Cerium (IV) oxide, or CeO2, nanomaterials have displayed antioxidant and enzyme mimetic activities due to a Ce3+/Ce4+ redox capability enhanced through oxygen vacancies and mobility. Tri-valent, fluorescent ions such as Eu3+ increase the Ce3+/Ce4+ ratio and oxygen vacancy concentration, while contributing fluorescent properties to the nanomaterial. The combination of these attributes make europium doped cerium oxide (EuCeO¬2) nanomaterials appealing candidates for various biological applications.
To complement our earlier efforts on the synthesis and properties of EuCeO2 nanowires, nanorods, and nanocubes, this presentation addresses a new, complementary structure, EuCeO2 nanotubes. The nanotubes are prepared via deposition and subsequent oxidation of Eu-doped Ce(OH)3 to form a EuCeO2 shell on sacrificial ZnO nanowires.
Previous synthetic routes to CeO2 nanotubes have been reported featuring carbon nanotubes as sacrificial templates, the etching of cerium-based nanorods, and other less-common methods . These routes have struggled with clear evidence for distinct nanotube formation, as well as control over nanotube dimensions. Our use of a ZnO core allows for facile manipulation of inner diameter and length of the nanotube following etching of the core.
The synthesized nanotubes were characterized using scanning and transmission microscopy (SEM and TEM) for morphology, energy dispersive x-ray (EDX) for elemental composition, and photoluminescence to track europium fluorescence. Synthesized nanotubes had inner diameters from 40 nm to 200 nm, based on the ZnO core. Following synthesis and characterization, the nanotubes will be tested for use as a drug delivery vector, using ibuprofen as a model.

This project is aimed to modify a leucyl-tRNA synthetase (LeuRS) to incorporate fluorescent amino acids into proteins to produce fluorescent proteins in living cells. Fluorescent proteins are useful because they are easily analyzed and tracked in living organisms. In a small scale, we successfully prepared the library of LeuRS variants in which five amino acids are randomized in the leucine-binding site of a functional LeuRS without its editing domain. Currently, we are working on a large scale production of viable bacterial cells that cover the whole diversity of library (at least 34 million different LeuRS molecules). Initially, we attempted two-step process in which an N-terminal library fragment (for two randomized amino acids) is generated first and a C-terminal fragment (for three randomized amino acids) is added later. However, this two-step cloning process did not produce enough viable cells to cover all the possible variants. In a new approach, a complete library of LeuRS will be produced by overlapping extension PCR and introduced to E. coli in a single step to ensure highest possible transformation efficiency. Consequently, the library of LeuRS variants will be subject to a genetic selection experiment to obtain LeuRS variants that incorporate only fluorescent amino acids into proteins.

Diffusiophoresis is the migration of a relatively large particle (e.g., protein, polymer, nanoparticle) induced by a gradient of salt concentration. The salt-induced diffusiophoresis of lysozyme, a model protein, at pH 4.5 and 25 °C was examined as a function of salt concentration for three chloride salts: NaCl, KCl and MgCl2. Diffusiophoresis coefficients were theoretically extracted from experimental multicomponent diffusion data by applying irreversible thermodynamics. A selected mass-transfer process was theoretically examined to show that concentration gradients of MgCl2 produce significant lysozyme diffusiophoresis. The dependence of lysozyme diffusiophoresis on salt nature was theoretically examined and linked to protein charge. The effect of salt type on hydrogen-ion titration curves was experimentally characterized to understand the role of salt nature on protein charge. Our findings indicate that diffusiophoresis may be exploited for diffusion-based separation of proteins in the presence of salt concentration gradients and for the enhancement of protein adsorption onto solid surfaces relevant to biosensing applications.

The randomization of 11 bases in the theophylline-binding domain generated a library containing millions of different theophylline riboswitch variants. The dual genetic selection of this molecular library successfully led to the identification of a caffeine-specific synthetic riboswitch. When a chloramphenicol-resistance gene was expressed under control of this caffeine riboswitch, E. coli cells showed chloramphenicol resistance only in the presence of caffeine. For a colorimetric or fluorescence assay, the caffeine riboswitch gene was inserted upstream of the B-galactosidase (LacZ) or green fluorescence protein (GFP) gene, respectively. When tested with various concentrations of caffeine, the enzymatic activity of LacZ or the fluorescence intensity of GFP was proportional to the amount of caffeine, clearly indicating the caffeine-dependent gene regulation by the caffeine riboswitch. The caffeine synthetic riboswitch can be further developed as a biosensor to detect caffeine in complex biological samples such as urine and blood.

Abacavir or Ziagen, is an antiretroviral medicine that is used in conjunction with other
medicines to treat HIV. Although it is not a cure, it has been clinically proven to be
effective in diminishing the rate of HIV replication. The synthetic process of creating
Abacavir is both timely and costly, so therefore a new synthetic process has been
created to generate a chemical analog (specifically a triazine derivative) that is cheaper
to produce that can be if not potentially more chemically effective than Abacavir. Once
the analog is produced, a series of analytical tests will be done on a micro organismic
level to determine if the analog is both effective and safe enough to be used in human
clinical studies further down the road.

The pyrrolophenanthridone alkaloid pratosine is a natural product related to hippadine, which is known to be a powerful but reversible inhibitor of spermatogenesis in rats. Hippadine has also shown cardiovascular as well as anticancer activity. Given the structural similarities between the two molecules, it is expected that pratosine and hippadine will demonstrate similar biological effects. Our work toward a laboratory synthesis of pratosine will facilitate large-scale production thus affording sufficient quantities of the material for a complete pharmacological study of its properties. Although we have a synthetic plan for preparing pratosine, several reactions have failed due to solubility problems. This research focuses on solving these problems by using an alternate starting material. The commercially available compound vanillin, which is extracted from vanilla beans, is a simple and inexpensive aldehyde with an appropriate structure for attaching other groups that should improve the solubility properties of several of the synthetic intermediates. Our goal is to find a specific substituent that will provide the required characteristics but which can also be removed later to generate the final product.

Porous silicon (pSi) is a unique nanostructured form of the elemental semiconductor Si. Due to its useful properties governed by its surface chemistry and porous morphology, pSi has been studied in the last few decades in diverse fields extending from electronic device technology to bio-relevant applications.1 Recently, one-dimensional porous nanotubes based on elemental Si (pSiNTs) with a tunable structure (sidewalls, inner void space and lengths) have been successfully synthesized.2 The well-defined structure of pSiNTs offers ample opportunities to study newly emerging properties of this material and innovative applications in multiple areas. For example, recent reports have revealed the use of SiNTs as an efficient template for loading superparamagnetic nanoparticles (Fe3O4), lithium storage and cycling, as well as acting as a template for formation of organometal perovskite nanostructures.3-5
Platinum (Pt) nanoparticles, both free-standing as well as anchored on various surfaces, have attracted widespread attention in nanocatalysis, electronics, and chemotherapeutics.6 In this work, it is suggested that pSiNTs after being functionalized with 3-(aminopropyl)triethoxysilane (APTES) can serve as a platform for Pt nanocrystal (Pt NC) formation. Particularly, incubation of APTES-functionalized SiNTs in potassium tetrachloroplatinate (II) (K2PtCl4) solution under ambient conditions subsequently yields Pt nanoclusters with sizes ranging from 1-3 nm on SiNTs. From high-resolution transmission electron microscopy (HRTEM), nanocrystals with characteristic lattice spacings associated with Pt (d = 0.21 nm) are observed on the nanotubes. The amount of Pt deposited on SiNTs can be sensitively tuned from 20-60 wt% (characterized by TEM Energy Dispersive X-ray Analysis, EDX) by varying concentration of K2PtCl4 and immersion time in this Pt salt precursor.
These findings suggest a new approach to prepare Pt NCs that are of potential benefit to a broad number of applications by using pSiNTs as a template. Further investigations into the properties of the newly discovered Pt NCs-SiNT composites are imperative to evaluate useful applications of this material.
REFERENCES
[1] Porous Silicon for Biomedical Applications, H. Santos, Ed. Cambridge: Woodhead Publishing, 2014.
[2] X. Huang, R. Gonzalez-Rodriguez, R. Rich, Z. Gryczynski, J.L. Coffer, Chem. Commun., 2013, 49, 5760-5762.
[3] P. Granitzer, K. Rumpf, R. Gonzalez, J. Coffer, M. Reissner, Nanoscale Res. Lett. 2014, 9, 413.
[4] R. Gonzalez-Rodriguez, N. Arad-Vosk, N. Rozenfeld, A. Sa'ar, J. L. Coffer, Small, 2016, 12, 4477-4480.
[5] A. T. Tesfaye, R. Gonzalez, J. L. Coffer, T. Djenizian, ACS Appl. Mater. Interfaces, 2015, 7, 20495-20498.
[6] A. Chen, and P. Holt-Hindle, Chem. Rev., 2010, 110, 3767-3804.

Urea is a low-cost, water-soluble fertilizer that is used as the major source of nitrogen in agricultural production. However, the problem with leaching, in which urea in soil is rapidly washed away through rain and irrigation, results in inefficiency in nutrient absorption, low crop yield, poor harvest, and economic failure for farmers (Broadbent 1958), as well as the environmental pollution of groundwater by the release of excessive amounts of nitrate, which adversely affects this non-rechargeable water source. Therefore, recent research attempts to design a suitable system to prolong the release of urea from water in soil to improve soil fertility, agricultural economy, and ground water protection. A prospective approach is to integrate urea into a stable matrix that releases the desired material with an optimal time window.

Porous Silicon (pSi) has been studied as the material of diverse interest, due to its surface chemistry and porous morphology that has promoted many nanotechnology advances, in conjunction with its biocompatibility and biodegradability (Canham 2014). Since pSi degrades slowly in aqueous media and does not react with the soil component, it is selected to be a possible matrix for sustaining urea release. pSi is believed to interact with urea via hydrogen bonds (via surface silanol species), and thus its porous structure is the key to trap urea particles for relatively long periods in water, while exposing the fertilizer to plants. This bioactive pSi material is produced from the eco-friendly Tabasheer-derived silica, during which pSi porosity is maintained (Kalluri et al. 2016). Loading of urea into pSi is carried out using ethanol as a solvent, with theoretical loadings ranging from 27-33% of the composite mass. Release kinetics of urea from water is currently being investigated using highly sensitive colorimetric assay that applies Jung’s method (Jung et al. 1975).

The urea-loaded pSi prepared in these experiments were characterized using several different techniques. X-ray diffraction (XRD) evaluates the crystallinity of pSi after fabrication, with the presence of three peaks consistent with a cubic unit cell structure [Si (111), (220), and (311)]. Thermal gravimetric analysis (TGA) gives the mass loss percentage between melting (132oC) and boiling (203oC) points of urea, which represents the practical loading of urea in a given sample. The results deviate 1-2% from the theoretical loading percentage. TGA also shows the stability of the composite over two months at room temperature, with the recent loading measurement analyses consistent with the previous ones. Differential scanning calorimetry (DSC) analysis confirms that the urea is incorporated in the pSi matrix. Loading and characterization studies were conducted in triplicate to ensure reproducibility of results.

Atomic partial charges obtained from computed wavefunctions are widely used for interpreting quantum chemistry simulations and chemical reactivities of molecules, solids, surfaces, and nanoparticles. In many cases, partial charge alone gives an incomplete picture of reactivity: PhS(-) is a better nucleophile compared to PhO(-) in SN2 reactions with MeI, though PhO(-) has a more negative charge on the nucleophilic atom, the carbons of benzene and cyclobutadiene, or those of diamond, graphene, and C60, possess nearly identical partial charges and very different reactivities, deprotonated amides perform nucleophilic attack via the less negative nitrogen, rather than the more negative oxygen, in anionic cyclization of o-alkynyl benzamides, halide anions F(-), Cl(-), Br(-) and I(-) have identical charges but different nucleophilicities, carbons in aromatic benzene and anti-aromatic cyclobutadiene have nearly identical partial charges, but different reactivities. Our atomic overlap distance complements computed partial charges by measuring the size of orbital lobes that best overlap with the wavefunction around an atom. Compact, chemically stable atoms tend to have overlap distances smaller than chemically soft, unstable atoms. Combining atomic charges and overlap distances captures trends in aromaticity, nucleophilicity, allotrope stability, and substituent effects. Applications to recent experiments in organic chemistry (counterintuitive Lewis base stabilization of alkenyl anions in anionic cyclization), nanomaterials chemistry (facile doping of the central atom in Au7 hexagons) and selective binding of ligands in proteins illustrate this combination’s predictive power.

Amaryllidaceae isoquinoline alkaloids, as well as their analogs, have long been of interest in research for drug discovery due to their biologically active nature. Many of these compounds have been found to be anti-tumor agents.1 Moreover, there have also been studies that show the effectiveness of these molecules against diseases such as Yellow Fever and other RNA-containing flaviviruses.2 Though these compounds are pharmaceutical drug prospects, their low natural abundance lowers that potential.3 For this reason, many synthetic chemists have pursued novel routes to synthesize a wide variety of these compounds.
Techniques toward the synthesis of Pancratistatin-type natural products are presented herein. Manipulations were tested and optimized on a model system to save both time and funds while developing a synthetic pathway to be utilized in the formation of more complex compounds. Setbacks such as controlling the stereochemistry of a tetrasubstituted alkene reduction have been encountered. However, adjustments are being made to avoid such difficulties. Ideally, the proposed scheme will ultimately allow for the synthesis of multiple biologically active Phenanthridone analogs.

A library of novel tetra-aza macrocyclic molecules, specifically 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene derivatives, capable of chelating metal ions in vivo have been synthesized. Applications of these complexes are currently being pursued as a 1) therapeutic focusing on radical scavenging and metal chelation and 2) diagnostic tool such as magnetic resonance imaging (MRI) contrast agents when complexed with specific metal ions. However, a full study of the electronic effects imparted by substitution to the pyridyl moiety (position 13) and the subsequent impact on the metal center have not been explored. The objective of the present study is to characterize metal complexes of four tetra-aza macrocyclic metal chelating molecules. The pyridyl functional groups studied include: A) unmodified pyridyl, B) p-hydroxyl, C) p-nitrile, and D) m-hydroxyl modified pyridyls on a pyclen base structure (position 13). Notable progress has been made in developing an optimal procedure for obtaining copper (II) complexes and will be presented. Analysis of the resulting copper (II) complex of the p-nitrile tetra-aza macrocycle indicate a six-coordinate metal center based on X-ray diffraction. UV-Visible spectroscopy and electrochemistry help to confirm donor strength among the ligand series as well as a comparison to other tetra-aza macrocycles. Ultimately, this project is focused on understanding the electronic contribution of these functional groups on the pyridine ring and the influence of the ligand and complexed systems as therapeutic and diagnostic agents.

Hippadine and pratosine are lycorine-type pharmacologically active Amaryllidaceae alkaloids. Various total syntheses of these natural products have been developed. However, most of these synthetic routes require prohibitively expensive materials and/or achieve yields that are subpar, making these schemes unlikely to be used in an industrial setting. Current research involves developing better synthetic methods for these two alkaloids starting with a 6,7-disubstituted isoquinoline. These syntheses are appealing since they utilize readily available starting materials and avoid expensive catalysts. The key step in the synthetic scheme centers around an intramolecular de Mayo photocyclization which involves a reaction between an alkene moiety in the isocarbostyril system and a 1,3-diketone (a functionalized tether on nitrogen), which forms a third ring in the structure of the molecule. When the photochemical reaction was attempted, an unexpected cyclic photoproduct was obtained; fortunately, this product is a cyclic hemiketal of the expected 1,5-dicarbonyl compound. A base-catalyzed aldol addition affords the final ring in the system; dehydration of this product affords a β-enone that can be transformed to a diene. Oxidation of the diene with DDQ affords the target natural products after simple chromatographic purification. This new synthetic pathway circumvents the need for catalysts that are either expensive or contain metals such as palladium or iridium; moreover, our method allows for the synthesis of various natural and unnatural alkaloids in high yields by modification of the N-tether.

Molecules previously developed by the Green Research Group (L2 and L3) have been shown to reduce reactive oxygen species (ROS) through multiple pathways of activity. Although unclear if ROS is the only source, Alzheimer’s disease and other neurodegenerative disorders are known to be initiated from the formation of these ROS. For these molecules to appropriately execute their antioxidant and radical scavenging ability, they must enter into the brain where the damaging ROS are located. The blood brain barrier (BBB) is a natural obstacle that prevents toxins and infections from reaching the brain. The L2 and L3 ligands must penetrate this barrier to be in the desired site of action to reduce the number of ROS. Addition of a glucose moiety to other therapeutic molecules has been shown to increase permeability across the BBB. The target of this project is to enhance these synthetic pathways of glycosylation and increase product yield. Initially, direct addition of the glucose moiety to the L2 and L3 molecules was achieved. However, challenges with purification techniques suggested a different route to purification or design should be considered and one new route is presented here. With L2 and L3 being inherently hydrophilic, addition of an aliphatic chain to the hydroxyl group of L2 or L3 should increase the hydrophobicity of the molecule allowing for different purification techniques, which can ultimately be glycosylated to give purified desired compounds.

A recent and promising development in solar energy involves a class of materials known as organometal halide perovskites, capable of efficiencies (>20%) comparable to the current industry standard of silicon. These materials also demonstrate strong light emission, a key property associated with energy-efficient sources of lighting, suggesting potential applications in light-emitting devices such as light-emitting diodes (LED). The goal of this project was to investigate the fundamental photoluminescence (PL) properties of perovskites housed in a nanoporous material known as semiconducting porous silicon (pSi).

pSi provides a nanoscale template to control the growth of the light-emitting perovskite structure and is an electrically-responsive host matrix, ideally regulating the flow of charge to/from the perovskite. Samples were prepared within the pores of surface oxidized pSi and hydride-terminated pSi, each with a mesoporous width in the 5 – 50 nm range. The perovskite-loaded pSi was fabricated through solution-loading of perovskite precursors into warmed pSi (60ºC), removal of excess reactant solution, and drying. While perovskites can feature a wide range of halide compositions (including mixed halides), this research thus far has focused on methylammonium lead iodide (MAPbI3) perovskite.

These perovskite nanostructures formed within pSi were characterized using a variety of techniques. Following synthesis, the stability of each prepared sample was monitored for 3 weeks through tracking its relative photoluminescence intensity at its maximum value. Perovskite morphology was evaluated by SEM (scanning electron microscope) and TEM (transmission electron microscope) imaging, crystalline structure was evaluated by XRD (x-ray powder diffraction), and elemental analysis was evaluated by EDX (energy-dispersive x-ray spectroscopy).

In this study, SEM imaging showed consistent perovskite particle size and ununiformed perovskite infiltration. It is found that the emission intensity for MAPbI3 formed within hydride-terminated pSi (at ~730nm) and oxidized pSi (at ~740nm) were relatively stable over a 3 week period, but the emission intensity for perovskite microrods formed in the absence of any pSi template actually decreased over time. More detailed measurements of the long term stability of these new nanoscale materials are currently under evaluation.

Significant increases in average life expectancy in the last century have brought a growth in human illnesses related to aging: chronic wounds, bone diseases, eye diseases and cancer. In this work, we demonstrate fabrication of biodegradable polymer scaffolds that can be used for drug delivery and tissue engineering to treat the above-mentioned ailments. Tissue engineering can be defined as the use of a combination of engineering and materials methods and appropriate biochemical factors to improve or replace biological tissues.
This project includes fabrication of solid and porous fibers from the biocompatible PCL polymer. This polymer is currently used for surgical sutures, nerve guides and three-dimensional scaffolds for use in tissue engineering. The drug release rate is faster when it is loaded into porous PCL fibers compared to solid PCL fibers, creating an advantage for porous fiber fabrication. Use of a technique known as electrospinning of a solution of PCL and chloroform results in solid fibers that are 4 (± 2.0) micrometers (μm) in diameter. The porous fiber scaffolds are fabricated using a 50% weight of PCL compared to volume of solvent (w/v) solution prepared in a mixture of solvents 9:1 dichloromethane (DCM):dimethyl sulfoxide (DMSO) and 60% w/v PCL in 8:2 DCM:DMSO. The porous fibers are collected at 0-5 oC with a pore size of 50.0 (± 10.0) nanmoeters (nm) and fiber diameter of 3.0 (± 1.0) μm. The porosity for 50% w/v PCL and 60% w/v PCL fibers ranges from 40-50%.
Fiber surface morphology is characterized using field emission scanning electron microscopy (FESEM). In addition, the melting temperature and percent crystallinity are determined via differential scanning calorimetry (DSC). The melting temperature was collected of PCL bulk, 30%w/w PCL solid fibers, 50% w/v PCL and 60% w/v PCL. The crystallinity of PCL in solid fiber and porous fiber forms ranges from 52-55%, compared to the 60% crystallinity of PCL bulk. Solid PCL fibers showed to be more crystalline compared to porous PCL fibers, which in turn can effect the degradation time.
In order for these composites to be identified as a major technological advancement, the aging and degradation of the polymer scaffold must also be understood. The degradation of a given polymer matrix impacts the potential drug delivery behavior when testing in vitro. Degradation studies of the above mentioned materials are currently ongoing.

While cis/Z-substituted alkenes are usually less stable than their trans/E-substituted counterparts, the cis-2-butenyl anion shows a higher preference over the trans-isomer. Calculations suggest that the discrepancy is due to two cooperating effects: electrostatic interactions between the anionic center (C1) to the methyl group (C4) and coupling between the C=C pi* antibonding orbital and both the CH2 pz and CH3 C-H sigma bonds. Supporting the charge transfer is the fact that substitution on C1 with EDG stabilizes the cis more while substitution on C4 with EWG stabilizes the cis more. For the coupling interaction the C=C bond was stretched which increased the cis stabilization by lowering the pi* orbital energy and increasing the coupling between the lone pair on C1 and pi*.

Oxidative stress in the brain is a known contributor to the development of neurodegenerative diseases, including Alzheimer’s. The focus of this project is to target the amyloid-β plaque formations and reactive oxygen species (ROS) derived from misregulated metal-ions that lead to disease-causing oxidative stress. The present investigation is measuring the antioxidant reactivity of the new molecule L4. L4 contains two radical scavenging pyridol groups along with a metal-binding nitrogen rich ligand system. It was hypothesized that increasing the number of pyridol groups in our small molecule library would increase the radical scavenging activity, which in turn may provide cells protection from oxidative stress. The radical scavenging ability of L4 was quantified using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay and this was compared to other radical scavenging small molecules to evaluate the effect of the additional radical scavenging group on the antioxidant activity. The interaction of L4 with redox active metal-ions such as copper(II) was also evaluated to show the molecule’s ability to target misregulated metal-ions in diseased tissues.

The combination of inorganic porous silicon (pSi) and flexible biocompatible polymers has been shown to yield more beneficial hybrid scaffolds for tissue engineering (i.e. use of synthetic materials to facilitate healing). PSi has a variety of tunable properties, including pore size, pore volume and non-toxic degradation; the addition of a flexible polymer component provides the benefit that such a construct can easily conform to any shape of the actual site of an injury/disease, suggesting that pSi/polymer composites can be suitable candidates for localized drug delivery.
In this work, composite materials consisting of oxidized porous silicon (ox-pSi) with particle size of ~ 30 μm and pore size of 40-100 nm and thin polycaprolactone (PCL) films. PCL solid films were fabricated from an initial fibrous structure that was exposed to a temperature of 65-80 oC causing fusion of these fibers into a solid film. Ox-pSi particles were then physically embedded into PCL films, resulting in ~30-40% loading of ox-pSi (ox-pSi/PCL film). Ox-pSi particles of the composite were loaded with a model cytotoxic (anticancer) drug-camptothecin (CPT). Drug release from the ox-pSi particles alone and ox-pSi/PCL film composites was monitored fluorometrically, showing distinct release profiles for each material.
Ox-pSi/PCL film composites release a CPT payload in accordance with the Higuchi release model and showed a significant decrease in burst effect compared to ox-pSi particles only. In addition, composite evolution after 5 weeks in a given solution was examined by determining weight loss and surface morphology/composition (FESEM). Overall weight loss of the composites was less then 10% mainly attributed to pSi particles detachment and dissolution.

Iron plays a pivotal role in metabolism and transport processes in nature but can also be used to accomplish important chemical transformations on the bench top; recently, iron(II) salts have been shown to catalyze direct Suzuki – Miyaura coupling of N-heterocyclic compounds and arylboronic acid derivatives in the presence of oxygen. Presented herein are three tetra-aza macrocyclic iron(III) complexes [L1Fe(III)(Cl)2]+ (L1Fe), [L2Fe(III)(Cl)2]+ (L2Fe), and [L3Fe(III)(Cl)2]+ (L3Fe) [L1 (Pyclen)=1,4,7,10-tetra-aza-2,6-pyridinophane; L2 =3,6,9,15-tetraazabicyclo[9.3.1]penta-deca-1(15),11,13-trien-13-ol; L3 =3,6,9,15-tetra-azabicyclo[9.3.1]penta-deca-1(15),11,13-trien-12-ol] that catalyze the coupling of pyrrole and phenylboronic acid. Following the synthesis and reactivity studies, investigation into the oxidation state of the iron center throughout the catalytic cycle was explored. The results of this work to date will be presented and will facilitate the understanding of challenging chemical reactions catalyzed using inexpensive earth abundant metals such as iron.

Nanomaterials based on cerium (IV) oxide, CeO2, have been extensively investigated due to interesting chemistry from a readily available transition between Ce3+ and Ce4+. Oxygen vacancies present in the oxide lattice combined with the available redox transition gives CeO2 materials antioxidant and enzyme mimetic behavior. The addition of tri-valent, fluorescent ions such as Eu3+ further increase the oxygen vacancy concentration, may allow control over the Ce3+/Ce4+ ratio, and may add fluorescence to the doped material. These properties give europium doped cerium oxide (EuCeO¬2) potential applications within biological systems.
Eumelanin is a complex dark brown pigment originating from the oxidation and oligomerization of tyrosine. The pigment can also be synthesized through the auto-oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA). While its structure has not been fully determined, eumelanin has shown antioxidant and free-radical scavenging behavior, strong UV-VIS absorption, and conductive properties. The pigment has been researched for its radiation damage protection, and for activity against amyloids associated with Parkinson’s and Alzheimer’s disease.
Our research thus far has focused on the controlled synthesis of various EuCeO2 nanomaterials, and their interaction with the auto-oxidation of L-DOPA to eumelanin as measured through the observation of eumelanin fluorescence at 471 nm. Nanorods, nanowires, and nanocubes of EuCeO2 were each synthesized with a range of dimensions and europium content. EuCeO2 nanorods and nanocubes were synthesized through precipitation of EuCe(OH)3 and a subsequent hydrothermal reaction between 100°C and 180°C. Nanowires were synthesized using electrospinning and annealing techniques. All materials were analyzed using transmission electron microscopy (TEM), energy dispersive x-ray analysis (EDX), and powder x-ray diffraction (XRD).
The presence of CeO2 or EuCeO2 materials in L-DOPA containing solutions consistently suppressed the eumelanin-associated fluorescence intensity. Various parameters, including temperature, pH, nanomaterial concentration and morphology, and europium doping concentration have been evaluated for their potential impact on the evolution of eumelanin from L-DOPA in the presence of these EuCeO2 nanomaterials.

Monika Hailey
SRS 2017
Neilson Group
Synthesis of Silicon-Nitrogen Polymer Precursors
The Neilson research group focuses on developing synthetic routes to new organic-inorganic hybrid polymers. Specifically, one class of potential polymers contain silicon-nitrogen bonds, alternating with organic spacer groups along the polymer backbone. These two elements were chosen in order to obtain a system whose stability is similar to that of organic (carbon-based) polymers. Organic polymers are very stable and can be found in everyday life. In addition, silicon-oxygen polymers are used in several commercial applications. Silicon-nitrogen polymers could possibly serve as precursors to other new polymeric and/or solid state materials.
Experiments were conducted to produce a variety of small molecule precursors to the new silicon-nitrogen polymer system. Seven silicon-nitrogen small molecules were synthesized, in fairly good yield, and characterized using 1H NMR spectroscopy. When attempting to purify some of these small molecules, there was some thermal decomposition, possibly leading to the desired polymer. Future experiments will investigate the synthetic potential of these new compounds.

Molecularly imprinted polymers (MIPs) are advantageous to chemists both in their ability to drive the equilibrium of a reaction toward a desired product and in chromatography. In this project we focused on the use of MIPs in a chromatographic sense to selectively isolate menthyl-(hydroxymethyl)-phenyl phosphinate in the SP form from a mixture of both diastereoisomers. Both R and S configurations are made in equal proportions but the yield from isolation and crystallization of each pure diastereoisomer is low. Production of a polymer containing pockets specific to the configuration of one diastereoisomer enables an easier method to isolate one diastereoisomer through absorption by the polymer and subsequent release. The potential for MIPs for these P-stereogenic compounds lies in the increase yield of pure crystals and therefor decreased cost of production.

This project was aimed to prepare stable isosteric analogs of S-adenosylmethione (SAM) whose sulfur atom is replaced by a nitrogen atom and to evaluate these analogs for the SAM riboswitch-binding activities and antibacterial activities. In bacteria, SAM binds to the SAM riboswitch, which regulates the biosynthesis of methionine and cysteine, two amino acids essential for survival. Therefore, synthetic molecules that bind to SAM riboswitches have the potential to kill bacterial cells.
Three different classes of SAM riboswitches exist in bacteria (SAM I, II, and III). Each class of SAM riboswitch gene under control of T7 promoter was prepared by the overlapping extension polymerase chain reaction of synthetic oligonucleotides. Each SAM riboswitch gene was successfully cloned into the pUC19 plasmid and verified by DNA sequencing. A high concentration of each SAM riboswitch DNA was prepared by PCR and further converted to the corresponding SAM riboswitch RNA molecules by in vitro transcription using T7 RNA polymerase. All three classes of SAM riboswitches will be tested for binding to the synthesized SAM analogs.

Plant based nanotechnology for drug delivery and anti-inflammatory therapy
Jhansi Kalluri, Julianna West, Giridhar Akkaraju, Leigh Canhm and Jeffery L. Coffer*
Abstract:
Chronic inflammation is one of the characteristics of Alzheimer’s, cancer, and selected auto inflammatory diseases. Medicinal plant extracts rich in polyphenols have shown the ability to aid in the prevention of degenerative diseases such as Alzheimer’s due to their anti-inflammatory and anti-oxidant properties. One of the problems of using polyphenols to treat these diseases is their potentially low bioavailability and short half-life in vivo. An alternative to using free compound is to use plant polyphenol-loaded nano/micro particles to increase their bioavailability and half-life.
Equisetum arvense is a silicon accumulator plant serving as a source for a viable eco-friendly route for fabricating nanostructured porous silicon (pSi) drug delivery carriers; at the same time, if selected plant components contain medicinally-active species as well, then the single substance can provide not only the nanoscale high surface area drug delivery carrier (pSi), but the drug itself. With this idea in mind, porous silicon was fabricated from stems/fronds of the silicon accumulator plant Equisetum arvense and the anti-inflammatory activity of the leaf components (aqueous ethanol extract) of Equisetum arvense was tested using a luciferase assay. We evaluated the dose dependent activity of the extract to inhibit TNF-induced NF- kB activation. Our long-term goal is to measure the anti-inflammatory activity of extract-loaded porous silicon particles in a sustained manner.

Semiconducting silicon (Si) is a promising element that has been extensively studied in various fields ranging from microelectronics to bio-relevant applications.1 In fact, nanostructured porous silicon has received widespread attention due to its unique chemical and physical characteristics.1 Another relatively more well-defined example of nanostructured silicon is Si nanotubes (SiNTs) with well-characterized sidewalls, inner void space and lengths, allowing opportunities to study its potential properties in diverse fields, such as Li ion batteries, solar cells.2,3 In particular, SiNTs are potential vectors in drug delivery systems. The available interior free space of the NTs offer the material the ability of confining a desired amount of payload of therapeutic agents. Moreover, the available silanol groups on the surface of the NTs also enable attachment to a linker, whose other end is subsequently attached to a drug molecule of interests. Within a biological environment, therapeutic molecules of interest can be released in a sustained manner into targeted sites through either dissolution of the SiNT carriers or their detachment from the linkers.
In terms of therapeutic candidates, cisplatin has been renowned for its ability to treat a variety of cancers including lymphomas, carcinomas, etc. Due to low chloride ions concentrations (4-12mM) in the intracellular environment of cancer cells, chloride ligands on cisplatin are readily displaced by water, producing either cis-[PtCl(NH3)2(H2O)]+ or cis-[Pt(NH3)2(H2O)2]2+ aquo complexes, which actively target DNA and trigger apoptosis.4 However, since drug resistance is developed in cancer cells and undesirable interactions between cisplatin and other biological molecules occur, the therapeutic effects become diminished and negative side effects are also observed.5,6 In order to enhance the therapeutic efficiency of cisplatin, in this project, SiNTs are employed as carriers that can be loaded with cisplatin and potentially deliver the drugs to the desired sites. For the purpose of controlling the release of cisplatin from SiNTs, 3-aminopropyltriethoxysilane (APTES) is employed as the linker, which can covalently bind to the nanotubes through the available silanol groups on the surface, and the amino group on the other end of APTES can subsequently coordinate cisplatin.
In this study, SiNTs with lengths less than 1 µm are used (for optimal cellular uptake), and a sidewall thickness ~ 10 nm for desirable dissolution within a biological environment. Moreover, the distinct porous morphology of the nanotubes permits infiltration of the molecules of interest. By varying solvents (acetone and toluene) of APTES solution and functionalization time, the amount of cisplatin loaded into SiNTs can be modulated ranging from 20-40 weight %, thereby suggesting the ability of SiNTs to carry therapeutic agents.
References
1. Canham, L.T. Hanbook of Porous Silicon. Switzerland: Springer International Publishing AG, 2014.
2. Tesfaye A, Gonzalez R., Coffer J., Djenizian T. Porous Silicon Nanotube Arrays as Anode Material for Li-Ion Batteries, ACS Appl Mater. Inter. 2015, 7, 20495−20498.
3. Gonzalez-Rodriguez R., Arad-Vosk N., Rozenfeld N, Sa’ar A, Coffer JL (2016) Control of CH3NH3 PbI3 Perovskite Nanostructure Formation through the Use of Silicon Nanotube Templates, Small 2016, 12, 4477–4480.
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