Author: Rebecca Ann JockuschPublisher:
ISBN:
Category :
Languages : en
Pages : 538
Book Description
Biomolecules and Their Noncovalent Complexes in the Gas Phase
Author: Rebecca Ann JockuschPublisher:
ISBN:
Category :
Languages : en
Pages : 538
Book Description
Nucleic Acids in the Gas Phase
Author: Valérie GabelicaPublisher: Springer
ISBN: 3642548423
Category : Science
Languages : en
Pages : 297
Book Description
This book gives physical chemists a broader view of potential biological applications of their techniques for the study of nucleic acids in the gas phase. It provides organic chemists, biophysicists, and pharmacologists with an introduction to new techniques they can use to find the answers to yet unsolved questions. Laboratory sciences have bloomed with a variety of techniques to decipher the properties of the molecules of life. This volume introduces techniques used to investigate the properties of nucleic acids in the absence of solvent. It highlights the specificities pertaining to the studies of nucleic acids, although some of the techniques can similarly be applied to the study of other biomolecules, like proteins. The first part of the book introduces the techniques, from the transfer of nucleic acids to the gas-phase, to their detailed physico-chemical investigation. Each chapter is devoted to a specific molecular property, and illustrates how various approaches (experimental and theoretical) can be combined for the interpretation. The second part of the book is devoted to applying the gas-phase approaches to solve specific questions related to the biophysics, biochemistry or pharmacology of nucleic acids.
Structural Influences of Noncovalent Interactions in the Gas Phase
Author: Terrence ChangPublisher:
ISBN:
Category :
Languages : en
Pages : 109
Book Description
The physical properties of molecules in solution, such as basicity and structure, depend on the cooperation and competition of noncovalent intra- and intermolecular interactions. Studying these interactions in the condensed phase is made difficult by the presence of competing influences from counterions and impurities. In the gas phase, however, specific ions, ion complexes and hydration states can be isolated and studied by Fourier transform mass spectrometry coupled with infrared (IR) laser spectroscopy. Using these two techniques, it is possible to isolate specific ions before inducing dissociation via absorption of IR photons. The extent of absorption at a given wavelength correlates to the relative abundance of product ions produced via dissociation, which can be measured using mass spectrometry. The absorption of IR photons only occurs at specific wavelengths depending on which functional groups are present and how their vibrational modes are influenced by interactions such as hydrogen bonding. Structural information is obtained from these spectra by interpreting the presence of certain bands and their frequencies. In addition, information can also be obtained by comparing the spectra from ions of interest to the spectra of reference ions, with known structures, or the simulated spectra of computed geometries. These types of studies provide valuable insight into how noncovalent interactions govern the structure of biomolecules and hydrogen-bonded networks. This dissertation reports experiments utilizing IR spectroscopy to study how water-ion interactions can affect both the structure of an ion solvated by an aqueous nanodrop as well as the hydrogen-bonding network of the nanodrop itself. In addition, the structural effects of ion-peptide interactions, which are relevant to understanding how ions influence biological processes, are also investigated. In order to study the ability of water to stabilize protonation sites on larger molecules, I investigated the influence of sequential hydration on the structure of protonated p-aminobenzoic acid (PABAH+), which has different preferred aqueous solution and gas-phase protonation sites. The preferred protonation site of PABA is the amine in aqueous solution, but the preferred protonation site is the carbonyl O atom of the carboxylic acid in the gas phase. The spectrum of PABAH+*(H2O)1 contains an absorption band at a particular photon energy indicating that protonation occurs at the carboxylic acid, i.e. there is a spectroscopic signature for the O-protonated structure. This absorption band persists for PABAH+*(H2O)2-6, indicating that these ions have a population of O-protonated isomers as well. Spectra for PABAH+*(H2O)6 are also consistent with presence of a second isomer, in which the amine is protonated. These results indicate that PABAH+ exists in the preferred gas-phase structure for PABAH+*(H2O)1-6, but there is a transition to the preferred solution-phase structure when the ion is solvated by six or more water molecules. In isolation, the excess charge associated with protonation at the carbonyl O atom of the carboxylic acid can be resonantly stabilized and delocalized into the phenyl ring and amine. When six or more water molecules are attached, however, a more favorable hydrogen-bonding network can be formed at the protonated amine than at the carboxylic acid. In contrast to PABAH+, protonation for m-aminobenzoic acid (MABA) occurs at the amine site even when solvated by only one water molecule due to orientation of the amine and carboxylic acid group. This orientation prevents the positive charge from being delocalized into the amine. Thus, MABAH+ serves as an ideal model for the solvation of the N- and C-termini of a protonated amino acid, for which the N- and C-termini typically interact with each other. The measured spectra for MABAH+*(H2O)1,2 are consistent with the attachment of water to a H atom of the protonated amine. For MABAH+*(H2O)3, the measured spectrum indicates that the dominant isomer has a hydrogen-bonded water bridge between the amine and carbonyl O atom of the carboxylic acid. This result indicates that the formation of this water bridge is more energetically favorable than the formation of a third ionic hydrogen bond to the amine group. The spectra for MABAH+*(H2O)n also indicate that water molecules attach to the carboxylic acid H atom, i.e. the ion is fully hydrogen-bonded when there are ≥6 water molecules attached. Ion spectroscopy can also be used to study how ion-water interactions influence hydration structures. Certain positive ions are known to induce cage-like clathrate structures when hydrated by 20 water molecules. The hydration of NH4+ as well as selected, protonated primary, secondary and tertiary amines solvated by 19 - 21 water molecules was investigated in order to elucidate details about how amines can stabilize clathrate structures. The spectra of NH4+ as well as monomethyl-, n-heptyl-, and tert-butylammonium+ with 20 water molecules attached are consistent with the nearly exclusive presence of clathrate structures, whereas nonclathrate structures are present for the more highly substituted amines. By comparison, nonclathrate structures are observed for all ions when 19 or 21 water molecules are attached. Spectroscopic evidence for clathrate structures for NH4+*(H2O)20 has been previously reported, but the location of the ion, whether at the surface or the interior, was difficult to determine based on the IR spectrum of this ion alone. Thus, the spectra of NH4+, monomethyl- and n-heptylammonium+ solvated by 20 water molecules were compared to those for Rb+ and tert-butylammonium+, which serve as references for clathrate structures with the ion located in the interior or at the surface, respectively. These comparisons indicate that NH4+ goes to the interior, whereas protonated primary amines are located at the surface, irrespective of the size of the alkyl group. In addition to ion-water interactions, ion-biomolecule interactions can also be probed by ion spectroscopy. Although there are several studies that have used ion spectroscopy to investigate cations coordinated to amino acids and peptides, there are fewer studies focused on these same biomolecules complexed with anion adducts. The ions Gly3*X-, Ala3*X- and Leu3*X- (X = Cl, Br and I) were studied in order to investigate how the size of anion adducts and alkyl side chains influence the coordination of halide anions to aliphatic peptides. The spectra of Gly3*Cl-, Ala3*Cl- and Leu3*Cl- suggest that all three complexes adopt similar structures, where Cl- coordinates to the peptides by accepting three or four hydrogen bonds from the amides as well as the N- and C-termini. These results indicate that the size of the alkyl chain does not have a significant influence on the coordination geometry of these complexes. These structures are "inverted" in comparison to previously reported structures for Gly3*Na+ and Ala3*Na+, where the Na+ coordinates to lone pair electrons of the N atom of the N-terminus, or the carbonyl O atoms of the amides and C-terminus. The spectra of Gly3*X-, Ala3*X- and Leu3*X- each appear similar to each other within each peptide, indicating that the size of the anion does not significantly affect the coordination geometry.
Gas-phase Non-covalent Complex
Author: Xin CongMass Spectrometry in Biophysics
Author: Igor A. KaltashovPublisher: John Wiley & Sons
ISBN: 0471705160
Category : Science
Languages : en
Pages : 320
Book Description
The first systematic summary of biophysical mass spectrometrytechniques Recent advances in mass spectrometry (MS) have pushed the frontiersof analytical chemistry into the biophysical laboratory. As aresult, the biophysical community's acceptance of MS-based methods,used to study protein higher-order structure and dynamics, hasaccelerated the expansion of biophysical MS. Despite this growing trend, until now no single text has presentedthe full array of MS-based experimental techniques and strategiesfor biophysics. Mass Spectrometry in Biophysics expertly closesthis gap in the literature. Covering the theoretical background and technical aspects of eachmethod, this much-needed reference offers an unparalleled overviewof the current state of biophysical MS. Mass Spectrometry inBiophysics begins with a helpful discussion of general biophysicalconcepts and MS-related techniques. Subsequent chaptersaddress: * Modern spectrometric hardware * High-order structure and dynamics as probed by various MS-basedmethods * Techniques used to study structure and behavior of non-nativeprotein states that become populated under denaturingconditions * Kinetic aspects of protein folding and enzyme catalysis * MS-based methods used to extract quantitative information onprotein-ligand interactions * Relation of MS-based techniques to other experimental tools * Biomolecular properties in the gas phase Fully referenced and containing a helpful appendix on the physicsof electrospray mass spectrometry, Mass Spectrometry in Biophysicsalso offers a compelling look at the current challenges facingbiomolecular MS and the potential applications that will likelyshape its future.
Structural Elucidation of Biomolecular Ions in the Gas Phase Using Novel Mass Spectrometric and Computational Methods
Author: Yang LiuPublisher:
ISBN:
Category :
Languages : en
Pages : 194
Book Description
Biological molecules such as protein and DNA play critical roles in various cellular reactions and carry out essential biological functions. But the mechanisms of these reactions, and the essential molecular structures to facilitate them are often poorly understood. Many efforts have been applied to these problems, but due to their complexity and various limitations of existing methods, the elucidation of biological reaction mechanisms and biological molecule or complex structures is still considered a challenge today. Therefore, the scientific community has been highly motivated to invent new methods to tackle these problems devise new angles of approach to grain insights into biomolecular structure. This dissertation summarizes some recent work in characterizing cation-radical reactions, and structures of gas-phase molecular complexes using novel mass spectrometry methods in combination with theoretical computational modeling. The novel mass spectrometric methods presented in this work are gas-phase photo-dissociative crosslinking techniques and UV-visible photodissociation action spectroscopy. They have several unique advantages in tackling structure elucidation of weakly bound complexes and transient radical species. 1) The mass spectrometer (MS) is a universal detector which is widely used to characterize various kinds of biological molecules. 2) MS works with ions of interest that are generated and stored in the gas phase at low pressure of an inert gas (He). It is the perfect system to study reaction mechanisms because of low interference from the ambient environment, such as solvent, counterions, surfaces, etc. 3) Methods exist to generate cation radicals in the gas phase, and thanks to the low pressure inside a mass spectrometer, the produced species are kinetically stable on the experimental time scale of several milliseconds. 4) MS is a perfect tool for conducting gas-phase reactions because it allows one to manipulate the ion population and select and focus the ions. It is advantageous for crosslinking reactions that often suffer from low concentrations of reactants when the reaction is attempted in condensed phase. 5) The experimental action spectra can be interpreted using sophisticated computational techniques providing vibronic transitions of multiple isomeric candidates. The new data generated with these new mass spectrometry methods offer unique insights, but also pose challenges to experimental data interpretation. Various computational approaches are used to supplement the experimental data, and the results from the computations are used to guide the interpretation. This dissertation also includes several novel approaches on the computational front, introducing the customized modeling pipeline with a combination of Born-Oppenheimer dynamics, density functional theory calculations, and machine learning techniques. The first chapter introduces some basic terms and outlines the background for the topic of study, including a quick review of the current challenges and techniques in the field of structure elucidation of biomolecules. Also introduced are the fundamentals of mass spectrometer, commonly used and newly developed ion activation methods, and computational modeling. This chapter lays the foundation of the work described in later chapters. A small neuroprotective peptide Cys-Ala-Gln-Lys (CAQK) has recently been discovered to mitigate adverse effects of brain trauma in mice, possibly because of specific interactions with yet-to-be identified proteins. In Chapter 2, an application of photo-crosslinking is described to study the noncovalent interactions of CAQK with several model target peptide motifs. The experimental results in combination with Born-Oppenheimer molecular dynamics revealed the structural preferences for binding to the amino acid residues of potential target peptides. In Chapter 3, inspired by the biological significance of CAQK, we employed the photo-dissociative crosslinking techniques to probe its interactions with several dinucleotides as structure motifs of nuclear DNA. This lysine-containing peptide can be viewed as a simplified surrogate of a histone interacting with DNA. We were able to show that in interactions with CAQK ions, even simple dinucleotides differ in their binding efficiency and stereochemistry. We provided structures of selected complexes obtained by electronic structure theory calculations using density functional theory (DFT). UV and energetic particle radiation can ionize DNA creating electron deficiency (hole) at nucleobases. These holes can migrate along the strand, leading to lesions and DNA damage by follow up radical reactions. Chapter 4 and chapter 5 are focused on the characterization of DNA cation radicals in the guanine and cytosine containing dinucleotide as model systems in probing the electron transfer mechanisms in DNA radiation damage. Experimental action spectra were obtained for these small nucleotides and the absorption bands were interpreted by finding the closest match from the calculated spectra. The last chapter features an ongoing project in which we have made an attempt, using photo-crosslinking techniques, to probe noncovalent interactions within a complex consisting of a chiral agonist and its binding motifs. The experimental results revealed high binding affinity of the native agonist regardless of chirality, however the crosslinking fragment was not observed. Several DFT optimized low energy structure had shown a consistently low "contact" rate of the phototag with the target peptide. A further characterization of ion structures will be complemented from the collisional cross section analysis by ion mobility (IM) measurements.
Principles of Mass Spectrometry Applied to Biomolecules
Author: Chava LifshitzPublisher: John Wiley & Sons
ISBN: 0470050411
Category : Science
Languages : en
Pages : 707
Book Description
An extensive compilation of articles by leading professionals, this reference explains the fundamental principles of mass spectrometry as they relate to the life sciences. Topics covered include spectroscopy, energetics and mechanisms of peptide fragmentation, electron capture dissociation, ion-ion and ion-molecule reactions, reaction dynamics, collisional activation, soft-landing, protein structure and interactions, thermochemistry, and more. The book empowers readers to develop new ways of using these techniques.
Mass Spectrometry of Non-Covalent Complexes
Author: Christoph A. SchalleyPublisher: John Wiley & Sons
ISBN: 0470131152
Category : Science
Languages : en
Pages : 593
Book Description
Details the many benefits of applying mass spectrometry to supramolecular chemistry Except as a method for the most basic measurements, mass spectrometry (MS) has long been considered incompatible with supramolecular chemistry. Yet, with today's methods, the disconnect between these two fields is not warranted. Mass Spectrometry and Gas-Phase Chemistry of Non-Covalent Complexes provides a convincing look at how modern MS techniques offer supramolecular chemists a powerful investigatory toolset. Bringing the two fields together in an interdisciplinary manner, this reference details the many different topics associated with the study of non-covalent complexes in the gas phase. The text begins with brief introductions to supramolecular chemistry and such relevant mass spectrometric methods as ionization techniques, analyzers, and tandem MS experiments. The coverage continues with: How the analyte's transition into the gas phase changes covalent bonding How limitations and pitfalls in analytical methods may produce data misinterpretations Artificial supramolecular aggregates and their examination Biomolecules, their complexes, and their examination After the general remarks making up the first section of the book, the following sections describe specific experimental procedures and are illustrated with numerous examples and short tutorials. Detailed citations end each chapter. Mass spectrometrists, supramolecular chemists, students in these fields, and interested readers from other disciplines involving the study of non-covalent bonds will all value Mass Spectrometry and Gas-Phase Chemistry of Non-Covalent Complexes as an innovative and practical resource.
Gas Phase Studies of Biomolecules Complexed to Ligated Platinum (II) Derivatives
Author: Michelle Leanne StylesPublisher:
ISBN:
Category : Gases
Languages : en
Pages : 536
Book Description
Author: Andrey Dyachenko