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A novel method for extracting butyrylcholinesterase (BuChE) from serum as a means of identifying and measuring nerve agent adducts to human BuChE is presented here. Antibutyrylcholinesterase monoclonal antibodies were conjugated to protein-G ferromagnetic particles and mixed with 500 [micro]L serum samples. The particle-antibody-BuChE product was rinsed and directly digested with pepsin. Native and isotopically enriched nonapeptides corresponding to the pepsin digest products for uninhibited BuChE, and satin, cyclohexylsarin, VX, and Russian VX nerve agent-inhibited BuChE were synthesized for use as calibrators and internal standards, respectively. Internal standards were added to the filtered digest sample, and the samples were quantified via high performance liquid chromatography-isotope dilution-tandem mass spectrometry. The ratio of adducted to total BuChE nonapeptides was calculated for each nerve agent-exposed serum sample using data collected in a single chromatogram. Nerve agent-inhibited quality control seram pools were characterized as part of method validation; the method was observed to have extremely low background noise. The measurement of both uninhibited and inhibited BuChE peptides compensated for any variations in the pepsin digestion before the internal standard peptide was added to the sample and may prove useful in individualizing patient results following a nerve agent exposure. 10.1021/ac101024z

The study explains and describes a concise, asymmetric and stereocontrolled total synthesis of stephacidins A, B and notamide B fungal metabolites, which act as extremely important functional groups for the formation of bridged bicyclic ring system. The synthesis technique makes use of the phenomenon of microwave heating, which shortens the reaction times and also increases the yield of the preparation of vital intermediates.

A novel and efficient synthetic method is described for (2S,3S)-3-amino-2-hydroxy-4-phenyl butyric acid derivatives, which are useful intermediates of enzyme inhibitors. Beta-amino alpha-hydroxy carboxylic acids are important pharmaceutical intermediates, and this method may provide a versatile synthesis from various amino acids in a few steps.

A 27 step total synthesis of the tuberculostatic macrocyclic peptide antibiotic capremycin IB was accomplished. The synthesis featured the use of an enolate condensation between a chiral glycine aluminum enolate and the benzyl imine of 3-tert-butyldimethylsiloxy-proponal as a means of preparing the cyclic guanidine amino acid (2S,3R)-capreomycidine.

Research has been conducted on the antiobiotic (+)-negamycin. The synthesis of this antibiotic carried out via stabilized Wittig olefination of the lactone carbonyl group and asymmetric hydrogenation is described.

The authors review the publications on the antitumor antibiotics belonging to the tetrahydroisoquinoline family. The topics of interest include the antitumor and antimicrobial activities of these antibiotics and other biological properties.

The study uses a new method for the formation of the allylic amine precursor to an azomethine ylide, which has been developed and exploited in an efficient dipolar cycloaddition to afford the key tetra cyclic intermediate used in the synthesis of tetrazomine.

The asymmetric biomimetic total synthesis of VM55599, utilizing an intramolecular Diels-Alder cycloaddition as a key step, is achieved. The synthetic material is utilized to elucidate the absolute stereochemistry of the natural product and the results are discussed in terms of a unified biogenesis of the paraherquamides and VM55599.

Research has been conducted on the benzoin. The lipase TL-mediated kinetic resolution of this benzoin has been investigated and the results indicate that it has given the corresponding optically pure (R)-benzoin.

The synthesis of alpha-hydroxy-beta-amino acids is described.

Carbon monoxide binding by de novo heme proteins from designed combinatorial libraries is explored.

The comparison of the rate of H/D exchange between CpW(CO)(sub 2)(PMe3)H and various acids with the rate of which these acids protonate the metal are described. The exchange rate data and the rate constant for deprotonation of CpW(CO)(sub 2)(PMe3)H(sub 2)(super +) by 4-tert-butyl-N,N-dimethylaniline, combined with the pK(sub a) data, provide quantitative evidence that the kinetic site of protonation of CpW(CO)(sub 2)(PMe3)H is the hydride ligand.

The arachno-[B6H11](super -) solution structure at -25 degrees C was clarified as fluxional compound by applying the ab initio/IGLO/NMR method. The elimination of asymmetric complex and C(sub s)-symmetric [mu-(BH3)B5H8)(super -) complex as most stable structure candidates of arachno-[B6H11](super -) reinforces the early geometrical bonding systematics for boranes and carboranes.

VM55599 is an insignificant metabolite of Penicillium sp. IMI332995 and has been isolated along with several members of the paraherquamide family. The total synthesis of VM55599 has been achieved using an intramolecular Diels-Alder cycloaddition of a reverse isoprene moiety across an azadiene system.

The semisynthesis and DNA cross-linking reactivity of the first photochemically triggered progenitor of dehydromonocrotaline are reported. This masked dehydromonocrotaline represents the first example of a new type of pyrrolizidine alkaloids that are capable of photochemical activation. Data from these studies establish the viability of masked DNA-reactive pyrrolizidine alkaloid progenitors that can be activated photochemically. These progenitors show potential as tools for understanding the mechanism of DNA-DNA and DNA-protein cross-linking.

DNA interstrand cross-linking compounds are used as clinical agents in the treatment of cancers and other medical disorders such as anemia and skin diseases. They are capable of inhibiting DNA strand separations which are vital in replication and transcription. The compounds are significant in the technique of selective drug activation through protein overexpression. The major groups of the compounds are inherently reactive agents, photoactivated cross-linking agents, oxidatively activated agents and hypoxia-selective agents.

Several factors must first be considered before purchasing a charge-coupled device (CCD) camera. Buyers must first examine the camera's quantum efficiency (QE) versus wavelength plot. QE measurements are often made by the CCD manufacturer and simply passed along to the camera maker. In choosing the right camera, the performance of the CCD must first be assessed against the user's requirements. Deciding how much read and dark noise can be tolerated for a specific use can pose a lot of problems. Low-read noise MPP cameras are used for low light level spectroscopy while TE-cooled cameras are used for high light level spectroscopy.

Electroabsorption and related spectroscopic studies were conducted on bimetallic tetraiminoethylenedimacrocyclic complexes. Additional near-infrared Raman investigations on mixed valent and isovalent diiron species support the observed delocalized mixed-valence ion behavior. Results also show that electroabsorption causes anomalous polarizability and that metal-to-ligand charge transfer excitation causes the blue green electronic absorption band in the mixed-valent complex.

A study was conducted to determine whether possible nido-8-vertex electron-count boranes, carboranes and heteroboranes could be found in the nido-8(V) configuration. Ab initio calculations were utilized in seeking for the existence of boranes, carboranes and heteroboranes in the 8-vertex electron-count class. Results revealed that the known derivatives of the nido-C4B4H8 carboranes contained ni-8(IV) configurations.

Nosocomial infections due to the methicillin-resistant Staphylococcus aureus (MRSA) are a clinically serious problem. Four new compounds identified as TAN-1057A-D from Flexibacter sp PK-74 and P-176, have been isolated, with potent activity against MRSA. The first synthesis of TAN-1057A-D is described, based on a new method of constructing the cyclic amidinourea.

The binding of arginine homologs to endothelial nitric oxide synthase disturbs the environment of the high-spin ferriheme. Four types of high-spin complex can be identified by employing electron paramagnetic resonance as a probe of heme ligation geometry. Addition of substrate L-arginine, intermediate N-hydroxy-L-arginine and L-arginine analog inhibitors resulted in ligand-specific high-spin ferriheme species.

A novel method of synthesizing amino acid (S)-m-tyrosine was developed through a hydrogenation process. The design featured the preparation of m-(benzyloxy)benzyl bromide which was converted into m-tyrosine through catalytic hydrogenation. The mixture of ethanol and m-(benzyloxy)benzyl bromide was triturated with Et2O, yielding (S)-m-tyrosine hydrochloride. 1H nuclear magnetic resonance spectrum of the resulting Mosher amide and GLC analysis revealed a very high optical purity..

A series of 25 mM phosphate buffer background electrolytes were prepared from phosphoric acid and mixtures of lithium hydroxide and tetrabutylammonium hydroxide as pH adjusters and sources of background electrolyte co-ions. These background electrolytes were used for the capillary electrophoretic separation of quaternary ammonium analytes. Abnormally distorted peaks, different from the simple characteristic triangular peaks usually attributed to electromigration dispersion, were observed. In order to understand the origin of the greatly distorted peaks, capillary electrophoretic separations with two co-ion background electrolytes were numerically simulated using a mathematical model of the electrophoretic process. Generalized peak shape rules were derived from the simulations which can be used to predict the shape of the analyte, co-ions, and counterion concentration peaks, as well as the local electric field strength changes. Abnormal peak shape and peak disappearance can occur when the analyte peak and the noncomigrating system peaks overlap.

An ab initio study of the transition structures for the intramolecular Diels-Alder cycloaddition of the biosynthetic key 2-azabutadienes to brevianamides is described. The results showed the different orientation of the vinyl group to the aza diene system caused the relative energies of the different transition states. The formation of the five-membered ring influenced this orientation.

Ab initio/IGLO, GIAO/NMR evaluations disprove the 11B chemical shift assignment for the close-carborane C,3-Me2-1,2-C2B3H3 structure. Some of the original experiments were repeated, but these did not reproduce the reported data, either. The elimination of the C,3-Me2-1,2-C2B3H3 structural assignment abolishes the sole exception to four established structural patterns of closo-carboranes.

The first stereocontrolled total synthesis of (+)-paraherquamide B, the simplest in the family of complex, heptacyclic, toxic mold metabolites isolated from various Penicillium species, was examined by applying the methodology originally developed for the stereocontrolled total synthesis of (-)-brevianamide B11. The key features of this biosynthesis are described.

The structures of the three known isomers of nido-C4B7H11 were determined. The results of the 3-step ab initio/IGLO/NMR computational analysis showed that the structures are nido-7,8,9,10-C4B7H11, nido-1,7,8,10-C4B7H11 and nido-2,7,9,10-C4B7H11. Comparison of the relative energies indicates that the most stable structures are those in which the carbons occupy low coordinate sites.

A synthesis scheme for biosynthetic intermediates in taxol biosynthesis is described. The compounds, taxa-4(20),11(12)-diene and taxa-4(5),11(12)-diene, were prepared using a synthesis route that uses an intramolecular Dielrs-Alder cyclization reaction forming the A/B-ring system with an aromatic C ring. The synthesis involves the cyclization of 1(S)-verticillene via a cation for the formation of taxa-4(5)11,(12)diene.

The antineoplastic antibiotic quinocarcin and (+/-)-quinocarcinamide can be synthesized by a (3 + 2) dipolar cycloaddition reaction involving NBS oxidation to form an azomethine ylide. During oxidation, the allylic tertiary amine is converted into an imminium ion, which forms the ylide. Analysis of the cycloaddition reaction during the ylide formation reveals that the cycloadducts possess a stereochemical conformation between C-8 and C-11. The sequence of dipolarophile is mediated by the configuration of the ylide.

A mutant form of recombinant-produced hepatitis B virus core antigen (HBcAg capsid), called HBeAg capsid, can be produced using in vitro proteolysis through a deletion mutant that lacks the C-terminal 39 residues. Physicochemical and biochemical analyses of the two capsids revealed a high level of alpha-helical contents and both triangulation numbers of three and four for the capsids' icosahedral lattices. The alpha-helical content levels are unique to all known icosahedral viral capsids from both plants and animals, suggesting an alternative to the canonical beta-barrel motif. A random coil conformation may be the structure of the C-terminal domain of HBcAg while the C-terminal may be involved in facilitating disassembly and the release of viral nucleic acid.

Ab initio/IGLO/NMR studies support the Shore's structure of nido-2-MeB6H9-(mu-3,4-H), Bb, and the Gaines' structure of nido-mu2,3-(Me2B)-B5H8, A. The 11B NMR studies of nido-2, 3-Me2B6H8 reveal that stabilities of the (mu-3,4-H)-, Cb, and (mu-4, 5-H)-isomers, Ca, are equal. Stability of nido-2,4-Me2B6H8-(mu-5,6-H), Da, is higher than the Ca and Cb isomers. Spectral data facilitate the determination of factors controlling the substitution patterns in the polyboranes and bridge hydrogen placement.

In order to obtain high separation efficiencies in capillary electrophoresis, electromigration dispersion has to be minimized either by using very dilute samples in concentrated background electrolytes or by matching the mobilities of the analyte and the co-ion of the background electrolyte. A dynamic mobility matching method is presented here that can be used advantageously in cyclodextrin-containing zwitterionic background electrolytes. A rigorous equilibrium model has been developed to describe the effective electrophoretic mobility of the co-ion of the background electrolyte as a function of the analytical concentrations of the cyciodextrin, the zwitterionic buffer, and the hydronium ion. With adjustment of these parameters, either simultaneously or individually, the co-ion mobilities can be easily varied over a 10-fold range. Using fenoprofen as an example, predictions of the model have been verified experimentally. The separation efficiency has been maximized by varying the analytical concentration of the zwitterionic buffer while the pH and the cyclodextrin concentration of the background electrolyte were kept constant to maintain the separation selectivity. The dynamically matched mobilities resulted in symmetric enantiomer peaks and good separations.

A new synthetic method for peptide coupling involves a regioselective ring-opening of the differentially N-protected bis-lactone form of meso-diaminopimelic acid. This technique facilitates the synthesis of gamma-D- and gamma-L-glutamyl-L-meso-diaminopimelic acid dipeptides. Diphenyloxazinones with N-t-BOC and N-CBz protecting groups help prepare the N-protected form of meso-diaminopimelic acid.

The molecular oxygen reduction reaction yields O2-influenced cleavage of single-stranded and double-stranded DNA. The cleavage is performed by the antitumor antibiotic tetrazomine. The redox self-disproportionation of the oxazolidine moiety of the tetrazomine is the basis for the results obtained. The results reveal that redox chemistry of the oxazolidine fraction is similar to that of quinocarcin.

The mechanism of boiological activity of aspichlorine is investigated. A model system is used to construct and analyze the core structure of the compound. Results show that that the model system is capable of synthesizing aspichlorine in 13 steps with moderate stereoselectivity. Its also found that the o-nitrobenzyl group can be used as a photolabile amide protecting group during the synthesis.

Asymmetric cycloaddition of different aldehydes and dimethyl malate to azomathine ylides is presented. The cycloaddition has high endo-selectivity with almost complete control of the generation of three stereogenic centers. Aldehydes longer than formaldehyde promote the generation of a fourth center with low stereoselectivity. The diastomers produced from the reaction can be purified using chromatography and modified through various cleavage reactions.

Diaminopimelic acid has important function in microbial cell wall structure and metabolism. Synthetic stereoisomer inhibitors thus have a potential as an antimicrobial agent. Procedures for the synthesis of diaminopimelic acid derivatives and a diaminosuberic acid are presented. One procedure utilizes enol borane aldol couplings in the preparation of the stereoisomers. Another procedure employs an enolate alkylation technique.

An ab initio/IGLO/NMR study of the closo-carboranes closo-C2B6H8, closo-CB7H8(super 1-) and closo-C3B5H7 was undertaken. The structure of closo-C2B6H8 was established as bisdiphenoidal. CB7H8(super 1-) was also shown to exhibit a fluxional closo structure. The structure of B8H8(super 2-) remained partially resolved. However, the ab initio/IGLO/NMR procedure correlates well with previous computational studies to provide proof that the carborane has a closo bisdiphenoid structure in solution.

Arylglycines, naturally rare but therapeutically vital nonproteinogenic amino acids, are obtained in chiral form either by enantiomeric resolution of racemates or by asymmetric synthesis. Racemic synthesis is usually carried out by aromatic substitution of glycinate equivalents. The d,l-mix is often resolved with the use of enzymes or by the more recent retroracemization. The most popular asymmetric synthesis methods are the Strecker route, alkylation of nucleophilicand electrophilic glycinates, electrophilic amination of enolates and nucleophilic amination of alpha-substituted acids.

Polyboranes, carboranes and carbocations represent the simplest and most abundant class of electron-deficient cluster compounds (those with more valence orbitals than valence electrons). They have the formulas closo-C0-2BnHn+2, nido-C0-4BnHn+4, arachno-C0-6BnHn+6 and hypho-C0-8BnHn+8, where 'n' is the number of boron atoms. The Chop-Styx system of naming these compounds, their electron distributions, the effects of heteroatom substituents and bridge hydrogens on their structures and chemical properties as well as other architectural features are discussed.