Chemistry & Biochemistry

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Research from the Department of Chemistry & Biochemistry. The department website may be found at https://www.ndsu.edu/chemistry/

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Diastereoselective Conjugate Radical Additions to ~-Pyrones
(North Dakota State University, 2009) Yu, Arvin Zillion
A convenient protocol for functionalization of ~-pyrones has been developed. Conjugate radical addition and tandem addition-trapping protocols allowed accessing highly substituted pyrones in a single operation with high selectivity. Different radical sources were utilized in the reaction. nOe experiments were performed to confirm the relative stereochemistry of the substituents in the conjugate addition products. Initial studies on the enantioselectivity of the reaction were carried out. Unfortunately, the catalysts chosen for the initial studies did not show any promise regarding enantioselectivity.
Synthesis and Photophysics of Platinum(II) Terdentate and Bidentate Complexes.
(North Dakota State University, 2010) Yi, Jing
Platinum(ll) terdentate and bidentate complexes possess square-planar d8 configuration. The moderate metal-to-ligand charge-transfer (1MLCT) absorption, 3MLCT emission, and broadband excited-state absorption are the unique spectroscopic features for these complexes. In my thesis work, two series of terdentate platinum(II) complexes and one bidentate platinum(II) complex were designed and synthesized. The photophysical properties, such as the electronic absorption, photoluminescence, and triplet excited-state absorption, are investigated systematically. Chapter I introduced the representative work on the synthesis and photophysical studies of the terdentate and bidentate platinum(II) complexes reported in the literature. The motivation for my thesis project was briefly discussed. In Chapter 2, the synthesis and photophysical properties of two platinum 6-phenyl-4- (9,9-dihcxylfluoren-2-yl)-2,2 '-bipyridine complexes with phenothiazinyl (PTZ) acetylide ligand were discussed. Their UV-vis absorption and emission characteristics in solutions and LB films were systematically investigated. The triplet transient difference absorption and reverse saturablc absorption were also studied for these complexes. Both complexes exhibit a broad metal-to-ligand charge-transfer / ligand-to-ligand charge-transfer / intraligand charge-transfer (1MLCTi1LLCTi11LCT) absorption band between 400 and 500 nm and a 'MLCT/'ILClill",ll"' emission band at -594 nm at room temperature, which blue shifts at 77 K. Both UV-vis absorption and emission spectra show negative solvatochromic effect. Both of the complexes also exhibit broad and moderately strong triplet transient absorption from the near-UV to the near-IR spectral region. In addition, LB films of them were prepared and characterized by AFM technique. The UV-vis absorption and emission spectra of the LB films of them were also investigated and compared with those obtained in solutions. In Chapter 3, the synthesis and photophysical studies of a series of platinum 6-phenyl- 4-(7-benzothiazolyl-9, 9-diethyltluoren-2-yl)-2,2' -bi pyridine complexes with different acetylides ligands, such as, nitrophenyl acetylide, tluorenyl acetylide, and benzothiazolyltluorenyl acetylide, were discussed. The complex bearing nitrophenyl acetylide ligand exhibited quite distinct photophysical properties compared to the other two complexes. In Chapter 4, one platinum bis(mesitylimino)acenaphthene complex was synthesized. The lowest-energy absorption band was attributed to 1MLCT transitions, which was much broader and red-shifted (extending from 490 nm to 800 nm) compared to those reported for other diiminc Pt(II) complexes.
Influence of Active Site Ligands and Nanoparticle Surfaces on Human Carbonic Anhydrase Isozymes
(North Dakota State University, 2010) Manokaran, Sumathra
Carbonic anhydrase (CA) is an ubiquitously distributed zinc containing metallo enzyme that catalyzes the reversible hydration of carbon dioxide to form bicarbonate and a proton. Existence of 16 isoenzymes of CA in the animal kingdom has been known so far with varying subcellular and tissue distributions. Due to their involvement in many physiological and pathological processes, these isozymes have been the target for drug designing for the past 6 decades. The present study was designed with the aim of understanding the effect of active site ligands and nanoparticle surfaces on human carbonic anhydrase isozymes. In an effort to identify a fluorescent probe for carbonic anhydrases, the quantum yields and binding affinities of a variety of naphthalenesulfonamide derivatives with human carbonic anhydrase isozymes (hCAs) were determined. In this pursuit, a highly sensitive fluorescent probe, JB2-48 was identified. Experiments involving the above flurophore with hCA I unraveled the contributions of the sulfonamide moiety and the hydrophobic regions of the ligand structure on the spectral, kinetic, and thermodynamic properties of the enzyme-ligand complex. The fluorescence data revealed that the deprotonation of the sulfonamide moiety of the enzyme-bound ligand increases the fluorescence emission intensity as well as the lifetime of the ligand. This is manifested via the electrostatic interaction between the active site resident Zn2 + cofactor and the negatively charged sulfonamide group of the ligand. Evidence was provided that the anionic and neutral forms of JB2-48 are stabilized by the complementary microscopic/conformational states of the enzyme. Investigations on the binding of the sulfonamide inhibitor, benzene sulfonamide (BS), with hCA isozymes II and VII, revealed that the binding is stabilized by polar interactions in the former case and hydrophobic interactions in the latter case. In addition, it was found that the binding of BS with hCA II is enthalpically driven at low temperatures, whereas it is entropically driven for its binding with hCA VII. Due to the prevalence of bipolar distribution of charges on hCA XII, the effects of the interaction of differently charged quantum dots, liposomes and polylysine on hCA XII were investigated. These charged particles were found to differently modulate the active site of the enzyme. The data revealed that whereas poly lysine and liposomes exhibited no influence on the binding and catalytic features of the enzyme, quantum dots had significant influence on the above features. Arguments were presented that the above differential feature exhibited by quantum dots, liposomes and poly lysine is encoded in the rigidity versus flexibility of the charged molecules. Studies on the denaturation of hCA isozymes II and XII unraveled their unfolding mechanism. It was found that the unfolding ofhCA XII followed a simple two state model from native to unfolded state; however hCA II unfolded with the formation of a stable intermediate.
Regioselective and Enantioselective Nitrone Cycloadditions to Alkynones.
(North Dakota State University, 2010) Dunkle, Kelsey Lynn
There has been a need in agriculture, medicine, and organic chemistry for enantiopure isoxazolines. A direct method for their synthesis is from the cycloaddition of 1,3-dipoles and alkynes. Alkynones are difficult substrates to use in cycloadditions due to their high reactivity and sometimes instability. Due to their high reactivity it is often difficult to control regio- endo/exo, and enantioselectivities in dipolar cycloadditions of alkynones. This thesis details the cycloadditions of nitrones and alkynones using chiral Lewis acids leading to isoxazolines with high regio-and enantiocontrol. A chiral bisoxazoline-zinc(II) complex successfully catalyzed the enantioselective 1,3-dipolar cycloaddition reaction of nitrone and alkynone derivatives. This is the second successful reported method for the catalytic enantioselective 1,3- dipolar cycloaddition of nitrones and alkynone derivatives. Yields for the cycloadducts were good to near quantitative and enantioselectivities were generally good reaching a high of 86 % ee. The 4-isoxazolines were isolated as single reg101somers.
Differential Modulation of the Structural and Functional Characteristics of Human Matrix Metalloproteinase Isozymes upon Binding to Different Ligands
(North Dakota State University, 2010) Ganguly, Bratati
Matrix metalloproteinases (MMPs) are a family of Zn2 + -dependent, Ca2 + -containing endoproteinases involved in tissue remodeling and degradation of the extracellular matrix (ECM). Human MMP isozymes are known to be involved in the progression and metastasis of many diseases like cancer, Alzheimer's, and etc. The different nanoparticles (e.g. gold nanoparticles, liposomes, and charged quantum dots) used in this study provides insights into nanoparticle-induced differential modulation in the structural-functional characteristics of MMP 7, 9 and 10 for better therapeutic intervention. To demonstrate the relationship between the rigid and flexible surfaces on the differential modulation of functional and structural characteristics of MMP-7, polylysine (PLL) and cationic gold nanoparticles (Au-CNP) were selected as representative examples. These cationic nano-structures were expected to serve as "soft" (flexible) and ''rigid" (hard) ligands, respectively. Steady-state kinetic analysis demonstrated that PLL induces activation and inhibition of MMP-7 at stoichiometric and super-stoichiometric concentrations respectively. Circular Dichroism spectroscopy was used to confirm that binding of Au-CNP to MMP-7 induces denaturation of the protein. In pursuit of understanding the molecular origin of the intrinsic selectivity in binding of human MMP isozymes to differently charged lipid membranes, steady-state kinetic studies and intrinsic tryptophan quenching studies were carried out. Results demonstrated that differently charged lipid membranes bind to all three MMPs; phosphotidylserine (POPS) liposomes are selective for MMP-7. The bipolar distribution of negative and positive charges on the surface of this enzyme dictates the binding of liposomes and perturbation of catalytic activity. An attempt to explain the molecular rationale for alternative binding modes of differently charged quantum dots (QDs) to the three MMPs, steady-state tryptophan quenching, steady-state kinetics, and time-resolved fluorescence measurements were carried out. Differently charged QDs bind to all the three MMP isozymes. Enzyme activity of these MMPs was perturbed upon binding to cationic and anionic QDs. Binding of MMPs to the differently charged QDs is reversible and is mediated via electrostatic interactions. Analysis of time-resolved fluorescence data indicates that the protein expenences different micro-environments, due to different distribution of intrinsic tryptophan residues (buried and exposed) on MMP isozymes or the existence of two distinct conformations of the protein. Binding to charged QDs perturbs enzyme activity of MMPs either by restricting the access of the substrate to the active-site or through allosteric modulation. In order to develop new isozyme-selective inhibitors, small molecule inhibitors (SMis) were designed, synthesized and screened for MMP-7, 9 and 10. Results indicate that hydroxamates and carboxylates are preferred SMis. Binding preference is based on either the micro-environments of the active-site pockets.
Interactions of Synthetic Metal Porphyrinates with PhuS, a Cytoplasmic Heme Trafficking Protein from Pseudomonas aeruginosa
(North Dakota State University, 2010) Moberg, Amber Elise
Pseudomonas aeruginosa is an opportunistic, Gram negative, bacterial pathogen that commonly establishes infection in immunocompromised individuals. It contains protein-based, iron uptake pathways that target both heme and nonheme iron sources in the host. When the Pseudomonas heme uptake system is compromised by genetic knockout of the cytoplasmic heme trafficking protein, PhuS, the ability to establish infection is lost. PhuS functions to transfer heme to a heme oxygenase, an 02 dependent heme metabolizing enzyme, so that it can be degraded to a usable form for the organism. Within the long-term goal of developing pharmaceutical agents to inhibit heme uptake by bacterial pathogens, this study aims to evaluate the general thermodynamic parameters of metalloporphyrin binding to PhuS. Two synthetic iron porphyrinates and the Ni(II) complex of protoporphyrin IX have been investigated and their binding constants have been determined. The implications of these results for inhibiting heme uptake will be discussed.
Biochemical and Epidemiological Analysis of Mycobacterium Avium Subspecies Paratuberculosis and Investigation of its Relationship to Crohn's Disease in Humans
(North Dakota State University, 2011) Uzoigwe, Jacinta Chinwe
Background: Crohn's disease is a chronic inflammatory disease of the intestine in humans, with no known cause. Johne's disease is a chronic intestinal disease of ruminants caused by Mycobacterium avium suhspecies paratuberculosis (MAP), and has some features similar to Crohn's disease. Although MAP has been purported to play an etiologic role in Crohn's disease, this causal link is still under debate. Objective: The overall aim of this project is to analyze MAP strains from different hosts (cattle, sheep and humans) and regions in North Dakota by biochemical and epidemiological methods, in order to better understand the pathogenesis and epidemiology of MAP strains and the relationship between MAP and Crohn's disease. The specific aims of this research are the following: Aim 1. Investigate the epidemiological evidence for MAP as a cause of Crohn's disease. Aim 2. Conduct a comparative causality study to investigate whether MAP or other enteric pathogens cause Crohn's disease. Aim 3. Evaluate the occurrence of MAP infections in cattle in North Dakota, 1995-2005. Aim 4. Analyze MAP strains from symptomatic and asymptomatic cattle. Aim 5. Investigate the biochemical variations of rapid and slow growing MAP strains. Aim 6. Evaluate MAP strains from low shedders and high shedders. Methods: MAP isolates were analyzed by biochemical methods of gas chromatography, high performance liquid chromatography and mass spectrometry. In addition, extensive literature review was performed to (1) determine the epidemiologic causal link between MAP and Crohn' s disease and (2) determine whether MAP or other enteric pathogens cause Crohn's disease. Results: Results from our study indicated the availablity of epidemiologic evidence supporting the causal role of MAP in Crohn's disease. It was also demonstrated that MAP is the most implicated organism in the etiology of Crohn's disease when compared to other infectious agents. Investigation of the occurrence of MAP infection in North Dakota showed an increase in number of MAP cases reported, with seasonal trends. Biochemical typing of MAP strains from symptomatic and asymptomatic cattle indicated that the symptoms status of isolates was significantly associated with mass spectra patterns and shedder status (p < 0.05). However, the association between symptoms status and HPLC and GC patterns was not significant (p > 0.05). Investigation of biochemical variations of rapid and slow growing MAP strains showed associations between the biochemical variability of MAP strains and their growth rate and presence of symptoms in the source cattle. Evaluation of MAP strains of different shedding characteristics by univariate logistic regression revealed that the shedder status of isolates was significantly associated with growth rate of isolates, symptom status, and source regions, but not with mass spectra patterns of isolates. Conclusion: Overall, this study strengthens the theories of strain sharing, intraspecies and interspecies transmission, and supports an association between MAP and Crohn's disease. In addition, the understanding of the biochemical variation among MAP isolates will help in the future design of diagnostics, therapeutics and vaccines for Johne's and Crohn's diseases.
Acyl Imidazole : A Promising Template for Asymmetric Lewis and Brønsted Acid Mediated 1,3-Dipolar Cycloadditions
(North Dakota State University, 2011) Rane, Digamber Sadanand
Construction of chiral complex molecules continues to be a challenge for organic chemists all over the world and to address this challenge numerous methodologies have been developed. 1,3-Dipolar cycloaddition reactions is one such simple and elegant method, which can be employed towards the construction of chiral heterocycles. The ability to construct multiple stereocenters in one operation is one of the salient features of dipolar cycloaddition reaction. Asymmetric dipolar cycloaddition via chiral Lewis or Bronsted acid catalyzed processes is aided by the development of various templates, which provide points of attachment for these catalyst. Application of acyl imidazoles as multifunctional templates has been investigated for Lewis and Bronsted acid catalyzed 1,3-dipolar cycloaddition of azomethine imines and nitrones. Chapter 1. A review of 1,3-dipolar cycloaddition towards to construction of chiral nitrogen containing heterocycles is discussed in this chapter. This chapter intends to provide the reader a current state of asymmetric 1,3-dipolar cycloaddition. Chapter 2. Development of exo and enantioselective Cu(II) catalyzed azomethine imine cycloaddition to pyrazolidinone acrylates is discussed in this chapter. The key issues approached in this chapter includes impact of metal geometry on diastereoselectivity as well as effect of N-l and C-5 substitution on enantioselectivity of cycloadducts. Investigation into the scope and limitation of azomethine imines and dipolarophiles has also been discussed. Chapter 3. This chapter introduces acyl imidazoles as multifunctional template for asymmetric azomethine imine cycloaddition. Limitation of substrate scope for azomethine imine cycloaddition encountered in the previous chapter has been resolved by the use of acyl imidazoles as templates. Synthesis of complementary diastereomers of azomethine imine cycloadducts via Lewis acid and Bronsted acid catalyzed reactions has been discussed in this chapter. Chapter 4. This chapter highlights the application of acyl imidazoles as template for first Bronsted acid catalyzed exo and enantioselective nitrone cycloaddition to electron deficient olefins. Study of appropriate chiral Bronsted acid and investigation of breadth and scope of nitrones and dipolarophiles has also been discussed here. Chapter 5. This chapter address one of the most challenging aspect of synthetic organic chemistry namely the construction of chiral quaternary stereocenters. This study highlights chiral Bronsted catalyzed nitrone cycloaddition to p,|3-disubstituted-a,P-unsaturated acyl imidazole leading to the formation of isoxazolidines with chiral quaternary stereocenter. This methodology is useful for the construction of chiral fluorinated heterocycles.
The Optimization of Whole Genome Amplification and Molecular Crowding for Use in Forensic Low Copy Number Samples
(North Dakota State University, 2011) Palmer, Megan Frances
Whole genome amplification has been used as a powerful tool to increase the amount of DNA template used for microarrays, STR and SNP assays in clinical and forensic settings. Our laboratory observed that multiple displacement whole genome amplification demonstrated a higher reliability for increasing DNA template than PCR primer extension pre-amplification of human genomic DNA. We also demonstrated a truncated reaction time for whole genome amplification was necessary to decrease artifact, while still increasing authentic DNA species. We determined that molecular crowding using polyethylene glycol and non-human DNA also increased sensitivity of our assays. Combining the modified whole genome amplification protocol with macromolecular crowding increased STR signals with as low as one haploid cell DNA equivalent.
Stereoselective Carbon-Carbon Bond Construction Using Indium and Bismuth: New Methods in Green Chemistry
(North Dakota State University, 2012) Balasubramanian, Narayanaganesh
Selective chemical reactions that can be accomplished with minimal waste using non-toxic catalysts and reagents will allow for new greener chemical processes for future environmentally sustainable technologies. This work will present an account on enantioselective nucleophilic addition to carbon-nitrogen and carbon-oxygen double bonds mediated by the environmentally benign indium and bismuth metals. The dissertation entitled “ Stereoselective carbon-carbon bond construction using indium and bismuth: new methods in green chemistry” is divided into three chapters Chapter one outlines a few concepts in green chemistry and background information on the vital role of indium and bismuth in present day organic synthesis. The development of a procedure for using allylic alcohol derivatives for ümpolung type allylation of chiral hydrazones is described in chapter two. This procedure affords homo allylic amines in good yields and excellent diastereoselectivity. An interesting study with respect to the mechanism of the reaction has been conducted. Switching gears towards the end of this chapter, ultrasound-promoted indium-mediated Reformatsky reaction of chiral hydrazones is described. This chapter describes a potential green chemical method for making β-amino acids. In chapter three, indium mediated enantioselective allylation of α-ketoamides is described. The developed procedure is applied in the allylation of linear and cyclic α- ketoamides. Overall, an operationally simple and environmentally benign stratergy development has been explained. The later section of this chapter discusses the Reformatsky reaction in isatin series using the same protocol applied for imines. To fully explore any organometallic reaction, it is important to understand the mechanism with which they operate at molecular level. Chapter three outlines some of our attempts to understand the enantioselective indium and bismuth mediated allylation and the nature of chiral- indium and bismuth Lewis acids. A postive non-linear effect has been observed and studied in bismuth-mediated allylation. Key findings obtained in each chapter and their implications to the future of our research is also discussed in each chapter. The chapters also details on what we understood about the potentials of organoindium and organobismuth chemistry towards developing new green chemical methods.
Biological Effects of Vasoactive Intestinal Peptide/Pituitary Adenylate Cyclase Activating Polypeptide Receptor 1 (VPAC1) and VPAC2 on Chemotaxis and its Regulation of the Tumor Suppressor Ikaros in Leukemic T Cells
(North Dakota State University, 2012) Van der Steen, Travis
One in three children diagnosed with cancer has leukemia. Leukemia patients with mutations in the tumor suppressor transcription factor Ikaros (IK), an anti-leukemic factor that is critical for the development of blood cells; have a poor prognosis despite modern chemotherapy. There is, therefore, a critical need to understand the biology of IK. Research by our laboratory has identified a neurotransmitter, called vasoactive intestinal peptide (VIP), which blocks proliferation through one of its receptors (vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide receptor 1(VPAC1)), but blocks apoptosis through a second inducible receptor (VPAC2), while both receptors have chemotactic properties in primary T cells. Some leukemia patients have reversed VIP receptor expression (low VPAC1; high VPAC2), and we hypothesizes that this contributes to a selective growth advantage. Understanding the biology by which VIP receptors regulate cellular growth (proliferation and apoptosis) and movement (chemotaxis) will be pivotal in establishing their signaling pathways as future drugs target candidates in the fight against leukemia. We hypothesized that VIP/VPAC1 signaling would alter the expression of IK protein and that VIP would direct cellular migration of both VPAC1 and VPAC2 expressing leukemic T cells. To test this hypothesis, we first asked whether VIP/VPAC1 signaling affects the expression and/or the phosphorylation profile of IK a transcription factor that regulates cellular growth. The second question was whether VPAC1 and/or VPAC2 signaling differentially control leukemic cell movement. By one- and two-dimensional polyacrylamide gel electrophoresis followed by Western blot analysis, we showed that VIP signaling suppresses IK expression and changes the isoelectric pools of IK protein in a human leukemia cell line. By using leukemia cells that only express VPAC1 or VPAC2 receptors; we demonstrated that VIP promoted cellular movement, but that this effect was controlled by different pathways elicited by VPAC1 versus VPAC2. Collectively, these data support the notion that the nervous system naturally contributes to normal blood cell function, but after leukemogenesis, the VIP signaling axis may exacerbate the leukemia phenotype.
Surface Chemistry Characterization of Hydrodesulfurization and Methanol Synthesis Model Nanocatalysts
(North Dakota State University, 2012) Komarneni, Mallikharjuna Rao
Surface science investigations of model catalysts have contributed significantly to heterogeneous catalysis over the past several decades. The unique properties of nanomaterials are being exploited in catalysis for the development of highly active and selective catalysts. Surface science investigations of model catalysts such as inorganic fullerene-like (IF) nanoparticles (NP), inorganic nanotubes (INT), and the oxide-supported nanoclusters are included in this dissertation. Thermal desorption spectroscopy and molecular beam scattering were respectively utilized to study the adsorption kinetics and dynamics of gas phase molecules on catalyst surfaces. In addition, ambient pressure kinetics experiments were performed to characterize the catalytic activity of hydrodesulfurization (HDS) nanocatalysts. The nanocatalysts were characterized with a variety of techniques, including Auger electron spectroscopy, x-ray photoelectron spectroscopy, electron microscopy, and x-ray diffraction. The adsorption kinetics studies of thiophene on novel HDS catalysts provided the first evidence for the presence of different adsorption sites on INT-WS2. Additionally, the adsorption sites on IF- MoS2 NP and silica-supported Mo clusters (Mo/silica) were characterized. Furthermore, the C-S bond activation energy of thiophene on Mo/silica was determined. These studies finally led to the fabrication of Ni/Co coated INT-WS2, which showed good catalytic activity towards HDS of thiophene. The studies of methanol synthesis catalysts include the adsorption kinetics and dynamics studies of CO and CO2 on Cu/silica and silica-supported EBL-fabricated Cu/CuOx nanoclusters. The adsorption dynamics of CO on Cu/silica are modeled within the frame work of the capture zone model (CZM), and the active sites of the silica-supported Au/Cu catalysts are successfully mapped. Studies on EBL model catalysts identify the rims of the CuOx nanoclusters as catalytically active sites. This observation has implications for new methanol catalyst design.
From Nanocontainer to Nanocatalyst: Mechanistic Studies of [2+2] Photodimerization of Coumarin Derivatives within Cucubit[8]URIL
(North Dakota State University, 2013) Pemberton, Barry Charles
Controlling photoreactions remains a formidable challenge to chemists who have developed several approaches with varying degrees of success to achieve high reactivity/selectivity. Following nature's footprints, chemists have explored the use of confined media for controlling photoreactions. This thesis explores catalytic aspects of a water-soluble supramolecule known as a cucurbituril. Cucurbituril is a macrocyclic oligomer with a large enough cavity to sequester two guest molecules of appropriate size. The guest molecules explored in this thesis is coumarins. The model investigation involves host-guest complexes between cucurbit[8]uril (CB[8]) and coumarin to study the [2+2] photodimerization in water through various spectroscopic techniques. Our initial investigations explored the formation of host-guest complexes with coumarin guests that interacted with CB[8] host. This host guest complexation was used to explore and control photochemical reaction and photophysical properties of encapsulated coumarin guest molecules. The host-guest complexation was found to be dependent on the polarity of the coumarin and the volume constraints imparted by the CB[8] cavity. Observational insights from various coumarins provided insights into formation of host-guest complexes with CB[8]. Some coumarins do not form complexes but if they do they can form 1:1 and 1:2 host guest complexes as well as dynamic host-guest complexes (mixture of 1:1 and 1:2 host-guest complexes). Using dynamic host-guest complexes, we explored the use of CB[8] as a photocatalysts. Photodimerization of 6-methylcoumarin was explored as a model system to understand the supramolecular aspects of photocatalysis. The mechanism for photocatalysis was elucidated using various spectroscopic techniques. Both steady state and time-resolved experiments were carried to ascertain the thermodynamic and kinetic aspects of the supramolecular catalytic process. Spectroscopic investigations provided insights into vital role of dynamic complexes in the catalytic cycle as well as the extrusion of photoproduct from the cavity to enable turnover in the system. Thus this investigation provided an opportunity to build an overall picture of a novel supramolecular photocatalytic process in water. This will undoubtedly foster further development in the area of supramolecular photocatalysis.
Synthesis, Photophysics, and Nonlinear Absorption of Platinum (II) and Iridium (III) Complexes
(North Dakota State University, 2013) Li, Zhongjing
Square planar d8 platinum(II) complexes and octahedral d6 iridium(III) complexes were synthesized. Their photophysics were studied in detail. Structure-property relationship was studied by varying the substitution on the ligands or the π-conjugation extent of the ligands. In Chapter 2, bipyridyl platinum(II) bisstilbenylacetylide complexes (2-1 – 2-6) with different auxiliary substituents on the stilbenylacetylide ligands were synthesized. While the substitution of H on the 4'-position of stilbene by Br and OMe groups does not alter the photophysical properties of the complexes eminently, the photophysical properties are significantly tuned by the CHO, NO2 and NPh2 substituents. In Chapter 3, platinum(II) complexes (3-1 – 3-6) containing 6-[7-R-9,9-di(2-ethylhexyl)-9H-fluoren-2-yl]-2,2'-bipyridine (R = NO2, CHO, benzothiazol-2-yl, n-Bu,carbazol-9-yl, NPh2) ligands were synthesized. It is found that electron-withdrawing substituents (NO2, CHO, BTZ) and electron-donating substituents (n-Bu, CBZ, NPh2) exert distinct effects on the photophysics of the complexes. In chapter 4, platinum(II) complexes (4-1 – 4-6) containing 6-[9,9-di(2-ethylhexyl)-7-R-9H-fluoren-2-yl]-2,2'-bipyridine ligands (R = 4-R'-phenylethynyl with R'= NO2, BTZ, H and OCH3 or R = 4'-BTZ-phen-1-yl or BTZ) were synthesized. The effects of terminal substituents and the different π-conjugated linkages between the BTZ component and the C^N^N core on the photophysics of these ligands and complexes were systematically investigated. In Chapter 5, iridium(III) complexes (5-1 – 5-5) featuring 7-(benzothiazol-2-yl)-9,9-di(2-ethylhexyl)-9H-fluoren-2-yl attachment to the 2-phenylpyridine was synthesized and studied. The effects of the extent of the π conjugation was studied in by the comparison between 5-1 and 5-2, and the effect of the number of the 7-(benzothiazol-2-yl)-9,9-di(2-ethylhexyl)-9H-fluoren-2-yl unit was compared in 5-3 – 5-5. In Chapter 6, bypyridyl iridium(III) complexes (6-1 – 6-7) with different cylometallated arylpyridyl ligands were synthesized. The effects of π-conjugation extension and direction were systematically investigated. Most complexes showed moderate to strong ns transient absorption from visible to near-IR region, indicating stronger excited-state absorption than ground-state absorption in the corresponding region and potential application as reverse saturable absorption materials. Thus, their application as nonlinear absorption materials was demonstrated by reverse saturable absorption (RSA) upon 532 nm ns laser. The RSA trend can be deciphered by the absorption cross section ratio between the excited states and ground states (σex/σ0).
Developing Platform Chemicals from Renewable Resources
(North Dakota State University, 2013) Wojciechowski, Kristin Lynn
The Department of Energy has listed 5-hydroxymethylfurfural (HMF) and 2,5-furandicarboxylic acid (FDCA) as two of the twelve building blocks derived from cellulosic biomass. HMF can serve as a renewable platform for the production of fuels and chemicals. Our research goal is to develop novel methods for the conversion of renewable resources to feedstock chemicals for polymer synthesis. The Diels-Alder reaction, the cycloaddition of alkenes and dienes, has become one of the most important synthetic methods used in organic chemistry. We were interested in carrying out Diels-Alder reactions with derivatives of HMF. Naphthalene analogs of terephthalic acid were synthesized by reacting HMF derivatives with benzyne which could lead to the formation of bio-based polyethylene terephthalate (PET) analogs.
Identification of Novel RPA-Protein Interactions Using the Yeast Two Hybrid Assay and Identification of Regions Important for Interaction Between RPA and Rad24
(North Dakota State University, 2013) Piya, Gunjan
Replication Protein A (RPA) [Replication Factor A (RFA) in yeast] is an ssDNA binding protein composed of Rpa1, Rpa2, and Rpa3 and involved in numerous DNA processing pathways such as Replication, Recombination, and Repair. It participates in such diverse pathways by its ability to interact with numerous proteins. The goal of my project was to find novel RPA-protein interactions using the yeast two hybrid assay. Using this method, we identified several known and unknown proteins that interact with Rfa1 and showed that these interactions were dependent on the phosphorylation state of Rfa2. Next, we determine the region important for interaction between Rfa1 and Rad24. Rad24 is a checkpoint protein important for initiation of the DNA damage checkpoint signaling. By using the β- galactosidase assay, we determined the N-terminal region of Rfa1 (DBD-F) and the C-terminal region of Rad24 (460-660 aa) to be necessary for their interaction.
Stereospecific Photochemical Transformations Involving Axially Chiral Acrylanilides and a-Oxoamides
(North Dakota State University, 2013) Ayitou, Anoklase Jean-Luc
Asymmetric photochemical transformations have been under-explored due to the ineffectiveness of conventional methodologies/reagents/catalysts (point chiral auxiliaries and inductors) that were generally employed for thermal reactions. This limitation to use point chiral auxiliaries for asymmetric photochemistry is partly due to the asynchronous behavior of photo-excitation and chiral transfer/induction processes. This dissertation describes a complementary approach to conventional methodologies involving light induced chirality transfer from atropisomeric viz axially chiral molecular reactants (acrylanilides and α-oxoamides) to enantiopure product(s) with point chirality. The study has revealed the importance of rotamers control in the ground state and how it can impact the stereospecificity during light induced excited state reactions leading to enantiopure product(s). Con-rotatory 6π-photocyclization of axially chiral acrylanilides was explored under various reaction conditions. For example, α,β-unsaturated acrylanilides gave the expected 3,4-dihydroquinolin-2- one photoproduct(s) with enantiomeric excess (ee) values > 90% in both direct and triplet sensitized irradiations. On the other hand, the solution phase direct irradiations of α-substituted acrylanilides yielded racemic photoproduct(s) whereas the triplet sensitized reactions led to ee values > 90% in the expected photoproduct(s). By changing the reaction medium from isotropic media to solid state, α-substituted acrylanilides gave photoproducts with ee values as high as 70%. In addition to the effect of the reaction medium and the reactive spin state on the enantioselectivity, preliminary evaluation of the role of Lewis acid(s) and heavy cations (Na+, K+ and Cs+) were explored. The initial observations were quite promising with ee values up to 90% in the photoproducts upon direct irradiation in isotropic media. The photochemical γ-hydrogen abstraction reaction involving axially chiral α-oxoamides leading to β-Lactam photoproducts was investigated. The enantiomeric ratio (e.r.) > 90:10 in the expected β- Lactam photoproducts was found to be dependent on the temperature under which the irradiation was performed. Furthermore, elevated pressure was employed to counter the effect of elevated temperature and slow the rotation around N-C(aryl) chiral axis leading enantioenriched β-Lactam photoproducts. This dissertation details the overall mechanistic rationales and photophysical control studies during the photochemical transformations of atropisomeric acrylanilides and α-oxoamides leading to chirally enriched products.
Synthesis, Characterization, and Application of Low and Reduced Band Gap Thieno[3,4-b]pyrazine-based Materials
(North Dakota State University, 2013) Mulholland, Michael Edward
Conjugated polymers are a class of materials receiving significant interest due to their unique combination of optical and electronic properties found in inorganics with the flexibility and processability of traditional organic plastics. These materials have become popular in application to electronic devices such as organic photovoltaics (OPVs), organic light-emitting diodes (OLEDs), sensors, electrochromics and field effect transistors (FETs). As the energetic gap between frontier orbitals, the band gap (Eg) is largely responsible for the energetic transitions of these materials and thus tuning of this parameter is of great interest. A popular method to reducing Eg is through the use of fused ring systems such as thieno[3,4-b]pyrazines (TPs). These TP-based materials have been previously applied to solar cells. However, all exhibited limited efficiency (<5% PCE). In an effort to improve the efficacy of TPs in electronic devices, the scope of available TP materials was expanded in an effort to study the effect of changing both side chain and comonomer has on the material properties. In an effort to study the effect of side chains Rasmussen and coworkers introduced a new method in 2008 toward synthesis of 2nd generation TPs with expanded electronic tuning. To further develop this work, preparation of new electron-withdrawing TPs were generated. Application of 1st and 2nd generation TPs in the production of homopolymeric and copolymeric materials was performed, along with characterization of their optical and electronic properties. Select materials with altering side chain and comonomeric unit were then applied to OPV devices and efficiencies were evaluated based on the changed parameter.
Mechanistic Studies on the Methionine Aminopeptidase and Peptide Deformylase Catalyzed Reactions
(North Dakota State University, 2013) Sule, Nitesh
In the search for novel antibiotic and therapeutic targets, methionine aminopeptidase (MetAP) and peptide deformylase (PDF) have recently been identified as eminently compelling. These enzymes are involved in the co-translational modification of nascent polypeptides, affecting majority of the cellular proteome across all the kingdoms of living organisms. As a result, the various isoforms of MetAP and PDF have been successfully targeted by antimalarial and anti-cancer drugs. However, in spite of great interest in the bacterial forms of these enzymes as potent antibiotic targets, efforts to develop such agents have failed. This investigation is a study of the biochemical and biophysical features of the E. coli isoforms of MetAP and PDF in order to understand the unique characteristics of these bacterial enzymes. The catalytic properties of these enzymes were studied using a combination of direct and coupled spectrometric assays. Potent inhibitors of MetAP were identified by screening a focused library of compounds and potential pharmacophores were determined. The inhibitor-enzyme interactions were further studied via steady-state and transient kinetic methods. While attempting to enhance the solubility of the tight-binding inhibitors using cyclodextrins, a novel substrate-driven mode of enzyme inhibition by 2-hydroxypropyl-β-cyclodextrin was discovered. The metal-ion binding properties of MetAP were studied and in this effort, the luminescence of the trivalent lanthanide ion europium was identified as a convenient signal for monitoring metal- ion binding to the enzyme. Moreover, europium was found to catalytically activate MetAP. These properties allowed the characterization of MetAP—metal-ion binding with various metals, and this represents the most comprehensive study of the MetAP metal-ion interactions. The C-terminal domain of PDF is implicated in imparting highly unusual properties to PDF, hence the stability of PDF was characterized with respect to this domain. The truncated form of PDF lacking the C-terminal domain was found to be remarkably robust with the secondary structure as well as catalytic activity being very resistant to loss by heat. The evidence suggests additional roles for the C-terminal domain in regulating PDF. Overall, the work described here provides new understanding and avenues for enzymological pursuits of MetAP, PDF and similar valuable targets.
Exciton Diffusion, Transport, and Localization in Conjugated Polymers
(North Dakota State University, 2013) Bjorgaard, Josiah August
Conjugated polymers are wide bandgap semiconductors which have a series of conjugated π-orbitals that extend along the polymer ‘backbone’. The π-orbital conjugation can be disrupted by twisting of the polymer, affecting their optical properties. These materials are very useful for devices, where they are frequently found in semicrystalline thin films. In thin films, Frenkel excitons diffuse on a nanometer scale. However, measurement of the diffusion length of excitons in conjugated polymer films is currently very difficult. Disordered packing and twisting of polymers plays a significant role, but has not been examined in detail. This dissertation presents methods of measuring exciton diffusion length in polymer films and nanoparticles and explains the effect of nuclear disorder on the optical spectra and exciton diffusion in semicrystalline polymer films.

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