NMR Insights into Fast Ion Conductors
P.-H. Chiena, X. Fenga, X. Lia, , J. Zhenga, M. Tanga, Y–Y. Hu a,b
a Dept. of Chemistry & Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL, USA 32306
b The National High Magnetic Field Laboratory, 1800 E. Dirac Drive, Tallahassee, FL, USA 32308
Fast ion conductors, also known as solid electrolytes, are widely used in energy storage technologies, including fuel cells, batteries, and sensors. New Li-ion conductors with high ionic conductivities have been “virtually” synthesized with computational efforts, panoramic synthesis strategies are necessary to effectively harvest the fruits. In our study, high-temperature in situ solid-state NMR is employed to follow the phase evolution and property changes of precursors, intermediates, and target compounds during the synthesis of fast Li-ion conductors. The interplay of thermodynamics and kinetics during the solid-state synthesis of fast ion conductors is also explored.
Ionic conductivity is determined by three factors, i.e., charge carrier concentration, ion dynamics, and ion transport pathways. Charge carrier concentration is affected by accessible Li sites, which are probed and quantified by Li NMR. Synthesis strategies are developed to increase the fraction of functional Li sites. Changes in Li NMR relaxation times with temperature have been measured, which reveal the motional rates and activation energies of Li ion dynamics. So far, the determination of Li-ion transport pathways has been mostly carried out with DFT calculations, while experimental studies are limited by the challenges to follow Li ion diffusional movement in complex systems. A solid-state NMR approach is devised on the basis of 6Li/7Li isotope replacement induced by a biased electric potential to determine Li ion transport pathways . This method was demonstrated on a few fast Li ion conductors. In summary, this talk discusses the unique contributions made with advanced solid-state NMR in investigating various aspects of fast ion conductors, including panoramic synthesis, simultaneous determination of phase evolution and ion dynamics, and improvement of ionic conductivities.
- Zheng, J.; Tang, M.; Hu, Y.-Y*. "Lithium Ion Pathway within Li7La3Zr2O12-Polyethylene Oxide Composite Electrolytes" Angewandte Chemie International Edition, 2016, 55, 1-6.
From solution to the gas-phase. What can we learn on the structure, dynamics and distribution of biomolecules?
Department of Chemistry and Biochemistry, Florida International University
Recent innovations in speed, accuracy and sensitivity have established mass spectrometry (MS) based methods as a key technology for the mapping and analysis of small molecules, lipids, peptides, protein, DNA and DNA-protein complexes in biological systems. In particular, Ion Mobility Spectrometry – Mass Spectrometry provides a powerful tool for the identification of structural motifs, and when complemented with theoretical calculations, it permits a better understanding of the main motifs that drive the dynamics across the free energy landscape. We have recently introduced a Trapped Ion Mobility Spectrometry coupled to Mass Spectrometry (TIMS-MS) as a high-throughput technique for the study of conformational states of biomolecules, as well as the kinetic intermediates involved during their folding as a function of the molecular environment (e.g., pH, organic and salt content). While this description holds true for most contemporary IMS analyzers, the higher resolving power (e.g., R= 150-250, 3x larger than traditional IMS systems) and the unique ability to hold and interrogate molecular ions for kinetic studies (e.g., millisecond-second time scale) provides TIMS-MS with unique capabilities for the study and interrogation as a function of the time after desolvation. Recently combined with hydrogen-deuterium exchange, HDX-TIMS-MS, a more detailed description of the accessible surface area and the folding can be achieved over time. That is, HDX-TIMS-MS has a significant advantage in the flexibility to interrogate, at the single molecule level, the molecular interactions that define the conformational space. In the present talk, recent results that reveal the kinetic intermediates and the main folding pathways for small molecules, peptides, proteins, DNA and DNA-protein complexes will be discussed as well as some novel chemical mapping strategies at the single cell level.
Quantum Chemistry without Wave Functions
A. Eugene DePrince, III
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390
Quantum-chemical computations have become an indispensable and routine component of modern chemical research. However, certain classes of chemical problems require such a sophisticated treatment of the electronic structure that computations become infeasible for large systems. Recent advances in electronic structure theory address the intractable complexity of such problems. I will discuss how one can abandon the wave function as the central variable in electronic structure theory in favor of the two-electron reduced-density matrix. In doing so, we can devise theories and algorithms that enable previously impossible computations on challenging systems.
DIRECT SELF-ASSEMBLY OF MULTI-LAYERED SUPRAMOLECULAR ARCHITECTURES
Department of Chemistry, University of South Florida, Tampa FL 33620, USA
Self-assembly as one of the main organizing principles of biological systems is also a widely applied strategy in supramolecular chemistry as the driving forces for the assembly of artificial structures from simple building blocks. Among the diverse fields of supramolecular chemistry, coordination-driven self-assembly offers a 'bottom-up' approach to mimic nature's activities and constructs various 2D and 3D metallo-supramolecules based on the highly directional and predictable feature of coordination. Up to date, the design of metallo-supramolecules has matured beyond the proof of principles and is ready to face more challenges with respect to the complexity of assembled architectures rather than relatively simple polygons and polyhedrons. With the goal of increasing the complexity of metallo-supramolecules, we designed and assembled a series of concentric, multi-layered architectures using multi-topic ligand. Using terpyridine-based building blocks, 2D macrocycles with concentric geometry were constructed; with multi-topic pyridine ligands, 3D sphere-in-spheres were assembled with increasing complexity and stability. Through further understanding of the design and self-assembly of supramolecular structures, our research is poised to advance the design, research and development of new synthetic materials with molecular level precision and high physical performance.
WATER QUALITY ISSUES AND ALGAL BLOOMS IN SOUTHERN FLORIDA
J. William Louda
Department of Chemistry and Biochemistry
And The Environmental Sciences Program
Florida Atlantic University
Boca Raton, Florida 33470 USA
As the human population of Florida and the World increases so does its effects on the natural environment. This talk centers on man’s addition of huge amounts of the primary plant nutrients nitrogen and phosphorus into the surface waters of southern Florida. This is termed ‘cultural eutrophication’ meaning that man’s activities (anthropogenic) over fertilize our natural waters (Lakes, streams, rivers, estuaries and oceans).
Most recently, the “algal”, actually cyanobacterial, bloom in Lake Okeechobee during June-July 2016 and its spread to the St. Lucie canal and Estuary, Indian River Lagoon, Caloosahatchee River and Estuary and the Palm Beach Canal and Lake Worth Lagoon grabbed national attention. The bloom forming cyanobacterium in this case was Microcystis aeruginosa and unfortunately it was also a toxic form. The toxin it produces is a neurotoxin and can be bio-amplified by aquatic organisms becoming a health hazard to man. In addition, just the contaminated water can cause skin rashes and respiratory problems.
Other blooms do indeed occur in southern Florida including, but not limited to, the Red Tide in the Gulf of Mexico on Florida’s west coast and the Brown Tide in the Indian River Lagoon.
We will explore the increasing nutrient problem (pollution) of our waters and cover some suggested paths to potentially and hopefully reverse these trends.
Development of an Acoustic Levitation Device for Probing Heterogeneous Chemistry in Planetary and Exoplanetary Atmospheres
Beni B. Dangi;*Jordan Dixon; Jared Golden
Department of Chemistry, Florida A & M University, Tallahassee, Florida
We report development of experimental laboratory dedicated to the understanding of fundamental heterogeneous chemical processes in planetary and exoplanetary atmospheres. Even though number of exploration and detection of habitable worlds continue exponentially, there is scarcity of laboratories around the world that can generate fundamental data to understand the physics and chemistry of atmospheres of the new exotic worlds which are potential future habitats. Hence, now is the ideal time to establish laboratories that can shed light on physico-chemical processes, such as formation or destruction of cloud and haze, and catalytic conversion of gases on metallic and dust particle surfaces in such environments.
An ultrasonic levitator, which provides bulk-and-support free condition, has been acquired and tested for its performance. An ultrasonic levitator utilizes sound waves to suspend a solid particle or a liquid droplet without any support, except the gas medium. Furthermore, as opposed to some other trapping techniques, the sample can be held independent of its physical properties such as electric charge and refractive index. A process chamber has been custom built and acquired to enclose the levitator and control identity, proportion and pressure of gases for desired experiments. Incorporation of spectroscopic probes into the instrument is currently being designed which will allow to probe the physico-chemical changes in situ.
Combinatorial Chemistry and Drug Discovery
Torrey Pines Institute for Molecular Studies
Port Saint Lucie, FL 34987
The last two decades has witnessed major breakthroughs in the identification of genes, gene products, metabolic pathways, and signaling pathways, as well as progress in miniaturization and robotics, enabling the development of high-throughput mechanism-based biological assays. One of the central objectives of organic and medicinal chemistry is the design, synthesis, and production of molecules having value as human therapeutic agents. Our research group is interested in the design, synthesis, analysis, conformations, dynamics and structure-biological activity relationships of diverse nitrogen heterocycles of different ring sizes. Diaza- and triaza-cyclic compounds with different substitution patterns and embedded in various molecular frameworks constitute important structure classes in the search for bioactivity. The compounds are designed to follow known drug-likeness rules including “Lipinski’s Rule of Five”. Examples of the synthesis and identifiaction of highly active compounds from mixture based libraries in different assays will be presnted.
LIGAND-MEDIATED CONTROL OF THE GLUCOKINASE REGULATORY PROTEIN
Brian G. Miller and Juliana Martinez
Department of Chemistry and Biochemistry, Florida State University, Tallahassee FL 32306
The glucokinase regulatory protein (GKRP) plays an essential role in glucose homeostasis by acting as a competitive inhibitor of human glucokinase (GCK) and triggering its localization to the hepatocyte nucleus upon glucose deprivation. Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized piperazines with potent in vivo antidiabetic activity disrupt the complex. Here, we establish the molecular basis by which these natural and synthetic ligands modulate the GCK-GKRP interaction. We demonstrate that GKRP displays conformational heterogeneity at the N-terminus and deleting this region eliminates the ability of sorbitol 6-phosphate to promote the GCK-GKRP interaction. Stabilizing ligands favor an extended N-terminus, which sterically positions two arginine residues for optimal coulombic interaction with a pair of carboxylate side chains from GCK. Conversely, disruptors promote a more compact N-terminus in which an interfacial arginine residue is stabilized in an unproductive orientation through a cation-π interaction with tyrosine 75. Elucidating the mechanistic origins of ligand-mediated control over the GCK-GKRP interaction is expected to impact the development and future refinement of therapeutic agents for diabetes and cardiovascular disease, both of which result from improper GKRP regulation of GCK.
Metal-Organic Frameworks as Versatile Platforms for Renewable Energy Applications
Natalia B. Shustova, Ekaterina A. Dolgopolova, Allison M. Rice, and Derek E. Williams
University of South Carolina
Efficient energy conversion is a research area necessary to address the grown demand of energy utilization. In the natural photosystem, the high efficiency of solar energy utilization is contingent on the ensemble chromophore behavior. To mimic a well-defined chromophore arrangement achieved in nature, the molecular self-assembly process for effective design of artificial light-harvesting arrays should be utilized. Such control of the chromophore order can be achieved in metal-organic frameworks, which possess a high degree of structural and chemical tunability, imposing a very few restrictions on the chromophore of choice. We built novel well-defined fulleretic and photochromic materials with a predesigned pathway for the energy transfer.1–3 The prepared systems allow us to control the excited state decay pathways in the large light-harvesting array through alternation of an excitation wavelength. Upon further development, we envision that the prepared well-defined hybrid materials could foreshadow a new avenue for the engineering of new sensors, solar cells, or light-emitting diodes in the future.
- Fellows, B. W.; Rice, A. M; Williams, D. E.; Dolgopolova, E. A.; Vannucci, A. K.; Pellechia, P.J.; Smith, M. D.; Krause, J. A.; Shustova, N. B. Angew. Chem. Int. Ed. 2016, 55, 2195–2199.
- Williams, D. E.; Godfrey, D. C.; Ermolaeva, E. D. Pellechia, P. J.; Greytak, A. B.; Smith, M. D.; Avdoshenko, S. M; Popov, A. A.; Shustova, N. B. Angew. Chem. Int. Ed. 2016, 55, 9070–9074.
- Williams, D. E.; Dolgopolova, E. A.; Pellechia, P.J.; Palukoshka, A.; Wilson, T. J.; Tan, R.; Maier, J. M.; Tan, R.; Greytak, A. B.; Smith, M. D.; Krause, J. A.; Shustova, N. B J. Am. Chem. Soc. 2015, 137, 2223–2226.
Preparation of Long-Lived Hyperpolarized Nuclear Spin States in Solution by Heterogeneous Hydrogenation Catalysis
Evan W. Zhao,1 Raghu Maligal-Ganesh,2 Wenyu Huang,3 and Clifford R. Bowers1
1. Chemistry Department, University of Florida, Gainesville, Florida.
2. Chemistry Department, Iowa State University, Ames, Iowa.
3. Ames Laboratory, U.S. Department of Energy, Ames, Iowa.
Mesoporous silica-encapsulated Pt-Sn intermetallic nanoparticles (iNPs), synthesized by a novel ship-in-a-bottle approach, were recently demonstrated to be effective and robust catalysts for parahydrogen induced hyperpolarization (PHIP). Here it is shown that these iNPs are also effective for the production of long-lived hyperpolarized states on dimethyl maleate and fumarate in solution by pairwise addition of parahydrogen to dimethyl acetylene dicarboxylate in a slurry reactor. The transformation of the singlet state spin order into NMR-observable hyperpolarized longitudinal spin order is demonstrated by two different methods: (i) low-field level-anti crossing state mixing and (ii) Spin-Lock Induced Crossing (SLIC). The hyperpolarized proton singlet state lifetime in dimethyl maleate was measured to be 196 s, consistent with the published value, and more than an order of magnitude longer than the ordinary spin-lattice relaxation time. Because the silica-encapsulated iNPs afford rapid, spontaneous separation of catalyst and product mixture, this advanced catalytic system has excellent potential for high-throughput continuous-flow production of long-lived hyperpolarized biomolecules for in vivo magnetic resonance imaging of metabolic processes on an extended time scale.
- C. R. Bowers and D. P. Weitekamp, Phys. Rev. Lett., 1986, 57, 2645–2648.
- C. R. Bowers and D. P. Weitekamp, J. Am. Chem. Soc., 1987, 109, 5541–5542.
- Y. Zhang, K. Basu, J.W. Canary and A. Jerschow, Phys. Chem. Chem. Phys., 2015, 17, 24370-24375.
- R.V. Maligal-Ganesh, C. Xiao, T.W. Goh, L.L. Wang, J. Gustafson, Y. Pei, Z. Qi, D.D. Johnson, S. Zhang, F. Tao, W. Huang, ACS Catal. 2016, 6, 1754-1763.
- E.W. Zhao, R. Maligal-Ganesh, C. Xiao, T.-W. Goh, Z. Qi, Y. Pei, H.E. Hagelin-Weaver, W. Huang, and C.R. Bowers, 2017, 56, 3925-3929.
Self-organization of layered inorganic membranes in microfluidic devices
Qingpu Wang, Megan R. Bentley, and Oliver Steinbock
Department of Chemistry and Biochemistry, Florida State University,
Tallahassee, Florida 32306-4390
Inorganic precipitate membranes play an important role in chemobrionics and origin of life research. They can involve a range of catalytic materials, affect crystal habits, and show complex permeabilities. We produce such membranes in a microfluidic device at the reactive interface between laminar streams of hydroxide and Co(II) solutions. The resulting linear membranes show striking color bands that over time expand in the direction of the Co(II) solution. The cumulative layer thicknesses (studied up to a total value of 600 µm) obey square root laws indicating diffusion control. The effective diffusion coefficients are proportional to the hydroxide concentration but the membrane growth slows down with increasing concentrations of Co(II). Based on spatially resolved Raman spectra and other techniques, we present chemical assignments of the involved materials. Electron microscopy reveals that the important constituent b-Co(OH)2 crystallizes as thin hexagonal microplatelets. Under drying, the membrane curls into spirals revealing mechanical differences between the layers. Our results also provide chemical insights into the pattern formation of chemical gardens.
Strain-release functionalization as an enabling strategy in medicinal chemistry and drug discovery.
Justin M. Lopchuk
Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612
Driven by the ever-increasing pace of drug discovery and the need to push the boundaries of unexplored chemical space, medicinal chemists are routinely turning to unusual strained bioisosteres such as bicyclo[1.1.1]pentane, azetidine, and cyclobutane to modify their lead compounds. Too often, however, the difficulty of installing these fragments surpasses the challenges posed even by the construction of the parent drug scaffold. This talk will describe the development and application of a general strategy where spring-loaded, strained C–C and C–N bonds react with amines to allow for the “any-stage” installation of small, strained ring systems. In addition to the functionalization of small building blocks and late-stage intermediates, the methodology has been applied to bioconjugation and peptide labeling. The most recent version of our strain-release methodology, stereospecific strain-release heteroatom functionalization, enables the stereospecific “cyclopentylation” of amines, alcohols, thiols, carboxylic acids, and other heteroatoms. The development, synthesis, scope of reaction, bioconjugation, and synthetic comparisons of four new chiral “cyclopentylation” reagents will be discussed.
EVIDENCE OF WASTEWATER-DRIVEN EUTROPHICATION AND HARMFUL ALGAL BLOOMS IN THE INDIAN RIVER LAGOON, EAST-CENTRAL FLORIDA
Dr. Brian E. Lapointe
Florida Atlantic University-Harbor Branch Oceanographic Institute, 5600 US 1 North, Ft. Pierce, FL 34946 USA
The Indian River Lagoon (IRL) has experienced problems associated with increasing macroalgal blooms, seagrass epiphytization, and hypoxia/anoxia for decades. Following significant rainfall in Spring 2011 that ended a multi-year drought, a severe “super bloom” of phytoplankton (> 100 µg/L Chl a) developed in the northern IRL. This was followed by a “brown tide” in the northern IRL and Mosquito Lagoon in 2012, which was followed by widespread seagrass die-off and wildlife mortality, including endangered manatees. To better understand the nutrient source(s) and dynamics surrounding these harmful algal blooms (HABs), seawater samples and benthic macroalgae were collected at a network of 20 stations throughout the IRL. High TDN concentrations (up to 152 µM) and TDN:TDP ratios (>100:1) in the poorly flushed northern IRL, Mosquito Lagoon and Banana River segments reflected the accumulation and cycling of N-rich groundwater and surface water inputs that produce P- limitation. Macroalgae del 15N values were enriched throughout the IRL (+6.3 o/oo) and similar to values reported for macroalgae from other sewage-polluted coastal waters. Because point-source sewage inputs to the IRL were largely eliminated through the IRL Act of 1990, these results suggest that non-point source N enrichment from septic tanks (300,000-600,000) represents a significant and largely ignored N-source to the IRL. The high degree of sewage N contamination of the IRL, combined with recent HABs, including toxic ecotypes of the red macroalga Gracilaria tikvahiae McLachlan, seagrass loss, and wildlife mortality, indicates a critical need for improved sewage collection and treatment, including nutrient removal.
Lithium Ion Pathways within Composite Electrolytes for All-Solid-State Batteries
Florida State University
Rechargeable lithium-ion batteries (LIBs) are one of the leading technologies for energy storage. To overcome safety issues caused by traditional liquid electrolytes, non-flammable solid-state electrolytes are emerging as a promising solution for developing high-performance rechargeable batteries. Current ceramic, glass, and polymer electrolytes all show limitations for application because of their perspective drawbacks in ionic conductivity, chemical stability, or mechanical robustness. For example, ceramics are brittle, most glassy electrolytes are not stable against Li metal, and polymers exhibit low Li-ion conductivity at room temperature. Composite electrolytes offer a new path to create better electrolytes with both high ionic conductivity and good mechanical properties. To improve the ionic conductivity of composite electrolytes, fundamental understanding of the relevant factors, including charge carrier concentration, ion dynamics, and transport pathways is critical. NMR has been proven to be a powerful tool to study local structural environments, dynamics, and transport pathways of Li ions. In this study, high-resolution solid-state 6, 7Li NMR was used to determine the local structural environments of Li ions in the polymer, the ceramic, and the interface of the Li7La3Zr2O12-polyethylene oxide (LiClO4) composite electrolytes. Moreover, through isotope exchange technique, the trail of Li ions passing through the composite electrolyte was determined, revealing the mechanism of Li-ion transportation within the complex system.
STABLE URANYL COMPLEXES FROM THE USE OF 2,6-DIACETYLPYRIDINE DIOXIME: EXPERIMENTAL AND IN-SILICO INVESTIGATION
Jacob T. Bryant,1 Sergio A. Corrales,1 Eric R. Williams,1 Dimitris I. Alexandropoulos,2 Theocharis C. Stamatatos,2 Ian Manual,3 Jason T. Haraldsen,3 Lev V. Gasparov,3 Pere Miro-Ramirez,1 Christos Lampropoulos.*,1
1 Department of Chemistry, University of North Florida, Jacksonville FL, 32224, USA.
2 Department of Chemistry, Brock University, St. Catharines, Ontario, Canada.
3 Department of Physics, University of North Florida, Jacksonville FL, 32224, USA.
In seawater, Uranium exists in ppb concentrations; estimates show that if 1% was extracted, the current U reserves would see a tenfold increase. Polymeric amidoximes have dominated the literature as uranium sequesters; they were initially suggested in the 1980s and later field-tested, retrieving 1 kg of U from the Pacific Ocean. Oximes (>C=N–OH) are known to be strong α-nucleophiles and very effective ligands for binding to transition metal and lanthanide ions. From the use of 2,6-diacetylpyridine dioxime (dapdoH2) in uranyl chemistry, a stable uranyl dimeric complex resulted, namely [(UO2)2Cl2(dapdoH)2]. The latter was studied with single-crystal x-ray crystallography, IR, NMR, absorption, fluorescence, and Raman spectroscopies, cyclic voltammetry, mass spectrometry, as well as DFT calculations. The ESI-MS and NMR data suggest that the complex is stable in solution, and the in-silico studies proved that dapdoH2 has a strong affinity for the uranyl cation. DFT studies were also used to investigate the electronic and vibrational properties of the complex, and data closely modeled the experimental Raman spectra.
CORE AND SHELL SIZE DEPENDENCES ON STRAIN IN CORE@SHELL PRUSSIAN BLUE ANALOGUE (PBA) NANOPARTICLES AND THE EFFECT ON PHOTOMAGNETISM
John M. Cain1, Caue Favero Ferreira1, Ashley C. Felts1, Steven A. LoCicero1, Jiamin Liang1, Mark W. Meisel2,3, Daniel R. Talham1
¹Department of Chemistry, University of Florida, Gainesville FL 32611-7200, USA
²Department of Physics, University of Florida, Gainesville FL 32611-7200, USA
³National High Magnetic Field Laboratory, E. Paul Dirac Dr, Tallahassee FL, USA
RbxCo[Fe(CN)6]y@KaNi[Cr(CN)6]b core@shell heterostructures have been shown to exhibit a photoinduced decrease in magnetization that persists up to the Tc = 70 K of the KNiCr-PBA component, which is not photoactive as a single-phase material. A magnetomechanical eﬀect can explain how the strain in the shell evolves from thermal and photoinduced changes in the volume of the core. Moreover, a simple model has been used to estimate the depth of the strained region of the shell, but only one size of core (347±35 nm) has been studied. Since the strain depth in the shell is expected to be dependent on the size of the core, three distinct RbCoFe-PBA core sizes were synthesized, and on each, three diﬀerent KNiCr-PBA shell thicknesses were grown. The magnetization of each core-shell combination was measured before and after irradiation with white light. Our results suggest the strain depth, as expected, increases from ≈ 50 nm in heterostructures with a core size of 328±29 nm to more than 90 nm in heterostructures with a core size of 575±113 nm. The data from the smallest core size also shows features indicating the model may be too simple.
Structure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway
Naga Sandhya Guntaka, Steven D. Bruner
Department of Chemistry, University of Florida, Gainesville, Florida 32611
Small molecule microbial secondary metabolites by regulating host-microbe interactions play an important role in all aspects of disease etiology and treatment. Colibactin is a secondary metabolite linked to the progression and pathogenesis of colorectal cancer (CRC) and inflammatory bowel disease (IBD) by inducing DNA damage in host cells. The chemical details of the colibactin and the biosynthetic pathway are emerging but clearly are unusual and noncanonical. Our research addresses a key aspect of colibactin biosynthesis, the occurrence of multiple metabolites and the biosynthetic rationale for this. Recent studies suggest an atypical role of ClbQ, a type II editing thioesterase in releasing pathway intermediates from the assembly line (1) and genetic deletion of ClbQ has been shown to abolish colibactin cytotoxic activity (2). Presented is an interdisciplinary approach to address the role of ClbQ, using enzyme structure, organic synthesis of substrates/intermediates and mechanistic analysis. The 2.0 Å crystal structure and biochemical characterization of ClbQ reveal that ClbQ exhibits greater catalytic efficiency toward acyl-thioester substrates as compared to precolibactin intermediates and does not discriminate between carrier proteins in the pathway. As reported in earlier studies (1), late-stage cyclized intermediates are not the preferred substrates for ClbQ. However, late-stage linear precolibactin intermediates are hydrolyzed. Our data, combined with previous reports, support a novel role of ClbQ in facilitating the promiscuous offloading of premature precolibactin metabolites and suggest novel insights into colibactin biosynthesis.
- Li, Z.-R., Li, J., Gu, J.-P., Lai, J. Y. H., Duggan, B. M., Zhang, W.-P., Li, Z.-L., Li, Y.-X., Tong, R.-B., Xu, Y., Lin, D.-H., Moore, B. S., and Qian, P.-Y. (2016) Divergent biosynthesis yields a cytotoxic aminomalonate-containing precolibactin. Nat. Chem. Biol. 12, 773–775.
- Cougnoux, A., Dalmasso, G., Martinez, R., Buc, E., Delmas, J., Gibold, L., Sauvanet, P., Darcha, C., Déchelotte, P., Bonnet, M., Pezet, D., Wodrich, H., Darfeuille-Michaud, A., and Bonnet, R. (2014) Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype. Gut. 63(12), 1932-42.
Ion Solvation of Transition Metals in Differential Mobility Spectrometry
Ayodeji, Ifeoluwa; Vazquez, Timothy; Bailey, Ronelle; Mancuso, Christina; Evans-Nguyen, Theresa.
University of South Florida; Department of Chemisty; Tampa, FL
Differential mobility spectrometry is a rapid means of chemical separation that is leveraged in place of chromatography prior to mass spectrometry. We have incorporated it as a filtration scheme for the separation of transition metals and recently small organic molecules. One mechanism for separation is speculated to involve the ions’ microsolvation by residual water vapor. Experimentally, such phenomena are ultimately tied to the ionization method. In previous work, we relied on a nanoelectrospray ionization method but more recently have incorporated other solvent-less methods such as atmospheric chemical ionization. In this manner, we hope to tease out the role of the water clusters in the separation observed by DMS. We shall present our preliminary work to understand this phenomenon.
Discovery of Selective Inhibitors for the Beta-catenin/B-cell lymphoma 9 Protein–Protein Interaction.Discovery of Selective Inhibitors for the Beta-catenin/B-cell lymphoma 9 Protein–Protein Interaction.
Logan R. Hoggard, John A. Wisniewski, Yongqiang Zhang, Min Zhang, Haitao (Mark) Ji*
Drug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Small-molecule α-helix proteomimetics, such as terphenyl, tris-benzamide, and derivatives, use rigid or pre-organized scaffolds to overlap with the backbones of α-helices and position three substituents to the area where the side chains of α-helical hot spots i, i + 3/4, and i + 7 are located. While the substituents on these designed proteomimetics are critical for biological activities, the scaffolds themselves are not involved in binding. α-Helical hot spots at positions i, i + 3/4, and i + 7 are the primary driving force for many α-helix mediated PPIs. The installation of functional groups to trigger inhibitor selectivity and maintain druglike properties has not been an easy task for small-molecule α-helix proteomimetics. In this study, a new generic scaffold that itself can mimic the binding mode of hydrophobic side chains of α-helical hot spots at positions i, i + 3, and i + 7 was designed. Compared to small-molecule α-helix proteomimetics, this generic scaffold has a much lower molecular weight and a higher ligand efficiency. Decoration of this generic scaffold can lead to small-molecule inhibitors that selectively disrupt α-helix mediated PPIs. Based on this scaffold, new potent inhibitors selective for the β-catenin/B-cell lymphoma 9 interaction were designed and synthesized. The biochemical and cell-based studies demonstrated that this new class of inhibitors can selectively inhibit canonical Wnt signaling, downregulate Wnt target genes, and suppress the growth of Wnt/β-catenin-dependent cancer cells.
- Hoggard, L. R.; Zhang, Y.; Zhang, M.; Panic, V.; Wisniewski, J. A.; Ji, H.* Rational design of selective small-molecule inhibitors for β-catenin/B-cell lymphoma 9 protein–protein interactions. Am. Chem. Soc. 2015, 137 (38), 12249–12260.
- Wisniewski, J. A.; Yin, J.; Teuscher, K. B.; Zhang, M.; Ji, H. Structure-based design of 1,4-dibenzoylpiperazines as β-catenin/B-cell lymphoma 9 protein-protein interaction inhibitors. ACS Med. Chem. Lett. 2016, 7 (5), 508–513. PMCID: PMC4867476.
- Teuscher, K. B.; Zhang, M.; Ji, H. A versatile method to determine the cellular bioavailability of small-molecule inhibitors. Med. Chem. 2017, 60 (1), 157–169.
Design and synthesis of Pt(II) precursors for focused electron beam induced deposition
Hang Lu1, Julie A. Spencer2, Yung-Chien Wu, D. Howard Fairbrother2 and Lisa McElwee-White1
1. University of Florida
2. Johns Hopkins University
Pt(II) precursors have been designed specifically for focused electron beam induced deposition (FEBID) and synthesized for mechanistic study of electron-induced reactions under ultrahigh vacuum (UHV) surface science conditions. In situ X-ray photoelectron spectroscopy, mass spectrometry and Auger electron spectroscopy were used to demonstrate electron-induced loss of ligands from cis-Pt(CO)2Cl2, providing a pathway to Pt deposits by FEBID. The results from cis-Pt(CO)2Cl2 were used to inform the design of additional FEBID precursors, which will be discussed.
Polymer-ceramic composite electrolytes for All-solid-state Batteries
Heather Dang, Jin Zheng, Yan-Yan Hu
Florida State University - Department of Chemistry & Biochemistry
Rechargeable lithium-ion batteries (LIBs) are the predominant power source in electronic devices and electric cars due to high-energy density and long cycling stability. However, liquid electrolytes using organic solvents found in commercial LIBs have safety issues such as flammability and leakage. Polymer-ceramic composite electrolytes have been investigated for the implementation in all solid-state lithium ion batteries with high perfomance. Polyethylene oxide (PEO) has been combined with Li7La3Zr2O12, a cubic-phase ceramic garnet, to create a thin-film, flexible composite electrolyte. Ionic conductivity needs to be improved to achieve high-performing all solid-state batteries. Small molecule additives, including TEGDME (tetraethylene glycol dimethyl ether) and succinonitrile, have been added to the LLZO-PEO composite electrolyte for enhancing the ionic conductivity. High-resolution solid state Li NMR was employed to understand Li ion pathways within the composite electrolyte in a symmetric battery cell, Li/LLZO-PEO/Li. This study provides guidance for the development of composite electrolytes with high ionic conductivity.
Mechanism of proton transfer in Class A β-lactamase function and inhibition by avibactam
Yu Chen, Orville Pemberton
Department of Molecular Medicine, University of South Florida
The hydrolysis of β-lactam antibiotics by Class A β-lactamases proceeds through an acylation step where the catalytic Ser70 forms an acyl-enzyme bond with the β-lactam substrate, and a deacylation step where the covalent linkage is cleaved by the catalytic water activated by Glu166. For the acylation reaction, the origin of the proton transferred to the β-lactam ring nitrogen has been debated with both Lys73 and Lys234 proposed as the source. Meanwhile, whereas the acyl-enzyme intermediate is usually transient for β-lactam substrates, the recent FDA-approved β-lactamase inhibitor avibactam is able to form an acyl-enzyme complex stable against deacylation by the catalytic water. Here we present a 0.83 Å resolution X-ray complex crystal structure of CTX-M-14 Class A β-lactamase with avibactam, shedding light on both the proton transfer process of the acylation reaction and the stability of the avibactam covalent complex. Particularly, we are able to determine the hydrogen atom positions of key catalytic residues, and demonstrate that both Lys73 and Glu166 are neutral. These observations suggest that avibactam is able to trap the acylation reaction at the very last stage after the proton is transferred, via Ser130, from Lys73 to the substrate, but before Lys73 can extract a proton from Glu166 and activate the latter to serve as the general base for the deacylation reaction. Our results have important implications for the catalytic mechanism of Class A β-lactamases and inhibitor discovery against these enzymes.
A PARTIALLY INTERPENETRATED NbO-MOF EXHIBITING SELECTIVE GAS ADSORPTION
Gaurav Verma,1 Sanjay Kumar,2 Tony Pham,1 Zheng Niu,1 Lukasz Wojtas,1 Jason A. Perman,1 Yu-Sheng Chen,3 and Shengqian Ma1
1 Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, Florida 33620, USA.
2 Department of Chemistry, Multani Mal Modi College, Patiala 147001, Punjab, India.
3 ChemMatCARS, Center for Advanced Radiation Sources, The University of Chicago, 9700 South Cass Avenue, Argonne, Illinois 60439, USA.
The use of interpenetration in metal organic frameworks (MOFs) has many added benefits with improvement in the robustness of the material, stepwise gas adsorption and selective adsorption. The control of the degree of interpenetration is further important has it has the advantage of enhancing the efficiency of the MOF through modulation of the pores. Partial interpenetration is rare in MOFs and can reduce the free space and increase the selectivity. Here we report on one such partially interpenetrated MOF, Cu2(pbpta) where H4pbpta = 4,4’,4”,4”’-(1,4-phenylenbis(pyridine-4,2-6-triyl))-tetrabenzoic acid. This material is the first example of a partially interepenetrated MOF with NbO topology and exhibits selective adsorption of CO2 and other heavier alkanes over CH4. The Cu2(pbpta) has a high BET surface area of 2537 m2/g and additionally shows good catalytic efficacy for the conversion of CO2 into industrially important cyclic carbonates through cycloaddition with epoxides.
TOXIN COMPOSITION OF THE 2016 MICROCYSTIS AERUGINOSA BLOOM IN THE ST. LUCIE ESTUARY, FLORIDA
Marliette Rodriguez, Stuart Oehrle, Cristian Zavala, Michael Cartamill, Ricardo Colon, Kathleen S. Rein*
Department of Chemistry and Biochemistry, Florida International University, Miami FL 33199, USA
Massive algal blooms have occurred in the St. Lucie Estuary, FL during the summers of 2016, 2013 and 2005. The release of nutrient laden waters from Lake Okeechobee reduced salinity in the Estuary. High nutrients, low salinity and warm, sunny days made the St. Lucie Estuary the perfect medium for the uncontrolled proliferation of Microcystis aeruginosa already present in the Lake waters. Microcystis aeruginosa can produce microcystins; a family of heptapeptides associated with acute hepatoxicity in humans and animals. During the 2016 bloom, the Florida Department of Environmental Protection detected Microcystin-LR equivalents up to 414 µg/L as compared to the safe drinking water limit of 20 µg/L for recreational use established by the World Health Organization. However, this study aimed to analyze the toxin distribution of the 2016 bloom and compared it to a previous bloom in 2005. UPLC/MS/MS analysis allowed for identification of variants present, classifying MC-LR as the most abundant variant followed by MC-LA with concentrations of 4500 and 815 µg/L respectively. Accurate characterization of the toxic profile of these blooms allow for the correct assessment of health hazard measures as well as future targeting and removal of toxins from water.
MECHANISMS OF ACTIVATED HUMAN GLUCOKINASE DISEASE VARIANTS
Shawn M. Sternisha and Brian G. Miller
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306
Human glucokinase (GK) acts as the body’s primary glucose sensor and plays a critical role in glucose homeostatic maintenance. GK is being actively pursued as a therapeutic target for diabetes. Gain-of-function mutations in the glk gene result in hyperactive enzyme variants that cause persistent hyperinsulinemic hypoglycemia. Past biochemical and biophysical studies support the postulate that activated disease variants can be segregated into two mechanistically distinct classes. In α-type activation, GK displays an increased affinity for glucose and the 1H-13C HMQC spectrum of 13C-Ile labeled enzyme resembles the glucose-bound state. Conversely, in β-type activation glucose affinity is largely unchanged and the 1H-13C spectrum reveals no change in the enzyme structure. Here, we use a combination of viscosity variation studies, chemical quench-flow, and hydrogen-deuterium exchange mass spectrometry to uncover the mechanistic basis for both activation types. Our work elucidates the molecular basis of GK disease variants and provides insights into the nature of GK’s unique kinetic cooperativity.