Physical Sciences and Mathematics Commons^™

Solution And Solid-State Emission Toggling Of A Photochromic Hydrazone, Baihao Shao, Massimo Baroncini, Laura Bussotti, Mariangela Di Donato, Alberto Credi, Ivan Aprahamian

Dartmouth Scholarship

The proliferation of light-activated switches in recent years has enabled their use in a broad range of applications encompassing an array of research fields and disciplines. All current systems, however, have limitations (e.g., from complicated synthesis to incompatibility in biologically relevant media and lack of switching in the solid-state) that can stifle their real-life application. Here we report on a system that packs most, if not all, the desired, targeted and sought-after traits from photochromic compounds (bistability, switching in various media ranging from serum to solid-state, while exhibiting ON/OFF fluorescence emission switching, and two-photon assisted near-infrared light toggling) in an …

Annual Variation In Event-Scale Precipitation Δ 2 H At Barrow, Ak, Reflects Vapor Source Region, Annie Putman, Xiahong Feng, Leslie Sonder, Eric Posmentier

Dartmouth Scholarship

In this study, precipitation isotopic variations at Barrow, AK, USA, are linked to conditions at the moisture source region, along the transport path, and at the precipita- tion site. Seventy precipitation events between January 2009 and March 2013 were analyzed for δ2H and deuterium ex- cess. For each precipitation event, vapor source regions were identified with the hybrid single-particle Lagrangian inte- grated trajectory (HYSPLIT) air parcel tracking program in back-cast mode. The results show that the vapor source re- gion migrated annually, with the most distal (proximal) and southerly (northerly) vapor source regions occurring during the winter (summer). This may …

Fluorocarbene, Fluoroolefin, And Fluorocarbyne Complexes Of Rh, Christopher Pell, Yanjun Zhu, Rafael Huacuja, David Herbert, Russell Hughes, Oleg Ozerov

Dartmouth Scholarship

The manuscript reports the synthesis, characterization, and analysis of electronic structure in a series of complexes of small perfluorocarbon ligands with the (PNP)Rh fragment (where PNP is a diarylamido/bis(phosphine) pincer ligand). Reactions of (PNP)Rh(TBE) as the source of (PNP)Rh with CHF3 and C2HF5 produced perfluoroalkylidene complexes (PNP)RhCF2 and (PNP)RhC(F)(CF3). (PNP)RhCF2 could also be obtained via the reaction of (PNP)Rh(TBE) with Me3SiCF3/CsF, with an admixture of (PNP) Rh(C2F4), where TBE = tert-butylethylene. Abstraction of fluoride from these neutral (PNP)RhCxFy complexes was successful, although only abstraction from (PNP)Rh]CF2 allowed unambiguous identification of the Rh product, [(PNP)Rh CF] +. DFT computational studies allowed …

Vapor Deposited Cr-Doped Zns Thin Films: Towards Optically Pumped Mid-Infrared Waveguide Lasers, Eric A. Karhu, Charles R. Ildstad, Stefano Poggio, Vedran Furtula, Nikolai Tolstik, Irina T. Sorokina, Joseph J. Belbruno, Ursula J. Gibson

Dartmouth Scholarship

Compact, affordable mid-IR lasers require the development of gain materials in waveguide form. We report on the high vacuum deposition of Cr:ZnS films with concentration ranging from 10¹⁸-10²⁰ dopants/cm³ . At low concentrations, films display well-isolated absorption associated with substitutional Cr²⁺ ions in the lattice. Spatial modulation of the dopant concentration suppresses the absorption associated with this substitution. Lateral crystallite sizes less than 30 nm are associated with the lowest substrate temperatures (<50 °C) used during deposition, and waveguide losses as low as 8dB/cm are observed. These materials are promising candidates as gain media for fabrication of waveguide mid-IR lasers.

Synthesis, Crystal Structures, And Dft Calculations Of Three New Cyano(Phenylsulfonyl)Indoles And A Key Synthetic Precursor Compound, William Montgomery, Justin Lopchuk, Gordon Gribble, Jerry Jasinski

Dartmouth Scholarship

Three cyano-1-(phenylsulfonyl)indole derivatives, 3-cyano-1-(phenylsulfonyl) indole, (I), 2-cyano-1-(phenylsulfonyl)indole, (II), and 2,3-dicyano-1-(phenylsulfonyl) indole, (III), and a key synthetic precursor 1-(phenylsulfonyl)-1-(1,1-dimethylethyl) indole-3-carboxamide, (IV), have been synthesized and their structures determined by single crystal X-ray crystallography. (I), C₁₅H₁₀N₂O₂S, is orthorhombic with space group P 2₁2₁2₁ and cell constants: a = 4.9459(3) Å, b = 10.5401(7) Å, c = 25.0813(14) Å, V = 1307.50(14) ų and Z = 4. (II), C₁₅H₁₀N₂O₂S, …

Biological Activity Of Recently Discovered Halogenated Marine Natural Products, Gordon Gribble

Dartmouth Scholarship

This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included.

(3+2)-Cycloaddition Reactions Of Oxyallyl Cations, Jimmy Wu, Hui Li

Dartmouth Scholarship

The (3+2)-cycloaddition reaction involving oxyallyl cations has proven to be a versatile and efficient approach for the construction of five-membered carbo- and heterocycles, which are prevalent frameworks in natural products and pharmaceuticals. The following article will provide a brief summary of recent disclosures on this process featuring chemo-, regio- and diastereoselective oxyallyl cycloadditions with both electron-rich and electron-deficient 2π partners.

Regulating Signal Enhancement With Coordination-Coupled Deprotonation Of A Hydrazone Switch, Justin T. Foy, Debdas Ray, Ivan Aprahamian

Dartmouth Scholarship

Proton relay plays an important role in many biocatalytic pathways. In order to mimic such processes in the context of molecular switches, we developed coordination-coupled deprotonation (CCD) driven signaling and signal enhancement sequences. This was accomplished by using the zinc(ii)-initiated CCD of a hydrazone switch to instigate an acid catalyzed imine bond hydrolysis that separates a quencher from a fluorophore thus leading to emission amplification. Because CCD is a reversible process, we were able to show that the catalysis can be regulated and turned “on” and “off” using a metalation/demetalation cycle.

Methyl 1-Benzyl-5-Methyl-2,4-Diphenyl-1h-Pyrrole-3-Carboxyl-Ate, Justin M. Lopchuk, Gordon W. Gribble, Jerry P. Jasinski

Dartmouth Scholarship

In the title compound, C26H23NO2, the dihedral angles between the pyrrole ring and the two phenyl rings are 58.1 (6) and 71.5 (5)°. The mean planes of the 5-methyl­benzene ring and the carboxyl group are twisted by 89.5 (3) and 22.1 (9)°, respectively, from the pyrrole ring. In the crystal, weak C—H⋯O inter­actions lead to supra­molecular layers in the ab plane.

Gene And Protein Sequence Optimization For High-Level Production Of Fully Active And Aglycosylated Lysostaphin In Pichia Pastoris, Hongliang Zhao, Kristina Blazanovic, Yoonjoo Choi, Chris Bailey-Kellogg, Karl E. Griswold

Dartmouth Scholarship

Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can …

The Importance Of The Rotor In Hydrazone-Based Molecular Switches, Xin Su, Timo Lessing, Ivan Aprahamian

Dartmouth Scholarship

The pH-activated E/Z isomerization of a series of hydrazone-based systems having different functional groups as part of the rotor (R = COMe, CN, Me, H), was studied. The switching efficiency of these systems was compared to that of a hydrazone-based molecular switch (R = COOEt) whose E/Z isomerization is fully reversible. It was found that the nature of the R group is critical for efficient switching to occur; the R group should be a moderate H-bond acceptor in order to (i) provide enough driving force for the rotor to move upon protonation, and (ii) stabilize the obtained Z configuration, to …

Variability Of Black Carbon Deposition To The East Antarctic Plateau, 1800-2000 Ad, M. M. Bisiaux, R. Edwards, J. R. Mcconnell, M. R. Albert

Dartmouth Scholarship

Refractory black carbon aerosols (rBC) from biomass burning and fossil fuel combustion are deposited to the Antarctic ice sheet and preserve a history of emissions and long-range transport from low- and mid-latitudes. Antarctic ice core rBC records may thus provide information with respect to past combustion aerosol emissions and atmospheric circulation. Here, we present six East Antarctic ice core records of rBC concentrations and fluxes covering the last two centuries with approximately annual resolution (cal. yr. 1800 to 2000). The ice cores were drilled in disparate regions of the high East Antarctic ice sheet, at different elevations and net snow …

3,3-Dimethyl-1,2,3,4-Tetra­Hydro­Cyclo­Penta­[B]Indole-1,2-Dione (Bruceolline E), Jason A. Jordon, Jeanese C. Badenock, Gordon W. Gribble, Jerry P. Jasinski, James A. Golen

Dartmouth Scholarship

The title compound, C13H11NO2, crystallizes with two mol­ecules in the asymmetric unit. The crystal packing is stabilized by N—H⋯O hydrogen bonds, which link the mol­ecules into chains along [10], and weak C—H⋯O inter­actions.

4-Phenyl­Sulfon­Yl-2-(P-Tolyl­Sulfon­Yl)-1h,8h-Pyrrolo­[2,3-B]Indole, Jeanese C. Badenock, Jason A. Jordan, Erin T. Pelkey, Gordon W. Gribble, Jerry P. Jasinski

Dartmouth Scholarship

The title compound, C23H18N2O4S2, contains a pyrrolo group fused onto the plane of an indole ring with phenylsulfonyl and p-toluenesulfonyl groups bonded to the indole and pyrrolo rings. The angles between the mean planes of the pyrrolo- indole ring and the phenylsulfonyl and p-toluenesulfonyl rings are 73.7 (6) and 80.6 (0)􏰈, respectively. The dihedral angle between the mean planes of the two benzene rings is 78.7 (4)􏰈. In the crystal, both classical N—H􏰇 􏰇 􏰇O and non-classical C— H􏰇 􏰇 􏰇O intermolecular hydrogen-bonding interactions are observed, as well as weak 􏰁–􏰁 interactions [centroid–centroid distances = 3.6258 (8) and 3.9298 (8) …

An Improved Synthesis Of A Ring-C Precursor To Cobyric Acid, Hui Wang, Peter A. Jacobi

Dartmouth Scholarship

Alkyne acid 10 was prepared in enantioselective fashion from allylic ester derivative (R)-18 via an E-selective Ireland-Claisen rearrangement followed by Si-assisted elimination of HBr. The present route offers significant advantages in terms of both scalability and overall yield compared to that previously described. Alkyne acid 10 is an attractive ring-C precursor for an ongoing synthesis of cobyric acid.

1, 2-Bis (Phenylsulfonyl)-1h-Indole As An Acceptor Of Organocuprate Nucleophiles, David C. Qian, Philip E. Alford, Tara L. S. Kishbaugh, Sean T. Jones, Gordon W. Gribble

Dartmouth Scholarship

1,2-Bis(phenylsulfonyl)-1H-indole is a novel example of an electron-deficient indole that undergoes nucleophilic attack at C-3. Though a variety of other organometallic nucleophiles fail to engender nucleophilic substitution, organocuprates produce 3-substituted 2-(phenylsulfonyl)-1H-indoles. These reactions contribute to the growing number of examples of nucleophilic addition to the indole core.

Synthetic Studies In Phytochrome Chemistry, Peter A. Jacobi, Imad Odeh, Subhas Buddhu, Guolin Cai, Sundaramoorthi Rajeswari, Douglas Fry, Wanjun Zheng, Robert W. Desimone, Jiasheng Guo, Lisa D. Coutts, Sheila I. Hauck, Sam H. Leung, Indranath Ghosh, Douglas Pippin

Dartmouth Scholarship

An account is given of the author’s several approaches to the synthesis of the parent chromophore of phytochrome (1), a protein-bound linear tetrapyrrole derivative that controls photomorphogenesis in higher plants. These studies culminated in enantioselective syntheses of both (2R)- and (2S)-phytochromobilin (4), as well as several ¹³C-labeled derivatives designed to probe the site of Z,E-isomerization during photoexcitation. When reacted in vitro, synthetic 2R-4 and recombinant-derived phytochrome apoprotein N-C produced a protein-bound chromophore with identical difference spectra to naturally occurring 1.

Crystal Structure Of The Gtpase Domain Of Rat Dynamin 1, Thomas F. Reubold, Susanne Eschenburg, Andreas Becker, Marilyn Leonard, Sandra L. Schmid, Richard B. Vallee, F. Jon Kull, Dietmar J. Manstein

Dartmouth Scholarship

Here, we present the 1.9-A crystal structure of the nucleotide-free GTPase domain of dynamin 1 from Rattus norvegicus. The structure corresponds to an extended form of the canonical GTPase fold observed in Ras proteins. Both nucleotide-binding switch motifs are well resolved, adopting conformations that closely resemble a GTP-bound state not previously observed for nucleotide-free GTPases. Two highly conserved arginines, Arg-66 and Arg-67, greatly restrict the mobility of switch I and are ideally positioned to relay information about the nucleotide state to other parts of the protein. Our results support a model in which switch I residue Arg-59 gates GTP binding …

Probabilistic Disease Classification Of Expression-Dependent Proteomic Data From Mass Spectrometry Of Human Serum, Ryan H. Lilien, Hany Farid, Bruce R. Donald

Dartmouth Scholarship

We have developed an algorithm called Q5 for probabilistic classification of healthy vs. disease whole serum samples using mass spectrometry. The algorithm employs Principal Components Analysis (PCA) followed by Linear Discriminant Analysis (LDA) on whole spectrum Surface-Enhanced Laser Desorption/Ionization Time of Flight (SELDI-TOF) Mass Spectrometry (MS) data, and is demonstrated on four real datasets from complete, complex SELDI spectra of human blood serum.

Q5 is a closed-form, exact solution to the problem of classification of complete mass spectra of a complex protein mixture. Q5 employs a novel probabilistic classification algorithm built upon a dimension-reduced linear discriminant analysis. Our solution is …

Regulation And Localization Of Endogenous Human Tristetraprolin, Anna-Marie Fairhurst, John E. Connolly, Katharine A Hintz, Nicolas J Goulding

Dartmouth Scholarship

Tumor necrosis factor (TNF) has been implicated in the development and pathogenicity of infectious diseases and autoimmune disorders, such as septic shock and arthritis. The zinc-finger protein tristetraprolin (TTP) has been identified as a major regulator of TNF biosynthesis. To define its intracellular location and examine its regulation of TNF, a quantitive intracellular staining assay specific for TTP was developed. We establish for the first time that in peripheral blood leukocytes, express

Synthesis Of Novel [3, 2-B] Indole Fused Oleanolic Acids As Potential Inhibitors Of Cell Proliferation, Heather J. Finlay, Tadashi Honda, Gordon W. Gribble

Dartmouth Scholarship

Seven new indole-fused oleanolic acid derivatives were synthesized from oleanolic acid for their ability to inhibit cell proliferation in NRP. 152 cells.

Reducing Mass Degeneracy In Sar By Ms By Stable Isotopic Labeling, Chris Bailey-Kellogg, John J. Kelley Iii, Cliff Stein, Bruce Randall Donald

Dartmouth Scholarship

Mass spectrometry (MS) promises to be an invaluable tool for functional genomics, by supporting low-cost, high-throughput experiments. However, large-scale MS faces the potential problem of mass degeneracy -- indistinguishable masses for multiple biopolymer fragments (e.g. from a limited proteolytic digest). This paper studies the tasks of planning and interpreting MS experiments that use selective isotopic labeling, thereby substantially reducing potential mass degeneracy. Our algorithms support an experimental-computational protocol called Structure-Activity Relation by Mass Spectrometry (SAR by MS), for elucidating the function of protein-DNA and protein-protein complexes. SAR by MS enzymatically cleaves a crosslinked complex and analyzes the resulting mass spectrum …

The Noesy Jigsaw: Automated Protein Secondary Structure And Main-Chain Assignment From Sparse, Unassigned Nmr Data, Chris Bailey-Kellogg, Alik Widge, John J. Kelley Iii, Marcelo J. Berardi, John H. Bushweller, Bruce Randall Donald

Dartmouth Scholarship

High-throughput, data-directed computational protocols for Structural Genomics (or Proteomics) are required in order to evaluate the protein products of genes for structure and function at rates comparable to current gene-sequencing technology. This paper presents the Jigsaw algorithm, a novel high-throughput, automated approach to protein structure characterization with nuclear magnetic resonance (NMR). Jigsaw consists of two main components: (1) graph-based secondary structure pattern identification in unassigned heteronuclear NMR data, and (2) assignment of spectral peaks by probabilistic alignment of identified secondary structure elements against the primary sequence. Jigsaw's deferment of assignment until after secondary structure identification differs greatly from traditional approaches, …

Chromium(Vi) Reduction By Ascorbate: Role Of Reactive Intermediates In Dna Damage In Vitro, D M. Stearns, K D. Courtney, P H. Giangrande, L S. Phieffer, Karen E. Wetterhahn

Dartmouth Scholarship

Reaction of chromium(VI) with one equivalent of ascorbate was studied by electron paramagnetic resonance spectroscopy in the presence of 0.10 M 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) at room temperature in 0.10 M (N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]) (HEPES) and 0.05 M tris(hydroxymethyl)aminomethane hydrochloride (Tris-HCl) buffers (pH 7.0 room temperature). Chromium(V), ascorbyl radical, and carbon-based DMPO-radical adducts were observed. A higher level of Cr(V) was observed in HEPES buffer and a higher level of the DMPO-radical adducts was observed in Tris-HCl buffer. Chromium-DNA binding studies were carried out in vitro for calf thymus DNA incubated with Cr(VI) and ascorbate in both buffers at 37 degrees C. Higher …

Evidence For Helical Structures In Poly(1-Olefin Sulfones) By Transmission Electron Microscopy, George C. Ruben, W H. Stockmayer

Dartmouth Scholarship

Transmission electron microscope images were obtained of fractions of poly(1-tetradecene sulfone) and poly(cyclohexene sulfone) cast from very dilute solutions (0.007%, wt/vol) and rapidly freeze-dried on a mica surface. The samples were then vertically platinum-carbon (Pt-C) replicated with 9 +/- 0.3-A Pt-C and held together with 128 A of electron-transparent evaporated carbon. The Pt-C coating enlarges the molecular chain diameters by approximately 5 A, so that a single polysulfone chain has an apparent diameter of 9-12 A in the transmission electron microscope. Poly(1-tetradecene sulfone) forms short helical regions that show irregular helical turns of pitch 7-18 A, two to eight turns …

Multiphoton Ionization Of Nitrobenzene In Non-Aqueous Solutions: Characterization Of The Cation And Ion-Molecule Chemistry, G. Siuzdak, J. J. Belbruno

Dartmouth Scholarship

The phenoxy cation has been generated in polar and nonpolar solutions by multiphoton ionization of nitrobenzene using nanosecond pulses of 266 nm and 355 nm light. The ions have been characterized by pulsed conductivity (ion mobility) measurements and transient absorption spectroscopy. The involvement of the phenoxy ion in ion-molecule chemistry with either neutral solute or solvent molecules has also been observed and the photochemical products and quantum yields of the ion-molecule products are presented and compared with the neutral photochemistry results.

Uv Multiphoton Induced Chemistry Of Nitrobenzene In Solution, Joseph J. Belbruno, Gary Siuzdak, Simon North

Dartmouth Scholarship

The technique of Multiphoton Induced Chemistry (MPIC) has been employed to initiate ion-molecule chemistry of organic molecules in solution. We report one of the first examples of the use of liquid phase multiphoton ionization (MPI) to prepare organic cations, which then react with the solvent in ionmolecule processes. The products obtained in this chemical sequence are significantly different from those observed in conventional or multiphoton-induced neutral chemistry in the same solvent. The particular example explored in this work is the reactivity of the nitrobenzene cation in methanol solvent. Products of the ion-molecule chemistry, detected by gas chromatography/mass spectrometry, are phenol …

The Homeo Domain Of A Murine Protein Binds 5' To Its Own Homeo Box., Abraham Fainsod, Leonard D. Bogarad, Tarmo Ruusala, Martin Lubin

Dartmouth Scholarship

Nuclear protein extracts from day 12.5 mouse embryos were used to study protein binding to DNA sequences 5' of the Hox 1.5 homeo box. Embryos of this developmental stage are known to express this gene. DNA binding protein blotting and retardation gel techniques show that murine embryonic nuclear proteins specifically bind a 753-base pair (bp) DNA fragment from the region upstream of the Hox 1.5 homeo box. A fusion protein containing the Hox 1.5 homeo domain constructed in lambda gt11 also binds the same 753-bp DNA fragment. Specific binding of the fusion protein to the upstream DNA fragment shows that …

Spermidine-Condensed Phi X174 Dna Cleavage By Micrococcal Nuclease: Torus Cleavage Model And Evidence For Unidirectional Circumferential Dna Wrapping., Kenneth A. Marx, Thomas C. Reynolds

Dartmouth Scholarship

Spermidine-condensed phi X174 replicative form (RF) II DNA was digested with micrococcal nuclease to yield seven identifiable DNA bands forming an arithmetic fragment-length series. The DNA monomer unit length was found to be 780 +/- 80 base pairs. This result is most consistent with a proposed model for micrococcal nuclease cleavage of a DNA torus organized by the unidirectional, circumferential wrapping of B-geometry DNA. By a topological consideration, the blunt-end-rod-fusion model for torus formation [Eickbush, T. H. & Moudrianakis, E. N. (1978) Cell 13, 295-306] is shown to be inconsistent with our empirical solution results. We propose a continuous, circumferential …

Excluded-Volume Effect On Quasi-Elastic Light Scattering By Flexible Macromolecules, Genzo Tanaka, Walter H. Stockmayer

Dartmouth Scholarship

First-order perturbation expressions are developed for the first cumulant (initial time derivative) of the dynamic structure factor observable by photon-correlation measurements of the light scattered by flexible chain molecules in solution. A dimensionless coefficient C, which measures the initial departure of the first cumulant from proportionality to the square of the scattering vector, is found to be only slightly altered by excluded-volume effects.