Assembly of dithiocarbamate-anchored monolayers on gold surfaces in aqueous solutions

Dithiocarbamates (DTCs) can be formed by the in situ condensation of polar alkylamines with CS 2, and assembled into dithiocarbamate-anchored monolayers (DAMs) on Au substrates in aqueous solutions. Primary and secondary amines can both be used to prepare DTCs, but have significant differences in their reactivities and product stabilities. Ultraviolet absorption spectroscopy provides a convenient method for monitoring in situ DTC formation as well as the formation of potential byproducts. The kinetics of DAM assembly on Au substrates as measured by second harmonic generation (SHG) indicated first-order rate processes and saturation coverages similar to those of alkanethiols on Au. However, the rate of adsorption did not change with DTC concentration in a manner expected of Langmuir kinetics, and is attributed to the competitive adsorption of alkylammonium counterions to the freshly oxidized Au substrate. These analyses establish a practical range of conditions for preparing DAMs from polar amines using in situ DTC formation.     

Development of novobiocin analogues that manifest anti-proliferative activity against several cancer cell lines

Recent studies have shown that the DNA gyrase inhibitor, novobiocin, binds to a previously unrecognized ATP-binding site located at the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at approximately 700 microM. As a result of these studies, several analogues of the coumarin family of antibiotics have been reported and shown to exhibit increased Hsp90 inhibitory activity; however, the monomeric species lacked the ability to manifest anti-proliferative activity against cancer cell lines at concentrations tested. In an effort to develop more efficacious compounds that produce growth inhibitory activity against cancer cell lines, structure-activity relationships were investigated surrounding the prenylated benzamide side chain of the natural product. Results obtained from these studies have produced the first novobiocin analogues that manifest anti-proliferative activity against several cancer cell lines.     

Nonbonded, attractive cation-pi interactions in azide-mediated asymmetric ring expansion reactions

The influence of attractive, nonbonded interactions on the reactions of 1,2- and 1,3-hydroxyalkyl azides with ketones has been investigated through experimental and computational means. A series of 1,3-hydroxyalkyl azides bearing electronically tuned aromatic groups at the 2 position were prepared and reacted along with several derivatives designed to conformationally restrict the rotational orientation of the aromatic substituent. These studies showed that a cation-pi interaction between an aryl moiety and an N2(+) leaving group plays a role in determining the stereoselectivity of these reactions. A series of ab initio calculations supported this hypothesis. A computational and experimental analysis suggested a primarily steric model for the analogous reactions of substituted 2-azido-1-ethanol analogues.     

Size-controlled synthesis of highly water-soluble silver nanocrystals

We describe a modified polyol process for the synthesis of silver nanocrystals with uniform sizes ranging from several nanometers to 20 nm. The use of polyacrylic acid, in place of polyvinylpyrrolidone in the conventional polyol process, significantly limits the growth of silver nanocrystals, prevents the interparticle aggregation and fusion, and leads to a uniform population of samples with high water solubility. The size of nanocrystals can be conveniently tuned by controlling the reaction time, the concentration and chain length of the polymeric surfactants, and the reaction temperature. Uniform silver nanocrystals within sizes below 20 nm are preferred candidates over larger particles for applications where high density of optical absorption is required, for example, for photothermal conversion in cancer therapy.     

The 21st Century Physics Classroom: What Students,Teachers, and Classroom Observers Report

Before we can effectively apply specific interventions through professional development, it is important to determine what is occurring in our high school physics classrooms. This study investigated common professional practices in physics teaching among a representative sample group of schools and teachers from a diverse, geographically large population. An adaptation of a convergent parallel design was utilized in this study. Three separate parallel studies were conducted to answer the overarching research question, what is the nature of the secondary physics classroom in our high schools as they exist today? The results provide a unique picture of the variables impinging on physics teachers in their current classroom setting that converges from the particular viewpoints found in each of the parallel studies.     

Cavitands as Reaction Vessels and Blocking Groups for Selective Reactions in Water

The majority of reactions currently performed in the chemical industry take place in organic solvents, compounds that are generally derived from petrochemicals. To promote chemical processes in water, we examined the use of synthetic, deep water‐soluble cavitands in the Staudinger reduction of long‐chain aliphatic diazides (C₈, C₁₀, and C₁₂). The diazide substrates are taken up by the cavitand in D₂O in folded, dynamic conformations. The reduction of one azide group to an amine gives a complex in which the substrate is fixed in an unsymmetrical conformation, with the amine terminal exposed and the azide terminal deep and inaccessible within the cavitand. Accordingly, the reduction of the second azide group is inhibited, even with excess phosphine, and good yields of the monofunctionalized products are obtained. In contrast, the reduction of the free diazides in bulk solution yields diamine products.     

Elucidating the mechanism of the asymmetric aza-Michael reaction

The mechanism of the palladium-catalysed asymmetric aza-Michael addition of aniline to alpha,beta-unsaturated N-imide was examined from several aspects using a combination of techniques, including X-ray crystallography, mass spectrometry, NMR, UV/Vis spectroscopy, and kinetic studies. The binding of aniline to the dicationic palladium(II) metal centre was found to occur in two consecutive steps: The binding of the first aniline is fast and reversible, whereas the binding of the second aniline is slower and irreversible. This occurs in competition with the binding of the N-imide, which forms a planar six-membered chelate ring with the metal centre; coordinating through the 1,3-dicarbonyl moiety. Isotopic labelling revealed that the addition of N-H occurs in a highly stereoselective manner, allowing the synthesis of optically active beta(2)- and beta(2,3)-amino acid derivatives. The stereochemistry of the addition is postulated to be syn. In situ kinetic studies provided evidence for product inhibition. The binding of the N-imide to the catalyst was found to be the rate-limiting step. Aniline was found to be an inhibitor of the pre-catalyst. The study culminated in the design of a new reaction protocol. By maintaining a low concentration of the aniline substrate during the course of the reaction, significant enhancement of yield and enantioselectivity can be achieved.     

Alpha-substituted 1-aryl-3-dimethylaminopropanone hydrochlorides: potent cytotoxins towards human WiDr colon cancer cells

A series of 1-aryl-2-dimethylaminomethyl-2-propenone hydrochlorides 1 were prepared which possessed IC(50) values of less than 10 microM when examined towards human WiDr colon cancer cells. The related 1-aryl-2-dimethylaminomethyl-3-hydroxypropanone hydrochlorides 2, formed by hydration of the analogs in series 1, also had IC(50) values in the low micromolar range. On the other hand, conversion of 2-dimethylaminomethyl-1-(4-nitrophenyl)-2-propenone hydrochloride 1c into the corresponding 2-mercaptoethanol of adduct 3c led to a 37-fold reduction in potency. Two thirds of the compounds prepared in this study were more potent than a reference drug cisplatin while one third of these molecules displayed greater cytotoxicity to the WiDr cells than human CRL-2522 fibroblasts. A stability study of the 4-nitrophenyl analog in each of the series 1-3 in deuterium oxide was undertaken. In the case of 1c, replacement of the dimethylamino hydrochloride group by a hydroxy function was noted while in series 2, the loss of both water and dimethylamine hydrochloride gave rise to a mixture of two enones. The mercaptoethanol adduct 3c underwent deamination. The data obtained provide guidelines for amplifying the project in the future.