Doctor of Philosophy, University of Akron, 2019, Chemical Engineering

Breast Cancer is the most common cancer among women and nearly 1 in every 8 American women suffer from it. Triple negative breast cancer, a type of breast cancer that can be only treated using chemotherapy, affects nearly 20% of the breast cancer diagnosed women. Early detection of breast cancer increases survival rates among patients. This dissertation discusses the development of a new two-functional folate-targeted poly(ethylene glycol)-based fluorescein-labeled conjugate (FA-FL-PEG-FL-FA) for potential applications in selective diagnosis of triple negative breast cancer. Since folate, or vitamin B9, receptors (FRs) are overexpressed in breast cancer cells, the diagnosis of these cells is targeted by using a γ-thiolated folic acid (FA-γ-SH) as the targeting precursor. α-carboxyl group present on folate is necessary for binding with the FRs, therefore, exclusive γ-thiolation was achieved by using n-butyllithium that selectively forms the lithium salt (FA-γ-Li) at the γ-carboxyl position due to its higher pKa. The subsequent thiolation was achieved by reducing FA-γ-S-S-γ-FA, which was prepared by reacting a dibrominated disulphide compound (Br-S-S-Br, synthesized via enzyme-catalyzed transesterification) with FA-γ-Li. To increase the retention time in the body and improve the solubility of the agent in water, functionalized PEGs were used as the hydrophilic linkers. Diamine, dithiol, and dibromide functionalization of PEGs were achieved using novel enzyme (Candida antartica Lipase B)-catalyzed esterifications and transesterifications. Specifically, three strategies to synthesize FA-FL-PEG-FL-FA were investigated for their synthetic convenience and feasibility. Strategy 1 used diamine-functionalized PEG (H2N-PEG-NH2), Strategy 2 used dithiol-functionalized PEG (HS-PEG-SH), and Strategy 3 used dibromide-functionalized PEG (Br-PEG-Br) as the precursors. The first strategy and the third strategy were not successful owing to not quantitatively yielding the interm (open full item for complete abstract)

Committee: Lingyun Liu (Advisor); Jie Zheng (Committee Member); Rebecca Kuntz Willits (Committee Member); Chrys Wesdemiotis (Committee Member); Mark Soucek (Committee Member) Subjects: Chemical Engineering; Chemistry; Molecules; Organic Chemistry; Polymer Chemistry; Polymers

Doctor of Philosophy, University of Akron, 2019, Chemical Engineering

The aim of this research was to synthesize polymer-diagnostic agent conjugates with two folate functionalities for potential diagnostic applications. Conjugates with fluorescein (FL) as an imaging agent, poly(ethylene glycol) (PEG) as a hydrophilic linker and two folic acid (FA) as targeting agents were synthesized by chemo-enzymatic method using Candida antarctica lipase B (CALB) catalyst for the multivalent targeting of folate receptors (FRs) overexpressed on cancer cells. In this dissertation work, imaging agent FL was first acrylated using acryloyl chloride (AcrCl) in the presence of triethylamine (TEA) to precisely synthesize fluorescein o-acrylate (FL-A, yield: 52.49%) and fluorescein o,o'-diacrylate (FL-DA, yield: 63.9%). A kinetic study of FL-DA synthesis was conducted using a Nuclear Magnetic Resonance (NMR)-750 MHz spectrophotometer instrument which demonstrated the formation FL-DA in 13 seconds reaction time. Hence, our FL-DA synthesis was extremely fast and easy to purify using silica gel. Acrylate moieties of FL-DA and FL-A allow the CALB-catalyzed Michael addition of thiol and amine to develop the conjugates. First, FL-A with single acrylate moiety was reacted with PEG-diamine (H2N-PEG-NH2) by the CALB-catalyzed Michael addition. However, the nucleophilic secondary amine of FL-NH-PEG-NH-FL interfered with the acrylation of 'OH' of FL-A. Hence, a new synthetic strategy was developed where H2N-PEG-NH2 was replaced by dithiol-functionalized PEG (HS-PEG-SH, Mn =899 g/mol, Ð=1.00, Mn =1160 g/mol, Ð=1.14 and Mn =2200 g/mol, Ð=1.09) and tetraethylene glycol (HS-TEG-SH, FW= 370.48 g/mol) which were synthesized in Dr. Puskas' lab to avoid the interference of the amine group in the acrylation reaction. Michael addition between FL-A and HS-TEG-SH, by CALB-catalysis was extremely fast and completed in 1 minute at 52°C. Reaction between FL-A and HS-PEG-SH without CALB catalysis did not go to completion even after 18 hours at 52°C but completed in 2 minutes when C (open full item for complete abstract)

Committee: Jie Zheng PhD (Advisor); Ge Zhang PhD (Committee Member); Chrys Wesdemiotis PhD (Committee Member); Bi-min Zhang Newby PhD (Committee Member); Mark Soucek PhD (Committee Member) Subjects: Biomedical Engineering; Chemical Engineering; Chemistry; Materials Science; Polymer Chemistry; Polymers

Doctor of Philosophy, University of Toledo, 2014, College of Engineering

The overall goal of this research is to apply the principle of green engineering to produce bio-sourced polycarbonate (PC) based composites with properties similar to BPA-PC. To synthesize PC in a more sustainable way, transesterification polymerization with diphenyl carbonate (DPC) was chosen as the production method. The bio-derived monomer, isosorbide, was chosen as the alternative monomer to the traditional petroleum monomer biphenyl-A (BPA). Alumina-polycarbonate (AL-PC) nanocomposites were produced through melt phase in-situ polymerization to improve mechanical and thermal properties. The first focus of this study was to produce nanocomposites of BPA-PC and ALNW using in-situ melt phase polymerization. The result will be compared to those from an earlier study using solution based polymerization Alumina nanowhiskers (ALNW) were used to synthesize AL-PC nanocomposites using melt phase polymerization, because the hydroxyl groups on the ALNW surface can react with DPC during polymerization. The presence of bonded BPA-PC on the ALNW surface was confirmed following in-situ polymerization. Molecular weight of PC produced are calculated using NMR end group analysis. The effect of solid state polymerization at gradually increased temperature is reported. Heat resistance and mechanical properties of BPA-PC and AL-BPA nanocomposites were compared and evaluated. Copolymer of isosorbide and BPA with a ratio of isosorbide/BPA= 95/5 was observed to have the highest molecular weight among all the isosorbide-based polymers. AL-isosorbide-BPA-PC nanocomposites were synthesized and structurally confirmed by FTIR. In order to optimize the isosorbide-based PC synthesis, kinetics study was done on the transesterification of BPA and isosorbide. The dependence of reaction temperature and monomer composition on the transesterification rate constant of BPA and isosorbide is studied. The unexpected equilibrium behavior of isosorbide transesterification was revealed. A model was b (open full item for complete abstract)

Committee: Maria Coleman (Advisor); Saleh Jabarin (Committee Member); Joseph Golba (Committee Member); Isebel Escobar (Committee Member); Yong-wah Kim (Committee Member) Subjects: Chemical Engineering

Doctor of Philosophy, University of Akron, 2014, Polymer Science

Polyisobutylene (PIB) has a unique combination of properties including chemical/oxidative resistance, low Tg (~70 °C) and hydrophobicity.1 PIB-based materials have also been found to have excellent biocompatibility and biostability: a PIB-based triblock copolymer thermoplastic elastomer (TPE) [poly(styrene-b-isobutylene-b-styrene)] (SIBS) is FDA-approved as a drug eluting coating for coronary stents.2 A new generation of PIB-based TPEs, with an arborescent or tree-like core (arbPIB) and plastic phases composed of blocks of polystyrene or poly(p-methyl styrene) (MS) has been developed in Professor Puskas group. These materials display unique TPE properties to make them very attractive for biomedical applications.3 The biocompatibility of these novel block copolymers has already been demonstrated in vitro and in vivo in rabbits.4 The Puskas group proposed to modify the surface properties of PIB-based TPEs using a modular approach. Using this approach it is possible to modify the surface chemistry and topology independently. The surface chemistry can be modified by “gluing” low molecular weight functionalized PIBs (PIB-X) to the surface of the TPEs. This “modular” approach will give unprecedented control over surface chemistry and topology and will contribute to new fundamental understanding of the effects of surface properties on the biocompatibility of polymeric materials. In this work PIB with a primary hydroxy head group (HO-PIB) was made in situ by living carbocationic polymerization using propylene oxide as initiator and titanium tetrachloride (TiCl4) as coinitiator. PIB functionalized with non-fouling moieties (PIB-X) was then synthesized from HO-PIB using Candida antarctica Lipase B (CALB) as enzymatic catalyst and spin coated onto the surface of the TPE. Protein adsorption studies using Surface Plasmon Resonance (SPR) demonstrated decreased fibrinogen (Fg) adsorption to the modified surface. XPS analyses provided clear evidence of the effectiveness of the mo (open full item for complete abstract)

Committee: Judit E. Puskas Dr. (Advisor); William Landis Dr. (Committee Chair); Gary R. Hamed Dr. (Committee Member); Chrys Wesdemiotis Dr. (Committee Member); Nic D. Leipzig Dr. (Committee Member) Subjects: Biomedical Research; Materials Science; Polymer Chemistry

Master of Science in Chemical Engineering, University of Toledo, 2011, Chemical Engineering

The concern over the increasing depletion of our nation's fossil fuels, high oil prices and greenhouse gas emissions, has motivated research for alternative sources of energy. One alternative energy source, biofuels, provides liquid transportation fuels from biomass derived from plant or animal sources. First generation biofuels are produced from food crops abundant in sugars or lipids such as corn and soy. Second generation biofuels are produced from woody, inedible crops such as poplar and switchgrass. The third generation of biofuels is derived from algae and is of growing interest due to its high yield of energy per unit area, use of carbon dioxide for growth, and minimal contribution as a food product. The main carbon rich components of algal biomass include lipid, carbohydrates and protein. Products such as biodiesel and jet fuel can be derived from lipids. Carbohydrates, in the form of fermentable sugars, can be used to produce bioalcohols. Protein can be used as a dietary supplement or as feed for livestock. This work addresses algal characterization and processing techniques that are helpful in utilizing algae as a feedstock for bioproduct processing. Methods for lipid analysis are compared to select a technique for small sample sizes and ease of handling. The hydrolysis of soybean oil to convert triglycerides (lipids) to free fatty acids is evaluated. A kinetic model is developed to predict reaction behavior and serve as a platform for algal hydrolysis. Characterization techniques to determine the content of algal biopolymers; lipids, carbohydrates and protein are discussed and applied to multiple algal species. Lastly, protein extraction from alga is investigated to prepare species for successful algal hydrolysis.

Committee: Constance Schall (Advisor); Dong-Shik Kim (Committee Member); Cyndee Gruden (Committee Member) Subjects: Alternative Energy; Chemical Engineering

Doctor of Philosophy, Case Western Reserve University, 1995, Macromolecular Science

The wholly aromatic copolymers of p-hydroxybenzoic acid (HBA) and 2-hydroxy-6-naphthoic acid (HNA) form nematic melts and maintain an extended chain structure upon solidification. The present work focuses on how this morphology influences physical and chemical changes that occur in blends of copolymers with different comonomer compositions. The X-ray diffraction data for these copolyesters contain non-periodic layer lines that indicate a completely random monomer sequence distribution and also provide analytical information on the monomer proportions. Hence these data provide a unique method to study transesterification between copolyesters of different composition. The melt transitions of the 75/25 and 30/70 copolymers occur at 288 and 303°C, respectively, but their 2:1 compatible blend has a much lower single melt transition at 227°C. This blend of the 75/25 and 30/70 copolymers initially shows the diffraction maxima characteristic of the two compounds, but transesterification occurs upon compression molding leading to the formation of the random copolymer of intermediate composition after one hour at 315°C. The progress of this reaction is followed by monitoring the positions of the first meridional maxima as a function of time, until they merge to give a single maximu m at the d-spacing characteristic of the random copolymer of intermediate composition. A progressive shift in the melt temperature from 227 to 248°C also indicates a gradual transition from a compatible blend to a random copolymer of intermediate composition during this time. Simulations of the diffraction effects are produced by incorporating terms into the correlation function to account for the changes in monomer nearest neighbor statistics that occur as transesterification progresses. The predicted scattering data are seen to follow the general trends of the observed data, and lead to the determination of an activation energy for the transesterification reaction that is comparable to values rep (open full item for complete abstract)

Committee: John Blackwell (Advisor) Subjects: Chemistry, Polymer

Master of Science, University of Akron, 2012, Polymer Science

Two of the most commonly employed bioadhesives used for wound closure applications today are fibrin-based and cyanoacrylate-based bioadhesives, both of which have adverse effects. Fibrin-based bioadhesives allow for the possible transmission of viral blood-borne pathogens, while cyanoacrylate-based bioadhesives have toxicity concerns due to their degradation into formaldehyde. To address these drawbacks and many others, it is proposed that a polyisobutylene-based bioadhesive be employed, since polyisobutylene has a long, successful history as a bio-friendly material. Potential polyisobutylene-based bioadhesives first were prepared by the difunctionalization of α-ω-dihydroxy polyisobutylenes with vinyl methacrylate through “green” enzyme catalyzed Candida antarctica lipase B (CALB) transesterification reactions at 50¿¿¿¿¿¿¿ within 24 hours with high yields. Four different compounded crosslinking solution formulations consisting of synthesized α-ω-dimethacrylate polyisobutylenes, 10% or 20% of the trifunctional crosslinker 2-ethyl-2-hydroxymethyl-1-,3-propanediol trimethacrylate (TMP-TMA) and a 20% solution of the ultra-violet (UV) reactive photoinitiator 2,2-dimethoxy-2-phenylacetophenone effectively demonstrated the ability to crosslink terminally functionalized linear polyisobutylenes into continuous film networks under ambient conditions quickly (< 5 min.) by the use of UV light. Various techniques were used to characterize their crosslinking and physical properties, as well as to determine that the molecular weight of α-ω-dimethacrylate polyisobutylenes had a greater effect on the characterizable attributes than the amount of TMP-TMA employed. Techniques used to characterize the continuous polyisobutylene film networks included: the evaluation of polyisobutylene film discontinuities; the measurement and calculation of their physical dimensions; aesthetic evaluation; solvent extraction and swelling assessments; FTIR; TGA; and DSC. These methods characterized th (open full item for complete abstract)

Committee: Judit E. Puskas Dr. (Advisor); Chrys Wesdemiotis Dr. (Committee Member) Subjects: Polymer Chemistry; Polymers

Doctor of Philosophy, University of Akron, 2009, Polymer Science

The objective of this research was to investigate the enzyme-catalyzed functionalization of polymers. For this purpose, first, model small molecules were employed in Candida antarctica lipase B (CALB)-catalyzed transesterification and Michael addition reactions. CALB-catalyzed transesterification of ethyl acetate and vinyl acetate with 2-phenyl-1-propanol (2PPOH), the model compound for primary hydroxyl-functionalized polyisobutylene (PIB) prepared from the α-methylstyrene epoxide (α-MSE)/TiCl4 initiator system, indicated that the latter was a more effective acyl donor as it formed unstable vinyl alcohol which instantly tautomerized to acetaldehyde and thus rendered the reaction irreversible. The comparison of the catalytic activity of CALB with that of a commercially available transesterification catalyst, bis[dibutylchlorotin(IV)] oxide, revealed that in the transesterification of vinyl acetate with 2PPOH, CALB was the more reactive catalyst. Ethylene glycol (EG) was reacted with vinyl methacrylate (VMA) in the presence of CALB as a model reaction for the methacrylation of poly(ethylene glycol) (PEG) and it was observed that the reaction proceeded in a consecutive fashion first yielding the monosubstituted product followed by disubstituted ester. Thymine was reacted with both vinyl acrylate (VA) and VMA through Michael addition in the presence of CALB as a model reaction for the addition of thymine to (meth)acrylated polymers. Quantitative conversion was observed in the case of VA whereas VMA gave 63% conversion. The resulting vinyl esters of thymine were then reacted with EG through transesterification using CALB as the model reaction for the addition of thymine to hydroxyl-functionalized polymers. It was observed that the majority of the product was the monosubstituted EG. These synthetic procedures were then applied to polymer functionalization.The primary hydroxyl-functionalized PIB prepared from α-MSE/TiCl4 was not reactive towards CALB. On the other hand, PI (open full item for complete abstract)

Committee: Judit E. Puskas PhD (Advisor) Subjects: Polymers

Doctor of Philosophy, University of Akron, 2006, Polymer Engineering

Transesterification between a model thermotropic liquid-crystalline polyester (TLCP) and a thermoplastic polyester (TPP) was investigated during melt blending in a twin-screw, mini-compounder at temperatures below and above the nematic-to-isotropic transition temperature (TNI) of the TLCP. For the investigation, two model TLCPs, poly[(phenylsulfonyl)-p-phenylene hexamethylene-bis(4-oxybenzoate)] (PSHQ6) and poly[(phenylsulfonyl)-p-phenylene dodecamethylene-bis(4-oxybenzoate)] (PSHQ12), were synthesized. These have a TNI of 206 °C and 162 °C, respectively, which are much lower than their thermal degradation temperatures (ca. 350 °C). PSHQ6 and PSHQ12, respectively, were melt-blended with poly(bisphenol A carbonate) (PC) and polycaprolactone (PCL) at temperatures below and above the TNI of PSHQ6 and PSHQ12. In the preparation of the blends, temperature and residence time in the compounder were varied. It was observed from differential scanning calorimetry (DSC), and further confirmed by 13C nuclear magnetic resonance (NMR) spectroscopy, that negligible transesterification occurred when a blend was prepared at temperatures below the TNI of the TLCP, while the extent of transesterification increased steadily as the melt blending temperature increased above the TNI of the TLCP. The mechanical properties of injection-molded specimens of the blends prepared under various processing conditions were investigated. The tensile strength and the impact strength of PC/PSHQ6 blends first increased with increasing melt blending temperature, maximizing at a temperature above the TNI of PSHQ6, and then decreased rapidly as the melt blending temperature increased further. On the other hand, the tensile strength of PCL/PSHQ12 blends maximized at an intermediate stage of transesterification during melt blending. The experimental observations indicate that there exists an optimum degree of transesterification that gives rise to the highest mechanical properties of PC/PSHQ6 and PCL/PSHQ12 (open full item for complete abstract)

Committee: Chang Dae Han (Advisor) Subjects: