Rapid parallel synthesis of combinatorial libraries of substituted 3-thio-1,2,4-triazoles and 2-thioimidazoles

Combinatorial libraries of substituted 3-thio-1,2,4-triazoles and 2-thioimidazoles were synthesized in good yield by alkylation of the products via the reaction of isothiocyanates and carboxylic acid hydrazides or beta-aminoketones, respectively. A total of 275 3-thio-1,2,4-triazoles and 283 2-thioimidazoles were synthesized out of the attempted 288 in each case. Most the yields were between 45% and 98%, and all the compounds synthesized were purified to >85% purity. Variations in yields revealed no definitive trends and were mainly attributed to bulky alkylating agents used and the plate well location of the reaction mixtures.     

A method for bioconjugation of carbohydrates using Diels-Alder cycloaddition

Diels-Alder-type cycloaddition of an electronically matched pair of saccharide-linked conjugated dienes and a dienophile-equipped protein gives neoglycoproteins at ambient temperature in pure water with a reaction half-life of approximately 2 h. Uncoupled saccharides can be recovered by diafiltration with complete conservation of the diene moiety, thus allowing their repeated use. The procedure described is the first for creating a carbon-carbon covalent bond in the bioconjugation step between a saccharide and a protein.     

Nonparametric tests for bounds on the derivative of a regression function

We consider two tests of the null hypothesis that the k-th derivative of a regression function is uniformly bounded by a specified constant. These tests can be used to study the shape of the regression function. For instance, we can test for convexity of the regression function by setting k=2 and the constant equal to zero. Our tests are based on k-th order divided difference of the observations. The asymptotic distribution and efficacies of these tests are computed and simulation results presented.Research supported by Natural Sciences and Engineering Research Council of Canada Grant OGP0007969.Research supported by National Science Foundation Grant DMS-9306738.     

THE INTERACTION OF 8-AZIDOETHIDIUM AND tRNA

Abstract Optical spectroscopy and proton nuclear magnetic resonance spectroscopy have been used to investigate the non-covalent and covalent binding of 8-azidoethidium (8-azido-3-amino-5-ethyl-6-phe-nyl-phenanthridium) with transfer RNA (tRNA) molecules. The nuclear magnetic resonance measurements demonstrate that ethidium and ethidium monoazide bind to the same unique binding site on tRNA molecules. However, the optical studies demonstrate that the photochemical reaction between ethidium monoazide and tRNA generates at least three different photoproducts. One of the covalent photoproducts has fluorescence properties which mimic those of intercalated, non-covalently bound ethidium, but it is produced only in about 10% yield. The major photoproduct(s) is(are) virtually non-fluorescent. The ethidium monoazide photochemistry with tRNA molecules is obviously complex and this may complicate its use as a photolabel of polynucleotides.     

The swelling interface number as a criterion for prediction of diffusional solute release mechanisms in swellable polymers

When a glassy polymer containing a uniformly dispersed solute is brought in contact with a penetrant, solute diffusion will be associated with the transport mechanism and penetration velocity of the penetrant in the polymer. Analysis and prediction of mechanisms of diffusional solute release may be obtained through a new dimensionless number, the swelling interface number, Sw, which compares the relative mobilities of the penetrant and the solute in the presence of macromolecular relaxations in the polymer. It is shown that a sufficient and necessary criterion for time-independent diffusional solute release rates from these swellable systems is that the Sw be smaller than 10^?2. The swelling interface number Sw may be related to easily determined structural and thermodynamic parameters of the solute/polymer/penetrant system. Preliminary experimental results of dynamic water swelling of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) and diffusional release of theophylline from initially glassy copolymers show that decreasing values of Sw are related to increased pseudo-case-II transport kinetics of the solute.     

Oxidation Products of Retinylidene Dimedone

Several oxidation products of the retinoid retinylidene dimedone (RD) have been synthesized and characterized for biological testing in the expectation that they may be found as metabolites of RD.     

Scanning tunneling microscopy and surface simulation of zinc-blende GaN(001) intrinsic 4x reconstruction: linear gallium tetramers?

Scanning tunneling microscopy images confirm electron diffraction studies that the zinc-blende GaN(001)-4x reconstruction consists of rows aligned along [110] with a spacing along [110] of 4a. Dual-bias imaging shows a 180 degree shift of the corrugation maximum position between the profiles of empty and occupied states, in agreement with surface simulations based on the 4 x 1 linear tetramer model of Neugebauer et al. [Phys. Rev. Lett. 80, 3097 (1998)]. Electronic structure calculations predict a surface band gap of 1.1 eV, close to the measured value of 1.14 eV and the previously predicted value (1.2 eV). Despite the successes of this model, high-resolution images reveal an unexpected 3x periodicity (not seen in diffraction) along the [110] row direction, indicating the need for a 4 x 3 model, and putting into question the existence of linear Ga tetramers.     

Tetrabromobutatriene: completing the perhalocumulene series

[structure: see text] Tetrabromobutatriene, C(4)Br(4), can be prepared directly from dibromobutadiyne by reaction with Br(2) at -25 degrees C in concentrated hexanes solution. The cumulene precipitates out of the reaction mixture as a yellow powder. Under palladium-catalyzed coupling conditions, C(4)Br(4) can undergo allylic rearrangement, giving a mixture of products, including some with butenyne backbones. However, in furan solution, C(4)Br(4) reacts cleanly at its central double bond to give the furan Diels-Alder adduct. Under Suzuki conditions, this adduct reacts at the furan double bond rather than at bromide.