Influence of N‑terminal Residue Composition on the Structure of Proline-Containing b₂⁺ Ions

To probe the structural implications of the proline residue on its characteristic peptide fragmentation patterns, in particular its unusual cleavage at its C-terminus in formation of a b₂ ion in XxxProZzz sequences, the structures of a series of proline-containing b₂⁺ ions were studied by using action infrared multiphoton dissociation (IRMPD) spectroscopy and fragment ion hydrogen–deuterium exchange (HDX). Five different Xxx-Pro b₂⁺ ions were studied, with glycine, alanine, isoleucine, valine, or histidine in the N-terminal position. The residues selected feature different sizes, chain lengths, and gas phase basicities to explore whether the structure of the N-terminal residue influences the Xxx-Pro b₂⁺ ion structure. In proteins, the proline side chain-to-backbone attachment causes its peptide bonds to be in the cis conformation more than any other amino acid, although trans is still favored over cis. However, HP is the only b₂⁺ ion studied here that forms the diketopiperazine exclusively. The GP, AP, IP, and VP b₂⁺ ions formed from protonated tripeptide precursors predominantly featured oxazolone structures with small diketopiperazine contributions. In contrast to the b₂⁺ ions generated from tripeptides, synthetic cyclic dipeptides VP and HP were confirmed to have exclusive diketopiperazine structures

Probing the Competition among Different Coordination Motifs in Metal–Ciprofloxacin Complexes through IRMPD Spectroscopy and DFT Calculations

The vibrational spectra of ciprofloxacin complexes with monovalent (Li⁺, Na⁺, K⁺, Ag⁺) and polyvalent (Mg²⁺, Al³⁺) metal ions are recorded in the range 1000–1900 cm^–1 by means of infrared multiple-photon dissociation (IRMPD) spectroscopy. The IRMPD spectra are analyzed and interpreted in the light of density functional theory (DFT)-based quantum chemical calculations in order to identify the possible structures present under our experimental conditions. For each metal–ciprofloxacin complex, four isomers are predicted, considering different chelation patterns. A good agreement is found between the measured IRMPD spectrum and the calculated absorption spectrum of the most stable isomer for each complex. Metal ion size and charge are found to drive the competition among the different coordination motifs: small size and high charge density metal ions prefer to coordinate the quinolone between the two carbonyl oxygen atoms, whereas large-size metal ions prefer the carboxylate group as a coordination site. In the latter case, an intramolecular hydrogen bond compensates the weaker interaction established by these cations. The role of the metal cation on the stabilization of ionic and nonionic structures of ciprofloxacin is also investigated. It is found that large-size metal ions preferentially stabilize charge separated motifs and that the increase of metal ion charge has a stabilizing effect on the zwitterionic form of ciprofloxacin

IRMPD Spectroscopy: Evidence of Hydrogen Bonding in the Gas Phase Conformations of Lasso Peptides and their Branched-Cyclic Topoisomers

Lasso peptides are natural products characterized by a mechanically interlocked topology. The conformation of lasso peptides has been probed in the gas phase using ion mobility–mass spectrometry (IM–MS) which showed differences in the lasso and their unthreaded branched-cyclic topoisomers depending on the ion charge states. To further characterize the evolution of gas phase conformations as a function of the charge state and to assess associated changes in the hydrogen bond network, infrared multiple photon dissociation (IRMPD) action spectroscopy was carried out on two representative lasso peptides, microcin J25 (MccJ25) and capistruin, and their branched-cyclic topoisomers. For the branched-cyclic topoisomers, spectroscopic evidence of a disruption of neutral hydrogen bonds were found when comparing the 3+ and 4+ charge states. In contrast, for the lasso peptides, the IRMPD spectra were found to be similar for the two charge states, suggesting very little difference in gas phase conformations upon addition of a proton. The IRMPD data were thus found consistent and complementary to IM–MS, confirming the stable and compact structure of lasso peptides in the gas phase

Watson–Crick Base Pair Radical Cation as a Model for Oxidative Damage in DNA

The deleterious cellular effects of ionizing radiation are well-known, but the mechanisms causing DNA damage are poorly understood. The accepted molecular events involve initial oxidation and deprotonation at guanine sites, triggering hydrogen atom abstraction reactions from the sugar moieties, causing DNA strand breaks. Probing the chemistry of the initially formed radical cation has been challenging. Here, we generate, spectroscopically characterize, and examine the reactivity of the Watson–Crick nucleobase pair radical cation in the gas phase. We observe rich chemistry, including proton transfer between the bases and propagation of the radical site in deoxyguanosine from the base to the sugar, thus rupturing the sugar. This first example of a gas-phase model system providing molecular-level details on the chemistry of an ionized DNA base pair paves the way toward a more complete understanding of molecular processes induced by radiation. It also highlights the role of radical propagation in chemistry, biology, and nanotechnology

Changes in Tricarbastannatrane Transannular N–Sn Bonding upon Complexation Reveal Lewis Base Donicities

Hypercoordinated complexes involving tricarbastannatrane cation [N­(CH₂CH₂CH₂)₃Sn]⁺ with various Lewis bases are investigated in the gas and solution phases using a combination of infrared multiple photon dissociation (IRMPD) spectroscopy, NMR spectroscopy, and density functional theory calculations. Coordination is found to occur at the apical position leading to a pentacoordinated Sn center. Strongly electron donating Lewis bases disrupt the N···Sn transannular interaction and induce higher degrees of geometric distortion at the metal center than weakly donating Lewis bases, an effect that manifests as anharmonic shifts in the vibrational spectra. Once characterized in the gas phase, [N­(CH₂CH₂CH₂)₃Sn­(Lewis base)]⁺ structures were embedded in a dichloroethane polarizable continuum model to investigate solution phase properties. Calculated ¹¹⁹Sn NMR chemical shifts were found to be in good agreement with those measured experimentally, thus suggesting that the bonding properties of [N­(CH₂CH₂CH₂)₃Sn]⁺ are essentially the same in the gas and solution phases

Cation−π Interactions in Protonated Phenylalkylamines

Phenylalkylamines of the general formula C₆H₅(CH₂)_<i>n</i>NH₂ (<i>n</i> = 1–4) have been delivered to the gas phase as protonated species using electrospray ionization. The ions thus formed have been assayed by IRMPD spectroscopy in two different spectroscopic domains, namely, the 600–1800 and the 3000–3500 cm^–1 regions using either an IR free electron laser or a tabletop OPO/OPA laser source. The interpretation of the experimental spectra is aided by density functional theory calculations of candidate species and vibrational frequency analyses. Protonated benzylamine presents a relatively straightforward instance of a single stable conformer, providing a trial case for the adopted approach. Turning to the higher homologues, C₆H₅(CH₂)_<i>n</i>NH₃⁺ (<i>n</i> = 2–4), more conformations become accessible. For each C₆H₅(CH₂)_<i>n</i>NH₃⁺ ion (<i>n </i>= 2–4), the most stable geometry is characterized by cation−π interactions between the positively charged ammonium group and the aromatic π-electronic system, permitted by the folding of the polymethylene chain. The IRMPD spectra of the sampled ions confirm the presence of the folded structures by comparison with the calculated IR spectra of the various possible conformers. An inspection of the NH stretching region is helpful in this regard

Does the Residues Chirality Modify the Conformation of a Cyclo-Dipeptide? Vibrational Spectroscopy of Protonated Cyclo-diphenylalanine in the Gas Phase

The structure of a protonated diketopiperazine dipeptide, cyclo-diphenylalanine, is studied by means of infrared multiple photon dissociation spectroscopy combined with quantum chemical calculations. Protonation exclusively occurs on the oxygen site and, in the most stable conformer, results to an intramolecular OH···π interaction, accompanied by a CH···π interaction. Higher-energy conformers with free OH and NH···π interactions are observed as well, due to kinetic trapping. Optimization of the intramolecular interactions involving the aromatic ring dictates the geometry of the benzyl substituents. Changing the chirality of one of the residues has consequences on the CH···π interaction, which is of C_αH···π nature for LD, while LL shows a C_βH···π interaction. Higher-energy conformers also display some differences in the nature of the intramolecular interactions

Infrared-Driven Charge Transfer in Transition Metal B₁₂F₁₂ Clusters

A combination of infrared multiple photon dissociation (IRMPD) spectroscopy and density functional theory calculations is used to investigate the structures and charge-transfer properties of clusters containing transition metals (TM = Co­(II), Ni­(II), Cu­(I), Zn­(II), Rh­(III), Pd­(II), Ag­(I), Cd­(II)) and the dodecafluorododecaboron dianion, B₁₂F₁₂^2–. In all cases, IRMPD resulted in transfer of electron density to the metal center and production of B₁₂F₁₂^–. Metals that exhibit the highest degree of charge transfer are found to induce reaction among the B₁₂F₁₂ cages, leading to production of B_<i>n</i>F_<i>m</i> (up to <i>n</i> = <i>m</i> = 24)

Exotic Protonated Species Produced by UV-Induced Photofragmentation of a Protonated Dimer: Metastable Protonated Cinchonidine

A metastable protonated cinchona alkaloid was produced in the gas phase by UV-induced photodissociation (UVPD) of its protonated dimer in a Paul ion trap. The infrared multiple photon dissociation (IRMPD) spectrum of the molecular ion formed by UVPD was obtained and compared to DFT calculations to characterize its structure. The protonation site obtained thereby is not accessible by classical protonation ways. The protonated monomer directly formed in the ESI source or by collision-induced dissociation (CID) of the dimer undergoes protonation at the most basic alkaloid nitrogen. In contrast, protonation occurs at the quinoline aromatic ring nitrogen in the UVPD-formed monomer