity in an HL60 cell culture system, whereas other hydroxyl scavengers were ineffective. The efficacy of thioureas was not due to blockage of intracellular paraquat uptake, inhibition of NADPH-P-450 reductase, or reaction with the paraquat radical. Thiourea also competitively inhibited the reduction of cytochrome c by the xanthine/xanthine oxidase superoxide-generating system, and the release of iron from ferritin by superoxide radicals. The reaction of superoxide with thiourea produced a sulfhydryl compound distinct from products formed by hydrogen peroxide or hydroxyl radicals. Spectrophotometric and chromatographic studies indicated the carbon-sulfide double bond was converted to a sulfhydryl group which reacted with Ellman's reagent. Additional confirmatory evidence for the sulfhydryl compound was obtained with carbon-13 NMR and mass spectroscopies. Thus, thioureas are direct scavengers of superoxide radicals as well as hydroxyl radicals and hydrogen peroxide. The rate constant for the reduction of thiourea by superoxide was estimated at 1.1 x 10(3) M-1 s-1. The implication of this finding on free radical studies, the mechanism of paraquat toxicity, and the metabolism of thioureas is discussed.     

Oxidation of Alcohols by Botrytis cinerea

Crude cell-free preparations of Botrytis cinerea were found to oxidize straight-chain primary alcohols (except methanol), aromatic primary alcohols, and unsaturated primary alcohols. The resulting products were the corresponding aldehydes and an equal molar quantity of hydrogen peroxide.     

Hydrogen peroxide-induced base damage in deoxyribonucleic acid

Aqueous solutions of calf thymus deoxyribonucleic acid (DNA) were exposed to hydrogen peroxide in the presence of air. Base products formed in DNA were identified and quantitated following acid hydrolysis and trimethylsilylation using gas chromatography-mass spectrometry. The yields of these products were dependent upon the hydrogen peroxide concentration, and increased in the following order: 8-hydroxyadenine, cytosine glycol, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 8-hydroxyguanine, thymine glycol, and 4,6-diamino-5-formamidopyrimidine. Previous studies have shown that these compounds are typically formed in DNA in aqueous solution by hydroxyl radicals generated by ionizing radiation. Hydrogen peroxide is thought to participate in a Fenton-like reaction with transition metals, which are readily bound to DNA in trace quantities, resulting in the production of hydroxyl radicals close to the DNA. This proposed mechanism was examined by exposing DNA to hydrogen peroxide either in the presence of a hydroxyl radical scavenger or following pretreatment of DNA with metal-ion chelators. The results indicate that trace quantities of transition metal ions can react readily with hydrogen peroxide to produce radical species. The production of radical species was monitored by determining the altered bases that resulted from the reaction between radicals and DNA. The yields of the base products were reduced by 40 to 60% with 10 mmol dm-3 of dimethyl sulfoxide. A 100-fold increase in the concentration of dimethyl sulfoxide did not result in a further reduction in hydrogen peroxide-induced base damage. DNA which was freed from bound metal ions by pretreatment with metal ion chelators followed by exhaustive dialysis was found to be an ineffective substrate for hydrogen peroxide. The yields of base products measured in this DNA were at background levels. These results support the role of metal ions bound to DNA in the site-specific formation of highly reactive radical species, most likely hydroxyl radicals, in hydrogen peroxide-induced damage to the bases in DNA.     

Oxidative Glycation and Free Radical Production: A Causal Mechanism of Diabetic Complications

Glucose may oxidise under physiological conditions and lead to the production of protein reactive ketoaldehydes, hydrogen peroxide and highly reactive oxidants. Glucose is thus able to modify proteins by the attachment of its oxidation derived aldehydes, leading to the development of novel protein fluoro-phores, as well as fragment protein via free radical mechanisms.

The fragmentation of protein by glucose is inhibitable by metal chelators such as diethylenetriamine pentaacetic acid (DETAPAC) and free radical scavengers such as benzoic acid, and sorbitol. The enzymic antioxidant, catalase, also inhibits protein fragmentation.

Protein glycation and protein oxidation are inextricably linked. Indeed, using boronate affinity chromatography to separate glycated from non-glycated material, we demonstrate that proteins which arc glycated exhibit an enhanced tryptophan oxidation. Our observation that both glycation and oxidation occur simultaneously further supports the hypothesis that tissue damage associated with diabetes and ageing has an oxidative origin.     

Oxidative Glycation and Free Radical Production: A Causal Mechanism of Diabetic Complications

Glucose may oxidise under physiological conditions and lead to the production of protein reactive ketoaldehydes, hydrogen peroxide and highly reactive oxidants. Glucose is thus able to modify proteins by the attachment of its oxidation derived aldehydes, leading to the development of novel protein fluoro-phores, as well as fragment protein via free radical mechanisms.

The fragmentation of protein by glucose is inhibitable by metal chelators such as diethylenetriamine pentaacetic acid (DETAPAC) and free radical scavengers such as benzoic acid, and sorbitol. The enzymic antioxidant, catalase, also inhibits protein fragmentation.

Protein glycation and protein oxidation are inextricably linked. Indeed, using boronate affinity chromatography to separate glycated from non-glycated material, we demonstrate that proteins which arc glycated exhibit an enhanced tryptophan oxidation. Our observation that both glycation and oxidation occur simultaneously further supports the hypothesis that tissue damage associated with diabetes and ageing has an oxidative origin.     

Aldehydes, hydrogen peroxide, and organic radicals as mediators of ozone toxicity

It is generally agreed that unsaturated fatty acids (UFA) are an important class of target molecule for reaction with ozone when polluted air is inhaled. Most discussions have implicated the UFA in cell membranes, but lung lining fluids also contain fatty acids that are from 20 to 40% unsaturated. Since UFA in lung lining fluids exist in a highly aquated environment, ozonation would be expected to produce aldehydes and hydrogen peroxide, rather than the Criegee ozonide. In agreement with this expectation, we find that ozonations of emulsions of fatty acids containing from one to four double bonds give one mole of H2O2 for each mole of ozone reacted. Ozonation of oleic acid emulsions and dioleoyl phosphatidyl choline gives similar results. with two moles of aldehydes and one mole of H2O2 formed per mole of ozone reacted. The net reaction that occurs when ozone reacts with pulmonary lipids is suggested to be given by equation 1. [formula: see text]. From 5 to 10% yields of Criegee ozonides also appear to be formed. In addition, a direct reaction of unknown mechanism occurs between ozone and UFA in homogeneous organic solution, in homogeneous solutions in water, in aqueous emulsions, and in lipid bilayers to give organic radicals that can be spin trapped. These radicals are suggested to be responsible for initiating lipid peroxidation of polyunsaturated fatty acids. Thus, aldehydes, hydrogen peroxide, and directly produced organic radicals are suggested to be mediators of ozone-induced pathology.