Recent advances in oxidase biocatalysts: Enzyme discovery,cascade reactions and scale up

Enzymatic oxidation reactions may offer ‘greener’ alternatives to chemical oxidation processes, which have typically involved toxic metal catalysts, generation of toxic byproducts or poor atom economy. Oxidases function at ambient temperature and pressure with no external cofactor recycling systems required. This review examines recent progress in oxidases, including enzyme discovery and engineering, and the application of these biocatalysts in cascade reactions. Process requirements including reactor design, oxygen supply and use of non-aqueous solvents are explored for the utilisation of oxidases on industrial scale.     

Dichlorocarbene modified butadiene rubber (DCBR): Preparation,kinetic study,and its properties in natural rubber/DCBR blend vulcanizates

Dichlorocarbene modified butadiene rubber (DCBR) was prepared via the addition of the dichlorocarbene group in the presence of 2 phase transfer agents (cetyltrimethylammonium bromide and tetraethylammonium chloride). The effects of the reaction temperature and time, amount of dichlorocarbene precursor, and the type and amount of phase transfer agent on the chlorine content were investigated. The highest chlorine content (30%) in DCBR was obtained using 0.062 mol chloroform and 0.003 mol cetyltrimethylammonium bromide at room temperature for 19 hours although 27.9% was obtained after 12 hours. The kinetics of this dichlorocarbene modification was best described by the pseudo–first order rate law with 2 rate constants. For practical applications, the DCBR with chlorine contents of 10%, 20%, or 30% were blended with natural rubber (NR) and then vulcanized using the sulfur‐curing system. Although the polarity of DCBR was increased, a good compatibility between NR and DCBR still existed, resulting in improved mechanical properties. The oil resistance, flame retardant, and ozone resistance properties of the NR/DCBR blend vulcanizates were enhanced compared to those of a NR/butadiene rubber blend vulcanizate, which was related to the amount of chlorine incorporated into the DCBR.     

Living polymers. Their discovery,characterization, and properties

The story of the discovery of living polymers is presented. Living polymers are polymers that retain their ability to propagate and grow to a desired size while their degree of termination or chain transfer is still negligible. Theoretical and mechanistic considerations are discussed. The living polymerization technique provides access to uniform polymers (Poisson molecular weight distribution) of controllable size, block copolymers, functional polymers, and star and comb-shaped polymers. The quantitative aspects of electron transfer are fully discussed. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: ix–xv, 1998     

Dichlorocarbene addition to cyclopropenes: a computational study

Reaction paths for addition of dichlorocarbene to 1,2-disubstituted cyclopropenes were calculated using hybrid density functional theory (B3LYP/6-31G) in the gas phase and in the presence of a continuum solvation model corresponding to acetonitrile. In both the gas phase and acetonitrile, :CCl2-cyclopropene addition follows an asymmetric, non-least-motion approach. Barriers to addition range from 0 to 2 kcal/mol. The reactions proceed in concerted fashion in both the gas phase and solution to yield 1,3-dienes or bicyclobutanes. The reaction pathway on this complex potential energy surface of this reaction appears to bifurcate, and the product distribution is believed to be controlled by reaction dynamics. At the present level of theory, there appears to be no minimum on the potential energy surface corresponding to a dipolar intermediate.     

5H-1,2-oxatelluroles and their benzo analogs: Synthesis and reactions

Tetracoordinated derivatives of 2-halo-2-aryl-5H-1.2-oxatelluroles and 1-halo-l-butyl-3H-benz-2.1-oxatelluroles were synthesized by the oxidation of 3-aryltelluro-2 propen-l-ols and the dehydrogenation of 2-butyldihalotellurobenzyl alcohols. The halogen atoms in these compounds are readily replaced in nucleophilic substitution reactions. The reaction of benzoxatelluroles with bromine is accompanied by cleavage of O-Te bonds and leads, depending on the nature of the substituent at C₍₃₎, to 2-(butylbromotelluro)benzaldehyde or 2-(butyldibromotelluro)benzophenone.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 266–279, February, 1994. Original article submitted December 22, 1993.     

Synthesis and reactions of thiophene analogs of chalcone

A method of synthesizing thiophene analogs of chalcone is described. It is based on condensation of chlorides of , -unsaturated acids with thiophene in the presence of an equimolecular amount of SnCl₄ in benzene or toluene solution. Addition of 2-nitropropane at the active double bond of the thiophene analogs of chalcone gives -nitroketones.     

Synthesis and reactions of thiophene analogs of chalcones

A new method of synthesizing thiophene analogs of chalcones, based on condensing aryl-β-chlorovinyl ketones with thiophene in the presence of stannic chloride, is extended. Hitherto undescribed thiophene analogs of chalcones are obtained in good yields. Addition of 2-nitropropane, nitromethane, and morpholine to the active double bond of thiophene analogs of chalcones gives γ-nitroketones and morpholine derivatives of ketones containing the benzene ring and thiophene. Oxidation with alkaline hydrogen peroxide gives an α-ketooxide of the thiophene analog of chalcone.     

Synthesis and reactions of thiophene analogs of chalcones

A new method of synthesizing thiophene analogs of chalcones, based on condensing aryl--chlorovinyl ketones with thiophene in the presence of stannic chloride, is extended. Hitherto undescribed thiophene analogs of chalcones are obtained in good yields. Addition of 2-nitropropane, nitromethane, and morpholine to the active double bond of thiophene analogs of chalcones gives -nitroketones and morpholine derivatives of ketones containing the benzene ring and thiophene. Oxidation with alkaline hydrogen peroxide gives an -ketooxide of the thiophene analog of chalcone.     

Water soluble nucleic acid analogs: Preparation and properties

In order to prepare water soluble natural and synthetic polymers, which contain nucleic acid base units as the functional side groups, a different sort of polymers, such as poly(ethyleneimine), poly(amino acids) and so on were used as the base materials. The properties of the polymers derived, in particular the specific interaction between nucleic acid base containing complementary polymers was studied in detail. Introduction of the base units onto hyaluronic acid was also carried out. Applicabilities of these polymers obtained, for example as the controlled release system by using reversible photodimerization reaction of thymine bases were also shown.     

二茂铁基Tamoxifen类似物的合成、结构与性质

合成了一系列二茂铁基Tamoxifen类似物并作了初步生化试验(RBA试验),研究了代表化合物二茂铁基羟基Tamoxifen的晶体结构和顺-反异构化。     

New reactions, functional compounds, and materials in the series of coumarin and its analogs

Data on the development of new functional compounds and materials based on the study of the reactions of coumarin and its analogs are generalized. Since coumarin derivatives are characterized by enhanced photochemically activity, special attention is given to the synthesis of photosensitive compounds and materials with intense fluorescence, including the structures capable of changing fluorescence under the action of various factors: solvent, pH of the medium, and interaction with bioorganic substrates. Pathways for design of fluorescent polymethine dyes, fluorescent labels for proteins, fluorescent photochromes, and photoacids for optical data storage with fluorescence read-out are reviewed. The role of isomerization transformations of the new compounds in their sensorial effects is established.     

Phosphorus-containing dendrimers bearing galactosylceramide analogs: self-assembly properties

We report the synthesis and the supramolecular auto-assembly of catanionic phosphorus-containing dendrimers mimicking multisite analogs of galactosylceramide.     

Electronic overlap population as measure of reactivity in electrocyclic reactions,Stilbenes and analogs

Differences in the Mulliken electronic overlap populations (due to electronic excitation) for pairs of centres undergoing bonding changes are suggested as a measure of reactivity in electrocyclic reactions. Good correlation of these quantities with the experimentally determined reactivity patterns was obtained for photocyclization in stilbenes, benzostilbenes and azastilbenes.     

Fluorescent HIV-1 Dimerization Initiation Site: design, properties, and use for ligand discovery

The HIV-1 Dimerization Initiation Site (DIS) is an intriguing, yet underutilized, viral RNA target for potential antiretroviral therapy. To study the recognition features of this target and to provide a quantitative, rapid, and real-time tool for the discovery of new binders, a fluorescence-based assay has been constructed. It relies on strategic incorporation of 2-aminopurine, an isosteric fluorescent adenosine analogue, into short hairpin RNA constructs. These oligomers self-associate to form a kissing loop that thermally rearranges into a more stable extended duplex, thereby mimicking the association and structural features of the native RNA sequence. We demonstrate the ability of two fluorescent DIS constructs, DIS272(2AP) and DIS273(2AP), to report the binding of known DIS binders via changes in their emission intensity. Binding of aminoglycosides such as paromomycin to DIS272(2AP) results in significant fluorescence enhancement, while ligand binding to DIS273(2AP) results in fluorescence quenching. These observations are rationalized by comparison to the sequence-analogous bacterial A-site, where the relative emission of the fluorescent probe is dependent on the placement of the flexible purine residues inside or outside the helical domain. Analysis of binding isotherms generated using DIS272(2AP) yields submicromolar EC50 values for paromomycin (0.5 +/- 0.2 microM) and neomycin B (0.6 +/- 0.2 microM). Other neomycin-family aminoglycosides are less potent binders with neamine, the core pharmacophore, displaying the lowest affinity of 21 +/- 1 microM. Screening of additional aminoglycosides and their derivatives led to the discovery of new, previously unreported, aminoglycoside binders of the HIV DIS RNA, among them butirosin A (5.5 +/- 0.6 microM) and apramycin (7.6 +/- 1.0 microM). A conformationally constrained neomycin B analogue displays a rather high affinity to the DIS (1.9 +/- 0.2 microM). Among a series of nucleobase aminoglycoside conjugates, only the uracil derivatives display a measurable affinity using this assay with EC50 values in the 2 microM range. In addition, similarity between the solution behavior of HIV-1 DIS and the bacterial decoding A-site has been observed, particularly with respect to the intra- and extra-helical residence of the conformationally flexible A residues within the bulge. Taken together, the observations reported here shed light on the solution behavior of this important RNA target and are likely to facilitate the design of new DIS selective ligands as potential antiretroviral agents.