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CHEM2017BARNETT42834 CHEM

Determining the antioxidant activity of small metal-binding ligands that target agents known to lead to neurodegenerative diseases

Type: Undergraduate
Author(s): Maddie Barnett Chemistry & Biochemistry Hannah Johnston Chemistry & Biochemistry
Advisor(s): Kayla Green Chemistry & Biochemistry
Location: Session: 1; B0; Table Number: 5

poster location

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.

(Poster is private)

CHEM2017BODIFORD28560 CHEM

Polymer/porous silicon (pSi) composite materials for tissue engineering: drug release and polymer degradation studies in vitro

Type: Graduate
Author(s): Nelli Bodiford Chemistry & Biochemistry Steven McInnes Chemistry & Biochemistry Nico Voelcker Chemistry & Biochemistry
Advisor(s): Jeffery Coffer Chemistry & Biochemistry
Location: Session: 1; 3rd Floor; Table Number: 2

poster location

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.

(Poster is private)

CHEM2017BREWER4655 CHEM

Catalytic and Mechanistic Investigation of Three Tetra-aza Macrocyclic Iron(III) Complexes

Type: Graduate
Author(s): Samantha Brewer Chemistry & Biochemistry Lara Turan Chemistry & Biochemistry
Advisor(s): Kayla Green Chemistry & Biochemistry
Location: Session: 2; B0; Table Number: 2

poster location

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.

(Poster is private)

CHEM2017BURNETT13289 CHEM

Immobilization of biotin-ferrocene biosensor derivatives using chitosan thin films

Type: Graduate
Author(s): Marianne Burnett Chemistry & Biochemistry Nelli Bodiford Chemistry & Biochemistry Jeffery Coffer Chemistry & Biochemistry
Advisor(s): Kayla Green Chemistry & Biochemistry
Location: Session: 2; 2nd Floor; Table Number: 8

poster location

Biotin-ferrocene biosensor platforms have been developed to serve as a model system for the quantification of proteins in solution using electroanalytical methods. This specific model system consists of a redox active ferrocene core and biotin, the receptor site that selectively binds to the avidin protein. Electroanalytical methods, such as cyclic voltammetry (CV) and square wave (SW), can be used to monitor the resulting changes in the electrochemical signal that occurs as biotin interacts with avidin. Under non-aqueous conditions, all electrochemical signals observed were robust and stable. While these results are encouraging, the current sensitivity and solubility must be improved for clinical applications that require detection of micromolar to nanomolar concentrations. As a method to overcome these limitations, the biotin-ferrocene platform was synthetically modified with known functional groups for immobilization purposes, using terminal thiols or amines. Successful immobilization of this biotin-ferrocene library was achieved using a chitosan film on a glassy carbon electrode. Each film was characterized by cyclic voltammetry and square wave voltammetry under aqueous conditions as well as field emission scanning electron microscopy (FESEM) to investigate film and signal stability of the complexes onto the electrode surface. Energy dispersive X-ray spectrometry (EDX) was also used for elemental analysis of each film. The surface morphology and electrochemical behavior of the chitosan-immobilized biotin-ferrocene complexes will be presented to show that chitosan is a potential method for obtaining immobilized biosensor complexes capable of quantifying biological species of interest.

(Poster is private)

CHEM2017BUTLER7314 CHEM

A Vaccine Against Cocaine

Type: Undergraduate
Author(s): Rachel Butler Chemistry & Biochemistry
Advisor(s): Jean-Luc Montchamp Chemistry & Biochemistry
Location: Session: 2; 2nd Floor; Table Number: 2

poster location

This project aims at preparing a compound that should prevent the effects of cocaine when injected into a human being. When administered to a patient, the patient’s immune system will respond by creating catalytic antibodies which will hydrolyze cocaine to a harmless molecule. To induce the response by catalytic antibodies, the molecule must be large enough. To achieve this, the molecule synthesized will ultimately be attached to a dendrimer. Synthesis of the molecule cannot be done using cocaine for regulatory reasons, so instead synthesis starts with nortropine. While the molecule synthesized from nortropine will be structurally simpler than cocaine, the vaccine should still perform cocaine hydrolysis. To synthesize the molecule, the amine group of nortropine is protected with a BOC group and an azodicarboxylate reagent must be prepared in order to complete a Mitsunobu reaction, which will invert the alcohol. Ultimately, the alcohol will be phosphonylated, the BOC group will be cleaved, a linker will be introduced, and the molecule will then be attached to the dendrimer.

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CHEM2017DACHILLE1815 CHEM

Suppression of Melanin Synthesis by Europium Doped Cerium Oxide Nanomaterials

Type: Graduate
Author(s): Anne D'Achille Chemistry & Biochemistry
Advisor(s): Jeffery Coffer Chemistry & Biochemistry
Location: Session: 2; B0; Table Number: 7

poster location

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.

(Poster is private)

CHEM2017FORD40435 CHEM

A New Route to Sugar Alcohols

Type: Undergraduate
Author(s): Tyler Ford Chemistry & Biochemistry
Advisor(s): David Minter Chemistry & Biochemistry
Location: Session: 2; B0; Table Number: 4

poster location

Sugar alcohols have long been utilized in many commercial products as sugar alternatives that can present fewer health problems while retaining nearly the same sweetness. Sugar alcohol alternatives do not raise blood sugar nor do they cause tooth decay. Sugar alcohols contain vastly fewer calories than natural sugars due to their low digestibility, which at the same time is the basis of their negative effects. The non-digestible portion of the sugar alcohol can undergo fermentation by small bowel flora thus creating unwanted bloating and diarrhea. Reducing these side effects is an important motive for exploring new sugar alcohol isomers as well as inexpensive approaches to their laboratory synthesis.
Sugar alcohols are currently synthesized by the reduction of natural sugars, but this process does not allow for controlling specific stereochemistry; and this could be the basis for their problematic digestibility. Using a different synthetic pathway that allows the control of stereochemistry of the sugar alcohol hydroxyl groups may produce new sugar alcohols that are resistant to fermentation. A methodological approach using aldol additions to cyclic ketones to produce higher order sugar alcohols will be investigated. Double aldol reactions would be expected to produce 7, 8 or 9-carbon sugar alcohols with specific isomers that have yet to be studied. Expanding this investigation to include cyclic ketones with bulky R-groups introduces another possibility for controlling stereochemistry. The ultimate result of this synthetic project would be a sugar alcohol homolog that can act as a viable low-calorie sweetener without gastrointestinal setbacks.

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CHEM2017GOETZ58823 CHEM

Synthesis and Properties of Fluorescent Eu-doped CeO2 Nanocubes

Type: Undergraduate
Author(s): Zane Goetz Chemistry & Biochemistry
Advisor(s): Dr. Jeffery Coffer Chemistry & Biochemistry Anne Moffitt Chemistry & Biochemistry
Location: Session: 2; 2nd Floor; Table Number: 3

poster location

Synthesis and Properties of Fluorescent Eu-doped CeO2 Nanocubes

Cerium(IV) oxide (or ceria, CeO2) has generated quite a bit of interest and research in the last few years due to its dual oxidation states of Ce3+ and Ce4+. While Ce4+ is generally more stable and forms CeO2 crystals with a fluorite structure, the presence of Ce3+ in the lattice increases oxygen vacancies. Reaction conditions such as pH, temperature, and dopants can be used to control the Ce3+/Ce4+ ratio in the synthesized materials, with higher concentrations of Ce3+ corresponding to higher oxygen vacancy concentrations. These oxygen vacancies, especially on the surface of ceria nanostructures, increase oxygen mobility, favor redox reactions and enhance catalytic activity. The multiple oxidation states of cerium also provide CeO2 with antioxidant activity. Doping ceria with the comparably sized europium(III) oxide (Eu2O3) theoretically increases the Ce3+/Ce4+ ratio and thus increases the amount of oxygen vacancies while giving the resultant nanostructures fluorescent properties, giving it the capacity to serve as a fluorescent label.

This research has focused on optimizing the hydrothermal synthesis of europium-doped ceria nanocubes and analyzing the size, crystallinity, and fluorescence of those structures produced. The nanocube morphology may likely expose the highly reactive {100} planes while more commonly studied nanoparticles typically expose the more stable {110} and {111} planes.

Eu-doped CeO2 nanocubes were synthesized through a hydrothermal procedure utilizing Ce(NO)3 and Eu(NO)3 in 20 mL of a highly basic solution (with a pH ~ 13). Purple-colored [Eu-doped] Ce(OH)3 precipitates out of the highly basic solution. After stirring, the mixture was transferred to a stainless steel autoclave and heated to temperatures between 140° C and 180° C for a minimum of 24 hours. The reaction solution was centrifuged and washed with DI water five times to remove impurities, dried at 95° C and the resulting powder ground before analysis via transmission electron microscopy (TEM), energy dispersive x-ray (EDAX), powder X-ray diffraction (XRD), and fluorescence spectroscopy.

In the present study, the reaction temperature, time, number of post-reaction washes, and Eu(NO)3 concentration were each varied and their effects on nanocube morphology, dimensions, and fluorescence analyzed.

CHEM2017HAILEY4468 CHEM

Synthesis of Silicon-Nitrogen Polymer Precursors

Type: Undergraduate
Author(s): Monika Hailey Chemistry & Biochemistry
Advisor(s): Robert Neilson Chemistry & Biochemistry
Location: Session: 1; 3rd Floor; Table Number: 3

poster location

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.

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CHEM2017HANCOCK8266 CHEM

SEPARATION OF MENTHYL-(HYDROXYMETHYL)-PHENYL PHOSPHINATE USING MOLECULARLY IMPRINTED POLYMERS

Type: Undergraduate
Author(s): Kari Hancock Chemistry & Biochemistry
Advisor(s): Jean-Luc Montchamp Chemistry & Biochemistry
Location: Session: 1; 3rd Floor; Table Number: 8

poster location

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.

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CHEM2017HERMANSON12391 CHEM

Bioisosteric analogs of S-adenosylmethionine as potential antibacterial SAM riboswitch inhibitors

Type: Undergraduate
Author(s): Kristina Hermanson Chemistry & Biochemistry
Advisor(s): Youngha Ryu Chemistry & Biochemistry
Location: Session: 1; B0; Table Number: 7

poster location

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.

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CHEM2017JOHNSTON1693 CHEM

Synthesis and characterization of novel manganese monomers and dimers with tetraazamacrocyclic ligands

Type: Graduate
Author(s): Hannah Johnston Chemistry & Biochemistry Marianne Burnett Chemistry & Biochemistry
Advisor(s): Kayla Green Chemistry & Biochemistry
Location: Session: 1; 1st Floor; Table Number: 6

poster location

Manganese containing enzymes are prevalent in nature; one specific example is the oxygen evolving complex (OEC) located in photosystem II (PSII) of green plants. Due to the biological relevance of manganese, model complexes with this transition metal are ubiquitous in the chemical literature, particularly those modeling the OEC in PSII. Historically, OEC models incorporate two multidentate nitrogen contain ligands coordinated to Mn(III) and Mn(IV) connected by two bridging oxygens. Although rudimentary models, these bimetallic complexes have shown the ability to perform several catalytic reactions. Recently, we have metalated pyridine- and pyridol- containing macrocycles with manganese to form both the historically significant Mn(III,IV) dimer complex as well as a Mn(III) monomer. The Mn(III,IV) dimer with a pyridol- containing macrocyclic ligand is the first of its kind synthesized to date. Characterization of both the monomeric and dimeric manganese complexes as it relates to the OEC includes: UV-Visible spectroscopy, X-ray diffraction (XRD), cyclic voltammetry (CV), and electron paramagnetic resonance (EPR). In the future, the catalytic activity of these complexes will be investigated.

(Poster is private)

CHEM2017LE35834 CHEM

Silicon Nanotubes as Drug Delivery Vectors

Type: Graduate
Author(s): Nguyen Le Chemistry & Biochemistry
Advisor(s): Jeffery Coffer Chemistry & Biochemistry
Location: Session: 2; 2nd Floor; Table Number: 6

poster location

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.
4. Ma P., Xiao H., Li C., Dai Y., Cheng Z., Hou Z., Lin J. Inorganic nanocarriers for platinum drug delivery, Materials Today 2015, 18(10), 554-564.
5. Martin L.P., Hamilton T.C., Schilder R.J. Platinum Resistance: The Role of DNA Repair Pathways, Clin Cancer Res. 2008, 14(5):1291-1295.
6. Xue X., You S., Zhang Q., Wu Y., Zou G., Wang P. C., Zhao Y., Xu Y., Jia L., Zhang X., Liang X. Mitaplatin Increases Sensitivity of Tumor Cells to Cisplatin by Inducing Mitochondrial Dysfunction, Mol. Pharmaceutics, 2012, 9 (3), 634–644.

(Poster is private)

CHEM2017OCHOA7485 CHEM

Intramolecular deMayo photocyclization: The total synthesis of hippadine and pratosine

Type: Graduate
Author(s): Charles Ochoa Chemistry & Biochemistry
Advisor(s): David Minter Chemistry & Biochemistry
Location: Session: 1; 2nd Floor; Table Number: 4

poster location

Various total syntheses of the Lycorine-type pharmacologically active alkaloids hippadine and pratosine 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. Research on a model system (an isocarbostyril without the substituents at positions 6 and 7) for these natural products has been done in order to elucidate the optimal conditions for each step on the synthetic strategy. Initial attempts were made in order to synthesize the 6,7-disubstituted isocarbostyril with the 1,3-diketone tether so that the deMayo photocyclization could be performed. However, the established synthetic strategy led to compounds along the synthetic route that had very undesirable solubility properties. To resolve this issue, the substituents were replaced with bulkier, more non-polar moieties in order to increase the solubility of the compound in ethyl ether.

(Poster is private)

CHEM2017WRIGHT4086 CHEM

Mutated Leucyl-tRNA Synthetase and its Use in the Incorporation of Unnatural Amino Acids

Type: Undergraduate
Author(s): Courtney Wright Chemistry & Biochemistry Courtney Nail Chemistry & Biochemistry
Advisor(s): Youngha Ryu Chemistry & Biochemistry
Location: Session: 2; B0; Table Number: 7

poster location

Traditionally the genetic code has utilized the canonical twenty amino acids in order to construct proteins and facilitate life. The process of translation involves an RNA template and codons that will be read and matched to corresponding tRNA molecules carrying charged amino acids. An aminoacyl tRNA synthetase specific to each amino acid is responsible for loading and charging the amino acid to the tRNA. In recent years, a few orthogonal pairs of the tRNA and aminoacyl tRNA synthetase have been utilized to expand the genetic code past the traditional 20 amino acids. Expanding the genetic code allows for new insight into protein function, structure, and interactions within the cell. The introduction of new amino acids could lead to proteins with new chemical or biological activity and even advantageously alter function leading to evolutionary events. In our research we attempt to incorporate unnatural amino acids using a leucyl-tRNA synthetase from Methanobacterium thermoautotrophicum and a tRNA which will suppress the amber stop codon (TAG). A mutant LeuRS lacking an editing domain (MLRS CP1) was generated. The best mutant was isolated and sequenced. The leucine binding site, determined from sequence homology, was randomized at five amino acids to create a library of mutants. The best mutant is selected through a positive selection process where only MLRS CP1 that add an amino acid to the tRNA will survive in the presence of chloramphenicol. Finally, in a negative selection step, those mutants which add natural amino acids to the tRNA will die in the presence of 5-fluorouracil. The library can then be used for further experiments to determine how effectively unnatural amino acids are incorporated.

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