Silicones are widely used polymeric materials due to their unique properties. The material properties of silicones may be altered by incorporating various organic groups. Traditional methods for linear silicone synthesis involve ring-opening polymerization, which leaves the growing chain susceptible to acid or base mediated chain redistribution and the formation of cyclic monomer byproducts. The Piers-Rubinsztajn (PR) reaction is an alternative siloxane synthetic route that avoids the use of tin- or platinum- based, or of Brønsted acid/base catalysts. Siloxane bond formation is catalyzed by tris(pentafluorophenyl)borane (B(C6F5)3) (R’3Si-H + RO-SiR”3 → R’3Si-O-SiR”3 + RH); alkoxysilanes can be replaced with silanols or alkoxybenzenes. The catalytic activity of B(C6F5)3 was shown to be hindered by trace water in solution; water acts as a Lewis base coordinating to B(C6F5)3. Since the hydrate-free form of B(C6F5)3 is required to initiate a PR reaction, water can act as an inhibitor. In a somewhat contradictory fashion, water was also shown to react with hydrosilanes via a B(C6F5)3 catalyzed hydrolysis reaction to give silanols, that themselves are reagents for the process. The reactivity of alkoxysilanes (or aryl ethers) in the PR reaction was found to be much quicker than water. This was exploited in the synthesis of Ax(AB)yAx triblock copolymers. The aryl rich AB core was first synthesized using the PR reaction. Excess silicone condensed via hydrolysis forming the A blocks. This method of exploiting relative reactivity to tune structure was applied to elastomers made using a single linker (eugenol) with multiple functional groups – elastomer morphology was controlled by changing order of addition. The development of aryl dense silicones is of interest for use in electronic devices. Phenylmethyl homopolymers and highly ordered phenyl pendant copolymers (Ph/Si ratio of 0.5-1.5) were synthesized from monomers to give polymers with high refractive indices (1.51-1.59) and Mw up to 170 kDa. Statistically relevant libraries of aryl functional silicones were developed using combinatorial chemistry in order to analyze their structure-property relationship. Incorporating aromatic groups into silicones worked to elevate thermal stability, refractive index and improve the mechanical strength of silicone rubbers. / Thesis / Doctor of Science (PhD) / Silicone fluids and elastomers possess numerous desirable characteristics which leads to their use in a wide range of applications in the automotive, electronics and biomedical fields, among others. Developing techniques to create well defined, ordered, modified silicones with improved optical properties, mechanical strength and thermal stability was the main focus of this thesis. These objectives were accomplished by incorporating aromatic groups into silicones using boron catalysis. Following the initial (intended) Piers-Rubinsztajn reaction, atmospheric moisture was utilized to promote further polymerization. Statistically relevant libraries of silicone elastomers were prepared using both standard and combinatorial chemistry techniques. This library of elastomers permitted the analysis of trends associated with small changes in elastomer formulation, which could not be accomplished using traditional one-by-one reaction methods in a timely fashion. The modified silicone materials exhibited high refractive indices (up to 1.59), elevated stiffness and improved thermal stability (maintain structure up to 500 °C) when compared to previously synthesized polymers.

<p dir="ltr">Mass spectrometry (MS) has long been recognized as a technology for bioanalysis. However, this thesis focuses on exploiting mass spectrometry for chemical reactions. The work described here covers the (a) investigation of chemistry at interfaces by MS, (b) utilization of MS to accelerate drug discovery processes, and (c) applications of MS techniques for organic synthesis. MS techniques are used to scrutinize the distinctive chemistry and super acidity mechanisms at the gas/liquid interfaces by reacting carbon dioxide (gas phase) with amines (solution, in droplets). The intriguing trace water effect in creating this unique environment at the interfaces is described. A systematic survey of reactions promoted by glass microspheres at liquid/solid interfaces is conducted, revealing that glass surface can act as strong base to speed up reactions. Additionally, the ability of glass surface to degrade biomolecules is revealed, which has implications for bioanalysis. Desorption electrospray ionization (DESI), an ambient ionization method, can be used as a rapid analytical technique for the direct analysis of complex reaction mixtures or bioassays without sample workup. Moreover, DESI can also be used as a small-scale synthetic tool due to accelerated reactions in generated microdroplets. These characteristics make DESI a core technology for high-throughput (HT) experimentation that prioritizes speed to achieve three major roles. <b>(i) HT reaction screening</b> leverages the reaction acceleration phenomenon for rapid chemical space exploration, especially for the late-stage diversification of drug molecules. The entire process, from sampling the reaction mixture by droplets to on-the-fly chemical transformation during millisecond timescales to analysis by MS, achieves an overall throughput of one reaction per second in an integrated fashion. Diverse chemical transformations for various functional groups were achieved, with over 10⁴ reactions explored and over 10³ analogs identified within three hours. <b>(ii) HT synthesis</b> is achieved using an automated homebuilt array-to-array transfer system. The synthetic system uses DESI microdroplets for transferring reaction mixtures from a precursor array to products on a product array. High conversions of diverse reactions with synthetic throughput of 0.2-0.02 Hz and scale of ng-µg (pmole-nmole) in a spatially resolved manner are demonstrated. Hundreds of modified bioactive molecules are generated in an array format, and the spatial distribution of the products is visualized by mass spectrometry imaging. <b>(iii) HT bioassays</b> are demonstrated by combining the label-free nature of MS with the high-speed analysis of DESI. The contactless feature, with high tolerance towards complex mixtures, allows direct bioassays with minimal sample preparation. An opioid receptor binding assay is described with an evaluation of the binding affinity of synthesized opioid analogs. An on-surface enzymatic assay is developed for measuring the bioactivity of deposited molecules <i>in situ</i>. The consolidation of (i) HT reaction screening, (ii) HT synthesis, and (iii) HT bioassays by a single but versatile technique, HT-DESI, can expedite the early drug discovery process. For applications, MS technologies are utilized to probe reactive intermediates and the reaction mechanisms of palladium-catalyzed coupling reactions. MS is also used to explore chemical reactions for natural products, rapidly generating analogs for bioactivity evaluation and benefiting bioanalysis through the discovery of derivatization reactions. HT tandem MS is demonstrated to be powerful for structural elucidation and reaction site identification.</p>