Vanderbilt Chemistry 2015

vanderbilt chemistry 2015 CONTENTS Greetings from the Chair 3 Research Highlights 4 Faculty 16 Graduate Students 20 0 Undergraduate Students 34 8 Colloquium Speakers 43 3

elcome to the 2014/2015 Department of Chemistry. I am pleased to report that • Vanderbilt Chemistry 2015 the Department continues its upward trajectory with renewed growth, recognition, and research success. We have new faculty hires, additional resources, Wrenovated lab space, and recruited an exciting class of graduate students. The Chemistry Department welcomes our newest hires. We successfully recruited Nathan Schley, as an assistant professor in inorganic chemistry. His particular area of interest is catalysis. We are also pleased to have recruited lecturers Alissa Hare for organic chemistry and David Kort for general chemistry. We would like to recognize the 30 years of service by Professor Tim Hanusa and the 35 years of service by Professor Prasad Polavarapu to the department, college and university. Professor Piotr Kaszynski left the department to pursue opportunities in his home country of Poland. Finally, it is with great sadness that I note the loss of Professor Richard Armstrong, who died in June after a brief illness. Richard’s approaches to mentoring, teaching, research and service remain an inspiration to his students and colleagues. A hallmark of our faculty is their dedication to research, teaching, and service. Once again, our faculty garnered awards both nationally and on campus. Examples include Pro- fessor Richard Caprioli, who won the VUMC Enterprise Faculty Award for his pioneering innovation in mass spectrometry; and Professor Jens Meiler, who was named to the inaugural class of Chancellor’s Faculty Fellows. The Chancellor’s Faculty Fellows represent the future of Vanderbilt. They offer energy and innovation for new basic discoveries, path-breaking scholarship, and creative expression. A team led by research assistant professor Joseph Conrad and graduate student Alexis Wong were recognized as Phase I finalists in the NIH CONTENTS Follow the Cell Challenge. Finally, I was named a fellow of Greetings from the Chair 3 the American Association for the Advancement of Science. Research Highlights 4 We are proud of all of our students both undergradu- Faculty 16 ate and graduate. This past year, we graduated 25 students Graduate Students 20 0 with ACS-certified bachelor degrees in Chemistry, most Undergraduate Students 34 8 of whom will pursue graduate or professional studies. We also graduated 11 students with the Master’s degree and Colloquium Speakers 43 13 students with the Ph.D. in chemistry. Our trainees are the recipients of a number of awards ranging from NIH training grant positions to the NSF Graduate Research Fellowship to GAANN (Graduate Assistantship in Area of National Need) fellowships. The stories in the following pages will provide you with some perspective about what Vanderbilt Chemistry researchers are doing, the changing faces of the Department, the recognition that we continue to earn, and some insights into our students, past and present. As always, we would love to hear from you.

David Wright Stevenson Professor and Chair Department of Chemistry Vanderbilt University research highlights

Infectious Disease Elimination Is Possible By Danielle Kimmel, Ph.D. and Joseph Conrad, Ph.D. Wright Lab

y incorporating global education initiatives, research and development of new therapies and diagnostic technologies, and careful surveillance of existing cases, the burden of many infectious diseases has been reduced and is nearing elimination. Currently, scientists, governments, and public/ Bprivate partnerships are devoting considerable research efforts toward new ways to eradicate devastating diseases, such as malaria. An interdisciplinary team of scientists at Vanderbilt University is contributing its research findings to global malaria eradication efforts with the help of a secret weapon, 3D printing.

Developing countries suffer from a high burden of infectious diseases as a result of limited resources supporting medical, water, and public health systems. Even with affordable and accessible treatments, high sensitivity diagnostic technologies used to detect infections in places like the United States are seldom available in the developing world. Unfortunately, it is precisely the effective identification of infections that is needed to reduce their spread, as well as speed delivery of care and treatment. Malaria is a parasitic infection that completes life cycle steps in humans and mosquito hosts. Mosquitoes that take a blood meal from an infected individual can later transmit parasites to another person. Infected individuals do not necessarily become symptomatic until the parasite has reproduced in their blood and the number of parasites pass a tipping point. A higher parasite concentration makes the transmission of malaria more likely with subsequent mosquito bites. In the case of malaria, the diagnostics that are used to detect malaria infection most often require a skilled microscopist, who examines blood specimens for the presence of infecting parasites. In low resource settings, the infrastructure and personnel to support microscopy is not readily available. One alternative diagnostic approach includes the use of rapid diagnostic tests (RDT), similar to a home pregnancy test. These lateral flow immunoassays are self-contained, do not require skilled technicians, electricity, or clean water. However, the sensitivity of these tests is insufficient to identify low level infections in individuals who may not have symptoms, but who may still transmit the disease to others. Rapid diagnostic tests are generally sensitive enough to return a positive result when the parasite loads are high. In areas where malaria control efforts have progressed toward elimination, parasite loads can be much lower. Individuals with low-level infections may not be symptomatic; thus, diagnosis through clinical assessment is impossible. Further, these individuals may not receive treatment, allowing for the spread of malaria through a community even in the absence of widespread, symptomatic malaria. Folk art, Macha, Zambia, Africa 2015 (photo courtesy of Danielle Kimmel, Ph.D.) At Vanderbilt, a cross-continental collaboration is working 5 • Vanderbilt Chemistry 2015

3-D printer completes RDT device. To watch a video of how the 3D printer works, please works, go to: a video the 3D printer watch how of To news.vanderbilt.edu/2015/01/3d-printer-helps-fight-malaria-in-africa/ Kneeling in the center is Joseph Conrad, Ph.D., Research Assistant Professor at Vanderbilt, Wright lab. Shown here with his in Team Macha, Zambia, August/September 2015: Left to right are: Christine Markwalter, Anna Bitting, Lauren Gibson, Lwiindi Mudenda (Zambian postdoctoral fellow for VZNIGHT), Hellen Matakala, (Zambian, training in the US to continue the research), Danielle Kimmel, Ph.D.,post doctoral fellow in the Wright lab, assistant director of the project), and Westley Bauer. (photo courtesy of Danielle Kimmel, Ph.D.) Supported in part by the National Institutes of Health, Fogarty International International Fogarty Health, of Institutes National part in the by Supported #D43 TW009348 Grant Center about the elimination of malaria. “Malaria is one of the leading of one is malaria. “Malaria of the elimination about especially in Zambia, rural in morbidity and mortality of causes the making therefore malaria limited, is of treatment where areas malaria to susceptible more the rural of community members in and printing 3D of introduction and the help With infection. detect malaria to hope we RDTs, enhanced of the development saving possible as early as treatment administer and infection malaria.” free of nation a healthy Zambia making and lives more

“Use of the 3D printer not only enables only not the 3D printer of “Use device design for her dissertation, highlights dissertation, her device design for - improv for the 3D printer of the importance sensitivity: RDT than more ing in these endemic capabilities diagnostic - a further col of also depth fosters but regions, and academic between world our laboration design.” which we for settings care of the point Working with the Vanderbilt-Zambia Network for for Network the Vanderbilt-Zambia with Working 3D manufacture, design and distributed a model of In with who worked graduate a recent D., Ph. Davis, Keersten Using a 3D printer to rapidly manufacture devices specific manufacture rapidly to a 3D printer Using a post-doctorial and fellow a Zambian Mudenda, Lwiindi Device manufactured by the 3D printer for Rapid Diagnostic Tests. Keersten Davis Keersten diligently to develop technologies to improve existing RDT existing improve to technologies develop to diligently 3D printing the use of incorporates their work of Part sensitivity. in Zambia. site on materials manufacture technology to an (VZ-NIGHT), Technology, in Global Health Innovation training funded research Center International NIH Fogarty the from scientists Chemistry, of in the Department program devices designed 3D printable have Zambia and States United them even perform make to the best tests “enhance can that make and tests performing the lower enhance and better, them adequately.” perform to design process be can utilized in the iterative printers send them for and Vanderbilt at device templates develop - collabora enables This Zambia. in Macha, in the lab printing go immediately devices unique and print to in Zambia tors test them.to the field into to a researcher’s needs provides a great step forward for low- for forward step a great needs provides a researcher’s to require that Devices settings. easily be can printed resource them ideal making electricity operate, to or running water no support. laboratory sophisticated without rural locations for very training little require the devices themselves Additionally, graduate a fourth-year Gibson, Lauren by noted as operate, to this device its is about me excites really that thing “One student. the enhance successfully a technician watched I have use. ease of of training.” minutes only after a malariasignal RDT of health in Zambia, improving to dedicated is VZ-NIGHT, for because its eradication towards efforts malaria and about care “I the future With disease.” fatal sometimes and a debilitating is it - undergo is Matakala, Hellen health in mind, Zambian of this continue can she so that States in the United training ing particularly is excited Hellen year-round. in Zambia, research research highlights

Fight Clubs Come to Vanderbilt

By David Salisbury

Bacterial Fight Club (Michael Smeltzer/ Vanderbilt University)

reating bacterial “fight clubs” is an effective way to find active compounds. There are an estimated five million trillion tril- new drugs from natural sources. That is the conclusion of lion bacterial cells on earth. They come in an astounding variety a team of Vanderbilt chemists who have been exploring with the best estimate of the number of distinct species ranging Cways to get bacteria to produce biologically from 120,000 to 150,000. Analysis of microbial genomes has shown active chemicals which they normally hold that individual bacteria carry the blueprints for hundreds of sec- in reserve. These compounds are called ondary metabolites. However, biologists have had a hard time either secondary metabolites. They are designed getting bacteria to produce them or synthesizing them directly so to protect their bacterial host and attack its they can assess their therapeutic value. enemies, so they often have the right kind of That’s where the “fight club” approach comes in. Research activity to serve as the basis for effective new Associate, Dagmara Derewacz, came up with the idea of apply- drugs. In fact, many antibiotics and anti- ing the analytical tools the Bachmann and McLean groups had cancer compounds in clinical use are either developed to analyze what happens when secondary metabolites or their derivatives. Brian Bachmann microbes compete. In a proof-of-concept test of the fight-club procedure, the research “It’s a ‘shoot first and ask questions later team headed by Associate Professor of Chemistry, Brian Bachmann, approach,’” said Bachmann, “which is oppo- and Stevenson Professor of Chemistry, John McLean, discovered a site of the traditional approach to natural promising new class of natural compounds that exhibit anti-cancer products drug discovery.” activity. The discovery is reported in the article “Mapping microbial The first microorganism the scientists response metabolomes for induced natural product discovery,” pub- put in the ring was Nocardiopsis, a bacteria lished online by the journal ACS Chemical Biology on June 17. that is found in the soil. They picked this Bacteria represent a vast untapped reservoir of biologically particular strain because when its genome John McLean 7 • Vanderbilt Chemistry 2015 - - purchas views, page your Internet your monitors Amazon thing. much the same do here using are we “The SOMs new a to discover chemists the allowed procedure This to ways of a number with experimented we’ve the past, “In Graphic representation of the process the Vanderbilt scientists used to discover the new antibiotic, ciromicin, with anti-cancer activity. (Bachmann Lab, Vanderbilt University) Dagmara Derewacz, Brian Bachmann, and Brett Derewacz,Dagmara and Bachmann, Brian Covington The research was supported by National Institutes of Health grants grants Health of Institutes National by supported was research The T32 GM 0650086. GM092218 and Amazon uses to make recommendations for the products they the products for recommendations make usesto Amazon McLean. said sell,” and you about they have information other history and ing a tile on pattern your puts It the data. of out a pattern makes Next, customers. other of millions its does for the same and the untilshare neighboring tiles around these tiles shuffles it pur last your recommend Then they patterns. similar most you. to purchases their last and neighbors your to chase all- about mol these have we in data the They take the patterns McLean. said similarly,” behave those that ecules match and activity broad-ranging with biomolecules of a class of member with contact into comes when Nocoardiopsis produced is that new this named The Rhodococcusscientists wratislaviensis. - war/cite/dis meaning word a Latin after ciromicin, compound several of that to similar is structure Ciromicin’s turb/invoke. - demon has new The compound antibiotics. FDA-approved to the capability and in vitro activity both anti-tumor strated cell death. in programmed involved genes modulate including their secondary bacteria metabolites, get produce to rare exposing them to and antibiotics them with poisoning method effective most is the approach club the fight earths, but McLean. said far,” by found, we’ve The chemists estimate that the cell co-cultures contain contain cell co-cultures the that estimate chemists The the wide from stems technical challenges the biggest of One look- were researchers the that The secondarymetabolites “self-organizing They callmethod the they developed In order to stimulate the bacteria to produce some of these of some the bacteria produce to stimulate to order In separately Nocoardiopsis “co-cultured” researchers The quantified and found lab in my Covington Brett “What determination make this to able were researchers The Sample dish with a series of co-cultures of competing microorganisms. somewhere between 20,000 to 50,000 different kinds of kinds between 50,000 different 20,000 to somewhere spectrometry these separates mobility-mass molecules. Ion which naturally ratio, molecules based their size-to-weight on proteins, to correspond that regions different sorts them into identify them to allows and etc., metabolites sugars, lipids, in each co-culture. 2,500 metabolites about molecules: the bacteria different of in concentrations range by others make but the dozen by compounds some produce the billions. so concentrations, low in relatively present generally are for ing them identify helped a methodwith that up they come to had their quantities. not based their qualities on these compounds the process to similar is “SOM SOM. or maps” metabolomics was sequenced it revealed the presence of 20 gene clusters that that clusters gene 20 of revealed the presence sequencedwas it secondary making metabolites. for carry blueprints - chal four with it matched the researchers compounds, novel Bacil Escherichia coli; - organism gut the common lengers: Tsukamurella model organism; a well-studied subtilis, lus immune compromised with which infects people pulmonis, which degrades Rhodococcus and, systems; wratislaviensis, hydrocarbons. microorganisms. the challenger each of with more in every that was co-culture—was case the product—the “The Bachmann. said monocultures,” the two of the sum than biologicalof kinds more significantly contained co-cultures combined.” monocultures themolecules two than capable chemistry analytical technique advanced an because of biological different of thousands identifying simultaneously of - pio helped have colleagues and which McLean compounds, spectrometry, mobility-mass called ion technology, This neer. iden- and which separates spectroscopy, mobility ion combines speedby the moleculestifies electrically with which charged spectrom- mass with a gas-filled through column, they travel quickly how molecules by individual “weighs” precisely etry, gas. of in the absence distance a given they travel research highlights Redesigned Antibodies May Control HIV Computational modeling predicts mutations that increase the affinity and broaden the specificity of anti-HIV neutralizing antibodies

By Bill Snyder

major challenge in the fight Working with colleagues at The Scripps against AIDS (acquired immu- Research Institute in La Jolla, California, nodeficiency syndrome) is the the Vanderbilt researchers began with a abilityA of the causative agent HIV (the “parent” antibody isolated from the blood human immunodeficiency virus) to evade of an HIV-infected person that was a the immune system. One mechanism that strong “neutralizer” of HIV in laboratory the virus uses to accomplish this goal is tests. The researchers then used the Rosetta the resistance of its Env protein to anti- computer program, which can predict the body attack. Env is a surface glycoprotein structure of a protein from its amino acid comprising a trimer of the transmembrane sequence, to “redesign” the antibody. gp41 subunit capped by a trimer of gp120. By changing a single amino acid, they Env plays a critical role in the fusion of were able to increase the stability of the HIV with a target cell membrane. Most antibody when it bound to HIV’s envelope antibodies that neutralize HIV bind to protein. The researchers didn’t change the gp120, suggesting that immune defense interface between the antibody and the against the virus is possible if a vaccine virus. Rather, by increasing its thermody- can be designed that leads to the efficient Jens Meiler, Ph.D., Assistant Professor of namic stability, the antibody became more production of gp120-targeted antibodies. Chemistry rigid and better able to fit the HIV protein However, this goal has been frustrated by like a lock and key. the presence of the gp120 V1/V2 domain University have “redesigned” an antibody “By changing a single amino acid, we that has a highly variable sequence, mak- that has increased potency and can neu- made it four times more potent, four times ing it difficult to produce single antibodies tralize more strains of the AIDS-causing stronger and it also started killing even that are effective against a broad range of human immunodeficiency virus (HIV) more HIV strains than the parent antibody,” viral strains. than can any known natural antibody. said Crowe. Now, Jens Meiler of Vanderbilt’s Their findings suggest that computer- The original, isolated antibody is now Department of Chemistry, in collaboration redesigned antibodies may speed the being produced in great quantities from a with James Crowe of Vanderbilt’s Depart- search for an effective therapy or vac- single clone of immune cells, and thus is a ment of Pathology, Immunology, and cine for a virus that so far has eluded all “monoclonal” antibody. It currently is being Microbiology, have collaborated to bring attempts to eradicate it. “There’s a con- tested in clinical trials. Crowe said the rede- a new approach to this vexing problem. sensus (in the HIV field) that the vaccine signed antibody could be added to the study [J. R. Willis, et al. (2015) J. Clin. Invest., that works is going to be a designed one,” as a second-generation version. published online May 18, DOI:10.1172/ said James Crowe Jr., M.D., director of the The field of redesigning antibodies has JCI80693]. Vanderbilt Vaccine Center, who led the grown quickly out of the need to treat and With the help of a computer program work with Jens Meiler, Ph.D., associate prevent debilitating and often-fatal viral called “Rosetta,” researchers at Vanderbilt professor of chemistry and pharmacology. infections, and from technological advances

“You couldn’t have this type of biomedical research,” Meiler said, “without that playful, curious aesthetic sense that you get with the Rosetta ‘community.’” 9 • Vanderbilt Chemistry 2015 Vanderbilt lands lands Vanderbilt to improve $9M grant flu vaccines - University research Vanderbilt Ph.D., and Dr. ers Jens Meiler, have received a James Crowe Jr. the National $9 million grant from design flu Institutes of Health to than those vaccines more effective currently offered. will also The five-year grant fund the study of new antibody therapies, according to a release. Current flu vaccines are weakened forms of the virus that trigger immune responses against viral proteins, but the proteins are constantly changing, meaning the vaccines are not 100% effective. About 30,000 Americans die every year from influenza complications, according to the release. could be improved if “Vaccines they induced immunity against the unchanging part of the proteins,” investiga- co-principal said Meiler, tor with Crowe, “or if universal antibodies could recognize every strain of the flu.” The project will be completed in collaboration with The Scripps Research Institute in La Jolla, California. going to design synthetic “We’re flu proteins to be better than the natural infection,” Crowe said. do it in the past, but couldn’t “We now we can design these vaccine we candidates on the computer, can synthesize them in the lab, and we can make a molecule that never existed before, and that’s better than the virus that existed in nature for inducing immunity.” providedFunding Institutes by National U19 AI117905. number grant Health of - - - they reveal the the reveal they - compu of power modeling tational in the design of with antibodies proper improved five of ties.Out tested,mutants the exhibited two properties desired Structure and proof of principle in principle of proof and Structure Meiler and Crowe end, that Toward dation grants DMR-0938330, EPS-1004083 and EPS-1004083 and DMR-0938330, grants dation Department Energy of grant CHE-1253105; U.S. Office ofDE-FG02-0946554; contract Science - Basic En ORNL’s by and DE-AC02-05CH11231; ergy Sciences/Materials Science Engineering and Directorateand Center for Nanophase Materials The study was supported in part by National National in part by wassupported study The AI078407, AI082362, grants Health of Institutes AI084817. AI100663 and based “Structure design Crowe; J. and Meiler J. (1U19 NIH (NIAID) vaccines”; and antibodies of 2020. 2015–31 May AI117905); 1 June Research was funded Science by National Foun tant savings in time and resources. The resources. in time and savings tant will continue groups Crowe and Meiler $9 mil- recent a through their efforts Institutes the National from grant lion apply them to will enable that Health of bet - of the theirdevelopment methodsto virus. influenza against vaccines ter - the com using now are scientists hand, antibodies neutralizing generate to puter that protein the envelope parts of against Crowe the road, Down change. don’t design … can “if computational said, in the future, viruses evolve how predict - design antibod potentially could we they viruses before for vaccines ies and occur in nature.” a Group, the Interface organized have across scientists of collaboration diverse expert an in game including campus, theory the interplay who modeling is system. between viruses the immune and - suggest affinity, binding increased of the for rate a high (40%) success ing much clearly is This approach. modeling expected rate the success higher than so this testing, and mutation random for impor and substantial leads to approach James Crowe, MD

that HIV is a wily opponent. Every day it it Every day a wily opponent. HIV is led by scientists 2013, Scripps In - col another and Crowe Last year, findings lab Crowe and Meiler The that have made it possible to “see” and and “see” to possible it made have that between the interactions strengthen virus-killingvirus and antibodies. protein the envelope alters or evolves, - detec evade to immune surface, its on HIV infected person with A single tion. the virus than of variations carries more - world isolated strains all the influenza system immune The said. Crowe wide, up. keep cannot simply Ward, Andrew and Ph.D., Wilson, Ian in the journal Science reported Ph.D., the structure of the HIV envelope the HIV envelope of the structure cryo- and crystallography using protein we that “Now microscopy. electron we said, Crowe looks like,” it what know it.” target to how understand better can Schief, Ph.D., William Scripps, league at Nature, in the journal, reported can design” protein “computational neutralizing potent be used induce to syncytial virus respiratory of antibodies respiratory of (RSV), cause a leading “That was children. young in infections agreed in which people paper the first a vaccine design of computer that said. he worked,” because they have only not exciting are potent the a more led discovery to of also because but HIV, against antibody research highlights Vanderbilt Team First to Blend High-End Imaging Techniques Vanderbilt University researchers have achieved the first “image fusion” of mass spectrometry and microscopy—a technical tour-de-force that could, among other things, dramatically improve the diagnosis and treatment of cancer.

By Bill Snyder

Caprioli 11 • Vanderbilt Chemistry 2015 - analy to the approaches fusion of image “Theapplication Plas, de Van by led was Raf project fusion image The - analy called regression approach a mathematical Using between experi drawn the line to - in concept similar It’s should the data what predicting “we’re way, the same In Image of a section of the brain shows the fusion of microscopy (pink area) and mass spectrometry (pixelated colors at bottom) to produce a detailed “map” of the distribution of proteins, lipids, and other molecules within sharply delineated brain structures (upper left). The research was supported in part by National Institutes of Health grants grants Health of Institutes National in part by supported was research The GM103391. GM058008 and has informed the study of human glioblastomas, as well as as well as glioblastomas, human of the study informed has recently, More lung. and prostate, colon, the breast, of tumors mass of fusion” “image the first reported team the Caprioli tour-de-force a technological spectrometry microscopy, and tissues of see to the make-up molecular scientists allows that in high resolution. spectrometry mass and is microscopy sections by tissue of sis these that way the change should that innovation a significant Sc.D., Douglas Sheeley, said used together,” are techniques ofGeneral Institute National officer in the scientific senior in the step important an is “It Sciences (NIGMS). Medical and spectrometry mass making accessible of data process said. he truly clinicians,” useful for biochemistry of who also professor assistant a research Ph.D., Technology in of University Delft at a faculty position has postdoctoral fellow were Other co-authors the Netherlands. research Ph.D., Spraggins, Jeffrey and Ph.D., Yang, Junhai biochemistry. of professor assistant spectrometry mass of pixel each mapped the researchers sis, to image the microscopy on spot the corresponding onto data image. “predicted” a new, produce curve, Caprioli in a standard determined points mentally were between those that points “real” no are There said. the previous by predicted is the line yet actually measured, experiments. said. he look like,” - in Feb 12, 366–372). icroscopy can yield high-resolution images of of images high-resolution yield can icroscopy molecular you give doesn’t really “it but tissues, senior Ph.D., Caprioli, Richard said information,”

Mass spectrometry provides a very precise accounting of of a very accounting spectrometry precise Mass provides - Stan the Caprioli, said phenomenal,” just is me to “That - surgi the redefine could the technique said Caprioli histology—the determined by is line that Currently pioneering his for known internationally is Caprioli

microscopy and mass spectrometry is a significant innovation that should change microscopy and mass spectrometry is a significant the way that these techniques are used together.” Nature Methods ruary 2015 (Nature but tissue, molecules in a given other and lipids, the proteins, the best Combining manner. pixelated or coarse in a spatially see to scientists modalities allows both imaging of features in high resolution. tissues of the make-up molecular chemistry, of professor Biochemistry, of Professor Moore ford Spectrometry Center. Research the Mass of director and cells normal and cells between the line cancer cal “margin,” the tumor. the scalpel remove where goes to But, the microscope. under examined cells of appearance could bewhat because That surgery. after recur cancers many their protein for when be cells, analyzed to normal appear in cells actually cancer are spectrometry, mass using content the making. - contribu His spectrometry. mass of in the field innovations micro-electrospray a patented of development include tions - multi-dimen as such techniques enables technology that spectrometry (LC/MS), chromatography/mass liquid sional identification. protein for used worldwide now which is and of analysis methods for ultra-high developed sensitivity He - in liv analysis molecular pioneered and neuropeptides, a developed lab 1990s, Caprioli’s the late In animals. ing spectrometry called mass technique imaging (IMS) using Essen - (MALDI). laser desorption/ionization matrix-assisted the measures the technique microscope,” tially a “molecular - in expres alteration and rearrangement, spatial distribution, molecules biological other and lipids, proteins, of levels sion and cancer to particular has relevance It tissues. and in cells author of the paper “Image fusion of mass spectrometry mass of and fusion “Image thepaper of author tissue molecular paradigm for multimodality a microscopy: Methods, Nature the in journal, published mapping,” M “The application of image fusion approaches to the analysis of tissue sections by “The application of image fusion approaches to the research highlights In the Lab with Craig Lindsley Posted on Axial, the ACS online newsletter

ashville, Tennessee, also known as Music City, is home to Vanderbilt NUniversity and musically connected ACS Chemical Neuroscience Editor-in-Chief, Craig Lindsley, Ph.D. ACS Axial caught up with Lindsley at his two labs, one on campus and one off, to find out what projects he is currently working on and which musicians he’s recently spotted around town. By day Lindsley is a co-Director at the Vanderbilt Center for Neuroscience Drug Discovery, where he serves as the Director of Medicinal Chemistry and Drug Metabo- lomics and Pharmokinetics. He is also a professor of pharmacology and chemistry at Vanderbilt University. His focus is on research that expands on possible treatments for diseases that most in big pharma have already written off—schizophrenia, autism, Parkinson’s, Alzheimer’s, and rare diseases like fibrodysplasia ossificans pro- gressiva (FOP). Craig in his office on campus at Vanderbilt At Lindsley’s on-campus lab, researchers focus on making tool compounds to Built to plans that Lindsley personally publish and validate novel targets. It is oversaw only five years ago, the lab is located home to six graduate students and two in an industrial park and houses a variety of postdocs. Research from the lab has been lab equipment seen at biotech companies. published in ACS Chemical Biology, ACS This off-campus lab is the staff-scientist arm Chemical Neuroscience, ACS Medicinal of the Vanderbilt Center for Neuroscience Chemistry Letters, Biochemistry, and the Drug Discovery, employing roughly 40 staff Journal of Medicinal Chemistry. scientists. Here, Lindsley and team develop However Lindsley is most excited about patented compounds for licensing. And they his laboratory at the Cool Springs Life have been quite successful. Sciences Center, a 20-minute drive from Results from recent research led to Vanderbilt’s main campus. several patents being licensed to large

Graduate student, Dan Jeffries, at work in A special editorial board for ACS Chemical Neuroscience located in Lindsley’s on-campus lab Lindsley’s on-campus lab. 13 • Vanderbilt Chemistry 2015 ers earned thisers by distinction thewriting - num greatest reportsber of officially by designated Essential Sci- Indicators ence Highly Cited Researchers are are Researchers Cited Highly Craig Lindsley Selected as Thomson Reuters Highly Cited Researcher The Department of Chemistry The Department Lindsley Craig congratulates being selectedon a Thomson as Researcher. Cited Highly Reuters as Reuters described Thomson by the world’s of some “represent[ing] minds. scientific influential most - research thousand three About Papers—ranking Cited Highly as for cited 1% most the top among - publi of year and field their subject of them the mark earning cation, impact.” exceptional In the evenings, Lindsley is a Lindsley is the evenings, In - col of years three which they received research. sponsored laborative for making time five, of father devoted he before homework and dinner, family, check. does a final email An avid Kiss fan, Lindsley has Lindsley has fan, Kiss avid An collabo - Lindsley has Over the years, he sees when hanging out downtown— out seeshe when hanging Robert spotted having mentions he White, Jack Krauss, Alison and Plant who others many and Urban, Keith in Tennessee. their homes made have Gene with Simmons himself of photos Twenty office. his the walls of covering Kiss’ Simmons, Lindsley met ago, years the first at rock-bassist, Israeli-born Cali in Burbank, - tour convention Kiss before sees he Simmons Now, fornia. in Nashville. plays when Kiss shows causes for celebrities other with rated - Founda Fox J. the Michael including he where Research, Parkinson’s for tion mapping for initial funding received group his portfolio PAM the mGlu4 out for and Squibb, BristolMyers licensed to - On the drive to the Cool Springs lab, lab, the Cool to On the drive Springs One of the stations inside Lindsley’s Cool Springs lab companies like Johnson & Johnson, & Johnson, Johnson like companies - Pharmaceuti AstraZeneca, La Jolla Seaside Therapeutics, cal Company, Ono. and Pharmaceuticals, Karuna new for paid turnhave in The patents fund the to helped have and research, oper from come expensesgeneral that Alex Geanes, third-year graduate student in the Vanderbilt. at lab medicinal a 15,000-square-foot ating chemistry drug and metabolism and in this space. lab pharmacokinetics - Nash for love his about Lindsley spoke per this seven, and, of ville, family his the musicians of some request, writer’s research highlights Study Sheds Light on Crucial DNA Binding Protein By Bill Snyder esearchers at Vanderbilt University have established the RPA is a very complicated protein and it has remained challeng- molecular basis for the function of Replication Protein A ing to understand how it functions. (RPA), a DNA binding protein that is a crucial “scaffold” for An important step forward was made when the Chazin group Rgenome replication, response to damage and repair. reported last month a description of the functional With colleagues at Yale University, they also deter- dynamics of RPA in the journal Structure. Chazin mined that the small, highly charged protein DSS1 and his colleagues used NMR (nuclear magnetic acts on RPA to function as an essential co-factor for resonance) techniques to define how RPA domains, the key tumor suppressor BRCA2 (breast cancer sus- portions of the protein with distinct biochemical func- ceptibility protein 2). Individuals with BRCA2 mutations, move in space. tions exhibit genomic instability and are predisposed Their work demonstrated how RPA is able to to breast, ovarian, and other cancers. use some of its eight domains to bind to sections In the journal Molecular Cell, the researchers of DNA of interest, and simultaneously use other report that DSS1 functions as a DNA “mimic” for domains to recruit the proteins required to replicate RPA. DSS1 “remodels” RPA so it releases its strong or repair this DNA. grip on DNA to enable processing by BRCA2 and In a commentary written in the same journal, repair of devastating DNA double-strand breaks. Patrick Loria, Ph.D., professor of chemistry and of However, DSS1 is elevated in tumor samples, and higher DSS1 molecular biophysics & biochemistry at Yale, noted, “In this elegant expression is associated with therapy resistance and poor progno- work, Chazin and co-workers show in part how the flexibility of RPA sis. Inhibition of DSS1 expression in these tumors, by alleviating enables such a complex set of interactions to occur.” resistance, could enhance standard chemotherapy, the researchers The two studies add to the growing body of data detailing the conclude. intricacies of DNA replication and repair, and suggest it may be pos- The DSS1 studies were led by Walter Chazin, Ph.D., Chancellor’s sible to modify the function (or compensate for the dysfunction) of Professor of Medicine, professor of biochemistry, and director of the various essential proteins, including BRCA2, RPA and DSS1, to stop Vanderbilt Center for Structural Biology; and Patrick Sung, D.Phil., tumor growth and improve therapeutic outcomes. Ph.D., professor of molecular biophysics and biochemistry and of The study in Structure was supported in part by National Institutes of Health therapeutic radiology at Yale. Claudia Wiese, Ph.D., assistant profes- grants GM065484 and CA092584. The study in Molecular Cell was supported in sor of radiation cancer biology at Colorado State University, was part by NIH grants ES0125252, ES007061, CA168635, CA092584 and ES021454. co-senior author of the Molecular Cell paper. “This study resolves a long-standing conundrum about how DNA gets transferred from RPA to BRCA2,” said Chazin. Sung added, “Our collaborative, multidisciplinary approach was essential for understanding the very high degree of biological and mechanistic complexity of DSS1 action at the critical initial stage of the repair of highly toxic DNA double strand breaks.” The importance of RPA in maintaining and propagating the genome is due to its ability to bind very strongly to single stranded DNA (ssDNA). Since DNA is so important, it is stored with a complete back-up copy, and the two copies together make up the well- known DNA double helix. This helical storage form of DNA is very stable, but in order to read the DNA code, it is necessary to unwind the double helix into its separate strands. Unwound single strands of DNA (ssDNA) are very susceptible to being damaged and readily form irregular tangles. Nature, therefore, evolved proteins such as the RPA protein in humans to protect ssDNA and keep it organized. 15 • Vanderbilt Chemistry 2015 - - visualize individual with along microbes inter their chemical - then, the micro Until actions with other with actions that allow scientists to scientists allow that microbes and their hosts. and microbes imaging capabilities capabilities imaging developed with multimodal with developed bial world will remain primar will remain world bial which new instruments can be can which new instruments ily out of sight and out of mind as it as mind of out and sight of out ily biomics will depend on the rate at will the rate depend on biomics - the biolo the chemist, to According bacte- on the research of most far “So - contri main his Cliffel, to According has beenhas in the past. gists want tools that don’t exist yet: instru- yet: exist don’t that tools want gists at non-destructively operate that ments scale, identify the small can the micron - bacteriamolecules commu use that to observe can and another one with nicate the methods the bacteria control use to their environments. riabiologists been has observational. The a hypothesis- this to from move to want a they where isolate approach, driven and fashion in some perturbsubject, it said. Cliffel responds,” it how measure that is thiswith approach problem “One certain that found have studies recent survive in cannot bacteria in the biome so and the veryisolation, isolation act of a As the system. observation changes - simulta to they need the capability result, activities the individual monitor neously communities.” entire of the members of recognition its is the manifesto to bution the is involved challenge the analytic that these barrier goals: realizing to biggest - of micro the fledgling field of Growth

- promise of increasing increasing of promise - agricultural produc whiletion decreasing pesticides, the need for water. fertilizers and • be can Microbes produce to engineered - rang new bio-products to biofuels from ing antibiotics. • the of Management microbial communities in communities microbial and around individuals has individuals around and - green of the concentration impact so gases in the atmosphere, house on global effect warming. an have soil microbes and plants holds holds plants and microbes soil the potential for treatment of asthma, of treatment for the potential diseases, infectious obesity, diabetes, - com other illnesses and psychiatric essential an is and afflictions mon medicine. precision for tool The authors argue that a vigor that argue authors The New tools needed tools New Foundation “TheKavli this high-powered got its for together group said meeting,” first Cliffel. they“Then they willrealized that need new technology to their so goals, achieve they who several us of invited this sort of instruments develop to participate.” • oceans in the and soils Microbes • between interactions Manipulating ous national and global public-private global public-private and national ous begin these could realizing partnership years. 10 within benefits , the Prof. David E. Cliffel . Nature

In recent years, however, however, years, recent In realization This growing

t is true that bacteria cause a number of bacteria true number a t is cause that explains that doubt serious illnesses. No has the public view that the negative - micro invisible of the multitude about Just us. all swarm around that organisms all sprays soaps, the anti-bacterial look at the market. wipes on and become have scientists the of aware increasingly microbial our fact that provide fellow-travelers a have and benefits many effect profound more much had we than lives our on realized. previously - in the announce culminated a high-level research of ment - the interac focus on would that initiative between and bacteria animals tions and humans. including plants, Profound potential the in Science article to According benefits from such a major program major a such benefits from becould profound. A “Unified Microbiome Initiative” was Initiative” Microbiome A “Unified the- Ameri of members key by proposed the with Society Microbiology can for Office House both the White of backing and Policy Technology Science and of CA. Oxnard, of Foundation Kavli The made was in arms callThis to scientific unified “A articles: complimentary two - microbi Earth’s harness to initiative in the journal Science published omes” a global “Create and Microbiology and in the published effort” microbiome journal ‘Microbial manifesto’ ‘Microbial

by David Salisbury

Vanderbilt Chemist Vanderbilt Research Initiative Research

Part of Major Microbiome Microbiome of Major Part I Faculty

IN MEMORIAM Richard N. Armstrong Vanderbilt professor and Biochemistry editor-in-chief made his mark in enzymology and structural biology

By John Howser

ichard Neil Armstrong received As a teacher, scholar, and adviser, a B.S. degree in chemistry from his efforts stood among the very best. RWestern Illinois University, and a Guiding students through the rigors of Ph.D. degree in organic chemistry from chemistry and biochemistry, Armstrong Marquette University. He was a postdoc- emphasized fundamentals through his toral fellow at the University of Chicago, numerous lectures. He selflessly served and a staff fellow at the National Institute the departments and community through of Arthritis, Metabolism, and Digestive committee work, meeting organization, Disease, National Institutes of Health, grant reviews, and activities of profes- and then joined the Chemistry Depart- sional societies. Remarkably, he somehow ment of the University of Maryland. From managed to find time to serve the world- 1995 until his death, he was professor of wide community as editor-in-chief of biochemistry and chemistry at Vanderbilt Biochemistry, an honor held by only two University. Armstrong also held a foreign other brilliant scientists in the journal’s adjunct professorship at the Karolinska distinguished 53-year history. Institute in Stockholm, Sweden. Armstrong, age 66, of Brentwood, died Armstrong’s research at Vanderbilt on June 18, 2015, at Vanderbilt Univer- focused on how enzymes detoxify foreign sity Medical Center, after a brief illness. molecules, including drugs, toxins, and He was born in Boonville, Missouri, on chemicals, through a multipronged chem- December 14, 1948. ical, structural, and molecular approach. He was founder and sole instruc- Armstrong was internationally known tor of Uncle Ricky’s Fishing School. He for his contributions to understanding was an avid and skilled pie maker, and detoxification enzymes, proteins that his dedication to his annual sour cherry break down foreign and potentially harm- crop bordered on the obsessive. An avid, ful chemicals, drugs, and other molecules. licensed ham radio enthusiast, he enjoyed Among other potential applications, his a parallel identity as KK4MQL. work could lead to new ways to prevent Armstrong was preceded in death by bacterial resistance to antibiotics. his mother, Grace, and brother, Clinton Among many honors and recogni- Armstrong. He is survived by his father, tions, Armstrong was elected as a Fellow Ernest Neil Armstrong, and by his wife of both the American Association for of 31 years, Mary Frances Clark, J.D.; his the Advancement of Science and the children, Kathryn Grace Armstrong and American Chemical Society. He won the Andrew Clinton Armstrong; and many ACS Repligen Award, the 2014 Arthur C. other family members, colleagues, and Cope Scholar Award, and the Vanderbilt close friends. Stanley Cohen Award. 17 • Vanderbilt Chemistry 2015 Richard Caprioli, Ph.D., Ph.D., Caprioli, Richard Award recipients were were recipients Award their faculty by nominated the by chosen and colleagues Faculty Enterprise Academic Selection Committee. Awards in Chair Moore Stanford of Biochemistry; professor pharmacology, medicine, chemistry;and director, and ward Winners society,” Chancellor Nicholas S. Zeppos Nicholas Chancellor society,” - inno leaders and proven “Already said. chosen have we in their fields, vators this critical in them at furtherto invest they ensure to in their careers point opportunities and resources ample have to and work body of their own build to post- to mentors serve outstanding as students graduate doctoral scholars, VUMC Academic Enterprise Faculty A Announced Medical Cen- University Vanderbilt 2015 The which Awards, Faculty Enterprise Academic ter Faculty 19 Spring the May during presented were - in Teach Excellence for awards meeting, included Research. to Contributions Outstanding and ing awarded was Spectrometry Center, Research Mass for Award Team a Multi-investigator of Leadership - in a Multidis or Collaboratively Working Faculty Biological Important Address to Manner ciplinary Diseases. and/or Processes The faculty members will hold the title of Chancellor’s Fac- of Chancellor’s will members the facultytitle hold The will Fellows alsomeetas a group Faculty The Chancellor’s and undergraduates.” and unrestricted an by be supported and years two for Fellow ulty 1,July to begin fiscal years two for $40,000 a year of allocation research, innovative used support can be 2015. The to funds will further activities that expression creative and scholarship, the awardee. of the career propel research of exchange foster to their awards of the course during that community intellectual a broader build and interests scholarship. trans-institutional advances - David Wright, Ph.D., Stevenson Professor of of Professor Stevenson Ph.D., Wright, David the Department Chemistry of Chairman and the of been has elected a fellow Chemistry, of the Advancement for Association American exceptional for Science this year (AAAS) of chemistry and bioinorganic to contributions disease infectious to diagnosis application its of particularly in the fields treatment, and viruses. RNA malaria and

Fifteen faculty members hailing from a diverse cross sec- cross a diverse from hailing members facultyFifteen discoveryand to education, commitment “Thestrong The new fellows will be recognized on Feb. 14 at 2015 the 14 Feb. willrecognizedon fellows new be The He is among 401 fellows from around the country selected by around from 401 fellows among is He and current its among fellows 106 AAAS has now Vanderbilt - these outstand of the contributions of very proud are “We

Jens Meiler, associate professor of chemistry and associate chemistry associate of and professor associate Meiler, Jens seeks fuse to research pharmacology—Meiler’s of professor proteins, to investigate experimental efforts and computational their interactions and biology, molecules of the fundamental probes. or therapeutics, smallwith molecule substrates, of the been selected cohort the first as have disciplines of tion (Health Aliyu Muktar program: Fellows Faculty Chancellor’s - Astron and Bocklemann Holley (Physics Policy/Medicine), (Sociology), (Biomedical Flores Guelcher Scott Stella omy), (Bassoon), Lacy Borden - (Biochem Kolkay Peter Engineering), (Psychiatry), (Chemistry), Olatunji Meiler istry), Bunmi Jens Preacher Biology), (Cancer Kristopher Page-McCaw Andrea Bernard Rousseau Development), Human and (Psychology Sean Engineering), Sciences, Speech Mechanical and (Hearing Rachel (Law), Teukolsky Sharfstein Daniel (Law), Seymore (Electrical Engineering/Physics). Weiss Sharon and (English), an having these is faculty members by demonstrated care serving of mission its and Vanderbilt on impact enormous Named Inaugural Chancellor’s Faculty Fellow Faculty Chancellor’s Inaugural Meiler Named Jens ing, and efforts to increase diversity in the sciences.” diversity to increase efforts and ing, - informa more California. For Jose, in San meeting annual AAAS website. the AAAS visit fellows, AAAS on tion their peers because of their “scientifically or socially distinguished their their peers “scientifically because of applications.” its or science to advance efforts fellows—59— of the half than More staff. faculty and emeritus remarkable reflecting years, four the last elected during were academic reputation. the university’s of growth and momentum the entire which enriches learning, discovery faculty to and ing Affairs Academic for Chancellor Vice and Provost university,” scientific their remarkable to addition “In said. R. Wente Susan been severalhave gratified that additionally we’re contributions, mentor their servicerecognized for community, the scientific to S Fellow David Wright Elected AAA Faculty

Nathan Schley, Ph.D., Joins Faculty as Assistant Professor of Chemistry

athan Schley was born in Chicago, Illinois, and raised in the Schley group is the application of organometallic chemistry to Sacramento, California. He completed a B.S. in chemistry at unmask latent reactivity in organic substrates. Oxidation of simple Nthe University of California, Davis, in 2007. While at Davis hydrocarbons provides functional groups which serve as handles he performed undergraduate research in the lab of Prof. Philip Power for further transformations, but methods for selective oxidation on tin hydrides stabilized by bulky ortho-terphenyl ligands. of C-H bonds are limited both in scope and by the factors which From Davis he moved to Yale University for his graduate work dictate selectivity. Our goal is to meet the challenge of enabling where he joined the lab of Prof. Robert H. Crabtree. At Yale, Nathan new oxidative, catalytic transformations of C-H bonds by making focused on catalysis related to issues of sustainability, including use of unconventional substrate activation strategies. developing catalysts for acceptorless alcohol oxidation and examining Recent developments in transition metal catalysis have shown the mode of action of a family of iridium half-sandwich complexes as that ligands that actively participate in chemical transformations catalysts for water oxidation. have the potential to have a profound impact on the reactivity of After completing his Ph.D. in 2012, Nathan joined the labora- metal ion in catalytic transformations. Broadly speaking, ligand tory of Prof. Gregory C. Fu at the California Institute of Tech- participation can include redox non-innocence, involvement in nology as an NIH Postdoctoral Fellow. While working in the concerted heterolytic bond formation or cleavage, and the ability Fu group, Nathan studied the mechanism of a series of nickel- to engage in activating, secondary coordination-sphere interac- catalyzed cross-coupling reactions. In the case of nickel-catalyzed tions with the substrate. We aim to introduce a diversity of func- stereoconvergent propargylic arylation, he found evidence for tional ligands as supporting platforms for catalysis that make use an unanticipated radical chain reaction with an diamagnetic of these and other modes of ligand participation in catalysis. Our nickel(II) resting state. Radical chain reactions are a well-studied long-term goal is to capitalize on the ability of functional ligands class of reactions that can give rise to new carbon-carbon bonds, to define the reactivity of the supported metal ion to develop new but this work for the first time implicated a radical chain in ste- non-precious metal catalysts for existing catalytic transformations reoconvergent nickel-catalyzed cross-coupling. requiring platinum-group metals. Schley began his independent career at Vanderbilt in 2015 and We can take inspiration from Nature to develop new strategies now leads a research group devoted to developing new, selective for approaching many of these goals. Nature has evolved highly catalysts for oxidative transformations of C-H bonds. The aim of specialized metal-containing enzyme active sites for a variety of 19 • Vanderbilt Chemistry 2015

Kort comes to us most recently recently most us to comes Kort from Purdue University in West in West University Purdue from an in 1997 with Indiana, Lafayette, chemistry. in inorganic emphasis where University Mason George from and a fair as earned a reputation he taught has He lecturer. entertaining general teaching disciplines across chemistry as chemistry inorganic and He courses. upper-level many as well Joins Chemistry

Kort received his Bachelor of Science degree from Hope Hope Science from degree of Bachelor his received Kort A native of Indiana, Hare earned Hare Indiana, of A native Caltech, to moved Hare postdoctoral work, her For David Kort has joined the faculty in the Department of the of faculty in the joined Department has Kort David General to addition In Chemistry lecturer. a senior as will he also be- teach Chemistry, Inorganic and Chemistry, Laboratory. Integrated Advanced ing earned Ph.D. his in 1991. He Michigan, College in Holland, services.- also con laboratory served of Kort director as curriculum, the laboratory of the development to tributed - chem general for procedures and experiments developing metal chemistry. chemistry transition and organic istry, Lecturer as Senior Joins Faculty Hare Joins Alissa the of faculty in the joined Department has Alissa Hare sophomore teaches She Chemistry lecturer. a senior as chemistry. organic chemistry physical and organic science in degree of bachelor her chemistry Calvin Col in 2006 from - attended MI. She Rapids Grand lege, school graduate for University Yale Professor under worked she where development on L. Jorgensen William the for small moleculeof antagonists - Inhib Migration Macrophage protein completed (MIF). Hare Factor itory awarded was in 2012 and Ph.D. her University. Yale Prize from Thesis Wolfgang the Richard Peter Professor with became a NIH NRSA Fellow she where of focused the development on Dervan. research B. Her - mol binding DNA specific sequence polyamides, Py-Im cancer. prostate of the treatment ecules, for David Kort Faculty as Senior Lecturer Our new single crystal X-ray diffractometer allows for the determination of the 3-dimensional molecular structure of crystalline samples. challenging transformations, and it has done so primarily so primarily done has it and transformations, challenging metal ions transition earth the use of abundant through to addition In metal ions. platinum-group rare, than rather polymetallic and bi- metal a single ion, containing enzymes certain enzymes. critical the function of to are sites active in a single metal ions or dissimilar similar of two use The resulting the to exploit the potential offers platform ligand - in cataly intermediates and ligands bridging of reactivity the production on will center in this area Oursis. studies - condi aerobic under μ-hydroxides late-metal reactive of and alkoxides hydroxides of late-metal reactivity The tions. dπ-pπ repulsion to been has attributed C-H bonds towards π-symmetry betweenwith the filledorbitals in late-metals - con of the availability as well as π-basic hydroxides, and use making By activation. bond for certed mechanisms early one incorporating μ-hydroxides heterobimetallic of - poten the redox modulate can metal, we late one metal and whichwill μ-hydroxides the resulting of π-basicity tials and protocols. oxidation new hydrocarbon develop to us allow graduatestudents

Bright Future for Quantum Dots By Noah Orfield, Ph.D.

ne of the main research thrusts in the lab of Professor Sandra J. Rosenthal involves studying Othe structure and properties of individual quantum dots. These tiny nanomaterials are promising candidates for improving the energy efficiency of many of the electronics that we use every day, such as televisions, smartphones, tablets, and overhead lighting. Adding to their ver- satility, quantum dots can be chemically synthesized to absorb and emit any desired wavelength of visible light. This high level of tunability is part of what makes quantum dots unique, and why implementation into commercially available televisions (QDVision) and tablets (Amazon Kindle Fire™) has recently come to fruition. Even though quantum dots are very small (usually containing hundreds to thousands of atoms) and are typically considered cubic, small variations in size and shape are persistent. A standard synthesis will result in trillions of individual quantum dots—many of which fail to emit light at all, reducing the efficiency of any device made with these materials. Most quantum dot studies investigate the properties of millions of these quantum dots at a time (the ensemble); this gives researchers a good idea of the average properties, but an abundance of information about dot-to-dot variation is not col- lected. This approach would be similar to assuming that, because the average height of American females is 5'4", every female you encounter will be this height! Taking a census of the height of a large number of individuals allows resolution of a much more complete picture of the distribution of heights in the country. In the same way, every quantum dot is unique. The placement and composition of atoms making up these nanometer-sized

Noah Orfield, a recent Ph.D. graduate of the Rosenthal Lab, displays the laser he used for his research. Noah heterostructures vary due to the nature has recently accepted a post-doctoral research position at Los Alamos National Laboratory in Los Alamos, of the high-temperature synthesis used to New Mexico. create the quantum dots. For this reason, 21 • Vanderbilt Chemistry 2015 - Correlation of atomic structure and photoluminescence of the same quantum dots. Prof. Rosenthal’s group as fluorescence measured a function of time for (a) dots. quantum individual A histogram reflects (b) the efficiency of single specific quantum dot structures, shown in (c). All of these quantum dots were isolated from the batch— synthetic same illustrating the need for investigating quantum dots one at a time. (courtesy of Noah Orfield) dots. The database of knowledge that that of knowledge database The dots. will future allow being acquired is and cost- even more create to chemists will dotsthat quantum energy-efficient energy the nation’s of reduction in aid consumption. ning transmission electron microscopy (Z-STEM), we have achieved correlation of photoluminescence (PL) data and atomic-level structural information from individual colloidal QDs. This investigation of CdSe/CdS core/shell QDs has enabled exploration of the fine structural factors necessary identified specific we have to control QD PL. Additionally, morphological and structural anomalies, in the form of inter nal and surface defects, that consistently vitiate QD PL. structure with the unique light-emitting light-emitting the unique with structure has the group this way, In properties. - indi makes what study to been able - unique—informa dots quantum vidual to how new ideas for provides that tion quantum of the properties fully control - this spring (Orfield 2015, et al., this spring In a size regime where every atom counts, rational design and synthesis of optimal nanostructures demands direct interrogation of the effects of structural divergence of indi- this end, we To viduals on the ensemble-averaged property. have explored the structure–function relationship of single quantum dots (QDs) via precise observation of the impact of atomic arrangement on QD fluorescence. Utilizing wide-field fluorescence microscopy and atomic number contrast scan- ACS Nano, 2015, 9 (1), pp 831–839 December 23, 2014 Publication Date (Web): By Noah J. Orfield, James R. McBride, Joseph D. Keene, D. Joseph Orfield,McBride, James R. J. Noah By Rosenthal J. M. Davis,Lloyd Sandra and Correlation of Atomic Structure and Photoluminescence of the Same Quantum Dot: Pinpointing Surface and Internal Defects That Inhibit Photoluminescence Although the process of sorting out sorting out of the process Although ensemble characterization techniques techniques characterization ensemble full a under provide to inadequate are 9 (1), 831–839). Using high-resolution high-resolution 9 (1), 831–839). Using in the Rosen - researchers microscopy, select to been a able have thal group collect a time and at dot quantum single - high resolu Subsequent it. from light (performed microscopy electron tion scanning Osiris Tecnai Vanderbilt’s with on microscope) electron transmission revealed dot the quantum exact same atoms the individual of the structure and dot, quantum that up make that the precise of correlation allowed standing of the fine details dictating dictating details the fine of standing such parameters important extremely and photobleaching, yield, quantum as be must that photocharging—factors - technolo dot quantum for optimized scale. a commercial on compete giesto dots quantum single measuring and Rosenthal Professor daunting, sounds the unfazed by were group her and - demon this as task, of magnitude in ACS published their work by strated Nano graduatestudents

From Colleagues to Collaborators: A Journey of Friendship and Research By Michelle Mitchener and Erin Shockley Graduate Students, Marnett Lab and Lopez Lab, respectively

t Vanderbilt, potential collaborators various scientific disciplines in an integra- try very different types of research, I might can be found down every hallway. tive manner,” Mitchener mused, adding not have learned that I prefer computational Sometimes, though, the perfect that she chose to pursue graduate studies research over wet lab projects.” Acollaborator may be much closer to home. through the Chemistry Department at Shockley and Mitchener moved to This was the case for graduate students Vanderbilt because of their emphasis on Nashville in 2012 to begin their graduate Michelle Mitchener and Erin Shockley, interdisciplinary scientific research. studies and continued to be roommates, members of the Chemistry Department Shockley entered graduate school at just as they had during their under- and the Chemical and Physical Biology the same time, but through the Quantita- graduate years. However, each joined very program, respectively. tive and Chemical Biology admissions different types of labs; Mitchener joined Mitchener, who hails from Troy, program, which accepts students from the Lawrence J. Marnett Lab, an experi- Michigan, and Shockley, who comes from primarily quantitative science backgrounds mental lab that studies the role of bioactive Parkersburg, West Virginia, first met who desire to use that knowledge to study lipids in inflammation and disease, while while attending Cedarville University in biological systems. She cites the program’s Shockley joined the Carlos F. Lopez Lab, Ohio to pursue undergraduate degrees in emphasis on varied lab rotation experiences a computational lab that models complex chemistry. “Perhaps it was our liberal arts as a primary reason for choosing Vander- networks of cancer-related proteins. “Our upbringing that first led us to think about bilt, saying, “Had I not been encouraged to labs really couldn’t be more different—let

Erin Shockley and Michelle Mitchener with a structural representation of COX-2 outside of Preston Research Building where they work. (photo courtesy of Stephen Doster, Vanderbilt University) 23 • Vanderbilt Chemistry 2015

Inhibitors Fa/y Acids Fa/y Acids Modulators Modulators Non-‐Substrate Non-‐Substrate Other Substrates Other Substrates The duo has submitted the results of results the submitted has duo The This work was supported by the National Institutes National the by This wassupported work GM15431 CA089450 and under grants Health of the C.F.L), K22CA151918 (to and L.J.M.), (to MCB- under grant Science Foundation National Evans P. Edward the and C.F.L.), 1411482 (to E.M.S. were M.M.M. and C.F.L.). (to Foundation Services Health S. Public Grant U. by supported T32 ES007028. broader impact on how scientists study study scientists how on impact broader research now, in the future; COX-2 and inhibitors, substrates, involving - con entail must allosteric modulators these molecules of interactions sidering allosteric and both with the catalytic Mitchener the enzyme,” of subunits Shockley “The added, explained. model - used also we is broadly approach ing proteins. multimeric other to applicable that kinetic modeling traditional Unlike model - the parameters, fitted single gives pos- of a range yields used we here ing the fit that values kinetic parameter sible probabilities. their associated and data definitive more make to us This allows specifically results, our about statements in have we can confidence of the degree modeling-basedeach assertion.” hasit and PNAS to efforts their combined publication. been for accepted , Func:onal Heterodimer Heterodimer Func:onal , Subunit Allosteric Homodimer She didn’t have to look far. “Erin and I and “Erin look far. to have didn’t She - conclu these immediate “Beyond al. turned to kinetic studies utilizing both utilizing kinetic studies to turned al. attempt in purified COX-2 and substrates phenomenon. this cellular understand to kinetic classical single, no that found “We the resulting represent to able model was adding, explained, Mitchener well,” data we certain that pretty I was point, that “At need help.” to going were so I dinner, over work talkusually about - work was she knew the projects types of help,” to be able might she that and on ing who normally Shockley, said. Mitchener hundreds of networks codes complex two Mitchener’s considered proteins, of system subunit enzyme substrate-two Shockley encoded comparison. by simple subunit substrate-enzyme the possible a model to calibrated and interactions experimental kinetics data. Mitchener’s model that A computational result? The revealing that experimental the data, fit both for betweensubstrates competition in results allosteric sites and the catalytic leads that COX-2 of regulation complex - arachi of oxygenation preferential its to acid. donic a will I think have this work sions, Subunit Cataly:c Cataly:c -

Ac=vity Inhibitors Substrates Heme Bound Cyclooxygenase Cyclooxygenase Cyclooxygenase-‐2: Structural Structural Cyclooxygenase-‐2: Yet, their research paths were to were paths their research Yet, — Michelle Mitchener, graduate student in the Marnett Lab — Michelle Mitchener, Biology, its juxtaposition of labs in different areas of study, and its numerous multidisciplinary its juxtaposition of labs in different areas of study, Biology, collaborative research.” seminar series, the University has poised itself for successful alone our day-to-day research work,” work,” research day-to-day our alone Mitchener. said - their respec into years a few only cross studying was Mitchener programs. tive of a target (COX-2), cyclooxygenase-2 common of actions the pharmacologic drugs, anti-inflammatory nonsteroidal Purified Aleve. and Advil including - sub canonical its metabolizes COX-2 the- endocan and acid, arachidonic strate, with 2-arachidonoylglycerol, nabinoid, efficiencies; equivalent approximately oxygenation the COX-2 in cells, however, acid exceed those arachidonic of products 500-1000- by 2-arachidonoylglycerol of COX- revealed that studies Previous fold. acts a as 2, while a structural homodimer, subunit one with functional heterodimer, as the other and site acting a catalytic as and Mitchener Thus, allosteric site. an differential that hypothesized colleagues for between substrates the two interaction for account might COX-2 of the subunits observed levels product in the disparate cor an inverse demonstrating After cells. acid levels between arachidonic relation oxygenation 2-arachidonoylglycerol and et Mitchener in macrophages, COX-2 by “With its location next to the medical center, its support of the Vanderbilt Institute of Chemical its support of the Vanderbilt “With its location next to the medical center, graduatestudents Carbon Dioxide Fixation Using a Chiral Brønsted Acid/Base Organocatalyst By Brandon Vara Graduate Student, Johnston Group The current global economic and environmental landscape

has accelerated research into carbon dioxide (CO2 ) technology across a broad range of chemical disciplines. The most notable advancements have been made in the areas of materials chemistry, polymers, and amine–based “scrubbing” system

to capture CO2 pollutants from industrial processes. Although the threat of carbon dioxide accumulation as a greenhouse gas has inspired numerous sequestration strategies, this gaseous reagent holds immense potential value as an abundant and nontoxic C1–building block for carbon-carbon bond formation and carbon-heteroatom functionalization reactions in chemical synthesis. Unfortunately, the underlying features that contribute to carbon dioxide’s low general toxicity and ease of handling render it relatively inert as a chemical reactant.

mparting a specific chirality or ‘handedness’ into small molecules is often the key to achieving desirable properties in Imaterials, such as potency and selectivity in drug development. Chemical reactions that achieve this—referred to as enantioselective—have grown exponentially over the past half century, leading to a collection of techniques and approaches that serve as readily accessible tools for organic synthesis. Yet, very few established methods exist incorporating carbon dioxide in such a way. To

expand the utility of CO2 as a chemical reagent in organic synthesis, new mild catalytic reactions are needed to mimic Nature’s elegant enzymatic reactivity and to overcome carbon dioxide’s rela- tive inert properties and narrow synthetic scope. There are highly evolved models within Nature to consider from the standpoint of biomimetic catalysis, including the magnesium and hydrogen bonding-dependent enzyme ribulose-1,5-bisphosphate carbox- ylase/oxygenase (RuBisCO), one of the most abundant protein

complexes on the planet. RuBisCO incorporates CO2 through carbon-carbon bond formation into glucose precursors. As a member of the Johnston Group at Vanderbilt University, I have dedicated my graduate career to exploring new modes of reactivity using various organocatalysts designed within the group, using 25 • Vanderbilt Chemistry 2015 - O h O O h O

48 , formed ee h 2 I O O ee 48 O H ee 48 3 O O 68% 69% (72%), I 93% Me (63%) (97%) I O h O O O 48 h ee MeO h O O O ee 48 ee 48 O 91% O is expelled in the process and is and expelled is in the process in the presence of a suitable a suitable of in the presence 2 (99%), I 2 90% 74% (88%) I (76%) I scope sample of that may ultimately benefit the organic the benefit ultimately may that Bu t 2 2 -containing molecules. The carbonates show molecules. carbonates The -containing 2 - pro in the hindrance a significant O) was 2 N NTf - 2 H H HNTf N N acid/base H ee ee ee N N H Since these types of chiral iodocarbonates have never been never have these iodocarbonates chiral Since types of (71%) (90%) (86%) H 91% 90% 91% Brønsted organocatalyst Research reported in this publication was supported by the National Institute of Institute National the by was supported reported publication this in Research Sciences (NIH GM 084333).General Medical gression of the catalytic cycle and ultimately resulted in catalyst in catalyst resulted ultimately cycle and the catalytic of gression deactivation this for The culprit deactivation. and poisoning acid (CO be to carbonic hypothesized is pathway chemistry community. wide utility accessing chiral oxygenated small molecules, some oxygenated chiral accessing wide utility - enantioselec other using prepare to challenging which are of at arrive can we reduction upon methods. Additionally, tive CO (see 1,3-diols chiral image). base). The formation of carbonic acid fortunately appears appears fortunately acid of carbonic formation base). The added. when are MS 4A catalyst active to reverting reversible, prepared were compounds 15 new carbonate chiral total, In approach. enantioselective this novel using - derivatiza various explore to wanted we previously, prepared the articulating use better of in hopes these compounds of tions CO these unique, of formally reduced to methanol or a methanol derivative. Ongoing Ongoing derivative. a methanol or methanol to reduced formally on addi- focusing are Group Research Johnston in the efforts use CO to ways tional by the addition of water to CO to water of the addition by ing one enantiomer to its mirror image) in the assembly of the of in the assembly image) mirror its to enantiomer one ing - opti during finding unusual A more iodocarbonates. desired 4A) sieves (MS molecular of the implementation was mization control careful After yields. improved with correlation its and the in water of amount the slightest that found we experiments, (< 1 μL H reaction found to be essential for high enantioselectivity in this reaction. high enantioselectivity be for to essential found up to achieve able was system acid/base catalyst Brønsted This 2.5 favor 97.5 to of a ratio excess’; 95% ee (‘enantiomeric to StilbPBAM• O OH N OH chiral O - O O OH O , was ee 2 Ph O Me Ph Me Ph 95% O 1 2 examples C to R R ° -fixation step, step, -fixation C 2 ° up 15 I 80 rt (1 atm) and and (1 atm) 0 2 SnH 3 LAH AIBN THF, THF, Bu A26–OH Amberlyst MeOH, benzene, MS O -fixation iodocyclization C, 2 catalyst ° mol% NIS O 5 toluene, CO -20 O ee BAM via Ph 91% I O . Following this critical CO . Following 3-component, 2 C atm) OH (1 O incorporation and/or assist in the stabilization of the of in the stabilization assist and/or incorporation 2 work 2 1 derivatizations R our R Throughout the optimization process, we arrived at highly arrived we process, optimization the Throughout For this current project, we posited that a properly balanced a properly that posited we project, this current For ) source and an alkene. If this could be achieved using a metal- be this could using achieved If alkene. an and ) source + free catalyst—an organocatalyst—the virtues of minimalism virtues of organocatalyst—the free catalyst—an impact. broad and easy implementation suggesting apply, would a carboxylation/alkene developing this design by validated We produce to alcohols homoallylic of reaction functionalization Soc. 2015, 137, Chem. Am. J. et al. (Vara cyclicchiral carbonates 7302–7305). CO a balloon of just using conditions robust rier CO to - hydro and nitrogen, life—carbon, of the basic elements of some can that solids stable moisture and air are These catalysts gen. the next. to reaction one used from and be easily out weighed a readily be from can constructed these catalysts Additionally, - highly enanti for allowing backbone, diamine chiral available been widely have these catalysts date, To oselective reactions. of whichproducts reaction—the inthe aza-Henry efficacious lead molecules compounds, anti-tumor into becan manipulated acids. amino non-natural disease, Chagas and targeting the bar lower could base organocatalyst acid-Brønsted Brønsted resulting addition product between a homoallylic alcohol start- between alcohol a homoallylic product addition resulting CO and material ing employing a catalyst designed in the Johnston group called group designed the in Johnston a catalyst employing (seealong image) chiralbackbone diamine The StilbPBAM. or HNTf triflimidic acid, acid the Brønsted achiral with - nucleo oxygen then act acid could an as carbonic the transient ring-opening iodonium enantioselective in a subsequent phile in the process. bond a new carbon-oxygen forge and reaction anis and an iodocyclization, as known formally is process This an iodine using newchiral centers to creating approach effective (I graduatestudents

Ion Mobility Mass Spectrometry as a separation technique for identifying complex biological mixtures Mass spectrometry measures a particular compound’s mass-to-charge ratio, or, simply put, its molecular mass. Ion mobility, however, measures a chemical’s three-dimensional shape.

By James Dodds Graduate Student, McLean Lab

n the McLean Lab at Vanderbilt, our separate molecules in two dimensions. Mass conditions in order to resolve (distinguish) studies explore the potential of utiliz- spectrometry measures a particular com- between compounds with similar masses. In ing ion mobility mass spectrometry pound’s mass to charge ratio, or simply put this light we have explored the main metric Ias a separation technique that aids in the its molecular mass. Ion mobility, however, of quantifying how well our ion mobility identification of complex biological mixtures. measures a chemical’s three-dimensional device functions, commonly termed as an The ion mobility cells in our instruments shape. In general, as a compound gets more ion’s resolving power. Resolving power is a provide a separation in supplemental fashion massive, the shape also increases. However, general term that describes the sharpness of to information gained by mass spectrometry as it turns out, for different biological systems a peak in a given spectrum. The term itself is alone. While both techniques (ion mobility of interest (lipids, proteins, carbohydrates, taken from mass spectrometry, but, is similar and mass spectrometry) have been around etc.) generally one of those biological classes to the idea of number of theoretical plates in for several decades, these two analytical has a different shape for a given mass. Ion liquid chromatography. Basically, a higher methods have only been recently employed mobility allows us to separate compounds numerical resolving power instrument will in a simultaneous fashion. that the mass spectrometer cannot differenti- give you more chances to separate one com- Part of the beauty of meshing both ion ate alone due to this varying size/shape ratio. ponent from another in a given mixture. This mobility and mass spectrometry is that both One of our most recent publications selectivity allows for more complex samples techniques measure different chemical prop- aims to discuss various ways to improve the to be analyzed in a given mixture while pre- erties; and, hence, possess the capability to ion mobility device and optimize operating serving identifiable components. The two main components that affect an ion’s resolving power in our instrument are the drift voltage and the ion gate width. The drift voltage is an applied field that pushes our compound of interest through the neutral drift gas. Smaller ions travel faster under a given applied field, and larger ions travel slower. This process is similar to size- exclusion chromatography or a gas phase gel electrophoresis. The gate width is essentially the size of the ion pulse that is sent into the instrument at a given time. Smaller ion pack- ets typically have smaller Columbic repulsive forces, but they also yield a smaller signal. This effect generally results in the typical analytical tradeoff between sensitivity and selectivity. To begin our analysis we needed to select a compound to test which provided strong 27 • Vanderbilt Chemistry 2015 journal and is available for view for available is journal and Support for this research came from the National National from the came research this for Support - Advanc for Center National Health of Institutes Grant Sciences (NIH-NCATS Translational ing Science National the 4UH3TR000491-3) and (MRI CHE-1229341). Foundation - ana for their instruments optimize and A full samples. relevant biologically lyzing in the published is paper our of version Analyst resolving “Broadscale is: The title online. a high precision of performance power spec - mobility-mass ion field uniform May, Jody C. are: authors The trometer.” Kurulugama, T. N. Dodds, Ruwan James and Fjeldsted, C. John C. Stafford, George A. McLean. John - effec to able was study our short, In small chemical compounds (proteins and (proteins small compounds chemical analysis our In respectively). metabolites, to a detailed adjustment provided we will that equations the proposed of some data. current with agree closely more the components key of two analyze tively spectrometer’s mobility ion detail an that how into insight provided and efficiency, components these instrumental of some allows study This be handled. should ouruseto in the field researchers other in data accurate more provide to findings Hopefully manner. time efficient a more like- other for the way paved have we findings our apply to minded scientists After selecting our control mixture, mixture, our control selectingAfter of the robustness ensure to Next, - resolv our also applied Our study signal in a consistent fashion in order to in order fashion signal in a consistent parameters the instrumental each of alter Ultimately, still data. possessand usable mixture a tuning decided analyze we to designer, instrument our by provided commonly which is Technologies, Agilent our for used calibration set to the mass does this only Not spectrometer. mass nitro-carbons fluorinated of mixture can we in the mixture but readily, ionize one so molecules 10 for or about measure to - col be data This allows analysis. given - run informa with sample one lected from peaks. multiple about tion varying experimental on our setwe out varied we testing During our parameters. 7-21 V/cm. from voltage tubethe drift peak our was width that noticed We time in the the retention with optimized It seems this 14 V/cm. about at tubedrift compromise adequate an provides setting peak width transmission, between ion was width gate the drift Also, time. and the resolving 100-500 µs and varied from setting optimum An recorded. was power this parameter 150-200 µs for about of ion improved provide to chosen was to minimal losses with given transmission peak width. chemicalother tested we findings, our samples see to if routine compounds chose We these trends. follow would (carbohydrates, classes biological various see to salts) if the newpeptides, and other to applicable were parameters most short, In well. as compounds this instrument on analyzed chemicals findings. Larger our with agree so far - myoglo like proteins as such complexes these follow not may ubiquitin and bin their massive to in correlation trends by being studied currently are and size, group. research our of members other theory the current to in data power ing the matched results to our thesee field if equations from expected predicted values turnsIt first-principles. from generated did indeed line data our of most that out current but conditions, routine for up stilltheory needs refinement area in our very and very of large areas extreme for graduaTE STudent RESEARCh highlights

Katherine Chong, Sulikowski Lab Natural products contain novel scaffolds and further our understand- by current drug discovery methods, we begin to traverse an area of ing of biological phenomena through their use as selective chemical pharmaceutical research in which we must move into new chemical probes. In fact, three fourths of small molecule anticancer drugs are space. The demand for new scaffolds is ever increasing, to produce natural product based, with almost half of those molecules being selective therapeutic agents in drug discovery—the “holy grail” in the natural products themselves or derived therefrom. Despite their industry being the ability to discriminate disease states from healthy vast utility, recent efforts have moved away from the use of natural cells. To do so, requires an in-depth understanding of fundamental products in drug screenings due to their challenging total syntheses biological phenomena. Glycosylated natural products have long and subsequent derivation. As typical “low hanging fruit” is scooped been explored for their excellent antitumor activity. We have found apoptolidin to have sub-nanomolar activity against tumor cells when glycosylated. When the sugars are removed, the aglycone loses activity (> 10 μM, H292 cells, human lung cancer). Accessing variants of apoptolidin as a function of glycosylation state will enable us to examine the role deoxy sugars play in the cytotoxicity profile of the apoptolidins against varying cancer cell types. As each cancer cell type displays a unique metabolic profile, and notably distinct from healthy cells, we hope to use our toolbox of apoptolidin glycovariants in the quantification of cellular uptake, localization, and subsequent activity as a function of glycosylation state of the apoptolidins and metabolic state of each cancer line. To access our apoptolidin glycovariants, we aim to combine techniques utilizing chemical synthesis, precursor directed biosynthesis, and biosynthesis. Herein describes our efforts toward the chemical synthesis of apoptolidinone C and preliminary results utilizing phospho-specific flow cytometry to measure cellular uptake and response of the apoptolidin glycovariants.

Anna Davis, Cliffel Lab Organ-on-a-chip (OoC) systems are designed to more realistically mimic in vivo cellular responses than traditional two dimensional tissue culturing platforms (such as well plates and culture flasks). The Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE), in collaboration with other institutions across the country, have been working to develop different OoCs to monitor responses to pharmaceuticals or environmental toxins. For meaningful information to be determined from long term studies on OoCs, the health of the cells needs to be monitored to observe real-time toxicological events and ensure the viability of additional results produced. Previous work has been done in the Cliffel lab using modified screen printed electrodes in a 26µL chamber to detect changes in cellular glucose metabolism; however, the volume of effluent produced from smaller OoCs require lower sample volumes for real-time analysis of cellular energet- ics. Additionally, gas permeable materials used to produce OoCs introduce the possibility of evaporation from circulating media, which could result in hypertonic stress causing damage to cellular with electrodeposition and ink-jet printing techniques. The modi- processes or apoptosis. As water evaporates from the media, the fied sensor was utilized to perform electrochemical detection of concentrations of ions increase, resulting in increased solu- glucose, lactate, oxygen, conductivity and acidification in a sub- tion conductivity which can be measured using electrochemical microliter multichannel PDMS sample chamber. Once developed impedance techniques. A nanoelectrode array has been fabricated the nanoelectrode array will be used to make automated offline using electron beam deposition and soft lithography and modified measurements from small volume OoCs. 29 • Vanderbilt Chemistry 2015 - ferent species as the α and β species the α and as ferent of the configurations anomeric NMR addition, In lesion. urea one-dimensional and TOCSY showed in water experiments in the remained lesion urea that between conformation trans proton NH amino the H1´ and - con the anomeric of regardless experiments Future figuration. lesion the urea will investigate as junction a primer-template at DNA. in duplex as well step of the algorithm, sets of compounds compounds sets of the algorithm, of step - “fit their biological for evaluated are based machine-learning using ness” - relation activity structure quantitative and two- which correlate models ship properties molecular three-dimensional activities. The best- biological with then are structures molecular scoring gener to together mixed or modified - Rosettapro Design improved the for AUC The RESULTS: specific a tested only has protocol The CONCLUSIONS: symmetry mode which makes it ideal for this study. Existing symmetry this study. ideal for it mode which makes models used create to are the wild-type of structures proteins itsof total energy wild-typethe The and the mutation. with experimentally reported to compared are variants respective - bacteriorho of 90 variants Nearly unfolding. ΔΔG for values - forma disulfide bond and GlpG, protease rhomboid dopsin, modeled. B were protein tion correctly Rosetta often can that which 0.718 indicates was tocol be to destabilizing. a mutation predict - the pro Additionally, experimental data. limited with system structures. input minimizing been for optimized not has tocol their and proteins set of a diverse test to continue to plan We Membrane and Rosetta Membrane fully to benchmark variants accurately how of understanding a thorough + Symmetry for mutations. of effects the stabilizing Rosetta predict can ate a subsequent set of candidate compounds. These steps are are steps These compounds. candidate set of a subsequent ate attained. is score activity biological a desired until repeated - this focused of library design appli the results present we Here BCL::EvoGen.3 cation, along this finding corroborated 1:1. NMR spectroscopy of and species. NOESY NMR different the two identifying with of used the resonances assign to were experiments TOCSY method. elimination of process by a nucleotides the different dif- of two the identity confirmed the experiments NOESY - - AIMS: Genetic variations can predispose can AIMS: Genetic variations - diseases of includ a number to humans syndrome, long-QT cysticing fibrosis, single disease.Many Alzheimer’s and been linked have variations nucleotide becauseis likely function. This of loss to in the a small change cause the variations its ther affect which can structure protein eiler Lab Meiler Duran, Amanda - pro membrane for is study focusof this The METHODS: modynamic stability. We propose to use the to Rosetta Molecular propose We stability. modynamic destabilizing. are whether mutations predict to Suite Modeling be can models used under to the computational Furthermore, This protein. of the structure the affect the mutations how stand are which therapies determining for be can valuable information variant. the particular protein for best suited looked have studies Few proteins. multi-meric including teins, and both a membrane Rosetta includes these systems. at 2´-Deoxyribosylurea (urea) lesions within DNA form from from form DNA within lesions (urea) 2´-Deoxyribosylurea - radicals a conse as hydroxyl with thymine of the cleavage urea addition, In radiation. ionizing to exposure of quence from results a lesion acid, oxaluric from formed are lesions in vitro 8-oxoguanine, with oxygen singlet of the reaction that concentration salt under Previous cells. to relevant are lesions urea of NMR studies showed level the nucleoside on (α) alpha of the equilibration the on betaand (β) anomers we 2´-deoxyribose ring. Here, within lesion a urea investigated 5´- the oligodeoxynucleotide (CTXA)-3´ in single (X=urea) Reverse phase DNA. strand of revealed the presence HPLC at a ratio species different two Drew Kellum, Stone Lab Lindsley Lab Alex Geanes, Meiler Lab and (vHTS) screening virtual high-throughput years, recent In the drug to discovery been applied successfully have techniques leveraged cases, these are vHTS techniques many In process. and acquisition for libraries chemical of subsets prioritize to that space the chemical However, screens. in physical testing be not may a particular to target pharmacological relevant is isit such as and libraries, compound pre-made in reflected designing of capable which are algorithms have to advantageous design. de novo as known a process new structures, chemical the part as of implemented was algorithm evolutionary An the Biochemistry within Library suite (BCL),BCL::ChemInfo iteratively to laboratory, a C++ library in the developed Meiler each At use focused as libraries. for compounds sets of generate graduatestudents Four Chemistry Students Win NSF Graduate Research Fellowship The National Science Foundation named four Vander- participation of women, underrepresented minorities, bilt graduate researchers to be recipients of Graduate persons with disabilities, and veterans. Research Fellowships. The program is aimed at aiding The NSF GRF provides three years of support within a individuals who have demonstrated notable potential five-year fellowship period. With a $34,000 annual stipend early in their research career. An additional goal is and $12,000 cost-of-education allowance, the fellowship increasing the diversity of the science and engineering supports 2,000 graduate students in science and engi- workforce, including geographic distribution and the neering nationwide.

Jade Bing Alex Geanes Jade Bing is a second-year graduate student Alex Geanes is a recent recipient of the NSF in the Johnston Lab, doing organic synthe- Graduate Research Fellowship Program sis. Bing found that scientific research cre- award, and is currently pursuing his Ph.D. ated an avenue by which she could support, in chemistry at Vanderbilt University. He is teach and encourage other first-generation, a second-year graduate student in the Jens low-income, disabled, or minority students Meiler and Craig Lindsley labs. like herself. Geanes received undergraduate degrees As a child, Bing suffered from Guillain- in chemistry and mathematics with honors Barre Syndrome, an acute inflammatory demyelinating polyneu- from Purdue University in West Lafayette, Indiana. His research ropathy that caused prolonged paralysis in her legs and arms. career started his freshman year at Purdue in Dr. Tong Ren’s labo- With no known cure for the disease, she engaged in years of ratory, where he worked to develop molecular wires and catalysts physical therapy to regain her ability to walk. This experience based around diruthenium paddlewheel complexes. Between his motivated her to gain a mechanistic understanding of chemistry junior and senior years Geanes participated in the Snyder Schol- and biochemistry to uncover new reactions and apply them in arship program at the University of Illinois Urbana-Champaign. the synthesis therapeutics, particularly for rare diseases. As an During his time at UIUC he worked under Dr. Scott Denmark, a undergraduate at Rider University, Bing was a Ronald E. McNair synthetic organic chemist, to synthesize chiral ligands for use in Scholar, Leadership Alliance Fellow, and ACS Project SEED men- asymmetric palladium-catalyzed cross coupling reactions. After tor and went on to work as research coordinator and counselor graduating from Purdue, Geanes spent a year as a student intern for the McNair program upon graduation. at the Pacific Northwest National Laboratory in Richland, Wash- Bing joined the Johnston laboratory to pursue chemistry that is ington, where he performed quantum-mechanical calculations to mechanistically innovative, medicinally relevant, and often aligns investigate how oxidizing chemicals interact with components of well with the principles of green chemistry. Currently, she is work- spent nuclear fuel. ing towards the on-demand synthesis of peptides that contain At Vanderbilt, Geanes is co-advised by Dr. Jens Meiler, a non-natural amino acids. Specifically, she is developing an effi- computational structural biochemist, and Dr. Craig Lindsley, a cient, enantioselective synthesis of non-natural, electron-rich aryl medicinal and organic chemist. His graduate research focuses on glycines and tyrosine derivatives. This approach uses bromoni- the development and application of ligand-based computational tromethane as an unusual precursor to the amide carbonyl. These algorithms to aid the drug discovery process. The research con- residues can be used to construct biaryl or biaryl ether bonds, a sists of a computational portion wherein Geanes writes programs motif commonly found in peptide therapeutics. However, the aryl capable of expediting and informing the drug discovery process, glycine residues are known to be racemization-prone when used and an experimental component where he uses those programs to in traditional peptide synthesis, making them prime candidates to direct the chemical synthesis of drug-like compounds relevant to be synthesized by a novel amide bond forming reaction discov- a specific medicinal chemistry project. ered in the Johnston laboratory. Increasingly large peptides have Geanes’ GRFP proposal centered around the design and appli- been successfully prepared by this method. Bing will employ cation of a computational algorithm that makes use of a series stereoselective, organocatalyzed reactions to generate bromoni- of biological activity models to generate molecular structures troalkane donors for use in Umpolung Amide Synthesis (UmAS) that are likely to exhibit strong interactions with specific biologi- to ultimately synthesize peptides for therapeutic development. cal targets. This proposal was inspired by his current research, 31 • Vanderbilt Chemistry 2015 - - In collaboration with Andries Zijlstra in Vanderbilt in Vanderbilt Zijlstra Andries with collaboration In Alexis Wong accepts the Phase I finalist award for the “Follow that Cell Challenge” from Roderic Pettigrew, Ph.D., MD, director of the Institute Bioengineering.National Biomedical and of Imaging ation for funding. for ation ticle technology to identify and measure gene expression expression gene measure identify technologyticle and to invited was team the I finalists, Phase As cells. in living Cell that the Follow II of in Phase their work continue to consider future for their results submit and Challenge elected as Lab Selected Wright for the I Finalists Phase Cell Challenge” “Follow that and Conrad, Joseph Alexis Wong, Lab members Wright selected I final- Phase as recently were Wright David the Cell a part of Challenge, that the Follow for ists the National by sponsored Cell Program Single Analysis Program Single The Analysis Cell Health. of Institutes the transcriptional examining investigators “supports measure to in order cells human individual of signatures spe - define to and heterogeneity cellular analyze and population, in a given ‘states’ cell cific cell and/or types of development focused early the discovery and on work high-risk/ stage, early for tools innovative exceptionally cell single improve and enable to projects high-impact and the integration accelerate that studies and analysis, cells.” single characterize to technologies of translation Pathology, of Department Center’s Medical University to proposed the team Immunology, and Microbiology, nanopar gold on basedprobes molecular use fluorescent - - Kendrick is from Hattiesburg, Hattiesburg, from is Kendrick Melinda Shearer Vander a former Shearer, Melinda bilt undergraduate who earned her undergraduate bilt in chemistry degree in May bachelor’s GRF NSF an also2014, was awarded research conducted Shearer this year. Cliffel David Professor of in the lab 2014, she In Vanderbilt. while at E. Pearson the Donald awarded was k Laken Kendric - gradu a first-year is Laken Kendrick - Gradu in the Vanderbilt student ate has She in Chemistry. Program ate chemistry the polymer joined of lab Harth. Eva Professor under her obtained and Mississippi, graduate degree in polymer science in polymer degree graduate Kendrick chose to pursue her graduate education in education graduate her pursue to chose Kendrick When asked about the best part of receiving the GRF, the GRF, receiving the best part of about asked When Award for Outstanding Graduating Senior Majoring in Senior Majoring Graduating Outstanding for Award of the University attends Shearer Chemistry Vanderbilt. at in materials Ph.D. a pursuing is and Wisconsin–Madison - characteriz and in synthesizing is research Her chemistry. cell applications. solar for materials ing from the University of Southern Mississippi (USM) in June in June (USM) Mississippi Southern of the University from career research a pursue to desire her discovered 2015. She - finish after USM experience at research a summer during involvement research continued high Through school. ing a awarded was Kendrick career, undergraduate her during a university and Mention Barry Honorable Goldwater M. thesis. honors funded senior her that grant research in polymers the use of explore to Vanderbilt chemistry at the in development especially is She interested biomaterials. - applica use in biomedical for polymers biodegradable of medical and device coatings, drug as delivery, such tions, engineering. tissue and Geanes plans on pursuing the goals he outlined in his in his outlined the he goals pursuing on Geanes plans and career. graduate his during GRFP proposal - shoul my of the worry will of off take a lot “It Geanes said, as concern without research focus on I can now since ders will lot a free and up from, coming is funding my where to my otherwise paying would to go that money project of the to I will have that the access Also, tuition. and stipend - in develop will help really resources supercomputing NSF’s they methods require since can theseing computational power.” computing substantial pretty graduatestudents

Introduction to SACNAS The Society for Advancement of Chicanos and Native Americans in Science By Audrey Ynigez-Gutierrez

he first Tennessee chapter of the I was immediately impressed by the vast Society for Advancement of resources at Vanderbilt, as well as the inter- Chicanos and Native Americans disciplinary collaborative efforts between inT Science (SACNAS) has been launched students and faculty, so I chose Vanderbilt at Vanderbilt. The Vanderbilt SACNAS to continue my development as a chemist. chapter represents the growth of this After successfully completing my first organization focused on encouraging and year in the Vanderbilt Chemistry graduate helping students of all backgrounds and program, I joined the laboratory of Brian heritages reach their goals in the science Bachmann, which focuses on chemi- community. Vanderbilt SACNAS will offer cal biology and antibiotic discovery and undergraduate students, graduate stu- research. My work will be focused towards dents, and post-doctoral researchers of all elucidating the biosynthesis of the natural backgrounds opportunities such as writing product everninomicin. Through a deeper workshops, outreach and volunteer oppor- understanding of how this unique natural tunities, and educational trips. product is produced, we hope to be able I was introduced to SACNAS dur- to manipulate the bacterial machinery to ing my undergraduate education at the make structural changes to this already University of Texas San Antonio (UTSA). potent antibiotic. Through SACNAS I was able to present The SACNAS community helped me my undergraduate research in a supportive prepare to apply to and succeed in graduate and encouraging environment. At the 2012 Conference in San Antonio, I took the programs and will continue to aid in my and 2013 SACNAS National Conferences, opportunity to learn about different edu- development as a scientist here at Vander- I presented in poster format my research cational opportunities from the hundreds bilt. I look forward to being part of the new from the lab of George R. Negrete, which of exhibits from various post-baccalaureate Vanderbilt chapter and seeing it grow into focused on the development of an efficient and graduate training programs. It was an impactful organization on campus. delivery modality for small interfering RNA at one of these many booths that I found Find out more about the VU SACNAS (siRNA) by utilizing cationic guanidine- the Vanderbilt Department of Chemistry. chapter through their page on Facebook. derived amphiphiles and bolaamphiphiles to anchor the sugar phosphate backbone of nucleic acids for use in lipoplexes or stable Mike Turo Awarded DOE Graduate nucleic acid lipid particles (SNALPs). Student Research (SCGSR) Award In 2013, I was a SACNAS Undergradu- ate Student Poster Presentation Awardee in Mike Turo, a fourth-year student in Janet Macdonald’s lab, has Chemistry for my presentation of this work. been selected by the U.S. Department of Energy (DOE) Office of As well, I met professionals in all different Science to receive an Office of Science Graduate Student Research career stages and fields who shared com- (SCGSR) award. Since February 2015, Turo has been working at mon experiences stemming from Chicano Lawrence Berkeley National Laboratory (LBNL) on his project, and Native American backgrounds. It was X-ray absorption spectroscopy and ab initio study on interfacial gratifying to meet people from similar charge transfer in CdSe@ZnS nanocrystals. Turo is a native of Slingerlands, New York; backgrounds who had been able to achieve he received his bachelor of science from Villanova University in Pennsylvania. careers in science and were willing to men- Further details of the DOE Office of Science Graduate Student Research Program tor rising minority students. are available at www.nsfgrfp.org. During the 2013 National SACNAS 33 • Vanderbilt Chemistry 2015

D. Graduates Ph. 2014–2015 Mariusz Butkiewicz Leipzig, Germany Strategies Activity Relationship Quantitative Structure Advancing Drug Design Computer-Aided in Ligand-Based Grove Kerri Jaye Minn. Andover, for the Elucidation of Lipid and Imaging Mass Spectrometry Nephropathy and Protein Changes in Diabetic Efficacy Assessment of Drug Christopher Peter Gulka Mass. Medway, for the Rapid Detection of Explosives Gold as a Sensing Platform and Malarial Biomarkers Sten Heinze Leipzig, Germany de novo Protein Structure Prediction Improvements to BCL::Fold Stephen Randall Jackson Paragould, Ark. Enhanced Molecular DNA-Functionalized Gold Nanoparticles for Sensing Joseph Daniel Keene Climax, N.C. on the Charge Effects of Surface and Chemical Composition Carriers of Alloyed Quantum Dots Glenna Jean Kramer Oakdale, Pa. of the K-26Pharmacology and Chemical Probe Development Family of Natural Product Angiotensin-1 Converting Enzyme Inhibitors Liang Li China Tianjin, to DNA Sequence Dependence of Structural Perturbations Lesions Induced by Aflatoxin B1 Formamidopyrimidine Amy Ng Mass. Fall River, Electron Characterization of Nanocrystal-Based Photovoltaics: via Microscopy & Electron Beam-Induced Current Scanning Electron Microscopy Jeffrey Scotten Niezgoda Del. Hartly, The Implementation of Quantum Dots in Photovoltaics: From Interactions to Current Visualization Semiconductor-Plasmon Matthew Charles O’Reilly Billings, Mont. Application of Organocatalysis to the Synthesis of Chiral Morpho- lines, Piperazines, Aziridines, Azetidines, beta-Fluoroamines, and gamma-Fluoroamines; Discovery of Selective Phospholipase D Inhibitors with Optimized in vivo Properties Jacek Grzegorz Pecyna Olawa, Poland Polar and Ionic Liquid Crystals Based on the [closo-1-CB9H10]- and [closo-1-CB11H12]- Boron Clusters James Senter Timothy Charlotte, N.C. A General and Stereoselective Approach for the Construction of Azabicyclic Compounds: Applications to the Synthesis of (+)-Amabiline and Grandisine D; Structure-based Design of Small Molecule Inhibitors of the Menin-MLL Protein-protein Interaction ichole ichole Bryson Howard Katherine Martin Any Poynter Kevin Winter Jonathan Witt . Armstrong . Armstrong ach year, the Vanderbilt Institute for Chemical Biology for Institute the Vanderbilt year, ach success and work hard for student one recognizes for Prize VICB the Thus, efforts. in their research

The winner of the 2015 Richard N. Armstrong Award in Award Armstrong N. of 2015 Richard the winner The

Cynthia Berry Eric Bierschenk Matthew Bryant Richard Dempster Braden Durbin Jason Gerding 2014–2015 Master of Science Larry Marnett presents the Richard N. Armstrong Award in Chemical Biology to Nichole Lareau. Lareau (McLean Lab) (McLean Lareau Inaugural Winner N Winner Inaugural Award in Chemical Biology Biology in Chemical Award Richard N Richard

Research Excellence is awarded to a single student whose student a single to awarded is Excellence Research - appli be eligible, To honor. this prestigious warrants research under MD/PhD or their PhD toward be working must cants year, This the VICB. of member active an who is a professor N. Arm- Richard of been in honor has named the award so in perpetuity. will remain and strong, student a fourth-year Lareau, Chemical Biology Nichole is A. McLean. John of in the lab E UNDERgraduatestudents

Beckman Scholars Program at Vanderbilt

By Sandra Ford

eckman Scholars Program awards of the Vanderbilt Association of Hispanic are institutional, university, or col- Students. Carter took organic chemistry as lege awards. Each year, the Arnold a freshman and gained research experience Band Mabel Beckman Foundation selects a through the Department of Epithelial Cancer number of research, doctoral, master’s, and Biology. In 2014 he began work with the baccalaureate universities and colleges to be Johnston laboratory in an effort to apply new invited to submit applications for the Beck- chemical methods to the synthesis of natural man Scholars Program. Each institution may products with interesting biological activity. submit one application for consideration for His postgraduate plan is to attend medical an award. school in pursuit of an MD/PhD dual degree, Arnold O. Beckman, founder-chairman eventually specializing in neurosurgery. emeritus of Beckman Instruments, Inc., rep- Professor Jeff Johnston is director of the resents nearly a century of outstanding scien- VU-Beckman Scholars Program for under- tific achievements. Considered one of the top graduate research. His research program five inventors of scientific instruments, Dr. has been recognized by several organiza- Beckman created devices that revolutionized tions, including the Boehringer-Ingelheim the study and understanding of human biol- New Investigator Award, the Yamanouchi VU Beckman Scholar Mentor: Jeff Johnston, ogy, ultimately saving countless lives around and Astellas faculty awards, an Amgen Stevenson Professor of Chemistry the world. Young Investigator Award, and an Eli Lilly He continued his training in organic chem- Vanderbilt Chemistry has been fortu- Grantee Award. istry at the Ohio State University working nate to participate in the Beckman Scholars In 2011, he was elected a Fellow of the with Leo A. Paquette. There, he developed Program, with Jeffrey N. Johnston, Ph.D., American Association for the Advancement the oxonium ion-mediated pinacol rear- serving as the Beckman representative and of Science (AAAS), awarded a Stevenson rangement and was involved with two mentor. During the past academic year and Endowed Chair, and was a recipient of the efforts in natural products total synthesis summer, Zachary Carter, now a senior at Chancellor’s Award for Research. He was (polycavernoside A, taxol). In 1997, he Vanderbilt, is the Beckman scholar, majoring a 2013 Japan Society for the Promotion of moved to Harvard to join Professor David in chemical engineering and chemistry, with Science (JSPS) Fellow, and received the ACS A. Evans as an NIH postdoctoral fellow. minors in biology and neuroscience. Born Arthur C. Cope Scholar Award in 2014. In the Evans group, he developed (with M. and raised in Chicago, Illinois, Carter is a Johnston obtained his B.S. (Honors) Willis, U. Bath) the first highly diastereose- Chancellor’s Scholar and continuing resident in chemistry (summa cum laude) in 1992 lective and enantioselective Mukaiyama- adviser for The Martha Rivers Ingram Com- from Xavier University. While at Xavier, Michael reactions using bisoxazoline mons living-learning community for first- he completed his undergraduate thesis copper(II) Lewis acids as catalysts while year students. He is also the Cultural Chair research with Professor Robert G. Johnson. delineating the associated mechanistic details. He began his independent career at Indiana University in 1999. Johnson was ultimately promoted to professor of chemistry with tenure. In 2006, he moved with his research group to Vanderbilt University, where he is currently a Stevenson Professor of Chemistry and a member of the Vander- bilt Institute of Chemical Biology. His research has resulted in both fundamen- tally new chemical reactions and powerful reagents for activation and stereocontrol to create carbon-carbon and/or carbon-heteroatom bonds. These transformations have been successfully applied to structurally and functionally complex natural products, Vanderbilt senior, Zach Carter typically alkaloids. 35 • Vanderbilt Chemistry 2015

ward ward ward ward in ward in ward wards in Chemistry for Outstanding Senior for Outstanding Senior Chemistry Major Brett Joseph Doliner Outstanding Chemistry Research A Natalie Paige Honkala Organic Chemistry A Alexandra Bahar Khodadadi Martin A Thomas W. in Physical Chemistry Samuel Marc Lazaroff Dilts A Robert V. Analytical Chemistry Jackson Mark Bennett Mark M. Jones A Inorganic Chemistry David Lee Bruns Donald E. Pearson A A Undergraduate Why the interest in the water? “Teeth “Teeth in the water? the interest Why Ayacucho and organized one to be to placed one organized and Ayacucho the dig site near in Pacaycasa, a school with at Huari. of signatures isotope the oxygen up pick drink animals and humans that the water gaining By formation. enamel throughout will the modernperspective we on values, data isotope with them in context analyze remains, drilled the Wari the teeth of from the of understanding greater for allowing individuals tested of origin geographic Miller. explains in climate,” changes and the rainy will throughout be sent Samples A concurrent case study at Grassmere Plantation (now Nashville Nashville (now Plantation Grassmere at case study A concurrent - Pro to awarded grant Science Foundation a National funded through Research Anthropology. of University Department Vanderbilt Tung, Tiffiny fessor season for analysis of the oxygen values. the oxygen of analysis season for and burials era slave Civil War methods to the same Zoo) applies participate. to Miller plans raduation Plans Post Graduation of Colorado engineering at Univ. Graduate school in chemical in Atlanta Job with Coca-Cola Company Medical school and then may attend medical school a year off Taking at a food company Job with the quality department Illinois University Medical school at Southern nuclear engineering US Navy, University of Miami Medical school at the company in Nashville Healthcare software Medical school Healthcare consultant, Dallas at Ohio State University for America, then medical school Teach Science Cal Tech–Material Graduate school in chemical engineering, at Birmingham Medical school at University of Alabama Research in Nashville then medical school Medical school at University of Louisville Medical scribe Medical school in Ohio Control, Atlanta Research associate for Centers for Disease [fall 2014 graduate] Seeking employment Medical school at University of Oklahoma Medical school at Vanderbilt MS in biotechnology at Johns Hopkins school St. Louis University for research then medical [summer graduate] At Professor Oster’s suggestion and and suggestion Oster’s Professor At Alex Jeffrey Anderson Elizabeth Angel Jackson Mark Bennett David Lee Burns Melissa Simone Charles Matthew Chet Cleveland Michael William Crowther Brett Joseph Doliner Banita Giri David Aaron Haynes Monica Elizabeth Herbst Natalie Paige Honkala Paul Andrew Kempler Alexandra Bahar Khodadadi Jabari Hakeem Knight Madison Bentley Kommor Siang Liang Lam Warren Samuel Marc Lazaroff Sicheng Ma Justin Martin Akwasi Fofie Opoku Aniruddha Chintan Parikh Katherine Sumarriva Emily Wang Rebecca Marie Wiesehan Zhewen Zhang hemistry Majors Chemistry Graduating 2015 Name Theresa Miller is a sophomore in organic organic in Milleris a sophomore Theresa Lake from Vanderbilt chemistry at to in addition Last year, Illinois. Zurich, Professor took she General Chemistry, seminar writing first-year Oster’s Jessica human and change climate regarding oxygen researching began history and systems. in cave isotopes analytical of knowledge her because of five Miller spent techniques, research - sum this past Peru, in Ayacucho, weeks taking part in cross-disciplinary mer, Tung, Tiffiny Professor Under research. the from bones Miller analyzed Vanderbilt, at a bioarchaeologist shed to disease and in order trauma of signs tracking Empire, Wari also She collapse. the empire’s the time of around patterns on light in local isotopes water stable regarding a side project conducted rivers three from samples collecting to water addition In sources. of in the city also a water-catcher the team set rainfall, up one and esearch Opportunities for Chemistry Undergraduates Research Opportunities The Indispensables Over 100 Years of Service to the Chemistry Department

They get little fanfare, but these staff members are a few of those who have helped make the Chemistry Department run smoothly. They certainly make the students’ experiences at Vanderbilt Chemistry great. Together, they have combined service of more than 100 years at Vanderbilt.

By Sandra Ford

Paulette Lynch Clara H. Chemistry Store- Johnson room Manager Senior Lab 46 Years Teaching Assistant 36 Years Paulette Lynch has worked at Vanderbilt Q: What do you do for 46 years, oversee- in an average day in ing the Chemistry your job? Storeroom operation, A: In an average day making certain that it in my job, I prepare is well supplied with and test routine labo- all of the essential ratory experiments; items needed to complete research in chemistry, from gloves to assist students and instructors; evaluate lab experiments and set up glassware to chemicals. She deals with vendors, assists faculty and and maintain the Organic laboratories. I also help in keeping the graduate students in sourcing whatever they may need, reconciles students safe in the laboratories. storeroom ledgers, works on acquiring new customers for the Q: What is your proudest accomplishment at storeroom, and, of course, resolves problems. Vanderbilt University? Q: What do you enjoy most about your job? A: My proudest accomplishment at Vanderbilt University is know- A: I enjoy the daily interaction with the faculty, staff, graduate stu- ing that I had a little part in helping some students accomplish their dents, and vendors, assisting others when they need it, and being lifetime goals and future. These students came through the Organic able to negotiate great pricing for our department. laboratories not knowing their future. One of my first students in Q: What is your proudest accomplishment at Vanderbilt? the Organic laboratory, Dr. Douglas R. Weikert, is now associate A: When I first started in the Chemistry Storeroom in 1971 we professor of orthopedics and rehabilitation at Vanderbilt, and he is kept our inventory manually on index cards with orange tabs to my hand doctor. One of the graduate students, Steven Townsend, let us know something was on order. Through the years, we kept became an assistant professor of chemistry at Vanderbilt, the first making changes, and today we have a state-of-the-art comput- African American faculty member in the Chemistry Department. erized inventory system, with barcoding ability and a built-in Q: What has changed at Vanderbilt University since you’ve chemical tracking system. been here? Q: What has changed at Vanderbilt since you’ve been here? A: The changes that I have seen since I have been here are six A: I have seen many changes since I came to Vanderbilt. Many chairmen, five African American staff, and one African American new buildings such as Stevenson Center Building 7 for Chemistry, faculty member in the Chemistry Department. The football team is a new Vanderbilt hospital, Monroe Carell Jr. Children’s Hospital, winning more games and going to bowl games. The basketball team MRBIII and MRBIV. Parking has gone from $5 per year to $408 is getting ranked. The baseball team is going to the championship per year. Last but not least, my hair has turned gray. games. All this would not happen if Vanderbilt University had not moved to a diverse university in the ’90s. This year I have seen the Q: What’s the most memorable thing that’s happened beginning of the separation of the university and the medical center. at Vanderbilt? A: My greatest memory is from 1996, when I was awarded the Q: What is the most memorable thing that’s happened at Storeroom Manager of the Year award by the National Associa- Vanderbilt University? tion of Scientific Material Managers at the annual conference in A: I saw the former President of the United States, Bill Clinton, Savannah, Georgia. It was a great honor to accept this award. getting out of his car going to speak on campus. 37 • Vanderbilt Chemistry 2015 -

Analyst I Research Asst. II Administrative Asst. I Computer Programmer Administrative Asst. III Asst. Research Professor Asst. Research Professor Asst. Research Professor AFF TIVE ST Y ACULT Keri Tallman James McBride Shellie Richards Jeffrey L. Mendenhall Tracy Johnson Salyard Tracy RESEARCH F 15 years 10 years 5 years amanda Kussrow ADMINISTRA 20 years years 5 10 years heather Lee Watkins 5 years Q: What is your proudest accomplishment at Vanderbilt? at accomplishment proudest your is Q: What - pro glass shops the university of none here, I got A: When the for glassware kit lab as such glassware, lab vided standard as keep to do this in order we I suggested labs. undergraduate possible. as in house funds many at happened that’s thing memorable most the Q: What’s Vanderbilt? at me to happened has that thing memorable most A: The the then by I received reception the warm was Vanderbilt staff. faculty and the entire and Hess, Andy Dr. chairman, at a heart attack having was occasion memorable Another the wonder and surgery, heart bypass the subsequent work, ful care given by all involved at VUMC, for which I will be for VUMC, at all involved by given ful care grateful. forever - Professor Professor Professor Professor Professor Jens Meiler Lybrand Terry David E. Cliffel Timothy J. Hanusa Timothy Prasad L. Polavarapu ears Y ACULT 10 years 15 years 15 years 30 years F 35 years The faculty and/or staff members listed below are celebrat- in the ing a service anniversary of their hire date at Vanderbilt celebrates these anniver Vanderbilt Department of Chemistry. Department of Chemistry Honors ServiceAnniversaries saries in five-year increments. Both faculty members and staff celebrate are given a pin with their anniversary year on it. We and thank our colleagues as they achieve these milestones. Vanderbilt is fortunate to to fortunate is Vanderbilt - Glassblow own its have the by operated Shop, ing - Chemis of Department scientific provide to try, - fab design and glassware and Both custom rication. are glassware standard significantly at available, the for prices, reduced - surround and University Vanderbilt at community scientific glassblower Our resident entities. teaching and research ing learned the art of Howe Howe. Tommy is 24 years the past for Tommy Yates. Cleon a friend in Houston, from glassblowing in 1987. Texas from Vanderbilt to came job? your in day do average in an do you Q: What and repair of: consists Vanderbilt at day average A: An materials, ordering and checking glassware, of fabrication needs of faculty in design and and/or grad students assisting - assist glassware, of repair or the fabrication I feel glassware. which type of knowledge my with in thedesign, along ing reach to me enable supply, of sources use bestglass and is to job faculty member’s or the grad making student goal of my up in summed I do can be thing important most The easier. service.” “provide words: two job? your about most enjoy do you Q: What in seeing them come the grad students, A: I especially enjoy - their ambi of some hear to and be to here, each fall, excited observe to achieve. get to them striving and dreams and tions helped them, have I “maybe feeling, from comes that The joy a smile inside. brings way,” in some Glassblower 24 Y Howe Tommy Construction of New Engineering and Science Building

The new Engineering and Science Build- ing is expected to be complete by summer 2016. Construction began in May 2014 on the seven-story structure, which will connect to Olin Hall. The new building is part of an effort to further strengthen the institution’s growing reputation as a major producer of intellectual leaders, entrepre- neurs, and innovators. The 230,000-square-foot building is designed to foster project teamwork and offer programs, instrumentation areas, and core research space that will promote interdisciplinary work, particularly in engineering and related fields, such as chemistry and nanoscience. “We want to continue to attract and recruit the best students and provide them with exceptional research experiences at the undergraduate and graduate A key feature of the new building is ciplinary teamwork and carry this model levels. This new facility will allow for even an Innovation Center designed to con- forward as they become leaders. greater collaboration between students nect students and faculty with technology A cleanroom and advanced imaging and faculty across disciplines so we can transfer and industry mentors to acceler- facilities will provide capabilities that deliver scholarship of the highest caliber to ate the transfer of laboratory discoveries students and faculty need to advance dis- address important societal issues,” Philippe and student-developed concepts to the coveries in areas such as nanocomposites, Fauchet, dean of the Vanderbilt School of marketplace. Students participating in the smart materials, advanced energy storage, Engineering, said. center will experience the value of interdis- and nano‐bio‐technology.

Power Plant Is Now Coal-Free: Smokestack Removed Vanderbilt’s co-generation power plant burned off its last lump of coal in Novem- ber 2014, bringing the campus’s 126-year reliance on coal to an end. The plant, which produces 23 percent of Vanderbilt’s electricity, 90 percent of its heat, and 40 percent of its cooling, now runs exclusively on natural gas. The structure, built in 1962, has been partially powered by natural gas since 1988, but still burned 105 million pounds of coal and produced 15 million pounds of ash waste per year. The environmental benefits of the conversion are significant. Greenhouse gas emissions will go down by as much as 40 percent; emissions of particulate matter will decrease by more than 50 percent; and emissions of mercury, hydrogen chloride, sulfur dioxide, and other air pollutants will be virtually elimi- nated. Demolition of the power plant’s iconic smokestack took place in June 2015. Chemistry Colloquium Series

The Chemistry Colloquium Series is a mainstay of VU Chemistry, broadening knowledge of emerging science and deepening connections between researchers at all levels. Following are 2014–2015 speakers.

Frederick Leroy Conover Prof. Natia Frank, University of Victoria, Prof. Sarah Reisman, California Institute Lecture “Organic-Inorganic Hybrid Functional of Technology, “From Alkaloids to Materials for Switching, Sensor, and Terpenoids: New Strategies and Tactics Professor Vicki Wysocki, The Ohio Spintronic Technologies" for the Synthesis of Polycyclic Natural State University, “Mass Spectrometry Products” in Structural Biology: Surface-induced Prof. Tomislav Friščić, McGill University, Dissociation/Ion Mobility of Protein “A (new) role for solid-state reactivity in Prof. Jonathan Sachs, University of Complexes” making molecules and materials” Minnesota, “Understanding the chem- Colloquia Speakers istry and appreciating the importance Prof. Vlad Iluc, University of Notre Dame, of methionine-aromatic interactions in 2014–2015 “Secondary Metal-Ligand Interactions: protein structure and function” Dr. John Anderson, Northwestern C-H Activation and Metal-Element University, “From Molecules to Materials: Multiple Bonding” Dr. Nathan Schley, California Institute Synthetic Iron Compounds as Constructs of Technology, “From Water Oxidation to Prof. Jonathan Irish, Vanderbilt to Explore Biological Systems” Cross-Coupling: A Mechanistic Approach University, “High dimensional single cell to Catalysis” Prof. Peter Andreana, University of Toledo, cancer research and chemical biology” “Diversity in Small Molecule Synthesis Prof. Peter Schmidt, Leipzig University, Prof. Mark Ji, University of Utah, “Hot and Entirely Carbohydrate-based Cancer “The Structure of Neuropeptide Y bound to Spot-Based Design of Small-Molecule Vaccines for Disease Prevention and its G protein-coupled Y2 receptor” Inhibitors for β-Catenin/T-Cell Factor Treatment” and β-Catenin/B-Cell Lymphoma 9 Prof. Kevin Shaughnessy, University of Prof. Stephanie Brock, Wayne State Interactions” Alabama, “Designing ligands for cross- University, “Nanostructured Architectures coupling reactions: Effects of size, flexibil- Prof. Ryan Julian, University of California, for Energy and the Environment” ity, and electron-donating ability” Riverside, “Probing Gas Phase Biomo- Prof. Jesse Carrick, Tennessee Technologi- lecular Structure via Excitation Energy Prof. Ryan Shenvi, Scripps Research cal University, “Experiential Investigations Transfer” Institute, “Chemical Synthesis of Secondary in Organic Synthesis” Metabolites” Dr. Tzu-Pin Lin, California Institute Prof. Steven Castle, Brigham Young of Technology, “Boryl-Mediated H2 Prof. Masahiro Terada, Tohoku University, “New Strategies for the Activation at Metal Centers: Applications University, “Enantioselective Catalysis by Synthesis of Unusual Peptides” in Catalysis” Chiral Brønsted Acids and Bases”

Prof. Andres Cisneros, Wayne State Prof. James Mack, University of Prof. S. Richard Turner, Virginia Tech, University, “Insights on DNA repair Cincinnati, “Grinding it out: the “Synthesis, Characterization, and enzymes from computational simulations” development of organic reactions Properties of Alternating Copolymers using mechanochemistry” with Sterically Congested Backbones” Prof. Cathy Clarke, University of California, Los Angeles, “The CoQ Prof. Charles Melancon, University of Dr. Nathan West, University of the synthome — a complex required for New Mexico, “An Integrated Approach to Sciences in Philadelphia, “Developing biosynthesis of coenzyme Q” Discover and Bioengineer Bacterial Natural Sustainable Chemical Feedstocks by Products” Utilizing Transition Metal Catalysts” Prof. Sean Elliott, Boston University, “The Metalloprotein Electric: electrochemi- Prof. Daniel Rabinovich, University of Prof. Mikhail Zamkov, Bowling Green cal and biochemical studies of multiheme North Carolina at Charlotte, “Synthetic State University, “Engineering semiconduc- cytochromes c” Analogues of Methanobactin” tor nanocrystals and nanocrystal solids for renewable energy applications” Prof. Harry Finklea, West Virginia Prof. Krishnan Raghavachari, Indiana University, “An Electrochemist’s View of University, “Electronic Structure Methods Solid Oxide Fuel Cells” for Large Molecules and Novel Applica- tions in Nanoscience” The 3D printer at Vanderbilt Chemistry

If you would like to see how the printer works, please go to http://news.vanderbilt.edu/2015/01/ 3d-printer-helps-fight-malaria-in-africa/

3D printing, also known as additive manufacturing, describes various processes used to make a three-dimensional object. In 3D printing, additive processes are used, in which successive layers of material are laid down with inkjet printer heads under computer control. These objects can be of almost any shape or geometry and are produced from a 3D model or other electronic data source. A 3D printer is a type of industrial robot.

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www.Vanderbilt.edu/chemistry Giving to Vanderbilt Chemistry College of Arts and Science Office of Development and Alumni Relations Editor Sandra E. Ford (615) 343-3118 Design and Photography vanderbilt.edu/cas/giving Vanderbilt University Creative Services