Factors that Influence Competitive Intermolecular Solvation of Protonated Groups in Peptides and Proteins in the Gas Phase

The ability of 18-crown-6 (18C6) to form noncovalent complexes with cationic groups in the gas phase has been leveraged in numerous, largely orthogonal mass spectrometry-based applications. Although the fundamental interaction between 18C6 and a charged group in the gas phase is quite strong, the strength of attachment of 18C6 to large molecules is more difficult to predict because intramolecular binding of the cation can be competitive. Herein, we demonstrate in experiments with model peptides that 18C6 adducts are not strongly attached to flexible molecules with numerous potential hydrogen bonding sites. 18C6 adduct stability is increased if intramolecular charge complexation is inhibited by sterics or competitive binding. It is demonstrated with molecular mechanics that significant structural changes occur upon loss of 18C6 in model peptides. Examination of the loss of 18C6 adducts from proteins following collisional activation reveals that lower charge states lose the most 18C6. The degree of 18C6 adduct stability may reflect the degree of structural reorganization that occurs following collisional activation, suggesting that lower charge states represent structures that are not similar to gas phase idealized states. In this regard, 18C6 may serve the function of protecting solution phase protein structure. Collisional activation of holomyoglobin with 18C6 adducts attached reveals that heme loss occurs primarily after 18C6 loss, further supporting the notion that 18C6 protects native structure by solvating charged sites.

Infrared Spectroscopy of Fragments from Doubly Protonated Tryptic Peptides

Most proteins in proteomics are identified from tandem mass spectra of doubly protonated tryptic peptides. Statistical studies indicate that these spectra fall into two distinct classes. IR spectroscopy experiments and DFT calculations performed on model b₂ ions show that peptides producing Class I spectra form protonated oxazolone ions (see figure) and not protonated diketopiperazines as proposed elsewhere.

     

Mid‐IR Spectroscopy and Structural Features of Protonated Carbonic Acid in the Gas Phase

An anti trihydroxycarbenium ion is revealed to be the gas‐phase structure of protonated carbonic acid by IR multiple‐photon dissociation spectroscopy (see picture for calculated structure and comparison of experimental and computed spectra). Deprotonation yields anti‐H₂CO₃ with a nominal gas‐phase basicity of 724 kJ mol^?1.

     

Scopine Isolated in the Gas Phase

The rotational spectrum of the tropane alkaloid scopine is detected by Fourier transform microwave spectroscopy in a pulsed supersonic jet. A nonconventional method for bringing the molecules intact into the gas phase is used in which scopine syrup is mixed with glycine powder and the solid mixture is vaporized with an ultrafast UV laser beam. Laser vaporization prevents the easy isomerization to scopoline previously observed with conventional heating methods. A single conformer is unambiguously observed in the supersonic jet and corresponds to the energetically most stable species according to quantum chemical calculations. Rotational and centrifugal distortion constants are accurately determined. The spectrum shows fine and hyperfine structure due to the hindered rotation of the methyl group and the presence of a quadrupolar nucleus (¹⁴N), respectively. This additional information allows the angle of N‐methyl inversion between the N?CH₃ bond and the bicyclic C‐N‐C plane to be determined (131.8–137.8°), as well as the internal rotation barrier of the methyl group (6.235(1) kJ mol^?1).     

Equilibrium Structure of Beryllium Dibromide from Combined Gas Electron Diffraction and Vibrational Spectroscopy Analysis

The molecular structure of BeBr₂ has been investigated by gas-phase electron diffraction at the temperature 800(10) K. The conventional analysis yielded the following values: r _g(Be–Br) = 1.944(6)Å, l(Be–Br) = 0.068(4)Å, r _g(Br–Br) = 3.848(8)Å, l(Br–Br) = 0.109(3)Å, k(Be–Br) = 1.1(1.1) × 10^–5 ų, (Br–Br) = 2.1(1.0) × 10^–5 ų. Three models of nuclear dynamics were used to simulate the conventional analysis values—infinitesimal vibrations and two models, which take into account the kinematic and dynamic anharmonicity of the bending vibration. All models give similar values of bond angle, amplitudes, and shrinkage, excluding the harmonic model, which yields too low value l(Br–Br). The equilibrium bond distance r _e(Be–Br) = 1.932(11) Å was estimated, taking into account the anharmonicity corrections for stretching and bending vibrations and centrifugal distortion.     

Vibrational Spectroscopy of Homo- and Heterochiral Amino Acid Dimers: Conformational Landscapes

The homo- and heterochiral protonated dimers of asparagine with serine and with valine were investigated using infrared multiple-photon dissociation (IRMPD) spectroscopy. Extensive quantum-chemical calculations were used in a three-tiered strategy to screen the conformational spaces of all four dimer species. The resulting binary structures were further grouped into five different types based on their intermolecular binding topologies and subunit configurations. For each dimer species, there are eight to fourteen final conformational geometries within a 10 kJ mol⁻¹ window of the global minimum structure for each species. The comparison between the experimental IRMPD spectra and the simulated harmonic IR features allowed us to clearly identify the types of structures responsible for the observation. The monomeric subunits of the observed homo- and heterochiral dimers are compared to the corresponding protonated/neutral amino acid monomers observed experimentally in previous IRMDP/rotational spectroscopic studies. Possible chirality and kinetic influences on the experimental IRMPD spectra are discussed.     

Vibrational Structure of a High-Resolution UV Absorption Spectrum of Methyl Vinyl Ketone in the Gas Phase

Moscow University Chemistry Bulletin - The resolved vibrational structure of a UV absorption spectrum of the molecule in the gas phase is obtained. The (0–0) bands of the isomers are found....     

Sites of Protonation and Unimolecular Fragmenta tion of Protonated N-Hydroxyphthalimide in the Gas Phase

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The Nucleoside Uridine Isolated in the Gas Phase

Herein we present the first experimental observation of the isolated nucleoside uridine, placed in the gas phase by laser ablation and characterized by Fourier transform (FT) microwave techniques. Free from the bulk effects of their native environments, anti/C2′‐endo‐g+ conformation has been revealed as the most stable form of uridine. Intramolecular hydrogen bonds involving uracil and ribose moieties have been found to play an important role in the stabilization of the nucleoside.     

质子化丙酮分子团簇的结构和振动光谱

The stable structures and vibrational spectra of protonated acetone molecule clusters with different sizes （CH3COCH3）nH +（n=1-7）are calculated at the 6-31G（d）level by means of density functional theory （B3LYP）quantum chemical calculations. The corresponding energies are analyzed at the level B3LYP/6-311+G（3df,2p）in order to obtain more accurate results. The proton affinity of neutral cyclic acetone molecule clusters increases with the increasing of cluster size. The calculated results show that the protonated acetone clusters have certain growth regularity with forming a solvation shell at the beginning and then new added acetone molecule attacking different active sites including the middle carbon atoms and the different methyl in solvation shell. The IR spectra of the protonated clusters are more complicate than that of neutral ones. The strongest peaks result from the movement of the proton between the two oxygen atoms in solvant shell apart from the case of n=1. Carbonyl stretching vibraional peaks split into the more and more and in general the corresponding intensities are weakened due to the protonation with the increasing of cluster size.     

腺嘌呤和质子化腺嘌呤的结构和振动光谱

用密度泛函方法B3LYP/aug-cc-pVTZ分析了腺嘌呤和质子化腺嘌呤的低能稳定异构体的结构和振动光谱. 结果发现, 对于中性腺嘌呤分子, 腺嘌呤的异构体N9H比N7H的能量低32.76 kJ·mol-1(在极化连续模型下为6.28 kJ·mol-1). 基于标度量子力场方法所得到的势能分布, 对异构体N9H的部分振动基频重新进行了归属. 在极化连续模型下, 质子化腺嘌呤分子有5种低能稳定构型, 其中N1位质子化的9-位氢腺嘌呤最为稳定. 基于振动模式分析, 对这种最稳定构型的振动基频进行了归属, 并对腺嘌呤在pH=1的高氯酸溶液中的实验拉曼光谱进行了指认.     

Pressure Effect on Conformational Equilibria of Analog Peptides in Aqueous Solution by Raman Spectroscopy

We investigated the pressure effect on the conformational equilibria of glycinamide (GA) and 2-chloroacetamide (MCA) in aqueous solution by Raman spectroscopy. Scattering intensities in the CH₂ scissoring mode of GA and the NH₂ rocking mode of MCA in aqueous solution were decomposed into two component bands by ab initio MO calculations at the HF/6-31G(d,p) level. From the pressure dependence of the Raman band intensities, we determined the difference in the partial molar volume (PMV) between the cis and trans conformers of each for GA and MCA. The volume changes for the isomerization of the cis to trans conformer are ?(1.9 ± 0.3) and ?(1.5 ± 0.3) cm³-mol^?1 for GA and MCA, respectively. The volume difference between the cis and trans conformers is due to the hydration effect, which seems to be mainly the result of local effects of solute–solvent interactions in both cases. This contribution is due to the influence of the solute–solvent interaction with water molecules on the PMV of the cis conformer being less than that of the trans conformer.     

What is the Structure of b2 Ions Generated from Doubly Protonated Tryptic Peptides?

A recent statistical study (Savitski, M. M.; Falth, M.; Eva Fung, Y. M.; Adams, C. M.; Zubarev, R. A. J. Am. Soc. for Mass Spectrom. doi: 10.1016/j.jasms.2008.08.003) of a large spectral database indicated that the product ion spectra of doubly protonated tryptic peptides fall into two distinct classes. The main factor distinguishing the two classes is the relative abundance of the y _N-2 fragment: for Class I spectra y _N-2 is the most abundant y fragment while for Class II other y ions dominate the corresponding spectra. To explain the dominance of y _N-2 for Class I spectra formation of a nontraditional b ₂ ion with a diketopiperazine (6-membered cyclic peptide) rather than an oxazolone structure was proposed. Here we present evidence from tandem mass spectrometry, hydrogen/deuterium exchange, and density functional calculations that do not support this proposal. Namely, that CID of doubly protonated YIGSR, YGGFLR, and YIYGSFK produce Class I product ion spectra, yet the b ₂ fragment is shown to have the traditional oxazolone structure.     

Selenium in Proteins: Conformational Changes Induced by Se Substitution on Methionine,as Studied in Isolated Model Peptides by Optical Spectroscopy and Quantum Chemistry

The side-chain of methionine residues is long enough to establish NH⋯S H-bonds with neighboring carbonyl groups of the backbone, giving rise to so-called intra-residue 6^δ and inter-residue 7^δ H-bonds. The aim of the present article is to document how the substitution of sulfur with a selenium atom affects the H-bonding of the Met system. This was investigated both experimentally and theoretically by conformation-resolved optical spectroscopy, following an isolated molecule approach. The present work emphasizes the similarities of the Met and Sem residues in terms of conformational structures, energetics, NH⋯Se/S H-bond strength and NH stretch spectral shifts, but also reveals subtle behavior differences between them. It provides evidence for the sensitivity of the H-bonding network with the folding type of the Sem/Met side-chains, where a simple flip of the terminal part of the side-chain can induce an extra 50 cm⁻¹ spectral shift of the NH stretch engaged in a 7^δ NH⋯S/Se bond.     

Structure and Dynamics of Oligonucleotides in the Gas Phase

By combining ion‐mobility mass spectrometry experiments with sub‐millisecond classical and ab initio molecular dynamics we fully characterized, for the first time, the dynamic ensemble of a model nucleic acid in the gas phase under electrospray ionization conditions. The studied oligonucleotide unfolds upon vaporization, loses memory of the solution structure, and explores true gas‐phase conformational space. Contrary to our original expectations, the oligonucleotide shows very rich dynamics in three different timescales (multi‐picosecond, nanosecond, and sub‐millisecond). The shorter timescale dynamics has a quantum mechanical nature and leads to changes in the covalent structure, whereas the other two are of classical origin. Overall, this study suggests that a re‐evaluation on our view of the physics of nucleic acids upon vaporization is needed.     

ChemInform Abstract: Protonated Nitric Acid. Structure and Relative Stability of Isomeric H2NO+ 3 Ions in the Gas Phase.

Gaseous H₂NO₃⁺ ions are generated by direct protonation of HNO₃ by H3⁺, H₃O⁺ and CH₅⁺ and by protonation of C₂H₅ONO₂ followed by C₂H₄ loss.