Hydrogen exchange and mass spectrometry: A historical perspective

Protein molecules naturally emit streams of information-rich signals in the language of hydrogen exchange concerning the intimate details of their stability, dynamics, function, changes therein, and effects thereon, all resolved to the level of their individual amino acids. The effort to measure protein hydrogen exchange behavior, understand the underlying chemistry and structural physics of hydrogen exchange processes, and use this information to learn about protein properties and function has continued for 50 years. Recent work uses mass spectrometric analysis together with an earlier proteolytic fragmentation method to extend the hydrogen exchange capability to large biologically interesting proteins. This article briefly reviews the advances that have led us to this point and the understanding that has so far been achieved.     

TIME-RESOLVED PHOTOACOUSTIC CALORIMETRY OF TRYPTOPHAN IN WATER AND ORGANIC SOLVENTS

Abstract: Very little has been done in the direct study of nonradiative decays of Trp, indole and derivatives, in spite of their relatively low fluorescence quantum yields. Time-resolved photoacoustic calorimetry is an ideal technique for this kind of study: it is very sensitive in the detection of small amounts of heat released and, in principle, allows a broad band of temporal resolution. The photoacoustic apparatus used for our measurements offers a temporal window between 10 ns and 10 μs. The analysis of the waveforms, based on a particular deconvolution method, simultaneously gives the fraction of energy released and the associated lifetime. In a broad sense, time-resolved photoacoustic spectroscopy can be seen as a complementary method to traditional radiative techniques such as static, time-resolved fluorescence and flash photolysis. The present work presents studies of Trp in different solvents in order to acquire new information about the interaction of this chromophore with solvents. From our measurements the high sensitivity of Trp to solvents is confirmed. The formation of complexes is evident at the excited state (exciplexes), between the chromophore and one or more molecules of solvent. These exciplexes are characterized by having an energy different from that of the singlet and triplet of Trp. Moreover, photoacoustic measurements detect, in water, the presence of another electronic state, which seems to have characteristics similar to a triplet-like state reported in other work.     

TIME-RESOLVED PHOTOACOUSTIC CALORIMETRY OF TRYPTOPHAN IN WATER and ORGANIC SOLVENTS

Abstract –Very little has been done in the direct study of nonradiative decays of Trp, indole and derivatives, in spite of their relatively low fluorescence quantum yields. Time-resolved photoacoustic calorimetry is an ideal technique for this kind of study: it is very sensitive in the detection of small amounts of heat released and, in principle, allows a broad band of temporal resolution. The photoacoustic apparatus used for our measurements offers a temporal window between 10 ns and 10 μs. The analysis of the waveforms, based on a particular deconvolution method, simultaneously gives the fraction of energy released and the associated lifetime. In a broad sense, time-resolved photoacoustic spectroscopy can be seen as a complementary method to traditional radiative techniques such as static, time-resolved fluorescence and flash photolysis. The present work presents studies of Trp in different solvents in order to acquire new information about the interaction of this chromophore with solvents. From our measurements the high sensitivity of Trp to solvents is confirmed. The formation of complexes is evident at the excited state (exciplexes), between the chromophore and one or more molecules of solvent. These exciplexes are characterized by having an energy different from that of the singlet and triplet of Trp. Moreover, photoacoustic measurements detect, in water, the presence of another electronic state, which seems to have characteristics similar to a triplet-like state reported in other work.     

Dissociative double photoionization of singly deuterated benzene molecules in the 26-33 eV energy range

This work provides new experimental and theoretical results about the formation and dissociation of benzene dication. The experiment has been carried out by using a vacuum ultraviolet radiation from a synchrotron source together with a time-of-flight spectrometer and a position sensitive ion detector. Isotopically labeled benzene molecules with a single deuterium atom have been used in order to study the symmetric dissociation of the benzene dication, not well evident in previous experiments. A threshold of 30.1 ± 0.1 eV has been observed for this dissociation reaction. Moreover, the lifetime of the dissociation of the benzene metastable dication producing CH(3)(+) and C(5)H(3)(+) has been obtained as a function of the photon energy, by the use of a Monte Carlo trajectory analysis of the coincidence distributions. The determined lifetime is independent of the photon energy and has an average value of 0.75 ± 0.22 μs. Theoretical calculations of the energy and structure of dissociation product ions have been also performed to provide crucial information about the dynamics of the charge separation reactions following the photoionization event.     

Hydrogen exchange mass spectrometry: what is it and what can it tell us?

Proteins are undoubtedly some of the most essential molecules of life. While much is known about many proteins, some aspects still remain mysterious. One particularly important aspect of understanding proteins is determining how structure helps dictate function. Continued development and implementation of biophysical techniques that provide information about protein conformation and dynamics is essential. In this review, we discuss hydrogen exchange mass spectrometry and how this method can be used to learn about protein conformation and dynamics. The basic concepts of the method are described, the workflow illustrated, and a few examples of its application are provided.     

Cyclic Voltammetry—“Electrochemical Spectroscopy”. New Analytical Methods (25)

Polarography is still the best known classical measuring method in electroanalytical chemistry. However, in recent years its position has been challenged by cyclic voltammetry (CV). Simple diagnostic criteria and relatively easily acquired measuring techniques have hastened this development. Cyclic voltammetry has the further attraction of providing information not only on the thermodynamics of redox processes but also on the kinetics of heterogeneous electron-transfer reactions and coupled chemical reactions. The characteristic shapes of the voltammetric waves and their unequivocal position on the potential scale virtually fingerprint the individual electrochemical properties of redox systems. For this reason the method has been labeled “electrochemical spectroscopy”.     

Modulated surface vibrational spectroscopy at the electrode—solution interface

Infrared spectroelectrochemistry can be used to examine reactions occurring at the electrode—solution interface. This vibrational probe can be applied to study the structure and orientation of molecules and the dynamics of adsorption—desorption processes at the electrode surface. The technique can reveal valuable information about the mechanisms and kinetics of surface reactions.     

The feasibility of standardless molecular spectral analysis of mixtures under conditions of photochemical transformations of molecules

The problem of standardless molecular spectral analysis of multicomponent mixtures with allowance for photochemical reactions of their molecules has been formulated and its formal procedure has been developed. The case when the time dependence of the spectrum of the mixture is determined only by the change in the concentrations of the components with time and the spectra of the individual components remain constant has been considered. The corresponding requirements for the physicochemical properties of the molecules have been identified and shown to be met for quite a wide range of polyatomic molecules and their reactions. The exception is molecules with metastable excited electronic states. A large set of model calculations relevant to the actual molecular entities and their experimentally observed photochemical transformations have shown the practicability of the approach. The solution of the problem converges to exact values and is resistant to uncertainty in setting the initial spectral data due to the peculiarities of the experimental procedure, the choice of theoretical models, and other factors. The resulting theoretical values of the concentrations meet the least squares test and their errors are measured by the variance per unit weight. The variance makes it possible to evaluate the noise level of the spectral data used in the analysis and reliability of the result and can serve as a criterion for the correctness of the initial hypotheses about the qualitative composition of a multicomponent mixture.     

Emerging supramolecular chemistry of gases

Molecular recognition of gases is an emerging area of chemistry. Supramolecular chemistry helps us to understand how gases interact with biological molecules and offers delicate insights into the mechanisms of their physiological activity. Principles of molecular recognition have been used for gas sensing, and have provided fundamental knowledge about the structure and dynamics of receptor-analyte complexes, and novel materials for gas sensing and storage have been developed. Supramolecular chemistry is also enabling us to learn how to transform gases into synthetically useful reagents. The rational design of novel catalysts for gas conversion and, more recently, encapsulation complexes with gases open novel directions in preparative synthetic chemistry.     

Recent advances in crossed-beam studies of bimolecular reactions

A critical overview of the recent progress in crossed-beam reactive scattering is presented. This review is not intended to be an exhaustive nor a comprehensive one, but rather a critical assessment of what we have been learning about bimolecular reaction dynamics using crossed molecular beams since year 2000. Particular emphasis is placed on the information content encoded in the product angular distribution-the trait of a typical molecular beam scattering experiment-and how the information can help in answering fundamental questions about chemical reactivity. We will start with simple reactions by highlighting a few benchmark three-atom reactions, and then move on progressively to the more complex chemical systems and with more sophisticated types of measurements. Understanding what cause the experimental observations is more than computationally simulating the results. The give and take between experiment and theory in unraveling the physical picture of the underlying dynamics is illustrated throughout this review.     

Photochemistry in Interstellar Space and Reactions Generating Interstellar Molecules

Over 20 different molecules and radicals have so far been detected in interstellar space. The number of such molecules and radicals and their frequently complicated structure raise the question of the processes leading to their formation. Diatomic molecules and radicals could arise in gas-phase reactions. Formation of polyatomic molecules can be explained in terms of reactions proceeding on the surface dust particles and possibly involving interstellar radiation. The author demonstrates, with the aid of a model, that the molecular abundances and distributions within dust clouds in certain regions can be explained by photocatalytic reactions.     

Spatiotemporal Control of Enzyme‐Induced Crystallization Under Lyotropic Liquid Crystal Nanoconfinement

Water nanoconfinement has important effects on the properties of biomolecules and ultimately on their specific functions. By performing experiments and molecular dynamic simulations, we show how intrinsic nanoconfinement controls the crystallization of small organic molecules converted by enzymatic reactions within the water nanochannels of lipid cubic phases (LCPs). By controlling the nanochannel size, enzymatic reactions in LCPs can be engineered to turn the same converted substrate into its soluble, microcrystal, or needle‐like crystal form due to the large variability in water dynamics. Differential scanning calorimetry studies, supported by molecular dynamics simulations, show that most of water within the mesophase nanochannels behaves differently due to interactions with the LCP interface, and that this mechanism has a larger impact for smaller channels. These findings suggest that the amount of free water in the core of the nanochannels is the key factor determining local substrate diffusion and self‐assembly within LCPs.     

共振增强多光子电离耦合飞行时间质谱研究甲烷脱氢芳构化反应

 采用共振增强多光子电离耦合飞行时间质谱技术，初步探测了甲烷无氧芳构化反应。实验结果表明，该技术具有灵敏度高，质量分辨率高，响应时间快等优点，改变波长能实现对目标产物的实时，高灵敏度检测，并且可以获得所有产物的信息。     

Hydrogen recombination on metals: vibrational excitation of desorbed molecules

The vibrational excitation of hydrogen molecules formed by recombination of hydrogen atoms on different metal surfaces has been studied. A recently developed experimental technique was used to determine vibrational state populations of the molecules up to v=7. Excitation of high vibrational levels is observed for molecules formed on metal surfaces which strongly chemisorb hydrogen. Metals with weaker chemisorption lead to vibrational excitation of lower levels, predominantly up to v=3. Knowledge of the vibrational state of desorbed molecules gives information on the energy of adsorbed hydrogen atoms and on the dynamics of surface reactions. This information is complementary to that obtained from studies of hydrogen reactions with metal clusters.     

A Photoacoustic Probe with Blood-Brain Barrier Crossing Ability for Imaging Oxidative Stress Dynamics in the Mouse Brain

Spatiotemporal assessment of the oxidative stress dynamics in the brain is crucial for understanding the molecular mechanism underlying neurodegenerative diseases. However, existing oxidative stress probes have poor blood-brain barrier permeability or poor penetration depth, making them unsuitable for brain imaging. Herein, we developed a photoacoustic probe that enables real-time imaging of oxidative stress dynamics in the mouse brain. The probe not only responds to oxidative stress in a reversible and ratiometric manner, but it can also cross the blood-brain barrier of the mouse brain. Notably, the probe displayed excellent photoacoustic imaging of oxidative stress dynamics in the brains of Parkinson's disease mouse models. In addition, we investigated the antioxidant properties of natural polyphenols in the brain of a Parkinson's disease mouse model using the probe as an imaging agent and suggested the potential of the probe for screening anti-oxidative stress agents.     

Translational diffusion of intermediate species in solutions

In this article, applications of the TG method to measurements of the translational diffusion of photochemically created intermediate species are reviewed. The intermediate species include unstable isomers, photochromic charged molecules, transient radicals created by photochemical reactions, and the electronically photoexcited species. Diffusional behaviors of these intermediates are different from those of stable molecules, which have been investigated extensively so far. The investigations of the diffusion of these species will provide opportunity to reveal the unique intermolecular interaction between the intermediates and matrix. Furthermore, by using products of photochemical reactions as probe molecules, the molecular dynamics of the system can be studied. This information will be valuable for understanding photochemistry in solution.     

Femtochemie. Elementare Schritte chemischer Reaktionen

Femtochemistry is about the investigation and control of ultrafast elementary molecular dynamics, which are the basis of every chemical reaction. The processes finally resulting in breaking of chemical bonds or molecular structure changes take place on a time scale of only femto to picoseconds. Solely femtosecond laser pulses are fast enough to resolve these fast processes. Different techniques were developed, which make use of a combination of femtosecond pulses having a relative temporal delay, in order to get access to the dynamics even in complex molecules. The knowledge of the elementary processes allows for a better understanding of the reaction mechanisms and their dependence on environmental conditions. The interaction with the molecules even before the final reaction path is entered, opens up new exciting possibilities for the control of chemical processes. A specific manipulation of the molecular dynamics using adapted pulse shapes appears to be realistic also for complex reactions and systems. The evolutionary optimization strategies, which exploit the experimental results as feedback, make selective chemistry come true even without knowledge of all system parameters.     

Mass Spectrometry—Finding the Molecular Ion and What It Can Tell You: An Undergraduate Organic Laboratory Experiment

Mass spectrometry is a widely used method to obtain information about the structures of molecules. This technique was introduced to beginning first-year organic chemistry students as an experiment that focused on the identification of the molecular ion from experimental data. After students had correctly identified the molecular ion in their samples, they learn other information that can be deduced from the molecular ion.     

Study of H-bond characteristics in sub- and supercritical methanol

Classical molecular dynamics simulations of various methanol phase lines near the saturation curve and the critical point have been performed to study the changes in H-bonded clusters structure at transition of methanol to supercritical state. Analysis of H-bonds statistics with combined distance-energy H-bond criterion showed that the correlations between topological characteristics of H-bonds and the mole fraction of H-bonded molecules have unique functional representation despite the phase path applied. In the present study, an attempt has been also made to evaluate the degree of hydrogen bonding by combining the DFT computations on classical MD configurations with the natural bond orbital analysis of the waves functions obtained.     

Anisotropy of the angular distribution of fragment ions in dissociative double photoionization of N2O molecules in the 30-50 eV energy range

The double photoionization of N2O molecules by linearly polarized light in the 30-50 eV energy range has been studied by coupling ion imaging technique and electron-ion-ion coincidence. For the two possible dissociative processes, leading to N++NO+ and O++N2+, angular distributions of ionic fragments have been measured, finding an evident anisotropy. This indicates that the molecules ionize when their axis is parallel to the light polarization vector and the fragments are separating in a time shorter than the dication rotational period. The analysis of results provides, in addition to the total kinetic energy of ionic fragments, crucial information about the double photoionization dynamics.