Empirical minimization

We investigate the behavior of the empirical minimization algorithm using various methods. We first analyze it by comparing the empirical, random, structure and the original one on the class, either in an additive sense, via the uniform law of large numbers, or in a multiplicative sense, using isomorphic coordinate projections. We then show that a direct analysis of the empirical minimization algorithm yields a significantly better bound, and that the estimates we obtain are essentially sharp. The method of proof we use is based on Talagrand's concentration inequality for empirical processes. Research partially supported by NSF under award DMS-0434393. Research partially supported by the Australian Research Council Discovery Porject DP0343616.     

Synthesis and characteristics of microspheres of polystyrene derivatives

Two sytrene derivatives formylstyrene and styrene sulfonylcholoride, were synthesized. Polymeric microspheres in diameters ranging from 0.1 to 2 μm were synthesized by polymerization of chlormoethylstyrene, formylstyrene, and styrene sulfonylcholoride in organic solvents, in the presence of appropriate surfactants. The kinetics of microsphere formation were studied. The molecular weight distribution of the products was determined by gel permeation chromatography. Conditions for binding various amino ligands to the microspheres were also established.     

Facile purification of rare cucurbiturils by affinity chromatography

A practical method for the separation and purification of cucurbituril (CB) hexamers was developed on the basis of affinity chromatography using aminopentylaminomethylated polystyrene beads. This recyclable resin, which can be used repeatedly, facilitates the general preparation of cucurbituril derivatives and compensates for the usually moderate yields and mixed products that characterize the acid-catalyzed synthesis of CB derivatives. This technique allows convenient, rapid isolation of rare substituted cucurbiturils, including hexacyclohexanocucurbit[6]uril and dodecamethylcucurbit[6]uril. [reaction: see text]     

Organo tin nucleophiles iii. Palladium catalyzed reductive cleavage of allylic heterosubstituents with tin hydride

Tributyl tin hydride, serving as an efficient hydride transfer agent, allows highly chemoselective palladium catalyzed reductions of allylic heterosubstituents even in presence of aldehydes, benzyl acetate and benzyl chloride.     

Highly efficient antibody-catalyzed deuteration of carbonyl compounds

Antibody 38C2 efficiently catalyzes deuterium-exchange reactions at the alpha position of a variety of ketones and aldehydes, including substrates that have a variety of sensitive functional groups. In addition to the regio- and chemoselectivity of these reactions, the catalytic rates (kcat) and rate-enhancement values (kcat/kun) are among the highest values ever observed with catalytic antibodies. Comparison of the substrate range of the catalytic antibody with highly evolved aldolase enzymes, such as rabbit-muscle aldolase, highlights the much broader practical scope of the antibody, which accepts a wide range of substrates. The hydrogen-exchange reaction was used for calibration and mapping of the antibody active site. Isotope-exchange experiments with cycloheptanone reveal that the formation of the Schiff base species (as concluded from the 16O/18O exchange rate at the carbonyl oxygen) is much faster than the formation of the enamine intermediate (as concluded from the H/D exchange rate), and both steps are faster than the antibody-catalyzed aldol addition reaction.     

A designed synthetic analogue of 4-OT is specific for a non-natural substrate

The substrate specificity of 4-oxalocrotonate tautomerase (4-OT) is characterized by electrostatic interactions between positively charged arginine (Arg) side chains on the enzyme and the dianionic substrate, 4-oxalocrotonate. To generate specific hydrogen-bonding interactions with a monoanionic substrate analogue, we have introduced a urea functional group into the active site by replacing arginine side chains with isosteric citrulline (Cit) residues. This design was based on the complementarity between the urea functionality of citrulline and the uncharged amide function of the substrate, as opposed to the guanidinium-carboxylate electrostatic interaction between the wild-type enzyme and the natural substrate. Indeed, the synthetic (Arg39Cit)4-OT analogue catalyzed the tautomerization of the non-natural monoamide-monoacid substrate while it was a poor catalyst for the natural diacid substrate. The specificity of (Arg39Cit)4-OT for the monoamide-monoacid substrate relative to that of the diacid substrate was found to be 740-fold greater than that of the wild-type enzyme for tautomerization of the non-natural substrate as compared with the natural one. The role of electrostatic interactions in the tautomerization of the monoamide-monoacid substrate was probed in detail with several other Arg to Cit analogues of this enzyme. This study has demonstrated that chemical manipulation of the functional groups within the active site of an enzyme can modify its catalytic activity and substrate specificity in a predictable way, suggesting that the incorporation of noncoded amino acids into proteins has great promise for the development of new enzymatic mechanisms and new binding interactions.     

Biologically Relevant Molecular Transducer with Increased Computing Power and Iterative Abilities

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The synthesis and characterization of thiol-based aryl diazonium modified glassy carbon electrode for the voltammetric determination of low levels of Hg(II)

Electrochemical determination of Hg(II) in aquatic solutions on bare and modified glassy carbon electrode (GCE) is reported. Optimizing the parameters used for a bare GCE, such as the electrolyte solution, the potential and time of deposition, resulted in linear response over a large range of Hg(II) concentrations (4–160 ppb) using linear sweep anodic stripping voltammetry. Modification of the electrode with 4,4′-disulfanediyldibenzenediazonium (DSBD) yielded a lowest detection limit of 1 ppb. Two procedures for DSBD synthesis are described for the first time, and the product was characterized by microanalysis, FTIR and ¹H-NMR. The electrochemical attachment of DSBD to the electrode was studied and compared with the electrochemical behaviour of DSBD analogous molecules, i.e. 4-aminophenyl disulfide, p-aminothiophenol and phenyl disulfide.