Synthesis of a sulfahydantoin library

A five-step solid-phase synthesis of sulfahydantoins from alpha-amino acids and aldehydes was developed. The synthetic method allows the use of hindered amino acids, including Val, Phg, and Aib, and use of aromatic aldehydes substituted with electron-withdrawing and -donating groups. Some limitations were encountered with amino acids with reactive side chains. A small but diverse library of compounds was produced for biological testing.     

Ruminations regarding the design of small mixtures for biological testing

Synthesis and screening of compound mixtures offer avenues to increase throughput and reduce cycle time in the discovery of new drugs and agrochemicals. Equations are derived which show that the efficiency of synthesis and screening of mixtures is a function of the screening hit rate and the number of compounds in each mixture when simple one-step deconvolution by retesting the individual compounds in each active mixture is employed. Values of hit rate and number of compounds in each mixture which afford various levels of increased efficiency are delineated. Two-step deconvolution, in which the active mixtures from the first round of testing are subdivided into mixtures with fewer compounds for a second round of mixture screening prior to final testing of individual compounds, is shown to be more efficient than simple one-step deconvolution under most conditions. For optimum efficiency, the number of compounds in each mixture in the second round testing should be the square root of the number of compounds in each mixture in the first round. At high hit rates the efficiency of the double scan or indexed approach to deconvolution is shown to be higher than that of simple deconvolution. This discussion is oriented mainly toward mixtures of 4-20 compounds and screens which give hit rates in the 1-10% range. The equations describing efficiency are applied in the context of a 49-member amide library produced as mixtures of seven compounds. This library includes the commercial herbicide pronamide and was screened for herbicidal and insecticidal utility.     

Almost Exponential Decay of Periodic Viscous Surface Waves without Surface Tension

We consider a viscous fluid of finite depth below the air, occupying a three-dimensional domain bounded below by a fixed solid boundary and above by a free moving boundary. The fluid dynamics are governed by the gravity-driven incompressible Navier–Stokes equations, and the effect of surface tension is neglected on the free surface. The long time behavior of solutions near equilibrium has been an intriguing question since the work of Beale (Commun Pure Appl Math 34(3):359–392, 1981). This paper is the third in a series of three (Guo in Local well-posedness of the viscous surface wave problem without surface tension, Anal PDE 2012, to appear; in Decay of viscous surface waves without surface tension in horizontally infinite domains, Preprint, 2011) that answers this question. Here we consider the case in which the free interface is horizontally periodic; we prove that the problem is globally well-posed and that solutions decay to equilibrium at an almost exponential rate. In particular, the free interface decays to a flat surface. Our framework contains several novel techniques, which include: (1) a priori estimates that utilize a “geometric” reformulation of the equations; (2) a two-tier energy method that couples the boundedness of high-order energy to the decay of low-order energy, the latter of which is necessary to balance out the growth of the highest derivatives of the free interface; (3) a localization procedure that is compatible with the energy method and allows for curved lower surface geometry. Our decay estimates lead to the construction of global-in-time solutions to the surface wave problem.     

Evaluation of solution and solid-phase approaches to the synthesis of libraries of alpha,alpha-disubstituted-alpha-acylaminoketones

Solid phase, solution, and hybrid approaches to the synthesis of small focused libraries of alpha,alpha-disubstituted-alpha-acylaminoketones have been explored. Solution and hybrid approaches that used support-bound reagents and scavenger resins were the most productive.     

ClnH6-nSiGe compounds for CMOS compatible semiconductor applications: synthesis and fundamental studies

We describe the synthesis of a new family of chlorinated Si-Ge hydrides based on the formula ClnH6-nSiGe. Selectively controlled chlorination of H3SiGeH3 is provided by reactions with BCl3 to produce ClH2SiGeH3 (1) and Cl2HSiGeH3 (2). This represents a viable single-step route to the target compounds in commercial yields for semiconductor applications. The built-in Cl functionalities are specifically designed to facilitate selective growth compatible with CMOS processing. Higher order polychlorinated derivatives such as Cl2SiHGeH2Cl (3), Cl2SiHGeHCl2 (4), ClSiH2GeH2Cl (5), and ClSiH2GeHCl2 (6) have also been produced for the first time leading to a new class of highly reactive Si-Ge compounds that are of fundamental and practical interest. Compounds 1-6 are characterized by physical and spectroscopic methods including NMR, FTIR, and mass spectroscopy. The results combined with first principles density functional theory are used to elucidate the structural, thermochemical, and vibrational trends throughout the general sequence of ClnH6-nSiGe and provide insight into the dependence of the reaction kinetics on Cl content in the products. The formation of 1 was also demonstrated by an alternative route based on the reaction of (SO3CF3)SiH2GeH3 and CsCl. Depositions of 1 and 2 at very low temperatures (380-450 degrees C) produce near stoichiometric SiGe films on Si exhibiting monocrystalline microstructures, smooth and continuous surface morphologies, reduced defect densities, and unusual strain properties.     

Modification of the BAX Salmonella test kit to include a hot start functionality (modification of AOAC Official Method 2003.09)

In 2010, the BAX System PCR assay for Salmonella was modified to include a hot start functionality designed to keep the reaction enzyme inactive until PCR begins. To validate the assay's Official Methods of Analysis status to include this procedure modification, an evaluation was conducted on four food types that were simultaneously analyzed with the BAX System and either the U.S. Food and Drug Administration's Bacteriological Analytical Manual or the U.S. Department of Agriculture-Food Safety and Inspection Service Microbiology Laboratory Guidebook reference method for detecting Salmonella. Identical performance between the BAX System method and the reference methods was observed. Additionally, lysates were analyzed using both the BAX System Classic and BAX System Q7 instruments with identical results using both platforms for all samples tested. Of the 100 samples analyzed, 34 samples were positive for both the BAX System and reference methods, and 66 samples were negative by both the BAX System and reference methods, demonstrating 100% correlation. No instrument platform variation was observed. Additional inclusivity and exclusivity testing using the modified test kit demonstrated the test kit to be 100% accurate in evaluation of test panels of 352 Salmonella strains and 46 non-Salmonella strains.