Princeton University Department of Chemistry

Summer Undergraduate Research Program

Poster Session 2015

Thursday, August 6th 10:00 – 11:30 AM Frick Laboratory

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Name Support University Advisor Title

Melina Acevedo g Princeton University Bruce Koel

Synthesis and Electrochemical Performance of Copper Nanowires for Hydrogen Reduction and Oxidation in Alkaline Conditions

Emily Adler cfgkm Princeton University Nozomi Ando Structural Characterizations of Proteins in an Antibiotic Biosynthesis Pathway Using Small-angle X-ray Scattering

Prince Aidoo a Philander Smith College John T. Groves Synthesis and Characterization of

Metal Porphyrazines

Isao Anzai fm Princeton University Nozomi Ando Creating a Whole Genome Knockout Library of a Novel Microbe

Marissa Applegate m Princeton University Samuel S. Wang

Mutagenesis of GCaMP Sped Decay Kinetics Ex Vivo

Kiwoon Baeg cdm Princeton University Bradley Carrow Buchwald-Hartwig Cross-Coupling of Pentafluoroaniline and Aryl Chloride with Novel Tri-alkyl Phosphine Ligand

Logan Blaine b Princeton University Martin Semmelhack

Synthesis of a Solvatochromic Fluorophore for Use in High-Throughput Screening of Staphylococcus Aureus Quorum Sensing Inhibitors

Alan Chen b Princeton University Gregory D. Scholes

Preparation of Nanoparticles comprised of 1,2,4,5-Tetracyanobenzene and Methylated Benzenes by the Reprecipitation Method

Rodney Chen cdm Princeton University Tom Muir Peptide Cyclization by Orthogonal Split Intein Trans Splicing Reactions

An Chu b Princeton University Andrew B. Bocarsly

Characterizing Redox Processes on Metal Electrodes under Acidic Conditions

Tom Colocci cghm Princeton University Gregory D. Scholes

Two's company, 10^21's a crowd: absorbance and fluorescence in macromolecularly crowded solutions

Bruce Culbertson m Princeton University Erik Sorensen

Modification of Rhodium Catalyzed C-H Amination Experimental Procedure Allows it to be Reproduced in a Teaching Environment

Menase Daemo a Jackson State University

David W.C. MacMillan

Decarboxylative Protein Functionalization Via Photoredox Catalysis

David Danielson a University of New Mexico Robert Knowles Bond Weakening: Activation of Allylic

C-H Bonds

Jake Essman b Princeton University Abigail G. Doyle

Progress Toward the Nickel-Catalyzed Iminium-Heck Reaction

Blake Feldman b Princeton University John T. Groves Acidic Conditions Yield Favorable Product Ratios for Manganese Porphyrin Catalyzed Oxidation

Leora Haber cfgm Princeton University Gregory D. Scholes

An Investigation into the Energy Transfer and Genetics of the Antenna Complexes of Cryptophytes

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Arun Habermann b Princeton University Satish Myneni Mineral-DOM Reactions and Impact of these on Carbon Dynamics in Natural Systems

Silvia Hanna a Rowan University Haw Yang Selection of Signaling Aptamers for Oxidated Proteins

Ivanny Jacome Ottati a

Millersville University of Pennsylvania

Abigail G. Doyle

Copper-Catalyzed Nucleophilic Fluorination of Diazo Compounds

Cathryn Jolley a Rutgers University David W.C. MacMillan

Synthetic Efforts Towards the Synthesis of the Natural Product Idiospermuline

Christopher King e Princeton University Herschel Rabitz Simulated Quantum Control of Multilevel Systems Using Shaped Ultrafast Laser Pulses

Logan Lee ckm Princeton University Mohammad Seyedsayamdost

Elucidating the Mode of Action of the Natural Product Antibiotic Tropodithietic Acid

Minhaz Mahbub cdm Princeton University Abigail G. Doyle

Progress Toward the Total Synthesis of (+)-Lysergic Acid

Rei Matsuura cm Princeton University Robert Knowles Achieving Pyrroloindoline Motifs Through PCET

Bennett McIntosh cm Princeton University Michael H. Hecht

A Combinatorial Protein Library for Amyloid Assembly

Saeed Naguib cdm Princeton University Robert Knowles Applying Photocatalysis to the Development of New Hydroamination Reactions

Arman Odabas b Princeton University Andrew B. Bocarsly

Palladium-Cobalt Cyanogels for CO2 Capture and Selective Filtration

Kai Okada cm Princeton University David W.C. MacMillan

Designing a Radical-Proof Iridium Photocatalyst for Synergistic Catalysis

Cecily O'Leary cm Princeton University Bradley Carrow Oxidative C-H Alkenylation of α-olefins Accelerated by AlkeneTethered Sulfide Ancillary Ligands

Hanley Ong ci Princeton University Paul Chirik Synthesis of Redox-Inactive Chelates Through Ligand Cyclometalation: Facilitating Base Metal Catalysis?

Madison Parry b Princeton University Bradley Carrow Synthesis of a Chiral Ligand for Organometallic Catalysis of Polymers

Summer Ramsay-Burrough b Princeton University Paul Chirik Nickel Catalysis: [2+2] Cycloaddition

and sp3 C-H Borylation

Stephanie Ribet cm Princeton University Robert Cava Electronic and Magnetic Properties of an Oxyfluoride Pyrochlore

Marlon Simms a Massachusetts College of Pharmacy and Health Sciences

Bradley Carrow Radical Process: Decarboxylative Alkenylation of sp3 C–H Bonds with Aryl-Substituted Acrylic Acids

Elizabeth Stanley b Princeton University Michael H. Hecht

Testing Synthetic Protein Library Functions Using Phage Display

Sean Treacy cdhm Princeton University Paul Chirik Nickel Catalyzed Hydrofunctionalization of Olefins

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Ashley Wang cjm Princeton University Tom Muir

Synthesis and Incorporation of Truncated Autoinducing Peptide on Surfaces to Inhibit Staphylococcus Aureus Virulence Pathway

Jeffrey Wu m Princeton University David W.C. MacMillan

Coupling Reactions of Alkyl Halide Radicals via Photoredox Catalysis

Ruomeng Zhang a Illinois Wesleyan University

Gregory D. Scholes

Investigating Singlet Fission in a Model Covalently-Linked Dimer: Steady-State and Time-Resolved Spectroscopy of (F-TIBS-ADT)2

Thompson Zhuang cm Princeton University John T. Groves Facile Synthesis of Organic Isocyanates

Judson Ziegler cm Princeton University Andrew B. Bocarsly

Deep Eutectic Solvents and the Direct Ethanol Fuel Cell

Summer research support provided with many thanks to:

a Summer Undergraduate Research Program for Diversity in Chemistry, supported by the Princeton University Graduate School and Office of the Provost

b Leach Summer Scholars Program supported by the Charles Henry Leach, II Endowment Fund for Student Research in the Sciences

c Evnin Fund d Office of the Dean of the College e Program in Plasma Science and Technology f Fred Fox Fund g Princeton Environmental Institute h Council on Science and Technology i Andlinger Center for Energy and the Environment j Program in Global Health and Health Policy k Health Grand Challenges m Faculty Advisor's Research Grants

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Synthesis and Electrochemical Performance of Copper Nanowires for Hydrogen Reduction and Oxidation in Alkaline Conditions

Melina Acevedo

Mentors: Clark Chen and Xiaofang Yang Advisor: Bruce Koel

Current electrocatalysts for hydrogen reduction and oxidation are limited by the density and reactivity of active sites. By synthesizing uniform copper nanowires from an aqueous solution of NaOH, ethylenediamine, CuCl2 and hydrazine, we can expose the most active reaction sites and increase activity. Copper nanowires in alkaline conditions were found to be active for hydrogen evolution, and poorly active for hydrogen oxidation. Doping these nanowires with other metals, such as cobalt and silver, may prove crucial for developing efficient electrocatalysts for energy conversion.

Structural Characterizations of Proteins in an Antibiotic Biosynthesis Pathway Using Small-angle X-ray Scattering

Emily Adler

Advisor: Nozomi Ando

Antibiotic resistance is a growing global crisis. By using small-angle X-ray scattering (SAXS) and size exclusion chromatography (SEC), we have investigated the structures of the proteins responsible for the biosynthesis of a promising antibiotic with no known resistance. We have found that SEC can help reduce aggregation in preparation for SAXS.

Synthesis and Characterization of Metal Porphyrazines

Prince Aidoo Mentor: Hongxin Gao

Advisor: John T. Groves

Metal porphyrazines have been proposed as potential catalysts for chlorine dioxide generation, and have been indicated as relevant to hydrogen atom abstraction. In order to study the reactivity and catalytic abilities of metal porphyrazines, iron (II) tetramethyl-2,3-pyridinoporphyrazine, iron (II) tetramethyl-3,4-pyridinoporphyrazine, copper (II) tetramethyl-2,3-pyridinoporphyrazine and cobalt (II) tetramethyl-2,3-pyridinoporphyrazine were successfully synthesized and characterized. Metal porphyrazines have been shown to have high activity, which supports them as potential catalysts for industrial applications in catalysis. This research establishes a foundation for the catalytic studies of metal porphyrazines in the future.

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Creating a Whole Genome Knockout Library of a Novel Microbe

Isao Anzai Mentor: Buz Barstow

Advisor: Nozomi Ando

After the genome sequence, a whole genome knockout library is the most important genomic tool for an organism; a library provides valuable insight into the basic biology of an organism, helps to elucidate obscure and poorly understood gene functions, unravels the network of connections between genes, and allows us to engineer an organism for applications ranging from medicine to energy. We have developed a DNA Sudoku based method that greatly reduces the cost, effort and time of generating non-redundant, highly complete, curated whole genome knockout libraries. We have used this technique to make the first complete library of a novel microbe that we will study and engineer for applications in sustainable energy.

Mutagenesis of GCaMP Sped Decay Kinetics Ex Vivo

Marissa Applegate Mentor: Laura A. Lynch

Advisor: Samuel S. Wang

Genetically Encoded Calcium Indicators allow for imaging neuronal activity with non-invasive monitoring, cell type specificity, and minimal tissue damage; however, the current state-of-the-art indicator, GCaMP6f, has kinetic responses to calcium that are too slow to resolve individual spike times on time scale of <0.1s. We used fluorimetry and stopped flow photometry to examine the biophysical and kinetic effects of site directed mutagenesis of the EF hands and RS20 domain of GCaMP6f. Several mutations to the RS20 domain of the protein successfully improved the decay kinetics of GCaMP6f. This will be applied in vivo to examine cerebellar Purkinje cells.

Buchwald-Hartwig Cross-Coupling of Pentafluoroaniline and Aryl Chloride with Novel Tri-alkyl Phosphine Ligand

Kiwoon Baeg

Mentor: Liye Chen Advisor: Bradley Carrow

Electron deficient aniline derivatives are less prone to oxidation than their parent anilines increasing the utility of electron deficient anilines in various industries. Many strategies for coupling anilines with a single electron-withdrawing group exist, but relatively few exist for anilines with more than one. The coupling of pentafluoroaniline with aryl halides has been particularly difficult. It was hypothesized that a novel tri-alkyl phospine ligand developed by the Carrow group could help solve this problem due to its specific properties. Through screening of various reaction conditions, the Buchwald-Hartwig coupling reaction between pentafluoroaniline and 4-chlorotoluene was optimized to give a yield of 92% with this ligand.

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Synthesis of a Solvatochromic Fluorophore for Use in High-Throughput Screening of

Staphylococcus Aureus Quorum Sensing Inhibitors

Logan Blaine Mentor: Dr. Jane Ni

Advisor: Martin Semmelhack

Multiple strains of the Gram-positive bacterium Staphylococcus aureus have developed resistance to common antibiotics, requiring the development of new treatment methods for staphylococcal infections. One promising approach involves disruption of quorum sensing-–a system of bacterial communication that allows cells to modify behavior based on population density. In S. aureus, an autoinducing peptide (AIP) binds to the AgrC trans-membrane receptor, ultimately resulting in changes in gene expression. Identifying small molecules capable of inhibiting AIP binding to AgrC can be accomplished using high-throughput screening (HTS). To that end, a dimethylaminophthalimide (DMAP) derivative was prepared, and the fluorophore was coupled to a truncated AIP variant (trAIP-II). The DMAP-coupled trAIP-II exhibits stronger fluorescence while bound to AgrC, making it possible to measure the binding affinity of other small molecules for AgrC.

Preparation of Nanoparticles comprised of 1,2,4,5-Tetracyanobenzene and Methylated Benzenes by the Reprecipitation Method

Alan Chen

Mentor: Tia Lee Advisor: Gregory D. Scholes

Electron transfer is an important step in solar cells, and understanding electron transfer could lead to improvements in solar cell performances. Gould and Farid studied electron transfer in solution, studying the states in which charge transfer occurred between aromatic hydrocarbon donors and cyano-aromatic acceptors, identifying contributors to exiplex bands. Solar cells are generally solid, unlike the solutions used by Gould and Farid, but we hypothesize that aqueous colloidal molecule nanoparticles could model solid state conditions. To that end here we report model nanoparticles, based on the donors and acceptors reported by Gould and Farid. Single-component nanoparticles from durene or pentamethylbenzene (donors), or tetracyanobenzene (acceptor) were prepared by reprecipitation method and characterized by UV-Vis absorption spectroscopy, where it is shown they were most likely created by shifts and shape changes in peaks relative to the spectra of the respective substituent isolated in solution. Donor-acceptor nanoparticles were then prepared and characterized by UV-Vis absorption spectroscopy. The preparation of nanoparticles from durene, pentamethylbenzene, and tetracyanobenzene is unprecedented and these are their first characterizations.

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Peptide Cyclization by Orthogonal Split Intein Trans Splicing Reactions

Rodney Chen Mentor: Adam J. Stevens

Advisor: Tom Muir

Cyclic peptide structures are currently not easily isolated from intracellular environments, so original methods for cyclic peptide isolation will facilitate research into the therapeutic effects of these small molecules. Here, we propose a novel method for peptide cyclization using orthogonal split internal protein (inteins) reactions. To date, the desired cyclic peptide precursors are shown to be capable of being expressed and isolated via affinity column chromatography. In future, reaction mixtures incubated with both precursor compounds will be analyzed and characterized using high pressure liquid chromatography (HPLC) and time of flight mass spectroscopy (TOF-MS) and will hopefully yield results in support of the desired cyclic peptide existing in the reaction mixture.

Characterizing Redox Processes on Metal Electrodes under Acidic Conditions

An Chu Mentor: James White

Advisor: Andrew B. Bocarsly

Imidazole and pyridine have been studied for their catalytic properties in the aqueous reduction of carbon dioxide into methanol on platinum electrodes, yet the processes underlying the redox events for these molecules in strongly acidic solutions and other metal electrodes remains a mechanistic mystery. Here, we perform cyclic voltammetry with a wide selection of weak acids, metal electrodes, and acidities to probe physical and periodic trends in redox behaviors. Of the redox events we observe in cyclic voltammetry, we attribute a unique redox couple belonging to that of protonated weak acid on gold electrodes in strongly acidic conditions. The redox couple unexpectedly appears as well on tungsten, cadmium, and titanium, suggesting different mechanisms of formation for the same reduction of protonated weak acid.

Two's company, 1021's a crowd: absorbance and fluorescence in macromolecularly crowded solutions

Tom Colocci

Mentor: Desmond Toa Advisor: Gregory D. Scholes

The field of quantum biology has emerged as one of the most exciting in the life sciences. Much excellent work has been done characterising some light harvesting proteins that feature quantum effects, but these experiments have been done almost exclusively in pristine, buffered solutions. Through the use of inert, simple crowding agents, the effects upon the proteins of macromolecular crowding is investigated. Crowding affects the polarity of the solution but not the steady state absorption and fluorescence spectra.

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Modification of Rhodium Catalyzed C-H Amination Experimental Procedure Allows it to be Reproduced in a Teaching Environment

Bruce Culbertson

Mentor: Aaron Bedell Advisor: Erik Sorensen

The Du Bois group at Stanford has developed a method for the selective amination of the benzylic C-H bond on ethylbenzene and related substrates, but their procedure is too vague to be reproduced by students. To address this problem, we carried out the amination of a variety of p-substituted ethylbenzene derivatives individually and in competition with ethylbenzene in order to obtain 1H NMR data and to maximize the time efficiency and reproducibility of the procedure. We found that the products were most easily and most effectively purified on a 40 mL column with ten percent ethyl acetate in hexanes as the eluent. The specificity that our results added to the C-H amination experimental procedure will allow it to be incorporated into teaching curriculums in the future.

Decarboxylative Protein Functionalization Via Photoredox Catalysis

Menase Daemo Mentor: Tracy Liu

Advisor: David W.C. MacMillan

Current cancer therapies lack tumor selectivity. Antibody Drug Conjugates make use of antibodies with specific affinity to antigens over expressed on tumor cells, thus conferring improved target specificity. However, controlling the Drug to Antibody Ratio (DAR) and achieving Site-Specific Conjugation continue to be challenges in this field. This research is focused on employing photoredox catalysis to address this problem. Decarboxylative functionalization of small peptides in aqueous/organic environment has been accomplished via visible light-mediated photoredox catalysis.

Bond Weakening: Activation of Allylic C-H Bonds

David Danielson Mentor: Lucas Nguyen

Advisor: Robert Knowles

Hydrogen atom transfer (HAT) is a fundamental mechanism for many radical reactions including those found in biological systems. Bond weakening catalysis provides a promising method to achieve selective HAT by substrate activation. Although there are many potential applications of this phenomena to synthetic organic chemistry, to this point they have remained largely unexplored. We will use different first row transition metals in order to activate an allylic C-H Bond. If successful, this project will establish more support for bond weakening as a platform for the activation/functionalization of substrates, and it will allow us to apply H-Atom transfer to systems that are traditionally inaccessible.

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Progress Toward the Nickel-Catalyzed Iminium-Heck Reaction

Jake Essman Mentor: J. Patrick Lutz

Advisor: Abigail G. Doyle

Intramolecular Heck reactions using pyridinium ion electrophiles could afford access to 1-substituted-1,2,3,8a-tetrahydroindolizines. Here, we report efforts towards the discovery of the nickel-catalyzed iminium-Heck reaction. A catalytic system consisting of a Ni0 source, ligand, and base is established. A series of screens on different bases, solvents, temperatures, and substrates eliminated a host of unviable conditions.

Acidic Conditions Yield Favorable Product Ratios for Manganese Porphyrin Catalyzed Oxidation

Blake Feldman

Mentor: Patrick Kates Advisor: John T. Groves

Porphyrins are a class of metal-centered compounds with tunable electronic properties, but the reactivity of manganese porphyrins is still not fully understood. In order to determine the thermodynamic activation parameters of C-H abstraction by Mn porphyrins, we observed the oxidation of IPBA by oxoMn(V)2TMPyP with stopped flow spectrophotometry at five temperatures and six substrate concentrations to collect the second order rate constants (k2) for several pH’s. Plotting k2 on an Eyring plot revealed the magnitudes of the enthalpy of activation (∆H‡) and entropy of activation (∆S‡). The plot revealed that ∆S‡ has a greater magnitude at low pH, and ∆H‡ has a greater magnitude at higher pH. This finding was further supported by an NMR spectra of three oxidations at pH 5.6, 6.7, and 9.7 which showed that the product ratio of alcohol to ketone, or entropic product to enthalpic product, was higher at pH 5.6 (31:1) and lower at pH 9.7 (9.5:1).

An Investigation into the Energy Transfer and Genetics of the Antenna Complexes of Cryptophytes

Leora Haber

Mentor: Desmond Toa Advisor: Gregory D. Scholes

This investigation focused on understanding the effects of varying light frequencies on the photosynthetic aparatus of cryptophytes, specifically the phycobiliproteins which comprise the antennae complexes.

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Mineral-DOM Reactions and Impact of these on Carbon Dynamics in Natural Systems

Arun Habermann Advisor: Satish Myneni

As Dissolved Organic Matter (DOM) is a major contributor to atmospheric CO2 levels in the global carbon cycle, understanding the mechanisms that control the rate at which terrestrial DOM carbon becomes atmospheric carbon can help with understanding the rate at which atmospheric CO2 levels increase. By using ATR FT-IR spectroscopy on samples of DOM collected from the Pine Barrens and reacted with different minerals under different conditions, we were able to determine major functional groups involved with the adsorption of DOM to mineral surfaces. We determined that carboxylic and carboxylate groups played the largest role and that amides, carbonyls, and carbohydrates are involved as well, with varying amounts of importance depending on mineral type. These results can assist in understanding the rate at which DOM carbon becomes atmospheric carbon in different areas based on the DOM and mineral types and compositions present in these different environments.

Selection of Signaling Aptamers for Oxidated Proteins

Silvia Hanna Mentor: Simon A. McManus

Advisor: Haw Yang

Oxidation of proteins in cells can result in protein damage which can lead to negative cellular effects such as DNA mutations, cellular aging, and neurodegenerative and metabolic diseases. The ability to detect carbonylated proteins in vitro by selecting for DNA structure-switching signaling aptamers could provide knowledge on the mechanism by which carbonylated proteins cause cellular damage. During this project, selection and purification of DNA aptamers proceeded for six rounds with no observed shortening of DNA aptamer length. The selection will continue until the population is enriched in aptamer sequences.

Copper-Catalyzed Nucleophilic Fluorination of Diazo Compounds

Ivanny Jacome Ottati Mentor: Erin E. Gray

Advisor: Abigail G. Doyle

Although not common in nature, fluorinated compounds are frequently used as pharmaceuticals, agrochemicals, materials, and medicinal tracers. Recently reported α-fluorinations of carbonyl compounds have advanced the field of organofluorine chemistry; however, several approaches face challenges in efficiency and scope. We have developed a copper-catalyzed nucleophilic fluorination of diazo compounds, in which a metal carbene readily reacts with potassium fluoride, a benign and abundant fluorine source. The mild reaction conditions enable the fluorination of a variety of substrates and facilitate late-stage fluorinations, thereby increasing the scope of available fluorinated compounds.

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Synthetic Efforts Towards the Synthesis of the Natural Product Idiospermuline

Cathryn Jolley Mentor: Jeffrey Lipshultz

Advisor: David W.C. MacMillan

The total synthesis of biologically-active natural products may aid the process of synthetic drug discovery and future organocatalysis research. In our approach towards the construction of the trimeric pyrroloindoline idiospermuline we made use of an enantioselective arylation-cyclization cascade that employs a ligated copper catalyst, a diaryliodonium salt, and an indole-based nucleophile. Despite different stereochemistry and an additional methyl group than other natural products synthesized previously in this manner, the dimerization proceeded more quickly, was isolated in good yield, and was found to have high enantioselectivity. The efficiency of this particular method shows promise as a viable route in the synthesis of the desired final product.

Simulated Quantum Control of Multilevel Systems Using Shaped Ultrafast Laser Pulses

Christopher King Mentors: Dr. Roberto Rey-de-Castro and Dr. Xi Xing

Advisor: Herschel Rabitz

Shaped ultrafast laser pulses have provided an effective method for the quantum control of dissociative ionization of small molecules such as CH2BrI, and experimental results have suggested that simple mechanisms transitions may govern these processes. With the ultimate goal of constructing effective models for these mechanisms, we have developed computational techniques for evaluating the time-evolution of simple multilevel systems and for optimizing the responses of such systems to shaped pulses. In particular using a genetic algorithm we optimized population transfer to the highest energy levels in both resonant and resonant-nonresonant systems, finding that only certain combinations of field strengths and transition couplings allow complete optimization. Using these techniques we can begin to investigate the experimental data from the dissociative ionization of CH2BrI, applying landscape Hessian analysis to determine possible structures for model systems.

Elucidating the Mode of Action of the Natural Product Antibiotic Tropodithietic Acid

Logan Lee Mentor: Rurun Wang

Advisor: Mohammad Seyedsayamdost

The prevalence of drug resistance necessitates the discovery and development of novel antibiotics to combat pathogens. We hope to elucidate the mode of action of the broad spectrum antibiotic tropodithietic acid (TDA), produced by the roseobacter clade of α-proteobacteria. We hypothesize that TDA functions by disrupting the bacterial transmembrane proton motive force; to test this, we will perform biochemical assays on candidate enzymes to monitor for inhibition by TDA. The first of our candidates, the E. coli γ-glutamylcyclotransferase ChaC, has been purified and functionally confirmed, permitting future assays with TDA.

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Progress Toward the Total Synthesis of (+)-Lysergic Acid

Minhaz Mahbub Mentor: Kevin Wu

Advisor: Abigail G. Doyle

Ergot alkaloids and their derivatives have seen extensive use as both medicinal and recreational psychedelic drugs. Targeting the 5-HT2 dopamine receptors, they can have a significant influence on neurological function. However, previous total syntheses of lysergic acid are too lengthy and inefficient for the production of these alkaloids on a useful scale. Using the Doyle lab's previous research in the area of iminium coupling, we propose a 4-step synthesis relying on an enantioselective pyridinium alkylation to set the key stereocenter, followed by a conjugate reduction/gamma-arylation cascade to install the indole precursor. Our synthesis will allow for the ready modification of the core structure to generate analogs for structure-activity studies.

Achieving Pyrroloindoline Motifs Through PCET

Rei Matsuura Mentor: Emily Gentry

Advisor: Robert Knowles

Pyrroloindoline motifs are found in many natural products. In nature, the syntheses of indols proceed via oxidative PCET. Therefore, we were interested in the possibility of achieving pyrroloindolines through PCET as well. Here, we present our discovery of two total syntheses: a four-step synthesis of calycanthidine, and a five-step synthesis of alline.

A Combinatorial Protein Library for Amyloid Assembly

Bennett McIntosh Mentor: Dr. Grant S. Murphy Advisor: Michael H. Hecht

Amyloid fibers, the characteristic protein misfolding of diseases such as Alzheimer’s, Parkinson’s, and Creutzfeldt-Jakob (“Mad Cow”) disease, are attractive targets for biotechnological design, as a strong, self-assembling platform with customizable properties. Rationally designed sequences can form functionalized biocompatible materials such as nanofibers and hydrogels. To sample large areas of unevolved sequence space for functional amyloid nanofibers, we designed a combinatorial library of peptide sequences, CA3S (Catalytic Amyloid – 3 Strands). The design uses binary patterning of polar and non-polar residues to encourage beta-sheet formation, and combinatorial variation of surface residues for diverse function. Genetic fusion with various folding reporters was used to probe the stability and oligomerization state of the designed peptides; interestingly, expression of many such constructs in E. coli is toxic, in a sequence-dependent manner. Continued efforts to express and characterize sequences from this library have the potential to yield self-assembling nanofibers with novel functions and illuminate the mechanisms of aggregate toxicity in prokaryotes.

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Applying Photocatalysis to the Development of New Hydroamination Reactions

Saeed Naguib Mentor: Drew Musacchio Advisor: Robert Knowles

The goal of the project I’ve been working on this summer is to expand the scope of a catalytic photoredox hydroamination reaction developed by Musacchio et al. The reaction, published in summer 2014, gives a protocol for the intramolecular anti-Markovnikov hydroamination of aryl olefins by an aniline. With Musacchio’s work as a foundation, we are attempting to develop an analogous hydroamination of alkyl olefins by an aniline. Formation of the desired product has been confirmed – and we are in the optimization process at the moment.

Palladium-Cobalt Cyanogels for CO2 Capture and Selective Filtration

Arman Odabas Mentor: Ivy Fortmeyer

Advisor: Andrew B. Bocarsly

Palladium-cobalt cyanogels, highly porous inorganic polymers, have previously demonstrated the ability to reversibly and selectively uptake large quantities of CO2, emissions of which contribute to current crises of climate change and ocean acidification. In order to determine whether Pd-Co cyanogels could be used as part of a selective gas filter, gas mixtures containing CO2 were flowed through a dried cyanogel, called a xerogel, and the mixtures were tested with rotational-vibrational IR spectroscopy before and after filtration in order to assess relative gas concentrations. Compared to methane, an IR-active standard in the gas samples used, the IR absorbance of CO2 fell significantly more during filtration. This result suggests that Pd-Co xerogels could be used as a component of a selective gas filter for CO2, which would be a safer and more efficient method than current CO2 capture technologies.

Designing a Radical-Proof Iridium Photocatalyst for Synergistic Catalysis

Kai Okada Mentor: Ryan Evans

Advisor: David W.C. MacMillan

Photoredox catalysis provides access to a tremendous amount of reaction space at very mild conditions, particularly when coupled to other platforms such as transition metal catalysis. However, the photocatalyst’s redox parameters must be well tuned with those of the substrates, and radicals may react with ligands on the catalyst itself, disrupting this balance and hindering reaction progress. Here, several heteroleptic iridium-based catalysts were designed to assess the relationship between ligand structure and the extent of catalyst deactivation in decarboxylative sp2-sp3 bond formation. Inspection by proton NMR and mass spectrometry revealed many side reactions on the ligands, including substitution at methoxy and fluoro groups and nucleophilic Minisci-type addition to aromatic rings.

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Oxidative C-H Alkenylation of α-olefins Accelerated by AlkeneTethered Sulfide Ancillary Ligands

Cecily O'Leary

Mentor: Long Wang Advisor: Bradley Carrow

Fast and efficient formation of C-C bonds is essential industrial pharmaceutical production. Palladium catalyzed Cross Dehydrogenative Coupling (CDC) efficiently forms C-C bonds without necessitating prefunctionalization. Ancillary ligands greatly increase selectivity and stability of catalysts. Thioether ligands, in particular, generate higher yields at higher rates than traditional CDC ligands. We have found that a tethered electron deficient ligand with an alkene can bind palladium and activate the C-H bond so the catalyst can catalyze previously difficult electron rich alkenes broadening the substrate scope.

Synthesis of Redox-Inactive Chelates Through Ligand Cyclometalation: Facilitating Base Metal Catalysis?

Hanley Ong

Mentor: Max Friedfeld Advisor: Paul Chirik

In order to replace financially and environmentally burdensome precious metal catalysts, base metal catalysts seem to require incorporation of “redox-active” ligands, which can freely donate and accept electrons to and from the base metal center. To investigate whether redox-active ligands are truly necessary for base metal catalysis, we synthesized redox-inactive pyridine imine (PI) chelates formed through cyclometalation, whose catalytic activity will be later compared to that of the well-studied, structurally analogous, and redox-active pyridine di-imine (PDI) chelates. We synthesized several PI(Co) complexes, the most noteworthy of which was a cyclometalated PI(Co)-pyridine complex formed as the major product of a reaction that was analyzed primarily through 1H NMR and COSY. This redox-inactive PI complex may prove to have comparable catalytic activity to redox-active PDI complexes, and thus support the idea that redox-inactive ligands can also facilitate base metal catalysis.

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Synthesis of a Chiral Ligand for Organometallic Catalysis of Polymers

Madison Parry Mentor: Maggie Tiedemann

Advisor: Bradley Carrow

In the synthesis of polymers through organometallic catalysis, the effects of chirality in the catalyst on polymer tacticity should be further explored. A TBS protected prolinol was utilized to make a chiral phosphonic diamide, which was transformed into a phosphine-phosphonic diamide ligand and coordinated to palladium to synthesize the precatalyst. The synthesis of the chiral precatalyst by coordination of the phosphine-phosphonic diamide to palladium was confirmed using 31P NMR spectroscopy. The resulting catalyst may afford a polymer with novel microstructure, which will potentially produce a bulk polymer with previously inaccessible properties and useful applications.

Nickel Catalysis: [2+2] Cycloaddition and sp3 C-H Borylation

Summer Ramsay-Burrough Mentor: Valerie A. Schmidt

Advisor: Paul Chirik

Nickel-catalyzed transformations allow chemists to access useful intermediates and forge new synthetic pathways. Two representative reactions are alkene cycloadditions and selective sp3 C-H functionalization. These processes have been successfully catalyzed by a variety of transition metals, but have not been fully explored with nickel, which is attractive for its relative natural abundance, synthetic ease, and the unique reactivity of organometallic nickel compounds. We screened reduced nickel with mono- and bidentate phosphine ligands as pre-catalysts for inter- and intramolecular [2+2] cycloadditions. NMR studies of these reactions show that these pre-catalysts are ineffective due to the low rate of ligand substitution of the substrate olefins to the nickel. We also screened nickel catalysts for selective mono- and diborylation at the benzylic position of arene substrates; due to analogous structural properties to DICoR2 compounds that catalyze sp3 C-H borylation, we synthesized several DINiR2 compounds and identified (iPrDI)NiMe2 as the most effective. For both [2+2] cycloadditions and selective sp3 C-H borylation, we were able to narrow the catalyst and substrate scope for future investigation.

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Electronic and Magnetic Properties of an Oxyfluoride Pyrochlore

Stephanie Ribet Mentor: Quinn Gibson Advisor: Robert Cava

Solid oxide compounds with the pyrochlore structure are known for interesting and occasionally dramatic magnetic and electronic properties due to the motif of corner sharing magnetic tetrahedra that they can contain. In this work, I have synthesized a pyrochlore in the Ca2Nb2O6F family. The compound is weakly diamagnetic and appears to have the Niobium in a predominantly +5 oxidation (4d0) state. This suggests the presence of calcium vacancies and/or the possibility of fluorine interstitials. We report on altering the properties of the compound by experimenting with dopants and different synthesis techniques.

Radical Process: Decarboxylative Alkenylation of sp3 C–H Bonds with Aryl-Substituted Acrylic Acids

Marlon Simms

Mentor: Dr. Wei Zhang and Long Wang Advisor: Bradley Carrow

Sulfide-sulfonate ligands promote dehydrogenative Heck reactions between electron-rich heteroarenes and electron-deficient alkenes. Aryl-substituted acrylic acids can be made at a higher rate with lower catalyst loading when these ligands are used. By exposing this chemistry to indoles, furans and thiophenes, and various acrylates, alkynelation process is efficacious. Hence the purpose of this project was to successfully decarboxylate via radical process aryl-vinyl acids by first activating the sp3 C–H bond of simple alcohols, hydrocarbons and ethers with trace amounts of copper powder.

Testing Synthetic Protein Library Functions Using Phage Display

Elizabeth Stanley Mentor: Katie Digianantoino Advisor: Michael H. Hecht

The Hecht lab has created de novo protein libraries designed using binary patterning of amino acids. These libraries have a huge number of potential functions, which can be screened for phage display. Phage display uses bacteriophages with a library protein expressed on the surface to select for and amplify specific library proteins with desired functions such as binding to a substrate or catalysis. By immobilizing BSA conjugated fluorescein (FBSA), insulin, and myoglobin on immunotubes and selecting phages that bind to these substrates, we discovered that libraries developed in the Hecht lab can bind FBSA but not insulin or myoglobin. In addition, we assayed for catalysis by incubating phages with L-OMe and Fmoc-T, amino acid derivatives known to form a gel when an amide bond forms between them, allowing phages that catalyze this reaction to be separated by centrifugation. We found that phages in Hecht lab libraries have the potential to catalyze this condensation. These results demonstrate that binary patterned protein libraries can be a starting point for finding biologically active proteins.

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Nickel Catalyzed Hydrofunctionalization of Olefins

Sean Treacy Mentor: Iralkis Pappas Advisor: Paul Chirik

The catalysts most commonly employed in hydrofunctionalizations reactions maintain circumscribed activities and selectivities. Although base-metal catalysts have been shown to catalyze hydrosilylation and hydroboration reactions, few examples utilize nickel as the site of reactivity. In-situ activations and isolated catalyst syntheses have identified Ni(II) diimine compounds as competent catalysts for hydrosilylation and hydroboration reactions. The size, tunability, and unique metal-ligand cooperativity of Ni(II) diimine catalysts show promise to promote reactivity in highly hindered olefins, opening unprecendented chemical space for reactions involving previously unfunctionalizable olefins.

Synthesis and Incorporation of Truncated Autoinducing Peptide on Surfaces to Inhibit Staphylococcus Aureus Virulence Pathway

Ashley Wang

Mentors: Aishan Zhao and Zachary Brown Advisor: Tom Muir

The regulation of virulon in human pathogen Staphylococcus aureus is achieved by the accessory gene regulator (agr) operon, in which the interaction between extracellular autoinducing peptide (AIP) and the AgrC receptor is critical. While the discovery of the truncated AIP-II (trAIP-II) as a global inhibitor across different agr specificity groups opens up many potential applications in biomedical research, the possibility of incorporating this molecule into readily available polymers or building blocks has not yet been explored. To examine the use of an inhibitor molecule on surfaces, this research project will first create an alkynated trAIP-II using Fmoc-based solid phase peptide synthesis to block the S. aureus communication system and prevent the release of harmful virulence factors. Then, this newly synthesized global inhibitor will be fused onto useful surfaces through click chemistry. So far, we’ve successfully synthesized the alkyanted trAIP-II molecule and demonstrated its ability to inhibit growth in S. aureus; the results offer significant potential for progress in the biochemical and medical fields.

Coupling Reactions of Alkyl Halide Radicals via Photoredox Catalysis

Jeffrey Wu Mentor: Patricia Zhang

Advisor: David W.C. MacMillan

Coupling reactions between electrophiles and nucleophiles are very common and are well studied. Reactions between two electrophiles are less common. Screens were run on a number of aryl and vinyl halides to couple with an alkyl halide using photoredox chemistry to determine reactivity. The reaction conditions used were determined to be unstable and led to inconsistent results, and so other conditions are being explored.

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Investigating Singlet Fission in a Model Covalently-Linked Dimer: Steady-State and Time-Resolved Spectroscopy of (F-TIBS-ADT)2

Ruomeng Zhang

Mentor: Jacob C. Dean Advisor: Gregory D. Scholes

Singlet fission has the potential to improve the efficiency of solar cell devices by generating high triplet quantum yield(s) which can exceed 100%. We investigated singlet fission in a covalently-linked homodimer of fluorinated anthradithiophene functionalized with triisobutylsilyethynyl (TIBS) side chains, a derivative of the well-known singlet fission reagent TIPS/TIBS-pentacene. By studying its spectroscopic properties and photo-induced dynamics via absorption, fluorescence, time-resolved fluorescence and transient absorption spectroscopy, we have found evidence that singlet fission is indeed occurring in this model compound, and the singlet fission rate increases in going from toluene (τSF = 1.75 ns) to the more polar acetone (τSF = 0.65 ns) solvent.

Facile Synthesis of Organic Isocyanates

Thompson Zhuang Mentor: Xiongyi Huang Advisor: John T. Groves

While the reactivity of organic isocyanates, driven by their high degree of unsaturation, provides crucial access to industrially- and biologically-relevant compounds including asymmetric ureas, urethanes, and amides, known syntheses of isocyanates are hindered by requirement of prior functionalization or use of highly toxic phosgene gas. Here, we report a facile synthesis of isocyanates with good yields. DFT calculations demonstrate the mechanism of isocyanation. These results capitalize on the versatility of the isocyanate functionality to add a synthetically useful method to the chemist’s toolbox.

Deep Eutectic Solvents and the Direct Ethanol Fuel Cell

Judson Ziegler Mentors: Jim White and Dr. Paul Majsztrik

Advisor: Andrew B. Bocarsly

Deep eutectic solvents have attracted attention for potential use in the development of fuel cells. This research aims to improve the efficiency of the direct ethanol fuel cell by altering the polymer exchange membrane, Nafion. Large, quaternary ammonium salt cations are exchanged with the protons of the Nafion sulfonic groups in hopes of decreasing ethanol crossover, without sacrificing the proton conductivity of Nafion significantly. Tetrapropylammonium and tetrabutylammonium cations exchanged into Nafion both yield smaller ethanol crossover rates than pure Nafion, which is encouraging for an actual fuel cell test, since their respective resistances are only a little higher than pure Nafion.