120 research outputs found

    Cooperative multiple hydrogen bonding in supramolecular chemistry

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    Instrumentation and development of a mass spectrometry system for the study of gas-phase biomolecular ion reactions

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    Gas-phase reactions of biomolecular ions are highly relevant to the understanding of structures and functions of the biomolecules. Mass spectrometry is a powerful tool in investigating gas-phase ion chemistry. Various mass spectrometers have been developed to explore ion/molecule reactions, ion/ion reactions, ion/photon reactions, ion/radical reactions etc., both at atmospheric pressure and in vacuum. In-vacuum reactions have an advantage of involving pre-selecting the ions for the reactions using a mass analyzer. Over the decades, a variety of mass analyzers have been employed in the research of ion chemistry. Hybrid configurations, such as quadrupole ion trap with a time-of-flight and or a quadrupole ion trap tandem with an Orbitrap, have been utilized to improve the performances for both the reaction (in trapping mode) and the mass analysis (accurate mass measurements). Complicated instrument structures, including ion optics, multiple mass analyzers and differential pumping for high vacuum, are typically required for the mass spectrometers for gas phase ion chemistry study. An alternative approach is to simplify the instrumentation by using pulsed discontinuous atmospheric pressure interfaces for introducing ionic or neutral reactants and a single ion trap as both the reactor and the mass analyzer. Such a simple mass spectrometry system was set up and demonstrated using two discontinuous atmospheric pressure interfaces in the study for this thesis. It was capable of carrying out ion/molecule and ion/ion reactions at an elevated pressure without the needs of ion optics or differential pumping system. Together with a pyrolysis radical source, in-vacuum ion/radical reactions were performed and their associated chemistry was studied. Radicals are important intermediates related to biochemical processes and biological functions. There are very limited techniques to monitor the reactive intermediates in-situ during a multi-step reaction in aqueous phase. On the other hand, these intermediates can be cooled down and preserved into a single-step procedure in gas-phase reactions since they only occur via collisions. Therefore, the fundamental study of gas-phase radical ion chemistry will provide evidences of the reactivity, energetics, and structural information of biological radicals, which has the potential to solve puzzles of aging, disease biomarker identification, and enzymatic activities. Using the system described above, a new reaction between protonated alkyl amines and pyrolysis formed cyclopropenylidene carbene was discovered, as the first experimental evidence of the reactivity of cyclopropenylidene. Given the important role of cyclopropenylidene in the combustion chemistry, organic synthesis, and interstellar chemistry, it is highly desirable to establish a fundamental understanding of their physical and chemical properties. The amine/cyclopropenylidene reactions were systematically studied using both theoretical calculation and experimental evidences. A proton-bound dimer reaction mechanism was proposed, with the amine and the carbene sharing a proton to form a complex as the first step, which was closely related to the high gas-phase basicity of cyclopropenylidene. Subsequent unimolecular dissociation of the complex yielded three possible reaction pathways, including proton-transfer to the carbene, covalent product formation, and direct separation. These reactions were studied with a variety of alkyl amines of different gas-phase basicities. For the covalent complex formation, partial protonation on cyclopropenylidene within the dimer facilitates subsequent nucleophilic attack to the carbene carbon by the amine nitrogen and leads to a C-N bond formation. The highest yield of covalent complex was achieved with the gas-phase basicity of the amine slightly lower but comparable to cyclopropenylidene. The results demonstrated a new reaction pathway of cyclopropenylidene besides the formation of cyclopropenium, which has long been considered as a dead end in interstellar carbon chemistry. Further reactivity study of cyclopropenylidene towards biomolecular ions was also carried out for nucleobases, nucleosides, amino acids, peptides, proteins, and lipids. The reaction to form proton-bound dimer for protonated biomolecular ions remained as the dominant reaction pathway. Interestingly, other possible reaction pathways, such as modifications of thiyl group or disulfide bonds, double bond addition, and single bond insertion, were inhibited in gas-phase ion/carbene reactions. Such results inferred that the reactivity of neutral species was not directly applicable to ion reactions, with the proton involved in the gas-phase biomolecular ion reactions

    Ab initio study of alanine-based polypeptide secondary-structure motifs in the gas phase

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    The Synthesis and Characterization Studies of Modified Nucleobase in PNA and DNA

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    Nucleic acids have been extensively studied not only for their importance in biological systems as the medium of genetic information but also for their potential uses in therapeutic, diagnostic and other biological applications. As such, modified oligonucleotides and oligonucleotide analogues have drawn the attention of researchers from various disciplines. Modification of oligonucleotides can enhance their desired characteristics and engender unique properties, such as fluorescence, giving rise to a variety of applications. Peptide nucleic acid (PNA) is an oligonucleotide mimic with a pseudo-peptide backbone based on N-(2-aminoethyl)glycine that is renowned for high target binding affinity and resistance to enzyme degradation. These properties of PNA are useful in their application as sequence-selective probes and other bioanalytical applications. Thus, the overall theme of this thesis was the synthesis and evaluation of nucleobase-modified PNA and DNA monomers and the investigation of their effects on the physicochemical and photophysical characteristics of oligonucleotides and analogues. The nucleobase modification 5-nitrouracil has only been investigated in-silico and these studies indicate that the 5-nitrouracil-adenine base pair is more energetically favourable than the uracil-adenine base-pair. We have constructed an experimental system to investigate the base-pairing ability of 5-nitrouracil in the context of a PNA oligomer. PNA oligomers possessing 5-nitrouracil substitution for uracil were studied in both duplex and triplex binding modes. 5-nitrouracil destabilized in the duplex forming sequence. However, in the triplex study, 5-nitrouracil formed stronger hydrogen bonds with adenine when it was incorporated into the Hoogsteen strand of a bis-PNA triplex. The discrimination of matched binding versus mismatched binding was also investigated. This study showed that 5-nitroU maintained the specificity for the matching complementary base pair. We have also investigated the synthesis of modified nucleobases which possess dark fluorophore properties so that they act as a quencher when paired with an appropriate fluorophore. Two fluorophore systems, that change conformation and switch between quenched and fluorescent states are known as molecular beacons. This work contributes to the design of a new model for a molecular beacon in which a base-pairing competent fluorescent nucleobase and a nucleobase quencher are incorporated in the stem region of a stem-loop sequence. An improved synthesis of the 5-(4-(N,N-dimethylamino)phenylazo-yl)uracil (DMPAU) PNA analog was achieved. Subsequently, its ability to hydrogen bond to adenine was determined by NMR methods, and it was found to associate with adenine as strongly as thymine, with a Ka ~ 120 in chloroform. The ability of DMPAU to quench the fluorescence of the intrinsically fluorescent 6-phenylpyrrolocytosine (PhpC) and a selection of other common fluorophores was examined. These results allow us to predict that the DMPAU-PhpC make a suitable fluorophore-quencher pair for molecular beacon development. Finally, an extension of the DMPAU base modification was developed for the 2′-deoxynucleoside, which resulted in 5-(4-(N,N-dimethylamino)phenylazo-yl)-2′-deoxyuridine (DMPAdU). A new synthetic route for starting with 2′-deoxyuridine was developed to avoid the need for a stereochemically-controlled glycoside bond formation which has been problematic in past syntheses from our lab. During the synthesis, the method for selective acylation of 2′-deoxyuridine was studied. The optimized condition for the diazotization of 5-amino-2′-deoxyuridine without glycosidic bond breakage was described. With the photophysical characterization of DMPAdU, the quenching ability was tested against 6-phenylpyrrolo-2′-deoxycytidine (PhpdC) fluorophore

    Complementary quadruple hydrogen bonding

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    Biological Systems Workbook: Data modelling and simulations at molecular level

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    Nowadays, there are huge quantities of data surrounding the different fields of biology derived from experiments and theoretical simulations, where results are often stored in biological databases that are growing at a vertiginous rate every year. Therefore, there is an increasing research interest in the application of mathematical and physical models able to produce reliable predictions and explanations to understand and rationalize that information. All these investigations are helping to overcome biological questions pushing forward in the solution of problems faced by our society. In this Biological Systems Workbook, we aim to introduce the basic pieces allowing life to take place, from the 3D structural point of view. We will start learning how to look at the 3D structure of molecules from studying small organic molecules used as drugs. Meanwhile, we will learn some methods that help us to generate models of these structures. Then we will move to more complex natural organic molecules as lipid or carbohydrates, learning how to estimate and reproduce their dynamics. Later, we will revise the structure of more complex macromolecules as proteins or DNA. Along this process, we will refer to different computational tools and databases that will help us to search, analyze and model the different molecular systems studied in this course

    Explicit treatment of hydrogen bonds in the universal force field: Validation and application for metal-organic frameworks, hydrates, and host-guest complexes

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    A straightforward means to include explicit hydrogen bonds within the Universal Force Field (UFF) is presented. Instead of treating hydrogen bonds as non-bonded interaction subjected to electrostatic and Lennard-Jones potentials, we introduce an explicit bond with a negligible bond order, thus maintaining the structural integrity of the H-bonded complexes and avoiding the necessity to assign arbitrary charges to the system. The explicit hydrogen bond changes the coordination number of the acceptor site and the approach is thus most suitable for systems with under-coordinated atoms, such as many metalorganic frameworks; however, it also shows an excellent performance for other systems involving a hydrogen-bonded framework. In particular, it is an excellent means for creating starting structures for molecular dynamics and for investigations employing more sophisticated methods. The approach is validated for the hydrogen bonded complexes in the S22 dataset and then employed for a set of metal-organic frameworks from the Computation-Ready Experimental database and several hydrogen bonded crystals including water ice and clathrates. We show that the direct inclusion of hydrogen bonds reduces the maximum error in predicted cell parameters from 66% to only 14%, and the mean unsigned error is similarly reduced from 14% to only 4%. We posit that with the inclusion of hydrogen bonding, the solvent-mediated breathing of frameworks such as MIL-53 is nowaccessible to rapid UFF calculations, which will further the aim of rapid computational scanning of metal-organic frameworks while providing better starting points for electronic structure calculations

    Poster Session

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    Posters presented by: P01: Adam S. Abbott, University of Georgia P02: Yasmeen Abdo, University of Mississippi P03: Vibin Abraham, Virginia Tech P04: Asim Alenaizan, Georgia Institute of Technology P05: Isuru R. Ariyanthna, Auburn University P06: Brandon W. Bakr, Georgia Institute of Technology P07: [Matthew Bassett, Georgia Southern University] P08: Alexandre P. Bazanté, University of Florida P09: Andrea N. Becker, University of Tennessee P10: Randi Beil, University of Tennessee P11: Andrea N. Bootsma, University of Georgia/Texas A&M University P12: Adam Bruner, Louisiana State University P13: Lori A. Burns, Georgia Institute of Technology P14: Chanxi Cai, Emory University P15: Katherine A. Charbonnet, University of Memphis P16: Marjory C. Clement, Virginia Tech P17: Wallace D. Derricotte, Emory University P18: Harkiran Dhah, University of Tennessee P19: Manuel Díaz-Tinoco, Auburn University P20: Vivek Dixit: Mississippi State University P21: Eric Van Dornshuld, Mississippi State University P22: Katelyn M. Dreux, University of Mississippi P23: Narendra Nath Dutta, Auburn University P24: William Earwood, University of Mississippi P25: Thomas L. Ellington, University of Mississippi P26: Marissa L. Estep, University of Georgia P27: Yanfei Guan, Texas A&M University P28: Andrew M. James, Virginia Tech P29: Yifan Jin, University of Florida P30: Dwayne John, Middle Tennessee State University P31: Sarah N. Johnson, University of Mississippi P32: Noor Md Shahriar Khan, Auburn University P33: Monika Kodrycka, Auburn University P34: Ashutosh Kumar, Virginia Tech P35: Elliot Lakner, University of Alabama P36: Robert W. Lamb, Mississippi State University P37: S. Paul Lee, University of Mississippi P38: Zachary Lee, University of Alabama P39: Conrad D. Lewis, Middle Tennessee State University P40: Guangchao Liang, Mississippi State University P41: Chenyang Li, Emory University P42: Hannah C. Lozano, University of Memphis P43: SharathChandra Mallojjala, University of Georgia/Texas A&M University P44: Zheng Ma, Duke University P45: Elvis Maradzike, Florida State University P46: Ashley S. McNeill, University of Alabama P47: Stephen R. Miller, University of Georgia P48: W. J. Morgan, University of Georgia P49: Apurba Nandi, Emory University P50: Daniel R. Nascimento, Florida State University P51: Brooke N. Nash, Mississippi College P52: Carlie M. Novak, Georgia Southern University P53: Young Choon Park, University of Florida P54: Kirk C. Pearce, Virginia Tech P55: Rudradatt (Randy) Persaud, University of Alabama P56: Karl Pierce, Virginia Tech P57: Kimberley N. Poland, University of Mississippi P58: Chen Qu, Emory University P59: Duminda S. Ranasinghe, University of Florida P60: Hailey B. Reed, University of Mississippi P61: Matthew Schieber, Georgia Institute of Technology P62: Jeffrey B. Schriber, Emory University P63: Thomas Sexton, University of Mississippi P64: Holden T. Smith, Louisiana State University P65: Aubrey Smyly, Mississippi College P66: B. T. Soto, University of Georgia P67: Trent H. Stein, University of Alabama P68: Cody J. Stephan, Georgia Southern University P69: Thomas Summers, University of Memphis P70: Zhi Sun, University of Georgia P71: Monica Vasiliu, University of Alabama P72: Jonathan M. Waldrop, Auburn University P73: Tommy Walls, Southern Louisiana University P74: Qingfeng (Kee) Wang, Emory University P75: Constance E. Warden, Georgia Institute of Technology P76: Jared D. Weidman, University of Georgia P77: Melody Williams, University of Memphis P78: Donna Xia, University of Alabama P79: Qi Yu, Emory University P80: Boyi Zhang, University of Georgia P81: Tianyuan Zhang, Emory University P82: Michael Zott, Georgia Institute of Technolog

    Infrared laser spectroscopy of isolated biomolecules in superfluid helium nanodroplets

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    The focus of this thesis is the identification and structural characterization of iso- lated biomolecules in superfluid helium nanodroplets. We have recently developed structural tools for studying isolated biomolecules, including nucleic acid bases (NABs) (cytosine, guanine, uracil, thymine, and adenine), their mono-hydrated complexes and other biologically important molecules, using high resolution infrared laser spectroscopy. The structural tool called vibrational transition moment angle (VTMA) has been developed for measuring the angle between the permanent dipole moment and transition dipole directions in these species and provides unambiguous structural determinations for many systems. This is a very powerful technique, especially for larger systems, be- cause relatively low level ab initio calculations are able to predict the correct VTMA, when the calculated and experimental vibrational frequencies do not agree. Another powerful tool for structural determination is used to determine the dipole moments of various isomers by measuring the intensity of a particular band as a function of direct current electric field. We have applied these new techniques to the study of the isolated biomolecules, such as tautomerism of NABs, their nonplanarities, energetics, and the intermolecular interactions in the hydrated NABs. These results provide benchmarks for the evaluation of ab initio calculations being carried out on these systems

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