PhD Celebration – Dr. Sean McDarby & Dr. Jozafina Milicaj

The Chemistry Department gathered at the beginning of the month to celebrate two of our graduate students who completed their PhD defenses this semester – Dr. Sean McDarby and Dr. Jozafina Milicaj.


Boston Cream Cake for Sean McDarby


Dr. Michelle Personick delivers a few remarks


Dr. Jozafina Milicaj pops a bottle of champagne 


Dr. Jozafina Milicaj & Dr. Sean McDarby


Dr. Erika Taylor & Dr. Jozafina Milicaj 


Tiramisu Cake for Jozafina Milicaj


Dr. Erika Taylor & Dr. Jozafina Milicaj 

Sean McDarby Receives PhD


Dr. Sean McDarby

Dr. Sean McDarby recently defended his Ph.D and thesis entitled, “Synthesis and Measurement of Noble Metal Nanoparticles with Well Defined Shapes by Electrochemical and Electroless Approaches.” Sean started at Wesleyan University in 2015 after completing his BS in Chemistry at Southern Connecticut State University where he conducted research under Dr. Gerald Lesley. His undergraduate research focused on the synthesis of novel MOF precursors involving the manipulation of air-free inorganic pathways. Upon starting at Wesleyan University, Sean joined the research lab of Dr. Michelle Personick and began a project to develop a new method to electrochemically synthesize shaped noble metal nanoparticles. The project was quickly successful, and the method was transitioned into a cyclical tool to create shaped nanoparticles by collecting electrochemical data about any particle growth reaction and translate that to either an electrochemical or colloidal approach. Further work involved the creation of novel shaped nanoparticles, mostly with palladium in both systems. Having completed his degree at Wesleyan, Sean will be starting his career as a federal contractor for Universities Space Research Association at NASA Glenn Research Center in Cleveland, Ohio where he is joining the Microgravity Sciences division and is focusing on the production and applications of boron nitride for space and aeronautics.

Jozafina Milicaj Receives PhD


Dr. Jozafina Milicaj 

Dr. Jozafina Milicaj recently defended her Ph.D. and presented her work entitled, “Biophysical Exploration of Heptosyltransferase I for Potent Inhibitor Discovery.” Jozie started at Wesleyan University in 2015 after completing her BA in Chemistry at Manhattanville College where she was heavily involved with the American Chemical Society chapter and even holding the position as president for her senior year.  Jozie’s undergraduate research project was focused on analytical chemistry and the quantification of antioxidants from açaí berry sources through various extraction methods and UV-Vis radical capture assays. Upon starting at Wesleyan University, Jozie joined the research lab of Dr. Erika Taylor and began working on projects pertaining to Heptosyltransferase I substrate biosynthesis and optimization. Her projects then shifted to understanding and biophysically characterizing HepI and other glycosyltransferases like MshA for the purposes of inhibition of HepI. Having completed her degree at Wesleyan, Jozie will soon be starting her career in industry at Ginkgo Bioworks, a biotech company in Cambridge that professes in novel protein engineering where she will be characterizing and kinetically examining new proteins of interest.

Dr. Colin Smith Receives CAREER Grant from National Science Foundation (NSF)


Colin Smith, Professor of Chemistry

“Dynamics of Computationally Designed Fluorescent Proteins”

The goal of the research is to study and optimize the movement of microscopic, computationally designed proteins that use light to track the locations of biological molecules and reveal how living organisms work. While the structure of a protein is almost always necessary for function, it is often not sufficient. This project focuses on the critical but often neglected role of protein motion in enabling absorbance and reemission of light, a process known as fluorescence. We will first determine which protein shapes either enhance or inhibit fluorescence through detailed analysis of computer simulations and extensive experimental structural characterization. Second, we will test our models through redesign and experimental examination of brighter fluorescent protein variants. As part of these efforts, we will develop a general-purpose computer algorithm that enables rapid evaluation of how thousands of potential mutations affect the shape of the protein. Third, we will investigate the structural determinants of other important properties like the ability of the protein to prevent or facilitate switching fluorescence on and off. The ultimate aim of this project is to develop a detailed understanding of how these fluorescent proteins can be redesigned to make them truly useful tools for biological research. This will enable the creation of even more advanced versions of these and other protein machines (like enzymes) that can also help in the manufacture and recycling of materials at the chemical level.

 

 

Chemistry Alumnus Jessica Garcia Awarded Eastman Chemical Company Fellowship

Jessica Garcia, a 2021 graduate of the BA/MA program in Chemistry, was recently awarded a fellowship through the University of North Carolina. The Eastman Chemical Company Fellowship program is a newly established award bestowed to first year graduate students at UNC for their committed effort to enhance the departmental mission to create a diverse and inclusive community. Sponsored by the Eastman Chemical Company, Eastman Fellows receive a stipend that supports the continuation of their contributions to the Carolina Chemistry community.  Jessica is among six students who were awarded this prestigious fellowship. Join us in congratulating her on this momentous achievement!

Andrea Lee Receives PhD

     

Dr. Andrea Lee

Dr. Andrea recently defended her Ph.D. dissertation entitled “Examining Chromium(III)-based Contrast Agents for Use as a Model for Understanding Prototropic Exchange in ParaCEST MRI Contrast Agents.” Andrea started at Wesleyan University in 2014 after graduating with honors from the University of New Haven where she received a B.S. in Forensic Science and a B.S. in Chemistry. Her undergraduate thesis work focused on analyzing the triglycerides in biofuel made from acorns using HPLC with detection by FT-IR and UV-Vis. Upon starting at Wesleyan University, Andrea joined the research lab of Professor Westmoreland and worked on many research projects exploring various transition metal-based MRI contrast agents and their properties in aqueous solutions. She also received many opportunities as a teaching assistant which included taking on many responsibilities in the Introductory Chemistry Laboratory. She was also awarded the Tishler Teaching Award in 2018. This fall, Andrea will be starting as an Assistant Teaching Professor at Drew University where she will be teaching Analytical Chemistry.

Dr. Andrea Lee


Tom Lee


Dr. David Westmoreland


From left to right: Kimberly Lee, Terrie Tin, and Samantha Lee


Dr. Andrea Lee and Dr. David Westmoreland


A captive audience


From top to bottom, left to right: Eric Zanderigo, Kaylah Medvec, Annika Velez, Dr. David Westmoreland,
Dr. Andrea Lee, Jozafina Milicaj, Angelika Rafalowski, Dr. Alison O’Neil, Dr. Colin Smith
Sean McDarby, Mohammed Ullah, Oliver Cho, Kat Blejec


Celebratory cake

From left to right: Tom Lee, Kimberly Lee, Dr. Andrea Lee, Terrie Tin, and Samantha Lee

 

Dr. Suara Adediran Publishes Paper in Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics

Dr. Adediran and co-authors Michael J. Morrison and R.F. Pratt have published a paper in Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics. The title is “Detection of an Enzyme Isomechamism by Means of the Kinetics of Covalent Inhibition.”

Unlabelled Image

Abstract

Turnover of substrates by many enzymes involves free enzyme forms that differ from the stable form of the enzyme in the absence of substrate. These enzyme species, known as isoforms, have, in general, different physical and chemical properties than the native enzymes. They usually occur only in small concentrations under steady state turnover conditions and thus are difficult to detect. We show in this paper that in one particular case of an enzyme (a class C β-lactamase) with specific substrates (cephalosporins) the presence of an enzyme isoform (E′) can be detected by means of its different reactivity than the native enzyme (E) with a class of covalent inhibitors (phosphonate monoesters). Generation of E′ from E arises either directly from substrate turnover or by way of a branched path from an acyl-enzyme intermediate. The relatively slow spontaneous restoration of E from E′ is accelerated by certain small molecules in solution, for example cyclic amines such as imidazole and salts such as sodium chloride. Solvent deuterium kinetic isotope effects and the effect of methanol on cephalosporin turnover showed that for both E and E′, kcat is limited by deacylation of an acyl-enzyme intermediate rather than by enzyme isomerization.

The full text of the paper can be found at: https://www.sciencedirect.com/science/article/abs/pii/S157096392100087X

 

 

Dr. Colin Smith Receives NIH Grant

Colin Smith, Professor of Chemistry

The Smith Lab studies protein structure and dynamics using a combination of computer simulation and nuclear magnetic resonance (NMR) spectroscopy. They are particularly interested in optimizing the dynamics of computationally designed proteins and understanding how mutations allosterically affect the functions of natural proteins.

To advance the understanding of atomic-level mechanisms behind critical protein functions like enzyme catalysis and allosteric regulation, it is important to first elucidate a true representation of the protein in solution. In an effort to achieve this long term goal, Dr. Smith will use the recently developed Kinetic Ensemble approach to transform the way in which nuclear magnetic resonance (NMR) data is computationally modeled to solve protein structures and measure protein motions. NMR is one of the most powerful techniques for elucidating the structure and dynamics of proteins. It enables their study in solution (unlike X-ray crystallography) and can capture critical structural rearrangements as they happen at room temperature (unlike cryo-electron microscopy). However, despite these advantages, there have been relatively few practical improvements to one of the foundational aspects behind the way protein structures are solved, namely the calculation of interatomic distances from nuclear Overhauser effect (NOE) experiments. Such methods have remained largely qualitative, resulting in large uncertainties in the atomic positions for most NMR structures. Also, the field has almost completely ignored how angular motion and kinetics affect the NOE, resulting in atoms appearing much further away from one another than they actually are. To overcome these significant deficiencies, Dr. Smith and his team will implement and test new Kinetic Ensemble-based refinement algorithms that are considerably more accurate and physically realistic than previous approaches, accounting for both angular motion and kinetics. To eliminate a significant fraction of the systematic and random structural errors resulting from poorly quantified NMR spectra, they will also integrate advances made by the FitNMR peak quantification software recently developed by their lab. These methods will be used to create better experimental NMR structures, more exhaustive models of side chain dynamics, and determine differences between solution and crystal states with unprecedented detail. This work will allow much more accurate determination of the structural dynamics in parts of the protein exhibiting significant fluctuations, including protein active sites, regulatory regions, and hidden binding sites. Such knowledge will advance our fundamental understanding of protein biophysics and facilitate rational design of new therapeutics.

Funding for this R15 Grant is provided by National Institute of General Medical Sciences (NIGMS).

Dr. Brian Northrop Receives NSF Grant

Northrop’s proposal, titled “Phenazine chemistry as a means of assembling multifunctional π-conjugated organic materials” is motivated by the desire to understand how the structure, functionality, and dimensionality of π-conjugated organic materials impacts their physical, optical, redox, and electronic properties. Toward this fundamental goal he and his students will use the condensation reactions between ortho-phenylenediamine derivatives with ortho-quinone compounds to prepare multifunctional phenazine derivatives. Phenazines are example N-heteroacenes that, similar to their hydrocarbon acene analogues, exhibit desirable electronic and optoelectronic properties. Phenazines, however, are more stable, better electron acceptors (n-type materials), and more synthetically modular. The majority of phenazine derivatives synthesized to date have been linearly functionalized azaacenes while very few examples of organic materials combining phenazine and other π-conjugated functionalities are known. Developing a thorough understanding of phenazine assembly and integration into multifunctional molecules will lead to entirely new classes of organic electronic materials and significantly advance our ability to investigate fundamental relationships between size, functionality, lattice topology, and dimensionality on the properties of π-conjugated materials. The principle objectives of the proposed research are to: (1) combine experimental synthesis and first principles calculations to investigate the formation and aromaticity of simple phenazine derivatives as well as the impact of functional groups on the favorability and reversibility of phenazine condensation reactions; (2) synthesize a library of o-phenylenediamine and o-quinone functionalized building blocks that will be used in the controlled assembly of one-dimensional multifunctional phenazine derivatives and oligomers; (3) apply new knowledge from fundamental and one-dimensional phenazine studies to prepare monodisperse, two-dimensional phenazine ladders and grids. The phenazine-based multifunctional materials are expected to have unique semiconducting and optoelectronic properties with potential applications as organic field-effect transistors, photovoltaics, light-emitting diodes, and sensors.