Research Experience for Undergraduates

IMPRESS: IMPlanting the ResEarch Seed in Students

Potential Mentors and Projects (Chemistry)

Dr. Brumaghim

Incorporation of S/Se atoms into chelating ligands for actinide and lanthanide ions has long been desired to examine the covalency of f-block metal ions and to enable separating the slightly covalent minor actinides from lanthanides in nuclear waste.  However, the S/Se atoms rapidly react with radicals generated by the radioactivity of the elements.19,20 To address this problem, Dr. Brumaghim’s group has formulated a series of S/Se-containing ligands for f-element chelation that are resistant to such degradation. Building on this work, REU students interested in this project will be introduced to the synthetic approaches in the labs (~3 weeks) and allowed to choose a target ligand (such as those shown in Figure 2). The bulk of the visit will focus on the synthesis of analogous thione- and selone-containing ligands and learning to characterize the non-radioactive La(III) and Eu(III) complexes using NMR and UV-vis spectroscopies (~5 weeks). Students will also conduct cyclic voltammetry studies of the target complexes (~2 weeks), since the predictive model for radical reactivity derives from the HOMO-LUMO gap of the metal-ligand complex, which the electrochemical potentials of the S/Se ligands with metal ions measure. Similar projects examining the coordination of thione and selone-containing ligands with copper and zinc have resulted in two recent publications with four undergraduate coauthors. Students interested in this project will have the opportunity to also receive mentoring, for example, from Dr. Modi Wetzler (ligand design) and Dr. Brian Powell (f-element chemistry).

Dr. Pennington

Deep eutectic solvents are ionic systems formed from a mixture of Lewis or Brønsted acids and bases and display a melting point much lower than either of the individual components. They represent green alternatives to perform a number of chemical reactions and have important applications for tuning the performance of iodide/triiodide redox couples used in dye-sensitized solar cells (DSSCs), lithium iodide batteries, and other devices. Dr. Pennington’s group has focused on expanding the number of Lewis-base elements involved in X-bonding interactions28 and recently documented the role of hybrid iodide salt-organoiodide mixtures as potential deep eutectic solvents (Figure 3). Bolstering these developments, REU participants interested in this project will first prepare a variety of binary mixtures of iodide (or polyiodide salts) and organoiodine molecules and explore the solid-state landscape of these salts by rationally varying the ratios of the components (~3 weeks). Students gain insights about the structural, thermal and bonding properties of these materials using techniques such as single-crystal and powder X-ray diffraction, thermal gravimetric analysis and differential scanning calorimetry (~4 weeks). These results will be complemented by measurements of electrical properties such as conductance and resistance of crystals and microcrystalline powders (~3 weeks). The project represents a unique learning opportunity for the participants, as the concepts included are not often discussed in the chemistry curriculum. On additional advantage of this project is that would allow students to continue their work at their home institution and then send the materials (or bring them) back to Clemson for further analysis, remaining engaged in the research and potentially supporting recruitment pipelines to our program. Students interested in this project will have the opportunity to also receive mentoring, for example, from Dr. Garcia (sensors integrating DES) and Dr. Saha (solar cells).

Dr. Marcus

Exosomes, the “next big little thing”, are 50-120 nm diameter microvesicles which have in the last 10 years become identified as key agents in the process of intra-cellular communication.  They are released from virtually all cell types, carrying a treasure trove of information of the points of origin.  Surface marker proteins identify the cell of origin, while the encased genetic material provides insights into the inner workings of that cell.  They are projected as being outstanding test materials for clinical diagnostics for a large number of diseases as well as being used as delivery vehicle for biotherapeutics. Owing to their importance, Dr. Marcus’ group has pioneered the development of a number of approaches to separate exosomes from biological matrices, including C-CP fiber platforms for LC and spin-down formats. Furthering these advances, REU students interested in this project will be introduced to the basic aspects of protein and bio-nanoparticle separations and how C-CP fibers35 can be implemented to provide high throughput and efficiency (Figure 4). They will work closely with senior-level graduates to gain hands-on expertise in C-CP fiber column packing and surface derivatization (~3 weeks), as well as operation of state-of-the-art one- and two-dimensional liquid chromatography systems (~2 weeks). Students will then apply these skills towards targeted separations of proteins towards proteomics applications or the isolation of exosomes/virus particles from cell culture media (~5 weeks). Every effort will be made to match any particular interests that the students have with project direction. Students interested in this project will have the opportunity to also receive mentoring, for example, from Dr. Kim (organic reactivity) and/or Dr. Anker (biosensors).

Dr. Tran

Noncentrosymmetric (NCS) magnetic materials featuring novel magnetic spin topologies have recently emerged due to their potential applications in racetrack memory and other low-power and high-density spintronic technologies. In this regard, Dr. Tran has previously designed effective strategies for the synthesis and characterization of new NCS compounds containing s- and p-blocks as well as a set of crystal-chemistry protocols for the discovery of new materials with exotic magnetic exchange interactions.Thus, and with the goal of deriving a reliable set of crystal-chemistry guidelines that dictate topological magnetic spin configurations, REU students interested in this project will explore the synthesis of A-T-P phosphides (A = Eu, Yb; T = Mn, Fe, Co, Ni, Cu, Figure 5) while receiving training in variety of solid-state synthetic tools, such as flux growth, chemical vapor transport, and arc-melting methods (~4 weeks). Students will then characterize the produced materials using single crystal, powder X-ray diffraction technique, and a newly-acquired physical property measurement system (~4 weeks). This project allows students making chemistry–property relationships for designing new topological magnetic spin textures. Students interested in this project will have the opportunity to also receive mentoring, for example, from Dr. Kolis (optical properties of crystals) and/or Dr. Dominy (computational).

Dr. Kim

As antibiotic resistance is one of the major threats to global health, generation of new antibiotic analogues are in high demand.  However, synthesis of these molecules often requires multi-step synthetic endeavors, and methods that allows direct modification of antibiotics is rare. To address this challenge, the Kim Group is interested in the development of new catalysts that will enable direct diversification of important antibiotics, such as aminoglycosides. In our initial efforts towards preparing new catalysts, we have made swift progress where we are only one simple step away from to the catalyst of target (Figure 6, top).  Based on this preliminary result this project aims to develop crown-ether-bearing catalysts that will be used to exploit the known molecular recognition between crown ethers and ammonium salts.44 Thus, REU Students interested in this project will focus on expanding the library of catalysts by derivatizing the thiourea motif (Figure 6, bottom).  They will first evaluate the structural and electronic properties of the H-bond donor motif (~4 weeks), which will allow us to explore and study selective O-functionalization of amino alcohol model compounds (~6 weeks). Through this work, they will gain fundamental training in synthetic organic chemistry including purification techniques, and detailed analysis of reaction mixture. Furthermore, the experience will also provide training in basic principles of designing catalysts, and retrosynthetic analysis.  In the span of Summer program, such training will allow to foster growth of the REU students by providing opportunities to input their own creativity in their synthesis.  Lastly, this project will raise awareness of antibiotic resistance, mechanism of the resistance, and perhaps, contribute towards potential solution of the global threat. Students interested in this project will have the opportunity to also receive mentoring, for example, from Dr. Casabianca (NMR techniques) and/or Dr. Arya (molecular recognition).

Dr. Thrasher

Thrasher’s group recently reported the first examples of S–Cl···O halogen bonding complemented by short F···F contacts between neighboring chains that resulted in stabilized crystals of ClSO2(CF2)4SO2Cl (Figure 7) and ClSO2(CF2)6SO2Cl. These findings are important because (1) they allow the study of intermolecular associations involving halogens where hydrogen bonding cannot be operative and (2) their study may provide additional insights into how such intermolecular forces influence other structural features, such as the alignment or helical rotation in perfluorinated alkyl versus alkyl chains. Thus, REU participants interested in this project will gain synthetic skills involving inert-atmosphere techniques and prepare a library of samples of the related BrSO2(CF2)nSO2Br derivatives (~5 weeks). Students will then characterize those samples by various spectroscopic methods (19F-NMR, FT-IR, MS, ~3 weeks) and be exposed to single-crystal growing techniques and X-ray crystallography (~2 weeks). Students interested in this project will have the opportunity to also receive mentoring, for example, from Dr. Pennington (halogen bonding) and/or Dr. Marcus (atomic and molecular mass spectrometry).

Dr. Saha

Owing to their unparalleled synthetic simplicity, structural and functional tunability, and tantalizing potentials to advance modern electronics and energy technologies, semiconducting and light-harvesting metal–organic frameworks (MOFs) have become one of the most coveted functional materials. The MOFs, however, must comprise adequate charge carrier density and charge transport pathways in order to display useful electrical conductivity. While the first criterion can be satisfied by simply introducing redox-active building clocks and guests into MOFs, the latter continues to be a much greater challenge and draws significant attention from researchers. To this end, we are developing electrically and ionic conducting MOFs by using various π-donor and π-acceptor ligands, such as tetrathiafulvalene (TTF), π-extended TTF, naphthalenediimides, thiazolothiazole, and hexaazatriphenylene hexacarbonitrile, and/or by doping the resulting MOFs with complementary redox-active guests that can promote charge transport either through the metal–ligand coordination bonds or through the π-stacked ligands and π-donor/acceptor stacks. We are also developing robust, precisely oriented MOF films on semiconducting ZnO surfaces that can be easily integrated into various optoelectronic devices, such as sensors and sensitized solar-cells. Working alongside my graduate students and postdocs, the REU students in my laboratory will design and synthesize of new electroactive ligands and MOFs; characterize their structures and compositions with NMR and IR spectroscopies, X-ray crystallography, mass-spectrometry; and investigate their optical and electronic properties with UV-Vis, fluorescence, and diffuse-reflectance, and EPR spectroscopies and various electrochemical and electrical measurements, including cyclic and differential pulse voltammetry and two-probe and four-probe current-voltage measurements. Furthermore, they will also learn to grow MOF films on different surfaces and incorporate them into electrical devices to measure their electrical and ionic conductivities as well as photovoltaic response. These interdisciplinary and multifaceted research experience will provide the REU participants broad knowledge and technical expertise in materials science, preparing them for graduate schools as well as highly technical jobs at various industries and national laboratories. I have a track record of training over 20 undergraduate students, including several REU students, in my laboratory, many of whom are pursuing doctoral studies, and previous participants have received Clemson’s REU poster award. Students interested in this project will have the opportunity to also receive mentoring, for example, from Dr. Tran (material characterization) and/or Dr. Smith (batteries).

Dr. Perahia

Students interested in this project will contribute to determining the structure and molecular motion of in structured ionic co-polymers, a family of macromolecules comprised of segments that enable ionic transport, tethered to ones that can enhance mechanical stability. Such polymers show promise as membranes for use in innovative technologies, including lightweight clean energy generation and storage, water purification, and biomedical applications. However, despite their immense potential, only limited control of the structures these polymers and their molecular motion has been achieved.  This presents a significant roadblock to their utilization, since molecular structure and motion determine the properties of the polymers.  Specifically, REU participants will use T1 and diffusion NMR measurements to probe the mobility of ionic co-polymers (polystyrene sulfonate), controlling solvent polarity and counterions (~6 weeks). Participants will also be introduced to modern computational techniques to complement the experimental work (~4 weeks). The latter offers unique opportunities for these students in terms of learning and to continue engaged in the project throughout the academic year. Students interested in this project will have the opportunity to also receive mentoring, for example, from Dr. Garcia (interaction kinetics) and/or Dr. Stuart (computational).

Dr. Garcia

Paper-based analytical devices (µPADs) are powerful tools for performing simple, low-cost, and on-site analytical determinations. Since their introduction, these devices have provided a clear path to develop devices that span from point-of-care (POC) diagnostics to paper-based electronics. In general, µPADs offer significant advantages over traditional platforms in terms of sample volumes, analysis time, cost, production procedures, portability, and ease-of-use. Among those, electrochemical paper-based analytical devices (ePADs) offer improved sensitivity and a tunable selectivity towards different analytes. This tuning is possible through the addition of biorecognition elements (enzymes, immunoglobulins, etc.) and the rational selection of the applied potential and the electrode material. Students interested in this project will a) investigate the reaction mechanism and assess the catalytic activity of carbon electrodes produced by pyrolysis of paper and b) develop and characterize paper-based analytical devices incorporating the new paper-derived carbon electrodes.

During the visit, students will learn to how to fabricate devices and gain fundamental knowledge on how to apply redox reactions in biomedical research. The proposed activities aim to integrate our paper-derived carbon electrodes with microfluidic devices, providing unique advantages with respect to state-of-the-art technology in terms of simplicity, stability, and sensitivity. As these electrodes can be designed to cover the entire area of the reaction zone, the strategy represents a significant departure from the traditional approaches of integrating electrodes by either stacking or paining. Aside from the cables, the resulting sensor will be fabricated entirely from paper, resulting in a versatile, inexpensive, stable, easily transportable platform that could be simply burned after use (no known toxicity).

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Dr. Daniel Whitehead and Dr. Joseph W. Kolis

Efficient chiral resolution represents one of the grand challenges of organic chemistry. Chiral alcohols and aldehydes represent extremely diverse and important functional groups, but their enantiomeric separation is a particularly difficult problem. Unlike amines for example, alcohols and aldehydes cannot be readily converted to cations and then resolved by diastereomeric crystallization using common resolving reagents like tartrates. We recently developed a new class of chiral resolving reagents that provide a straightforward route to resolution of alcohols and other compound with R-OH functional groups by diastereomeric crystallization.

The senior graduate student (B. Brummel) who developed the chemistry and obtained the preliminary proof of concept work will mentor the participant. The sulfation chemistry is straightforward and a considerable supply of the chiral guanidinium resolving agent is on hand. The students can pursue the research according to their own particular interest. They can expand the organic functional groups that can be resolved or they can examine only a few well behaved crystallizations in more detail to understand the crystallization process. Since all the crystallization processes are driven by the strong hydrogen bonding between the sulfate and guanidinium, a careful examination of the H-bonding in the crystal structures will enhance future resolution protocols. In any event the student will join an ongoing collaboration with an active team. The team meets regularly and the REU student will be a part of that team and learn a great deal about an important interdisciplinary project.

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Dr. Jeff Anker

We are developing a simple and rapid assay to study molecular binding and dissociation as part of a larger project to make a rapid, highly sensitive and specific assay for biomarkers from SARS CoV-2 and other pathogens. We functionalize both buoyant and magnetic microbeads with antibodies that specifically bind to the analyte of interest (e.g., SARS-CoV-2 nucleocapsid protein). When both types of microbeads bind to the same molecule, they form a buoyant and magnet (BAM) complex. These BAM complexes can be pulled to the bottom of a cuvette using a magnet and separated from buoyant but non-magnetic beads. Removing the magnet allows the BAM complexes to rise towards the surface, while the non-buoyant magnetic particles stay where they are or sink slowly. In saliva mimic, we observe almost 100% capture efficiency at low molecule concentrations (one BAM complex per molecule), with 0-2 BAM complexes when no nucleocapsid molecules are added, but we get some non-specific crosslinking in real saliva. We are pursuing several ways to reduce this; one that is interesting comes from our observation of spontaneous dissociation of some of the non-specifically bound buoyant-magnetic beads due to the opposing forces between magnetic and buoyant beads (see Figure 1). We would like leverage this to find conditions where we can distinguish specific and non-specifically bound BAM complexes. The work will involve generating BAM complexes and studying rate of binding and dissociation as a function of temperature, pH, surfactants, enzymes and other parameters.

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Dr. Casabianca

Plastic pollution is ubiquitous in our lakes, rivers, and oceans. This plastic breaks down over time and poses a danger to wildlife. Animals can become trapped in plastic or mistake plastic for food. Plastic pollution in water also acts as a source for persistent organic pollutants (POPs), which include harmful substances such as endocrine disruptors and carcinogens.1 Understanding the interactions between different kinds of plastics and POPs is important in designing mitigation strategies as well as screening tools for POPs that move up the food chain and find their way into fish intended for human consumption. Our previous work in the field has focused on developing NMR techniques to study the interactions between small molecules and polystyrene nanoparticles. This work has allowed us to deduce the main interactions that are responsible for amino acids interacting with nanoparticle surfaces, namely pi-pi interactions, electrostatic effects, and hydrophobic effects. Thus, we propose to extend our previously-developed Saturation-Transfer Difference (STD-NMR) technique to study the interactions between POPs and different kinds of plastic nanoparticles. This approach is innovative because although NMR has been used before in the field of plastic pollution, this technique is not being used to its full potential. The STD-NMR technique that we use in our lab has the advantage that it can be used for epitope mapping, in other words it can be used to deduce which part of the small molecule interacts more strongly with the nanoparticle surface.

Students interested in this project will perform STD-NMR experiments on different combinations of plastics and POPs. They will analyze the resulting data to determine which combinations result in binding interactions, explore the relative binding energy between the different combinations, and use the epitope-mapping power of STD-NMR to deduce which interactions are responsible for binding in each case. The proposed project provides training in NMR operations and the theory behind NMR. Students will also learn to analyze data and think critically about their results. This is a unique learning opportunity that is critical for those students who intend to go on to graduate school. In addition, students interested in this project will also have the rare opportunity to become certified users of our NMR facilities, an option that allows them to continue with the project during the school year and continue collaborations with our department.

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Derivatization of amides is a useful strategy for the discovery of therapeutic drug candidates.  However, chemical modification of amides often requires harsh conditions and is wasteful.  The objective of this research program is to devise a new chemical toolbox for stereo- and site-selective diversification of amides via transition metal catalysis.  Recently, in the Kim Group, we developed a titanium-based catalytic system that converts an amide to an enamine under a mild condition.  Furthermore, we have demonstrated sequential functionalization of the enamine to generate chiral amine in a one-pot process.  We envision that, working along with a REU student, various chiral ligands will be synthesized (2 weeks) and applied in the titanium catalytic system to develop a sequential, stereoselective catalysis for amide diversification (8 weeks).

Dr. Jacobson

Membrane proteins (MPs) are biologically important because they connect biological cells and their surroundings.  MPs are synthesized by the ribosome as a chain of amino acids, which folds up into the three-dimensional structure that gives the protein its function.  This folding happens spontaneously as a result of various physiochemical interactions, including van der Waals forces, hydrophobicity, and hydrogen bonding.  An emerging way to study these interactions is to apply mechanical force to the protein (e.g., using an atomic force microscope, AFM); the strength of the interactions is related to how much force it takes to overcome them.  Modern AFM techniques, using cantilevers with low noise and fast time response, allow this force-induced unfolding to be monitored at near-single-amino-acid resolution.  These advanced techniques have begun to be applied to alpha-helical MPs, but not yet to the beta-barrel MPs found in Gram-negative bacteria.  Understanding bacterial MP folding and dynamics is important both because of their role in infectious disease and because they are a widely studied model system. In this project, the student will perform the first AFM-based unfolding measurement of a beta-barrel membrane protein using high-time-resolution techniques.  In particular, they will use molecular biology and biochemistry to express and purify a bacterial outer membrane protein sample, reconstitute the protein into a surface-supported lipid bilayer, use surface chemistry so that a chemical bond can be formed between the protein and the AFM cantilever, and then use the AFM to exert force on the protein.  They will learn biophysical techniques to analyze the data, compare with existing lower-resolution measurements, and communicate their results.

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Dr. Chris Chouinard 

The drug crisis plaguing our nation has been exacerbated by the introduction of many new psychoactive substances (NPS) including fentanyl analogues and synthetic cannabinoids. These drugs are designed to have varying effects/potency in comparison with their traditional counterparts and can also evade conventional drug screening tests. As such, their proliferation in the illicit drug market has created an urgent need to develop advanced measurement techniques capable of identifying and characterizing emerging substances. Our research group develops ion mobility-mass spectrometry (IM-MS) methods and technology to study these compounds, both for identification purposes and also to better understand their fundamental gas-phase properties. This project specifically will be geared towards method development for quantifying these substances and their metabolites in biological samples.

Additional Mentors and Projects
  • Dev P. Arya, Discovery of new motifs for the molecular recognition of biological macromolecules for development of novel antibiotics
  • George Chumanov, Synthesis and characterization of plasmonic nanoparticle assemblies
  • Jason McNeil, Advanced fluorescence applications based on nanoparticles consisting of one or more conjugated polymer molecules
In addition to the research activities, students receive training and opportunities in:
  • Literature: search, read, and interpret journal articles related to their project
  • Research skills – experimental design, statistical analysis, and data interpretation
  • Instrumentation: hands-on training in the fundamentals, usage, and data interpretation
  • Professional development, communication skills, ethical considerations and research integrity
  • Career planning
  • Professional networking
  • Diversity in science