Competition between diketopiperazine and oxazolone formation in water loss products from protonated ArgGly and GlyArg

The mechanism of peptide "b" fragment formation in collision-induced dissociation (CID) is generally understood as a nucleophilic attack from a carbonyl oxygen onto the electron deficient carbon of the dissociating amide bond forming a five-membered oxazolone ring structure. Nonetheless, other nucle-ophiles, such as the N-terminus and side-chain moieties (e.g., imidazole, guanidine), can in principle engage in a nucleophilic attack to induce amide backbone cleavage. Here, we apply a combination of infrared multiple photon dissociation (IRMPD) spectroscopy and computational chemistry to characterize the water loss, [M+H-H2O](+), product ions from protonated ArgGly and GlyArg. IRMPD spectra for [M+H-H2O](+) from ArgGly and GlyArg differ in the presence and absence of a characteristic band at 1885 cm(-1), which is indicative of an oxazolone structure for ArgGly. The remaining parts of the vibrational spectra are consistent with the vibrational signatures of diketopiperazine structures. Conversely, there is no match between the experimental spectra and any of the putative structures arising from guanidine side-chain attack. These results show that the presence of a basic residue, such as arginine, facilitates the formation of diketopiperazine structures, and that residue order matters in the competition between diketopiperazine and oxazolone pathways. (c) 2012 Published by Elsevier B.V

Infrared spectroscopy of phenylalanine ag(i) and zn(ii) complexes in the gas phase

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Metal Cation Binding to Gas-Phase Pentaalanine: Divalent Ions Restructure the Complex

Ion-neutral complexes of pentaalalanine with several singly- and doubly charged metal ions are examined using conformation analysis by infrared multiple photon dissociation (IRMPD) spectroscopy and density functional theory (DFT) computations. The infrared spectroscopy in the 1500-1800 cm(-1) region is found to be conformationally informative; in particular, the frequency of the C=O stretching mode of the terminal carboxyl group is diagnostic for hydrogen bonding of the terminal hydroxyl. The doubly charged alkaline earth metal ions (Ca2+ and Ba2+) enforce a highly structured chelation shell around the metal ion, with six strongly bound Lewis-basic chelation sites, and no hydroxyl hydrogen bonding. With the more weakly binding alkali metal ions (Na+, K+, and Cs+), structures with intramolecular hydrogen bonds are more favorable, leading to dominance of conformations with lower degrees of metal ion chelation. The favored coordination mode correlates with ionic charge and binding strength but is not related to the ionic radius of the metal ion

Metal ion binding to peptides: Oxygen or nitrogen sites?

Infrared multiple-photon dissociation (IRMPD) spectroscopy was used to probe the conformations of gas-phase metal-ion complexes between a series of five metal ions and six small peptide ligands. This report is presented in recognition and tribute for the Armentrout group's long and hugely productive interest in metal-ion binding to gas-phase ligands. The metal ions (K+, Ba2+, Ca2+, Mg2+, Ni2+) span a range of ligand binding strengths, and the ligands include several dipeptides and tripeptides, and one tetrapeptide. The weaker metal ions generally form charge-solvated (CS) complexes binding amide carbonyl oxygen, while the strongest metal ion, nickel, deprotonates the amide nitrogens, probably through iminol tautomerization, and binds to the amide nitrogens. The Amide II vibrational mode (1500–1550 cm−1) is found to be an excellent marker for the presence or absence of protons on amide nitrogens in a complex. The magnesium ion marks a boundary between these two structural motifs, forming iminol complexes with the dipeptides and switching to CS complexes for the tripeptides FGG and FGGF. Compared with solution-phase behavior, the iminol binding mode shown by Mg2+ for the smallest peptides is surprising, since this ion is considered as generally binding in a CS mode in solution. The present results for the larger peptides reconcile this surprising difference, showing that larger peptide ligands revert to the expected CS binding pattern for gas-phase Mg2+

Metal Cation Binding to Gas-Phase Pentaalanine: Divalent Ions Restructure the Complex

Ion-neutral complexes of pentaalalanine with several singly- and doubly charged metal ions are examined using conformation analysis by infrared multiple photon dissociation (IRMPD) spectroscopy and density functional theory (DFT) computations. The infrared spectroscopy in the 1500-1800 cm(-1) region is found to be conformationally informative; in particular, the frequency of the C=O stretching mode of the terminal carboxyl group is diagnostic for hydrogen bonding of the terminal hydroxyl. The doubly charged alkaline earth metal ions (Ca2+ and Ba2+) enforce a highly structured chelation shell around the metal ion, with six strongly bound Lewis-basic chelation sites, and no hydroxyl hydrogen bonding. With the more weakly binding alkali metal ions (Na+, K+, and Cs+), structures with intramolecular hydrogen bonds are more favorable, leading to dominance of conformations with lower degrees of metal ion chelation. The favored coordination mode correlates with ionic charge and binding strength but is not related to the ionic radius of the metal ion

Oxazolone versus macrocycle structures for Leu-enkephalin b2-b4: Insights from infrared multiple-photon dissociation spectroscopy and gas-phase hydrogen/deuterium exchange

The collision-induced dissociation (CID) products b(2)-b(4) from Leu-enkephalin are examined with infrared multiple-photon dissociation (IR-MPD) spectroscopy and gas-phase hydrogen/deuterium exchange (HDX). Infrared spectroscopy reveals that b(2) exclusively adopts oxazolone structures, protonated at the N-terminus and at the oxazolone ring N, based on the presence and absence of diagnostic infrared vibrations. This is correlated with the presence of a single HDX rate. For the larger b(3) and b(4), the IR-MPD measurements display diagnostic bands compatible with a mixture of oxazolone and macrocycle structures. This result is supported by HDX experiments, which show a bimodal distribution in the HDX spectra and two distinct rates in the HDX kinetic fitting. The kinetic fitting of the HDX data is employed to derive the relative abundances of macrocycle and oxazolone structures for b3 and b4, using a procedure recently implemented by our group for a series of oligoglycine b fragments (Chen et al. J. Am. Chem. Soc. 2009, 131(51), 18272-18282. doi: 10.1021/ja9030837). In analogy to that study, the results suggest that the relative abundance of the macrocycle structure increases as a function of b fragment size, going from 0% for b, to similar to 6% for b(3), and culminating in 31% for b4. Nonetheless, there are also surprising differences between both studies, both in the exchange kinetics and the propensity in forming macrocycle structures. This indicates that the chemistry of "head-to-tail" cyclization depends on subtle differences in the sequence as well as the size of the b fragment

Gas-phase metal ion chelation investigated with IRMPD spectroscopy: A brief review of Robert Dunbar's contributions

With the passing of Prof. Robert C. Dunbar on 31 October 2017, the field of ion chemistry lost one of its modern heroes. Throughout his career in mass spectrometry, two of his main research interests involved the interaction of trapped ions with electromagnetic radiation and the chelation motifs of metal ions with organic ligands. The focus of his early career was on the fundamental processes that take place in molecules upon ultraviolet and infrared excitation. From 2003 to 2017, his scientific interests shifted to more structural questions, notably to resolving the structures and binding motifs of metal ion chelation complexes by application of infrared photodissociation spectroscopy. These experiments were carried out during numerous visits to the (Free Electron Laser for Infrared eXperiments) (FELIX) facility in the Netherlands and were complemented by extensive theoretical investigations by Rob. As a tribute to our friend, we present in this contribution a brief review of this work