Synthesis of 1,1'-(Hexane-1,6-Diyl)Bis(5-Oxopyrrolidine-3-Carboxylic Acid) as a Monomer for a Polyanhydride Drug Delivery System

Polyanhydrides have been given much attention in the literature recently because of their desirable properties as controlled drug delivery solutions. Drug therapies could be loaded into a polyanhydride matrix and protected from denaturation and removal from the body while being slowly eluted as the polyanhydride degraded yielding a tailorable concentration profile in the bloodstream at therapeutic levels. To that end, this report discusses the synthesis of a novel monomer for polyanhydride synthesis: 1,1'-(hexane-1,6-diyl)bis(5-oxopyrrolidine-3-carboxylic acid) henceforth known as CPyH monomer for (carboxypyrrolidone)hexane monomer.

Growth, modification and integration of carbon nanotubes into molecular electronics

Molecules are the smallest possible elements for electronic devices, with active elements for such devices typically a few Angstroms in footprint area. Owing to the possibility of producing ultrahigh density devices, tremendous effort has been invested in producing electronic junctions by using various types of molecules. The major issues for molecular electronics include (1) developing an effective scheme to connect molecules with the present micro- and nano-technology, (2) increasing the lifetime and stabilities of the devices, and (3) increasing their performance in comparison to the state-of-the-art devices. In this work, we attempt to use carbon nanotubes (CNTs) as the interconnecting nanoelectrodes between molecules and microelectrodes. The ultimate goal is to use two individual CNTs to sandwich molecules in a cross-bar configuration while having these CNTs connected with microelectrodes such that the junction displays the electronic character of the molecule chosen. We have successfully developed an effective scheme to connect molecules with CNTs, which is scalable to arrays of molecular electronic devices. To realize this far reaching goal, the following technical topics have been investigated. 1. Synthesis of multi-walled carbon nanotubes (MWCNTs) by thermal chemical vapor deposition (T-CVD) and plasma-enhanced chemical vapor deposition (PECVD) techniques (Chapter 3). We have evaluated the potential use of tubular and bamboo-like MWCNTs grown by T-CVD and PE-CVD in terms of their structural properties. 2. Horizontal dispersion of MWCNTs with and without surfactants, and the integration of MWCNTs to microelectrodes using deposition by dielectrophoresis (DEP) (Chapter 4). We have systematically studied the use of surfactant molecules to disperse and horizontally align MWCNTs on substrates. In addition, DEP is shown to produce impurityfree placement of MWCNTs, forming connections between microelectrodes. We demonstrate the deposition density is tunable by both AC field strength and AC field frequency. 3. Etching of MWCNTs for the impurity-free nanoelectrodes (Chapter 5). We show that the residual Ni catalyst on MWCNTs can be removed by acid etching; the tip removal and collapsing of tubes into pyramids enhances the stability of field emission from the tube arrays. The acid-etching process can be used to functionalize the MWCNTs, which was used to make our initial CNT-nanoelectrode glucose sensors. Finally, lessons learned trying to perform spectroscopic analysis of the functionalized MWCNTs were vital for designing our final devices. 4. Molecular junction design and electrochemical synthesis of biphenyl molecules on carbon microelectrodes for all-carbon molecular devices (Chapter 6). Utilizing the experience gained on the work done so far, our final device design is described. We demonstrate the capability of preparing patterned glassy carbon films to serve as the bottom electrode in the new geometry. However, the molecular switching behavior of biphenyl was not observed by scanning tunneling microscopy (STM), mercury drop or fabricated glassy carbon/biphenyl/MWCNT junctions. Either the density of these molecules is not optimum for effective integration of devices using MWCNTs as the nanoelectrodes, or an electroactive contaminant was reduced instead of the ionic biphenyl species. 5. Self-assembly of octadecanethiol (ODT) molecules on gold microelectrodes for functional molecular devices (Chapter 7). We have realized an effective scheme to produce Au/ODT/MWCNT junctions by spanning MWCNTs across ODT-functionalized microelectrodes. A percentage of the resulting junctions retain the expected character of an ODT monolayer. While the process is not yet optimized, our successful junctions show that molecular electronic devices can be fabricated using simple processes such as photolithography, self-assembled monolayers and dielectrophoresis.

Synthesis, structure, and stability of metal-organic frameworks

Metal-organic frameworks (MOFs) obtained much attention because of their unusual structures and properties as well as their potential applications. This dissertation research was focused on (1) the effects of synthesis conditions on the structures of MOFs, (2) the thermal stability of MOFs, (3) pressure-induced amorphization, and (4) the effect of high-valent ions on the structure of a MOF. This research demonstrated that the crystal structure of MOF-5 could be controlled by drying solvents. If the vacuum solvent is dimethylformamide (DMF), the crystal structure of MOF-5 is tetragonal. In contrast, if the DMF is displaced by CH2Cl2 before the vacuum, the obtained MOF-5 occupies a cubic structure. Furthermore, it was found that the tetragonal MOF-5 exhibited a mediate surface area (300-1000 m2/g). The surface area of tetragonal MOF-5 is also dependent on Zn(NO3)2/H2BDC (H2BDC: terephthalic acid) molar ratios used for its synthesis. The optimum ratio is 1.38, at which synthesized tetragonal MOF-5 exhibits the highest crystallinity and surface area (1297 m2/g). The thermal stability and decomposition of MOF-5 were systematically investigated. The thermal decomposition of cubic and tetragonal MOF-5s resulted in the same products: CO2, benzene, amorphous carbon, and crystal ZnO. The thermal decomposition is due to breaking carboxylic bridges between benzene rings and Zn4O clusters. Identifying structural relationships between crystalline and noncrystalline states is of fundamental interest in materials research. Currently, amorphization of solid materials at ambient temperature requires an ultra-high pressure (several GPa). However, this research demonstrated that MOF-5 and IRMOF-8 can be irreversibly amorphized at ambient temperature by employing a low compressing pressure of 3.5 MPa, which is 100 times lower than that required for amorphization of other solids. Furthermore, the pressure-induced amorphization (PIA) of MOFs is strongly dependent on the changeability of bond angles. If the geometric structure of a MOF can allow bond angles to be changed without breaking bonds, it can easily be amorphized by compression. This can explain why MOF-5 and IRMOF-8 can easily be amorphized via compression than Cu-BTC. It is generally recognized that zeolitic imidazolate frameworks (ZIFs) occupy much higher stability than other types of MOFs. The representative of ZIFs is Zn(2-methylimidazole)2 (ZIF-8) exhibiting high-decomposition temperature and high chemical resistance to various solvents. However, so far, it is still unknown whether the high stability of ZIF-8 can be challenged by ions, which is important for its modification by doping ions. In this research, we performed aqueous salt solution treatment on ZIF-8, and the results showed that anions (Cl¯ and NO3¯) in a solution exhibited no effect on the crystal structure of ZIF-8. However, the effect of cations (in a solution) on structure of ZIF-8 strongly depends on the cation valences. The univalent metal cations showed no effect on the structure of ZIF-8, whereas the bivalent or higher-valent metal cations caused the collapse of ZIF-8 crystal structure. Therefore, structure stability of ZIF-8 is considered when it is subjected to the application, in which high-valent metal cations are involved.

Boron nitride nanotubes : synthesis, characterization, functionalization, and potential applications

Boron nitride nanotubes (BNNTs) are structurally similar to carbon nanotubes (CNTs), but exhibit completely different physical and chemical properties. Thus, BNNTs with various interesting properties may be complementary to CNTs and provide an alternative perspective to be useful in different applications. However, synthesis of high quality of BNNTs is still challenging. Hence, the major goals of this research work focus on the fundamental study of synthesis, characterizations, functionalization, and explorations of potential applications. In this work, we have established a new growth vapor trapping (GVT) approach to produce high quality and quantity BNNTs on a Si substrate, by using a conventional tube furnace. This chemical vapor deposition (CVD) approach was conducted at a growth temperature of 1200 °C. As compared to other known approaches, our GVT technique is much simpler in experimental setup and requires relatively lower growth temperatures. The as-grown BNNTs are fully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron energy loss spectroscopy (EELS), Energy Filtered Mapping, Raman spectroscopy, Fourier Transform Infra Red spectroscopy (FTIR), UV-Visible (UV-vis) absorption spectroscopy, etc. Following this success, the growth of BNNTs is now as convenient as growing CNTs and ZnO nanowires. Some important parameters have been identified to produce high-quality BNNTs on Si substrates. Furthermore, we have identified a series of effective catalysts for patterned growth of BNNTs at desirable or pre-defined locations. This catalytic CVD technique is achieved based on our finding that MgO, Ni or Fe are the good catalysts for the growth of BNNTs. The success of patterned growth not only explains the role of catalysts in the formation of BNNTs, this technique will also become technologically important for future device fabrication of BNNTs. Following our success in controlled growth of BNNTs on substrates, we have discovered the superhydrophobic behavior of these partially vertically aligned BNNTs. Since BNNTs are chemically inert, resistive to oxidation up to ~1000°C, and transparent to UV-visible light, our discovery suggests that BNNTs could be useful as self-cleaning, insulating and protective coatings under rigorous chemical and thermal conditions. We have also established various approaches to functionalize BNNTs with polymeric molecules and carbon coatings. First, we showed that BNNTs can be functionalized by mPEG-DSPE (Polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a bio-compatible polymer that helps disperse and dissolve BNNTs in water solution. Furthermore, well-dispersed BNNTs in water can be cut from its original length of >10µm to(>20hrs). This success is an essential step to implement BNNTs in biomedical applications. On the other hand, we have also succeeded to functionalize BNNTs with various conjugated polymers. This success enables the dispersion of BNNTs in organic solvents instead of water. Our approaches are useful for applications of BNNTs in high-strength composites. In addition, we have also functionalized BNNTs with carbon decoration. This was performed by introducing methane (CH4) gas into the growth process of BNNT. Graphitic carbon coatings can be deposited on the side wall of BNNTs with thicknesses ranging from 2 to 5 nm. This success can modulate the conductivity of pure BNNTs from insulating to weakly electrically conductive. Finally, efforts were devoted to explore the application of the wide bandgap BNNTs in solar-blind deep UV (DUV) photo-detectors. We found that photoelectric current generated by the DUV light was dominated in the microelectrodes of our devices. The contribution of photocurrent from BNNTs is not significant if there is any. Implication from these preliminary experiments and potential future work are discussed.

Advanced Nanostructured Electro-Catalysts for Electricity Generation and Biorenewable Alcohol Conversion

In my Ph.D research, a wet chemistry-based organic solution phase reduction method was developed, and was successfully applied in the preparation of a series of advanced electro-catalysts, including 0-dimensional (0-D) Pt, Pd, Au, and Pd-Ni nanoparticles (NPs), 1-D Pt-Fe nanowires (NWs) and 2-D Pd-Fe nanoleaves (NLs), with controlled size, shape, and morphology. These nanostructured catalysts have demonstrated unique electro-catalytic functions towards electricity production and biorenewable alcohol conversion. The molecular oxygen reduction reaction (ORR) is a long-standing scientific issue for fuel cells due to its sluggish kinetics and the poor catalyst durability. The activity and durability of an electro-catalyst is strongly related with its composition and structure. Based on this point, Pt-Fe NWs with a diameter of 2 - 3 nm were accurately prepared. They have demonstrated a high durability in sulfuric acid due to its 1-D structure, as well as a high ORR activity attributed to its tuned electronic structure. By substituting Pt with Pd using a similar synthesis route, Pd-Fe NLs were prepared and demonstrated a higher ORR activity than Pt and Pd NPs catalysts in the alkaline electrolyte. Recently, biomass-derived alcohols have attracted enormous attention as promising fuels (to replace H2) for low-temperature fuel cells. From this point of view, Pd-Ni NPs were prepared and demonstrated a high electro-catalytic activity towards ethanol oxidation. Comparing to ethanol, the biodiesel waste glycerol is more promising due to its low price and high reactivity. Glycerol (and crude glycerol) was successfully applied as the fuel in an Au-anode anion-exchange membrane fuel cell (AEMFC). By replacing Au with a more active Pt catalyst, simultaneous generation of both high power-density electricity and value-added chemicals (glycerate, tartronate, and mesoxalate) from glycerol was achieved in an AEMFC. To investigate the production of valuable chemicals from glycerol electro-oxidation, two anion-exchange membrane electro-catalytic reactors were designed. The research shows that the electro-oxidation product distribution is strongly dependent on the anode applied potential. Reaction pathways for the electro-oxidation of glycerol on Au/C catalyst have been elucidated: continuous oxidation of OH groups (to produce tartronate and mesoxalate) is predominant at lower potentials, while C-C cleavage (to produce glycolate) is the dominant reaction path at higher potentials.

Trifluoroacetic acid: A more effective and efficient reagent for the synthesis of 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones and 3-arylmethyl-2-amino quinolines from Baylis-Hillman derivatives via Claisen rearrangement

Trifluoroacetic acid has been discovered to be a highly effective and efficient reagent for the tandem Claisen rearrangement and cyclisation reaction to yield 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones from compounds obtained from the SN2 reaction between anilines and acetyl derivatives of Baylis-Hillman adducts of acrylates in the presence of DABCO. In contrast similar compounds obtained from the acetyl derivatives of Baylis-Hillman adduct of acrylonitrile on treatment with trifluoroacetic acid directly furnish 3-arylmethyl-2-amino-quinoline via tandem Claisen rearrangement, cylisation and isomerisation.

A key role for lipoic acid synthesis during Plasmodium liver stage development.

The successful navigation of malaria parasites through their life cycle, which alternates between vertebrate hosts and mosquito vectors, requires a complex interplay of metabolite synthesis and salvage pathways. Using the rodent parasite Plasmodium berghei, we have explored the synthesis and scavenging pathways for lipoic acid, a short-chain fatty acid derivative that regulates the activity of α-ketoacid dehydrogenases including pyruvate dehydrogenase. In Plasmodium, lipoic acid is either synthesized de novo in the apicoplast or is scavenged from the host into the mitochondrion. Our data show that sporozoites lacking the apicoplast lipoic acid protein ligase LipB are markedly attenuated in their infectivity for mice, and in vitro studies document a very late liver stage arrest shortly before the final phase of intra-hepaticparasite maturation. LipB-deficient asexual blood stage parasites show unimpaired rates of growth in normal in vitro or in vivo conditions. However, these parasites showed reduced growth in lipid-restricted conditions induced by treatment with the lipoic acid analogue 8-bromo-octanoate or with the lipid-reducing agent clofibrate. This finding has implications for understanding Plasmodium pathogenesis in malnourished children that bear the brunt of malarial disease. This study also highlights the potential of exploiting lipid metabolism pathways for the design of genetically attenuated sporozoite vaccines.

Fluorinated olefinic peptide nucleic acid: synthesis and pairing properties with complementary DNA

The fluorinated olefinic peptide nucleic acid (F-OPA) system was designed as a peptide nucleic acid (PNA) analogue in which the base carrying amide moiety was replaced by an isostructural and isoelectrostatic fluorinated C-C double bond, locking the nucleobases in one of the two possible rotameric forms. By comparison of the base-pairing properties of this analogue with its nonfluorinated analogue OPA and PNA, we aimed at a closer understanding of the role of this amide function in complementary DNA recognition. Here we present the synthesis of the F-OPA monomer building blocks containing the nucleobases A, T, and G according to the MMTr/Acyl protecting group scheme. Key steps are a selective desymmetrization of the double bond in the monomer precursor via lactonization as well as a highly regioselective Mitsunobu reaction for the introduction of the bases. PNA decamers containing single F-OPA mutations and fully modified F-OPA decamers and pentadecamers containing the bases A and T were synthesized by solid-phase peptide chemistry, and their hybridization properties with complementary parallel and antiparallel DNA were assessed by UV melting curves and CD spectroscopic methods. The stability of the duplexes formed by the decamers containing single (Z)-F-OPA modifications with parallel and antiparallel DNA was found to be strongly dependent on their position in the sequence with T(m) values ranging from +2.4 to -8.1 degrees C/modification as compared to PNA. Fully modified F-OPA decamers and pentadecamers were found to form parallel duplexes with complementary DNA with reduced stability compared to PNA or OPA. An asymmetric F-OPA pentadecamer was found to form a stable self-complex (T(m) approximately 65 degrees C) of unknown structure. The generally reduced affinity to DNA may therefore be due to an increased propensity for self-aggregation

Deoxynucleoside triphosphates bearing histamine, carboxylic acid, and hydroxyl residues--synthesis and biochemical characterization.

Modified nucleoside triphosphates (dA(Hs)TP, dU(POH)TP, and dC(Val)TP) bearing imidazole, hydroxyl, and carboxylic acid residues connected to the purine and pyrimidine bases through alkyne linkers were prepared. These modified dN*TPs were excellent substrates for various DNA polymerases in primer extension reactions. Moreover, the combined use of terminal deoxynucleotidyl transferase (TdT) and the modified dNTPs led to efficient tailing reactions that rival those of natural counterparts. Finally, the triphosphates were tolerated by polymerases under PCR conditions, and the ensuing modified oligonucleotides served as templates for the regeneration of unmodified DNA. Thus, these modified dN*TPs are fully compatible with in vitro selection methods and can be used to develop artificial peptidases based on DNA.