Development of Chip-Based Electrochemically- and Light-Directed Peptide Microarray Synthesis

abstract: ABSTRACT Peptide microarrays may prove to be a powerful tool for proteomics research and clinical diagnosis applications. Fodor et al. and Maurer et al. have shown proof-of-concept methods of light- and electrochemically-directed peptide microarray fabrication on glass and semiconductor microchips respectively. In this work, peptide microarray fabrication based on the abovementioned techniques were optimized. In addition, MALDI mass spectrometry based peptide synthesis characterization on semiconductor microchips was developed and novel applications of a CombiMatrix (CBMX) platform for electrochemically controlled synthesis were explored. We have investigated performance of 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) derivatives as photo-labile protecting group. Specifically, influence of substituents on 4 and 5 positions of phenyl ring of NPPOC group on the rate of photolysis and the yield of the amine was investigated. The results indicated that substituents capable of forming a π-network with the nitro group enhanced the rate of photolysis and yield. Once such properly substituted NPPOC groups were used, the rate of photolysis/yield depended on the nature of protected amino group indicating that a different chemical step during the photo-cleavage process became the rate limiting step. We also focused on electrochemically-directed parallel synthesis of high-density peptide microarrays using the CBMX technology referred to above which uses electrochemically generated acids to perform patterned chemistry. Several issues related to peptide synthesis on the CBMX platform were studied and optimized, with emphasis placed on the reactions of electro-generated acids during the deprotection step of peptide synthesis. We have developed a MALDI mass spectrometry based method to determine the chemical composition of microarray synthesis, directly on the feature. This method utilizes non-diffusional chemical cleavage from the surface, thereby making the chemical characterization of high-density microarray features simple, accurate, and amenable to high-throughput. CBMX Corp. has developed a microarray reader which is based on electro-chemical detection of redox chemical species. Several parameters of the instrument were studied and optimized and novel redox applications of peptide microarrays on CBMX platform were also investigated using the instrument. These include (i) a search of metal binding catalytic peptides to reduce overpotential associated with water oxidation reaction and (ii) an immobilization of peptide microarrays using electro-polymerized polypyrrole.Dissertation/ThesisPh.D. Chemistry 201

Understanding the Structure-Function Relationship in Peptide-Enabled High Entropy Alloy Nanocatalysts

The structural complexity in high entropy alloy nanocatalysts (HEAs), afforded by the homogeneous mixing of five or more elements, has resulted in a limited understanding about the origin of their promising electrocatalytic properties. This thesis investigates the structure-function relationship in HEAs using advanced material characterization techniques. At first, a methodology for resolving the atomic-scale structure of peptide-enabled HEAs was developed using high-energy X-ray diffraction (HE-XRD) coupled with atomic pair distribution function (PDF) and reverse Monte Carlo (RMC) simulations, yielding structure models over the length scale of HEAs. Coordination analysis of the structure models revealed a multifunctional interplay of geometric and electronic attributes of surface atoms in HEAs that was responsible for the catalytic activity enhancement during the methanol electrooxidation reaction. Using the methodology for resolving the atomic scale structure of HEAs and peptide sequence engineering, the structure-function relationship of model PtPdAuCoSn HEAs during ethanol electrooxidation reaction (EOR) was studied. Compositional analysis of the PtPdAuCoSn HEA structure models revealed distinct miscibility characteristics that were attributed to the unique biotic-abiotic interactions. Analysis of the structure models identified the rapid dehydrogenation of CH3CHO intermediate into CH3COads in an optimized adsorption configuration as the contributing factor for the high selectivity towards CH3COO- in PtPdAuCoSn HEAs. Armed with these insights, a study was designed for understanding the effect of changing the concentration of Pt in the structure-function relationship of PtPdAuCoSn HEAs using spatiotemporal structural insights from in-situ PDF. The structure models demonstrated a degree of metastability as a function of their corresponding configurational entropy. Analysis of the structure models revealed that high selectivity towards CH3COO- in PtPdAuCoSn HEAs during EOR originates from the enhanced distribution of Pd and Co surface atoms. In summary, this thesis uses atomic PDF and RMC simulations to draw structure-function correlations in HEAs, presenting a path forward for developing strategies for the rational design of HEAs. Through collaborative efforts from theoreticians and experimentalists, the methodology presented here can form the basis for accelerating the discovery of promising HEA configurations for emerging electrocatalytic applications

Aspects of Green Design in the Polymer Industry

This dissertation study addresses two important topics - development of a non-phosgene route for manufacture of isocyanates & a life cycle analysis comparison between polycarbonate and Tritan. Isocyanates are currently manufactured by the phosgenation route which involves reaction of an amine with phosgene. This process requires handling of hazardous chemicals and is not considered environmentally benign due to issues related to disposal / recycle of the hydrochloric acid formed as a byproduct. William McGhee et al have previously worked on a non-phosgene route for manufacture isocyanates from primary amine, carbon dioxide, nitrogenous base and an electrophilic dehydrating agent. However, due to the generation of large amount of salt of the dehydrating agent and the base, and due to the absence of an appropriate recycling strategy this route could not be commercialized. To reduce the salt formed, a modification to this route is presented by eliminating the use of the nitrogenous base and carrying out the reaction in excess of carbon dioxide. The effect of different solvents, dehydrating agents, varying temperature and pressures on the conversion to isocyanate and a recycling strategy for the by-products formed has been studied. The energy requirement for this process is compared with the traditional route using ASPEN Plus. The results have been used to understand the potential roadblocks in the commercialization of the new process and the future direction of work to improve it. The second part of the study is a life cycle analysis (LCA) comparison of polycarbonates with Tritan, which has been claimed to be an effective replacement for polycarbonates as it does not contain bisphenol-A, but still matches its physical and mechanical properties. However, the environmental impacts due the production of Tritan had not been studied yet. Hence, LCA study for polycarbonate and Tritan is performed on the basis of published literature. Effect due to different recycling strategies and different allocation techniques are studied on the overall environmental impact of these polymers. The study indicates that Tritan has lower impacts compared to polycarbonates in most of the impact categories studied. However, the extent to which Tritan performs better strongly depends on the functional unit considered

Comparison of a-Fe2O3 electrodes grown by direct plasma and thermal oxidation of iron for photoelectrochemical water splitting.

Iron oxide, Fe2O3, is a promising material for water splitting reaction using solar energy due to its stability and optimal bandgap of 2 eV. Even the recent efforts, however, using Fe2O3 thin film materials reported low efficiencies due to poor carrier transport within these films. A novel plasma oxidation method was used to synthesize arrays of a-Fe2O3 which are single crystal and have highly ordered oxygen vacancy planes. As one-dimensional nanostructures, these nanowires offer many other benefits to photoelectrochemical electrolysis, including high surface area, reduced charge carrier diffusion distance, and a preferential direction for charge diffusion. Furthermore, due to the ordered-oxygen vacancy planes in these nanowires, the high resistivity that has plagued this material may become a non-issue. The photoelectrochemical performance of these samples was compared to that of nanowire (and nanobelt) arrays grown by thermal oxidation of iron foils. Hematite samples grown by plasma oxidation were found to have considerably greater photoactivity than by thermal oxidation. This was attributed to the presence of a large (7.5 µm) mixed-phase interfacial layer in the latter, wherein the charge carriers are lost to recombination. Due to the fast growth process in plasma oxidation, the interfacial layer is much thinner (1 µm) and may in fact contain only hematite, rather than a mixed phase. Studies are currently underway to determine the interfacial layer composition. It is concluded that further studies of hematite for photoelectrochemical electrolysis should be performed using nanowire arrays grown by direct plasma oxidation

More is Different: Modern Computational Modeling for Heterogeneous Catalysis

La combinació d'observacions experimentals i estudis de la Density Functional Theory (DFT) és un dels pilars de la investigació química moderna. Atès que permeten recopilar informació física addicional d'un sistema químic, difícilment accessible a través de l'entorn experimental, aquests estudis es fan servir àmpliament per modelar i predir el comportament d'una gran varietat de compostos químics en entorns únics. A la catàlisi heterogènia, els models DFT s'utilitzen habitualment per avaluar la interacció entre els compostos moleculars i els catalitzadors, vinculant aquestes interpretacions amb els resultats experimentals. Tanmateix, l'alta complexitat trobada tant als escenaris catalítics com a la reactivitat, implica la necessitat de metodologies sofisticades que requereixen automatització, emmagatzematge i anàlisi per estudiar correctament aquests sistemes. Aquest treball presenta el desenvolupament i la combinació de múltiples metodologies per avaluar correctament la complexitat d'aquests sistemes químics. A més, aquest treball mostra com s'han utilitzat les tècniques proporcionades per estudiar noves configuracions catalítiques d'interès acadèmic i industrial.La combinación de observaciones experimentales y estudios de la Density Functional Theory (DFT) es uno de los pilares de la investigación química moderna. Dado que permiten recopilar información física adicional de un sistema químico, difícilmente accesible a través del entorno experimental, estos estudios se emplean ampliamente para modelar y predecir el comportamiento de una gran variedad de compuestos químicos en entornos únicos. En la catálisis heterogénea, los modelos DFT se emplean habitualmente para evaluar la interacción entre los compuestos moleculares y los catalizadores, vinculando estas interpretaciones con los resultados experimentales. Sin embargo, la alta complejidad encontrada tanto en los escenarios catalíticos como en la reactividad, implica la necesidad de metodologías sofisticadas que requieren de automatización, almacenamiento y análisis para estudiar correctamente estos sistemas. Este trabajo presenta el desarrollo y la combinación de múltiples metodologías con el objetivo de evaluar correctamente la complejidad de estos sistemas químicos. Además, este trabajo muestra cómo las técnicas proporcionadas se han utilizado para estudiar nuevas configuraciones catalíticas de interés académico e industrial.The combination of Experimental observations and Density Functional Theory studies is one of the pillars of modern chemical research. As they enable the collection of additional physical information of a chemical system, hardly accessible via the experimental setting, Density Functional Theory studies are widely employed to model and predict the behavior of a diverse variety of chemical compounds under unique environments. Particularly, in heterogeneous catalysis, Density Functional Theory models are commonly employed to evaluate the interaction between molecular compounds and catalysts, lately linking these interpretations with experimental results. However, high complexity found in both, catalytic settings and reactivity, implies the need of sophisticated methodologies involving automation, storage and analysis to correctly study these systems. Here, I present the development and combination of multiple methodologies, aiming at correctly asses complexity. Also, this work shows how the provided techniques have been actively used to study novel catalytic settings of academic and industrial interest