Seminars begin at 3:30 pm on Friday afternoons in Merrill Lecture Room 4, except as noted, and are preceeded by refreshments at 3:15.
Discussion seminars begin at 3:30pm on Friday afternoons in Merrill Science Center Room 315.
Fri, Sep 9, 2016
Fri, Sep 16, 2016
Chemistry Seminar with Professor Malcolm D. E. Forbes. Bowling Green State University; Professor of Chemistry and Director of the Center for Photochemical Sciences.
Seminar Title: "Photodynamic Therapy, Toils and Troubles: Problems Solved with Tiny Bubbles.”
ABSTRACT: Photodynamic therapy (PDT) uses visible light, a sensitizer such as a porphyrin, and oxygen gas to create singlet oxygen (1O2), a reactive oxygen species that can kill cancer cells. Historically, PDT has remained a non-invasive treatment, using red light and ambient oxygen after intravenous administration of the sensitizer. Here we describe an invasive methodology for PDT that uses highly efficient blue light coupled with localized microbubble-based delivery of sensitizer and oxygen. Lipid-based air bubbles with stabilizers are administered via a teflon or stainless steel catheter containing a concentrically placed fiber-optic cable. Ultrasound transducers are used to acoustically image the catheter and bubbles. Ultrasound can also be used to manipulate the bubbles (moving or popping). The kinetics and topology of singlet oxygen production can be studied quantitatively by reacting secondary amines with the 1O2 to produce stable nitroxide radicals, detectable at μM concentrations by electron paramagnetic resonance (EPR) spectroscopy.1 The sensitivity of nitroxide EPR spectra to local order in heterogeneous structures such as bubbles, vesicles, and micelles will also be presented and discussed.
1Zigler, et al., Photochem. Photobiol. Sci. 2014, 13, 1804–1811.
Professor Forbes' research interests span a wide area of physical organic chemistry. His primary focus is studying free radical structure, dynamics and reactivity using a variety of magnetic resonance techniques. Current projects include the fundamentals of ‘‘spin chemistry,’’ proton-coupled electron transfer reactions, singlet oxygen topology in heterogeneous media, drying and curing processes in thin films and coatings, and the photodegradation and chain dynamics of polymers. Malcolm has published more than 110 papers and book chapters, and has presented more than 160 invited lectures.
Fri, Sep 23, 2016
Md Bhuiyan. Seminar Title: “Making Discrete, Self-Assembling Naphthalenediimide Nanotubes”
In 2007, the Sanders group at the University of Cambridge reported the serendipitous discovery of α-amino acid functionalized naphthalenediimides (NDIs) forming a dynamic combinatorial library (DCL) in chloroform where NDIs self-assemble into helical nanotubes. Held together by intermolecular hydrogen bonds, these structures exist in dynamic equilibrium as the terminal NDIs regularly disassociate from the nanotube while free NDIs [re]associate. Three NDI subunits complete one turn of the nanotubes such that every i and i+3 NDIs are coplanar. Horizontal hydrogen bonds form between adjacent carboxylic acids of NDIs i and i+1. Interestingly, weaker diagonal hydrogen bonds also form between the aromatic naphthyl core hydrogens and imide carbonyls of NDIs i and i+3. L,L-amino acid functionalized NDIs form left handed helices while their D,D-counterparts form right handed helices. The NDIs are readily synthesized via reaction of naphthalene dianhydride (NDA) and the amino acid(s) of interest under microwave irradiation. The self-assembly of helical supramolecular structures is generally realized through a cooperative binding mechanism because of the increase in number of interactions between subunits upon completion of the first turn. Unexpectedly, the Sanders nanotubes were found to assemble via a noncooperative, isodesmic process because of enthalpy-entropy compensation effects. The nanotubes also display a wealth of intriguing host-guest chemistry, having shown the ability to complex C60, ion-pairs, and extended aromatic molecules. The preparation of self-assembling nanostructures of discrete size is a current challenge in the field of supramolecular chemistry. In chlorinated aprotic solvents, NDIs self-assemble uncontrollably, forming nanotubes of varying length. Molecular modeling studies done by the Hansen group suggest that making a single substitution into the aromatic naphthalene core of NDIs would limit the size of the nanotubes to a two-turn helix as the bulkier substituents could sterically prevent further assembly at the bases of the nanotubes. Because existing halogenating reactions of NDA give a mixture of difficult-to-separate mono-, di-, tri-, and tetra- substituted NDAs, the Hansen group attempted to nitrate NDA via electrophilic aromatic substitution (EAS) chemistry. While initial attempts using sulfuric and nitric acid failed, even more vigorous conditions employing superacids developed by George Olah were successful. The monosubstituted nitro NDA required further modification before being functionalized by amino acids to eliminate the possibility of nucleophilic aromatic substitution (NAS) chemistry at the nitro position, and to ensure successful imide condensation. Following reduction of the nitro group, and its subsequent acetylation, the monosubstituted N-acetyl bis-trityl cysteine NDI was successfully synthesized via microwave chemistry. Determination of nanotube formation and further investigations will be done using variable temperature CD and 1H NMR spectroscopy in the coming weeks. If we are successful in controlling the size of the naphthalene diimide nanotubes, we would like to characterize their thermodynamic properties, further explore their host-guest chemistry, assemble them in protic solvents, and investigate the relationship between their aromatic core electronic structures and nanotube formation.
Adrian Chan. Seminar Title: “Allosteric Activation of Engineered Protein Tyrosine Phosphatases by Biarsenical Small Molecules”
Protein Tyrosine Phosphatases (PTPs) are important components in cellular signaling pathways. In 2015, the Bishop Lab developed a mutant form of PTP1B that can be activated upon incubation with biarsenical small molecules. The mutant had three cysteine point mutations at positions 184, 186, and 187 in the highly conserved WPD loop, and is hence called 3C-PTP1B. The thesis 's aim is threefold: (1) to test the generalizability of Knowlton’s approach, (2) to identify any potential problems in applying this activation strategy in a cell-signaling study, and (3) to identify any patterns present in the biarsencial-mediated activation of each of these mutants. If proven generalizable, this activation strategy can be used in cell-signaling studies to investigate the in vivo substrate specificities and physiological function of different PTPs.
Jesse Fajnzylber. Seminar Title: “Targeting a Cryptic Allosteric Site for Selective Inhibition of Shp2”
The protein tyrosine phosphatases (PTPs) are a family of cell-signaling enzymes that dephosphorylate phosphotyrosine in protein substrates. Proper regulation is essential to maintaining homeostasis in human cells and misregulation of this family is associated with many human diseases. One PTP, Shp2, has been linked to many cancers when it is hyperactive. Therefore finding a molecule that could selectively inhibit Shp2 could have therapeutic effects. It is, however difficult to inhibit a specific PTP due to similarities of active sites within the family, and therefore targeting a unique PTP with active-site directed inhibitors is immensely difficult. Furthermore, because PTP active sites bind to negatively charged phosphotyrosine-containing substrates, drug-like compounds that would effectively mimic a phosphotyrosine are often negatively charged and therefore are not cell-permeable. An alternative approach to inhibition is binding to an allosteric site, which would allow the substrate to be bioavailable and also specific to a single PTP. Recently, the Bishop lab discovered that the molecule FlAsH binds well to Shp2. Upon further investigation, it was established that FlAsH binds to an allosteric site that is unique to this specific protein. FlAsH itself cannot be used pharmaceutically because it contains arsenic, which is toxic, and it also binds to many other proteins outside of the PTP family; however, it provided a realistic non-toxic method for Shp2 inhibition. The goal of my work in the summer of 2015 was to establish a library of small drug-like compounds that could potentially bind to the allosteric site that was previously discovered. Of the library, one of compounds seems to have moderate success with uniquely inhibiting Shp2. Going forward, I will synthesize derivatives of this molecule in the hopes of finding a more potent Shp2-unique inhibitor.
Tomorrow - Fri, Sep 30, 2016
Eric Conklin. Seminar Title: TBD
Niyi Odewade. Seminar Title: TBD
Samantha Nyovanie. Seminar Title: TBD
Fri, Oct 7, 2016
Acha Mbatang. Seminar Title: TBD
Megan Tracy. Seminar TItle: TBD
Fri, Oct 14, 2016
Miles Wronkovich. Seminar Title: TBD
Sidney Lin. Seminar Title: TBD
Fri, Oct 21, 2016
Fri, Oct 28, 2016
Fri, Nov 4, 2016
Fri, Nov 11, 2016
Fri, Nov 18, 2016
Fri, Nov 25, 2016
Fri, Dec 2, 2016
Fri, Dec 9, 2016
Fri, Apr 21, 2017
Chemistry Seminar with Professor Eric Herbst. University of Virginia; Commonwealth Professor in the Departments of Chemistry, Astronomy, and Physics.
Professor Eric Herbst; Seminar Title - TBD