Synthesis of Chiral Silanes

The lack of a simple, single step synthesis of chiral silanes is an obstacle to the use of chiral silanes in the synthesis of chiral drugs or materials because there are no naturally occurring chiral, nonracemic silicon compounds. Therefore, it would be useful to find a method that provides high yields of chiral, nonracemic, silicon compounds that can be used in synthesizing chiral drugs. Initial studies done in Sommer’s et al. (1964) laboratory required a multistep synthesis for preparing chiral silicon compounds. This method had poor yields and required much time and hence hindered the use of chiral silicon compounds. Therefore, finding the development of a single-step synthesis for making chiral silanes is important and can lead to several advantages over a multistep synthesis such as it is more efficient, it is less expensive, and it would take less time to make. A previous GVSU student has shown that reaction of a pro-chiral dimenthoxyphenylmethylsilane with nucleophiles can produce a chiral silane with good selectivity for phenyl and methyl groups. In our current study, the overall goal of this project was to find a single-step synthesis that can yield a single enantiomer when the substituents are a phenyl and a vinyl group. The starting material, dimenthoxyphenylvinylsilane was prepared from dichlorophenylvinylsilane. Dicholorophenylvinylsilane reacted with 2 equivalents of menthoxyllithium in THF solvent to produce dimenthoxyphenylvinylsilane, which was then purified by column chromatography and the product was isolated in a 72.6 % yield. The dimenthoxyphenylvinylsilane was used for the reactions in preparing chiral silicon compounds. Napthyllithium, butyllithium, methyllithium, and tert-butyllithium reacted with the dimenthoxyphenylvinylsilane to form the chiral silicon compounds. These reactions were performed under N2, in hexane solvent at -78o C except the reaction of dimenthoxyphenylvinylsilane with tert-butyllithium which was done in diethyl ether solvent. After the products were made, these compounds were purified by column chromatography, then they were analyzed with the use of NMR, GC- Mass Spectrum, and HPLC. The yields of these reactions varied from 18.4% to 72.05% and in the case of the methyllithium substitution initial results were consistent with a high selectivity for one enantiomer. Our hypothesis for the selectivity observed in these reactions is that nucleophiles are more likely to attack the silicon at the more open-side that would lead into a higher selectivity. The crowded side of the dimenthoxyphenylvinylsilane is less likely to undergo nucleophilic substitution because steric-effect would occur and would prevent the nucleophile from attacking the electrophilic silicon atom. We have investigated the reactions of dimenthoxyphenylvinylsilane with different organolithiums to produce a series of chiral silanes which have been isolated in moderate to good yield. Future studies of these compounds will involve further characterization of the new compounds made and substitution of the menthoxy group with hydride and bromide to form a silicon compound that can be readily used in the synthesis of chiral organic molecules. *This scholar and faculty mentor have requested that only an abstract be published

Two-dimensional monadicity

The behaviour of limits of weak morphisms in 2-dimensional universal algebra is not 2-categorical in that, to fully express the behaviour that occurs, one needs to be able to quantify over strict morphisms amongst the weaker kinds. F-categories were introduced to express this interplay between strict and weak morphisms. We express doctrinal adjunction as an F-categorical lifting property and use this to give monadicity theorems, expressed using the language of F-categories, that cover each weaker kind of morphism

Well-defined protein-polymer conjugates—synthesis and potential applications

During the last decades, numerous studies have focused on combining the unique catalytic/functional properties and structural characteristics of proteins and enzymes with those of synthetic molecules and macromolecules. The aim of such multidisciplinary studies is to improve the properties of the natural component, combine them with those of the synthetic, and create novel biomaterials in the nanometer scale. The specific coupling of polymers onto the protein structures has proved to be one of the most straightforward and applicable approaches in that sense. In this article, we focus on the synthetic pathways that have or can be utilized to specifically couple proteins to polymers. The different categories of well-defined protein-polymer conjugates and the effect of the polymer on the protein function are discussed. Studies have shown that the specific conjugation of a synthetic polymer to a protein conveys its physico-chemical properties and, therefore, modifies the biodistribution and solubility of the protein, making it in certain cases soluble and active in organic solvents. An overview of the applications derived from such bioconjugates in the pharmaceutical industry, biocatalysis, and supramolecular nanobiotechnology is presented at the final part of the articl

Impact of slowdown of Atlantic overturning circulation on heat and freshwater transports

Recent measurements of the strength of the Atlantic overturning circulation at 26°N show a 1 year drop and partial recovery amid a gradual weakening. To examine the extent and impact of the slowdown on basin wide heat and freshwater transports for 2004–2012, a box model that assimilates hydrographic and satellite observations is used to estimate heat transport and freshwater convergence as residuals of the heat and freshwater budgets. Using an independent transport estimate, convergences are converted to transports, which show a high level of spatial coherence. The similarity between Atlantic heat transport and the Agulhas Leakage suggests that it is the source of the surface heat transport anomalies. The freshwater budget in the North Atlantic is dominated by a decrease in freshwater flux. The increasing salinity during the slowdown supports modeling studies that show that heat, not freshwater, drives trends in the overturning circulation in a warming climate

A generic framework for context-sensitive analysis of modular programs

Context-sensitive analysis provides information which is potentially more accurate than that provided by context-free analysis. Such information can then be applied in order to validate/debug the program and/or to specialize the program obtaining important improvements. Unfortunately, context-sensitive analysis of modular programs poses important theoretical and practical problems. One solution, used in several proposals, is to resort to context-free analysis. Other proposals do address context-sensitive analysis, but are only applicable when the description domain used satisfies rather restrictive properties. In this paper, we argüe that a general framework for context-sensitive analysis of modular programs, Le., one that allows using all the domains which have proved useful in practice in the non-modular setting, is indeed feasible and very useful. Driven by our experience in the design and implementation of analysis and specialization techniques in the context of CiaoPP, the Ciao system preprocessor, in this paper we discuss a number of design goals for context-sensitive analysis of modular programs as well as the problems which arise in trying to meet these goals. We also provide a high-level description of a framework for analysis of modular programs which does substantially meet these objectives. This framework is generic in that it can be instantiated in different ways in order to adapt to different contexts. Finally, the behavior of the different instantiations w.r.t. the design goals that motivate our work is also discussed

Applications of omics approaches to the development of microbiological risk assessment using RNA virus dose–response models as a case study

The last decade has seen a huge increase in the amount of “omics” data available and in our ability to interpret those data. The aim of this paper is to consider how omics techniques can be used to improve and refine microbiological risk assessment, using dose response models for RNA viruses, with particular reference to norovirus through the oral route as the case study. The dose response model for initial infection in the gastrointestinal tract is broken down into the component steps at the molecular level and the feasibility of assigning probabilities to each step assessed. The molecular mechanisms are not sufficiently well understood at present to enable quantitative estimation of probabilities on the basis of omics data. At present, the great strength of gene sequence data appears to be in giving information on the distribution and proportion of susceptible genotypes (for example due to the presence of the appropriate pathogen-binding receptor) in the host population rather than in predicting specificities from the amino acid sequences concurrently obtained. The nature of the mutant spectrum in RNA viruses greatly complicates the application of omics approaches to development of mechanistic dose response models and prevents prediction of risks of disease progression (given infection has occurred) at the level of the individual host. However, molecular markers in the host and virus may enable more broad predictions to be made about the consequences of exposure in a population. In an alternative approach, comparing the results of deep sequencing of RNA viruses in the faeces/vomitus from donor humans with those from their infected recipients may enable direct estimates of the average probability of infection per virion to be made