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Published Content: Jeedimalla, N.; Jacquet, C.; Bahneva, D.; Youte Tendoung, J.-J.; Roche, S. P. J. Org. Chem. 2018, 83, 12357. The present thesis will be focused on the study of House-Meinwald Rearrangement (HMR) reactions for the congested trisubstituted spiro-epoxide molecules. Including their regio-selective, chemo-selective, enantio- selective selective and stereo-selectivity’s will be discussed in detailed by the mechanistic study approach of HMR reaction of trisubstituted spiro-epoxides. Chapter 1 will present the efforts towards the biomimetic total synthesis of meroterpenoid natural product (+)-liphagal, which possess a recognizable biological activity. The shortcomings associated with its stereochemical assignment, and also the revision of stereochemical assignment of siphonodictyal B, through which the biosynthesis of (+)-liphagal was proposed were discussed. Chapter 2 will focus on the study of regio and chemoselective HMR reaction. In addition, a three-step sequence for the synthesis of α-arylated cyclohexanones and the most challenging cycloheptanones is reported. First, an efficient one-pot synthesis of β, β’-disubstituted benzylidene cycloalkanes using the palladium-catalyzed Barluenga reaction from readily available feedstock chemicals is described. Second, an epoxidation followed by the HMR of spiro-epoxides is reported to produce a number of α -arylated cycloalkanones upon the ring expansion. Reactions catalyzed by bismuth triflate underwent quasi-exclusively ring expansion for all substrates (electronically poor and rich), demonstrating the difficulty to achieve the ring enlargement for electron deficient spiro-epoxides. On the other hand, via catalysis with aluminium trichloride the rearrangement proceeded typically in high yields and with remarkable regioselectivity. In this case, a switch of regioselectivity was achieved for spiro-epoxides with electron-withdrawing substituents which enabled this method to be successfully extended to some chemo specific arene shifts and it can also synthesize aldehydes derivatives bearing a α-quaternary carbon. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

The p-conjugated supramolecular aggregates have gained significant interest in recent years. The cyanine dye aggregates are particularly interesting due to their unique optical and excitonic properties, which cannot be found in individual molecules. Cyanine dyes can form different kinds of aggregates. H-aggregates are formed when dye molecules are packed in a face-to-face fashion, which gives rise to a blue-shift absorption band and strong emission quenching compared to the monomer. J-aggregates are composed of individual dye molecules in a head-to-tail stacking, which leads to a red-shift absorption band and a sharp intense emission band with a small Stoke shift compared with the monomer. The oblique aggregates are formed when dye molecules are twisted and show both H and J-band, which split from the monomer band. Using organic dye as a fluorescent probe for detection is not a novel idea. However, the unstable and high fluorescence blocked the application. The cyanine dye aggregates have great potential to be used as a stable, sensitive, and accurate probe. Serum albumins are the most crucial protein in the blood, and it carries essential physiologic functions. The serum albumin level in urine can be used as an indicator of patient's health condition. The presence and elevated concentration level of serum albumin can be caused by several diseases, such as diabetes, liver and kidney disorders. People have developed many SA detection methods; however, most of them are time-consuming and need expensive equipment. In this dissertation, we studied the self-assembly behavior of 3,3'-ditetradecyloxacarbocyanine (DiOC14(3)) and 3,3'-Dioctadecyloxacarbocyanine (DiOC18(3)) in methanol/water mixture with and without the presence of ammonia. We studied how the structure of dye molecules, the concentration, and OH^-will influence the morphology and property of aggregates. Then we used different DiOC14(3) aggregates as a fluorescence probes to detect BSA in synthetic urine. We found DiOC14(3) non-crystalline aggregates has highly specific turn-on fluorescence property to BSA. The sensitivity and selectivity of found DiOC14(3) non-crystalline aggregates have great potential for early diagnosis of liver, kidney disorders, and other diseases.

Charged therapeutics such as nucleic acids and proteins can treat a vast range of human diseases that are traditionally undruggable. Their broadness in treating disease is due to their ability to influence cellular function. However, their high charge density and physiological barriers such as enzymatic degradation, hinder the deliverability of these molecules to the sites of disease. Polyelectrolyte complex (PEC) micelles are core-corona nanostructures that can encapsulate charged molecules and offer a platform for delivery. PECs form the core, when two oppositely charged polyelectrolytes are mixed in an aqueous solution, and the micelle corona is a neutral hydrophilic polymer that is conjugated to either one or both polyelectrolytes. The core promotes the encapsulation of charged therapeutics, while the corona offers protection, biocompatibility, and can be decorated with targeting ligands for improved bioavailability. PEC micelles can be highly tunable systems, allowing for features such as on-demand release capabilities to be engineered by altering the corona or core properties. In the first part of the dissertation, we use a thermoresponsive polymer to change the corona properties and study the structural changes at a physiologically hyperthermic temperature using dynamic light scattering (DLS) and small-angle x-ray scattering (SAXS). The structural changes were a function of the composition of the corona, with severe structural loss with a fully thermoresponsive corona and a preserved structure within larger aggregates for a partially thermoresponsive corona. Understanding the encapsulation capabilities and the effect of the PEC core properties on the micellar shape and size is of fundamental significance to the design of these micelles as drug delivery carriers. Using several physiochemical characterization techniques such as optical microscopy, fluorescence spectroscopy, DLS, SAXS, Förster resonance energy transfer (FRET) and transmission electron microscopy (TEM), we determined fundamental properties affecting the encapsulation capabilities and studied the structural changes and molecular dynamics of PEC micelles.

Colloidal materials are highly diverse and present complex physicochemical properties which define their utilities in applications spanning diverse industries. In particular, nano-scale colloids have received tremendous attention due to their unique, specific activities as compared to larger-sized preparations. Within the biomedical sciences, nano-colloids are routinely used as inert carriers of therapeutics and/or diagnostic agents. Beyond this, researchers have developed functional colloids which demonstrate bio-active or diagnostic properties themselves: often related to an optimized, or tuned, surface character. Among these, nanoscale cerium oxide (nanoceria) has shown great promise as a bi-functional, therapeutic material: producing pro- or anti- oxidative chemical response in bio-systems via unique redox reactions mediated by the material surface. Studies investigating these reactions have highlighted details of material synthesis and, in particular, of the physicochemical environment interfacing with the material. Attention has been especially focused on the impacts of surface hydration/hydroxylation; ligand and co-/counter- ion adsorption/complexation; and re-structuring/micro-structuring on redox chemistry. This work seeks to address the complex surface character of several nanoceria formulations and to engineer novel formulations with potentiated redox activity. In particular, the influence of synthesis/processing conditions on colloidal stability, and surface properties are examined. The first section provides an introduction/overview of related colloid science and implications to nanoceria. Sections 2 and 3 highlight specific physicochemical properties relating to colloid formation and the effects of ageing on a peroxide-based nanoceria synthesis. Further, the developed understanding of these properties is used to produce surface-modified formulations with optimized redox properties for material use in biomedical applications. Section 4 details a study into the preparation of novel silver-modified nanoceria formulations, as well as highlights the variation in material surface character with unique synthesis conditions/processing. Further, syntheses of doped cerium oxide formulations are performed to produce particles of varying oxygen vacancy densities. Electroanalytical techniques (voltammetric techniques) are used to provide detailed characterization of fundamental material character related to surface activity. Assays for enzyme-mimetic activities are used throughout to compare and optimize formulations.

The self-assembly of oppositely charged polymers provides a versatile platform to design materials for diverse applications in biology and medicine. Electrostatically-driven phase separation of oppositely charged polymers in aqueous solution gives rise to the formation of a polymer-rich phase called a polyelectrolyte complex (PEC). PECs can be in the form of liquid droplets (complex coacervates) or amorphous solid precipitates. Unlike synthetic polymers, peptides are good candidates for developing tailor-made formulations and structure-property relationships due to their biocompatibility, precise control over sequences, and ability to program hydrogen bonding interactions. However, little is known about the effect of combining additional molecular interactions with electrostatic interactions in PECs. We have created a library of oppositely charged polypeptides to examine the effect of increased hydrophobic and π-interactions on polyelectrolyte complexes. Characterization of the designed polypeptides is confirmed by matrix-assisted laser desorption ionization–time of flight mass spectroscopy, circular dichroism, and proton nuclear magnetic resonance spectroscopy. First, we discuss the role of increased hydrophobicity of the peptide pairs on complex formation. By designing a new pattern of peptide sequences, we show the experimental evidence (turbidity measurements, infrared spectroscopy, and optical microscopy) that liquid complexes form by disrupting hydrogen bonds through steric hindrance and increased hydrophobicity results in higher stability of complexes against salt and temperature. Subsequently, we address the ability of these materials to encapsulate small hydrophobic molecules. Then, we evaluate the effect of π-interactions on polypeptide complexes. π-interactions together with other forces affect the amount of hydrogen bonding in polypeptide complexes, which is correlated to the phase behavior. We discuss the stability of the complexes against different ionic strengths considering the interplay between ionic and non-ionic interactions. Finally, the encapsulation efficiency of a model molecule containing π-bonds highlights the role of the cooperative effect of ionic and π-interactions on the encapsulation properties of PECs.

The need for nanoscale, non-invasive functional characterization has become more significant with advances in nano-biotechnology and related fields. Exploring the ultrastructure of plant cell walls and plant-derived materials is necessary to access a more profound understanding of the molecular interactions in the systems, in view of a rational design for sustainable applications. This, in turn, relates to the pressing requirements for food, energy and water sustainability experienced worldwide. Here we will present our advanced characterization approach to study the effects of external stresses on plants, and resulting opportunities for biomass valorization with an impact on the food-energy-water nexus. First, the adaption of plants to the pressure imposed by gravity in poplar reaction wood will be discussed. We will show that a multiscale characterization approach is necessary to reach a better understanding of the chemical and physical properties of cell walls across a transverse section of poplar stem. Our Raman spectroscopy and statistical analysis reveals intricate variations in the cellulose and lignin properties. Further, we will present evidence that advanced atomic force microscopy can reveal nanoscale variations within the individual cell wall layers, not attainable with common analytical tools. Next, chemical stresses, in particular the effect of Zinc-based pesticides on citrus plants, will be considered. We will show how multiscale characterization can support the development of new disease management methods for systemic bacterial diseases, such as citrus greening, of great importance for sustainable agriculture. In particular, we will focus on the study of new formulations, their uptake and translocation in the plants following different application methods. Lastly, we will consider how plant reactions to mechanical and chemical stresses can be controlled to engineer biomass for valorization applications. We will present our characterization of two examples: the production of carbon films derived from woody lignocellulosic biomass and the development of nanoscale growth promoters for food crop. A perspective of the work and discussion of the broader impact will conclude the presentation.

Tissue grafts are the gold standard for replacing large volume tissue defects. Yet, they present several risks, including infection, low functional outcomes, and reduced graft integrity. Tissue engineering (TE) combines cells and biomaterial scaffolds to foster tissue growth and remodeling. Bone marrow stromal cells (BMSCs) have been shown to respond to the stiffness of their microenvironment, resulting in differentiation into different lineages. 3D porous chitosan-alginate (CA) scaffolds have been previously demonstrated for bone TE with osteoblasts and BMSCs; however, only a single scaffold composition (4 wt%) was studied. Three CA scaffold compositions (2, 4, 6 wt% CA) were produced. Scanning electron microscopy images were obtained to determine average pore sizes for 2, 4, and 6 wt% CA scaffolds, which were 233, 208, and 146 ?m. Compression testing was performed on CA scaffolds in dry and wet conditions, where higher concentrations yielded higher stiffnesses ranging from 0.22 to 5.34 kPa and 21.1 to 47.3 Pa, respectively. Fourier transform infrared spectroscopy performed on the CA scaffolds confirmed polyelectrolyte complex formation for all compositions. Human BMSCs from three donors were seeded on CA scaffolds, cultured in growth media for 14 days, then cultured in adipogenic or osteogenic differentiation media for 28 days to promote differentiation. Our hypothesis was that scaffold stiffness would influence BMSC differentiation, with softer scaffolds promoting adipogenesis and stiffer scaffolds promoting osteogenesis. BMSCs formed multicellular spheroids in all CA scaffold concentrations, while the 2 wt% CA scaffolds had smaller spheroids compared to the 4 wt% and 6 wt% CA scaffolds. Osteogenic and adipogenic differentiation were evaluated with Alizarin Red and Oil Red O staining, respectively. While positive staining was observed in all scaffold compositions, more robust differentiation was expected, thereby disproving our hypothesis. The polysaccharide composition of the CA scaffolds likely contributed to the spheroid formation and limited differentiation.

The Body-on-a-Chip (BoaC) is a microfluidic BioMEMs project that aims to replicate major organs of the human body on a chip, providing an in vitro drug testing platform without the need to resort to animal model testing. Using a human model also provides significantly more accurate drug response data, and may even open the door to personalized drug treatments. Microelectrode arrays integrated with human neuronal or human cardiac cells that are positioned on the electrodes are essential components for BoaC systems. Fabricating these substrates relies heavily on chemically patterned surfaces to control the orientation and growth of the cells. Currently, cells are plated by hand onto the surface of the chemically patterned microelectrode arrays. The cells that land on the cytophobic 2-[Methoxy(Polyethyleneoxy)6-9Propyl]trimethoxysilane (PEG) coating die and detach from the surface, while the cells that land on the cytophilic diethylenetriamine (DETA) coating survive and attach to the surface exhibiting normal physiology and function. The current technique wastes a significant amount of cells, some of which are extremely expensive, and is labor intensive. Cell printing, the process of dispensing cells through a 3D printer, makes it possible to pinpoint the placement of cells onto the microelectrodes, drastically reducing the number of cells utilized. Scaled-up manufacturing is also possible due to the automation capabilities provided by printing. In this work, the specific conditions for printing each cell type is unique, the printing of human motoneurons, human sensory neurons and human cardiac cells was investigated. The viability and functionality of the printed cells are demonstrated by phase images, immunostaining and electrical signal recordings. The superior resolution of cell printing was then taken one step further by successfully printing two different cell types in close proximity to encourage controlled innervation and communication.