Justin Kai-Chi Lau

Metal Ion Complexes with HisGly: Comparison with PhePhe and PheGly

Gas-phase complexes of five metal ions with the dipeptide HisGly have been characterized by DFT computations and by infrared multiple photon dissociation spectroscopy (IRMPD) using the free electron laser FELIX. Fine agreement is found in all five cases between the predicted IR spectral features of the lowest energy structures and the observed IRMPD spectra in the diagnostic region 1500-1800 cm(-1), and the agreement is largely satisfactory at longer wavelengths from 1000 to 1500 cm(-1). Weak-binding metal ions (K(+), Ba(2+), and Ca(2+)) predominantly adopt the charge-solvated (CS) mode of chelation involving both carbonyl oxygens, an imidazole nitrogen of the histidine side chain, and possibly the amino nitrogen. Complexes with Mg(2+) and Ni(2+) are found to adopt iminol (Im) binding, involving the deprotonated amide nitrogen, with tetradentate chelation. This tetradentate coordination of Ni(II) is the preferred binding mode in the gas phase, against the expectation under condensed-phase conditions that such binding would be sterically unfavorable and overshadowed by other outcomes such as metal ion hydration and formation of dimeric complexes. The HisGly results are compared with corresponding results for the PheAla, PheGly, and PhePhe ligands, and parallel behavior is seen for the dipeptides with N-terminal Phe versus His residues. An exception is the different chelation pattern determined for PhePhe versus HisGly, reflecting the intercalation-type cation binding pocket of the PhePhe ligand. The complexes group into three well-defined spectroscopic patterns: nickel and magnesium, calcium and barium, and potassium. Factors leading to differentiation of these distinct spectroscopic categories are (1) differing propensities for choosing the iminol binding pattern, and (2) single versus double charge on the metal center. Nickel and magnesium ions show similar gas-phase binding behavior, contrasting with their quite different patterns of peptide interaction in condensed phases.

Infrared Multiple-Photon Dissociation Spectroscopy of Tripositive Ions: Lanthanum-Tryptophan Complexes

Collision-induced charge disproportionation limits the stability of triply charged metal ion complexes and has thus far prevented successful acquisition of their gas-phase IR spectra. This has curtailed our understanding of the structures of triply charged metal complexes in the gas phase and in biological environments. Herein we report the first gas-phase IR spectra of triply charged La(III) complexes with a derivative of tryptophan (N-acetyl tryptophan methyl ester), and an unusual dissociation product, a lanthanum amidate. These spectra are compared with those predicted using density functional theory. The best structures are those of the lowest energies that differ by details in the π-interaction between La(3+) and the indole rings. Other binding sites on the tryptophan derivative are the carbonyl oxygens. In the lanthanum amidate, La(3+) replaces an H(+) in the amide bond of the tryptophan derivative.

Alkali-Metal-Ion-Assisted Hydrogen Atom Transfer in the Homocysteine Radical

Intramolecular hydrogen atom transfer (HAT) was examined in homocysteine (Hcy) thiyl radical/alkali metal ion complexes in the gas phase by combination of experimental techniques (ion-molecule reactions and infrared multiple photon dissociation spectroscopy) and theoretical calculations. The experimental results unequivocally show that metal ion complexation (as opposed to protonation) of the regiospecifically generated Hcy thiyl radical promotes its rapid isomerisation into an α-carbon radical via HAT. Theoretical calculations were employed to calculate the most probable HAT pathway and found that in alkali metal ion complexes the activation barrier is significantly lower, in full agreement with the experimental data. This is, to our knowledge, the first example of a gas-phase thiyl radical thermal rearrangement into an α-carbon species within the same amino acid residue and is consistent with the solution phase behaviour of Hcy radical.

Investigation of Fragmentation of Tryptophan Nitrogen Radical Cation.

AbstractThis work describes investigation of the fragmentation mechanism of tryptophan N-indolyl radical cation, H3N+-TrpN• (m/z 204) studied via DFT calculations and several gas-phase experimental techniques. The main fragment ion at m/z 131, shown to be a mixture of up to four isomers including 3-methylindole (3MI) π-radical cation, was found to undergo further loss of an H atom to yield one of the two isomeric m/z 130 ions. 3-Methylindole radical cation generated independently (via CID of [CuII(terpy)3MI]•2+) displayed gas-phase reactivity partially similar to that of the m/z 131 fragment, further confirming our proposed mechanism. CID of deuterated tryptophan N-indolyl radical cation (m/z 208) suggested that up to six H atoms are involved in the pathway to formation of the m/z 131 ion, consistent with hydrogen atom scrambling during CID of protonated Trp. Graphical Abstractᅟ

Fragmentation of Peptide Radical Cations Containing a Tyrosine or Tryptophan Residue: Structural Features That Favor Formation of [x(n–1) + H]•+ and [z(n–1) + H]•+ Ions

Peptide radical cations A(n)Y(•+) (where n = 3, 4, or 5) and A5W(•+) have been generated by collision-induced dissociation (CID) of [Cu(II)(tpy)(peptide)](•2+) complexes. Apart from the charge-driven fragmentation at the N-Cα bond of the hetero residue producing either [c + 2H](+) or [z - H](•+) ions and radical-driven fragmentation at the Cα-C bond to give a(+) ions, unusual product ions [x + H](•+) and [z + H](•+) are abundant in the CID spectra of the peptides with the hetero residue in the second or third position of the chain. The formation of these ions requires that both the charge and radical be located on the peptide backbone. Energy-resolved spectra established that the [z + H](•+) ion can be produced either directly from the peptide radical cation or via the fragment ion [x + H](•+). Additionally, backbone dissociation by loss of the C-terminal amino acid giving [b(n-1) - H](•+) increases in abundance with the length of the peptides. Mechanisms by which peptide radical cations dissociate have been modeled using density functional theory (B3LYP/6-31++G** level) on tetrapeptides AYAG(•+), AAYG(•+), and AWAG(•+).

Fragmentation Chemistry of [Met-Gly]•+, [Gly-Met]•+, and [Met-Met]•+ Radical Cations

AbstractRadical cations [Met-Gly]•+, [Gly-Met]•+, and [Met-Met]•+ have been generated through collision-induced dissociation (CID) of [CuII(CH3CN)2(peptide)]•2+ complexes. Their fragmentation patterns and dissociation mechanisms have been studied both experimentally and theoretically using density functional theory at the UB3LYP/6-311++G(d,p) level. The captodative structure, in which the radical is located at the α-carbon of the N-terminal residue and the proton is on the amide oxygen, is the lowest energy structure on each potential energy surface. The canonical structure, with the charge and spin both located on the sulfur, and the distonic ion with the proton on the terminal amino group, and the radical on the α-carbon of the C-terminal residue have similar energies. Interconversion between the canonical structures and the captodative isomers is facile and occurs prior to fragmentation. However, isomerization to produce the distonic structure is energetically less favorable and cannot compete with dissociation except in the case of [Gly-Met]•+. Charge-driven dissociations result in formation of [bn – H]•+ and a1 ions. Radical-driven dissociation leads to the loss of the side chain of methionine as CH3-S-CH = CH2 producing α-glycyl radicals from both [Gly-Met]•+ and [Met-Met]•+. For [Met-Met]•+, loss of the side chain occurs at the C-terminal as shown by both labeling experiments and computations. The product, the distonic ion of [Met-Gly]•+, NH3+CH(CH2CH2SCH3)CONHCH•COOH dissociates by loss of CH3S•. The isomeric distonic ion NH3+CH2CONHC•(CH2CH2SCH3)COOH is accessible directly from the canonical [Gly-Met]•+ ion. A fragmentation pathway that characterizes this ion (and the distonic ion of [Met-Met]•+) is homolytic fission of the Cβ–Cγ bond to lose CH3SCH2•.

Thermochemistry of phosphorus fluorides: a Gaussian-3 and Gaussian-3X study

Abstract The Gaussian-3 (G3) and Gaussian-3X (G3X) models of theory have been used to calculate the thermochemical data for phosphorus fluorides, as well as their singly charged cations and anions. The quantities calculated include the heats of formation (ΔHf) and bond dissociation energies (DEs) of all the species, as well as the ionization energies (IEs) and electron affinities (EAs) of the neutrals. By comparing the well-established experimental data of PF3 and PF5 with the G3 and G3X results, we have found that the G3X ΔHf values are in better agreement with the experimental values. On the other hand, the G3 and G3X methods give similar results in predicting the IE of PF3. On the basis of these findings, the G3X method is used to assess the sometimes conflicting experimental data, and a set of self-consistent thermochemcial data is recommended for PFn and their ions. In addition, the alternating patterns of the ΔHf, DE, IE, and EA values of the phosphorus fluorides and their ions are rationalized in terms of the electronic configuration around the central P atom for the species involved.

Interconversion between 4-Imidazolone Ions; Isomers of [b4]+ Derived from Protonated Tetraglycine

Collision-induced dissociations of isotopically labeled protonated tetraglycines establish that the [b4]+ ion formed by loss of water from the second amide bond (structure II) rearranges to form N1-protonated 3,5-dihydro-4H-imidazol-4-one (structure I), the product of water loss from the first amide bond. Structure II is slightly higher in energy than I (ΔH at 0 K is 5.1 kJ mol-1, as calculated at M06-2X/6-311++G-(d,p)), and the barrier to interconversion is 139.8 kJ mol-1 above I. The dominant dissociation pathway is the loss of methanimine (HN=CH2) from ion I with a barrier of 167.1 kJ mol-1, giving [GlyGlyGlyGly + H - H2O - HN=CH2]+, ion III; a minor channel, loss of NH3, has a slightly higher barrier (181.5 kJ mol-1). Using labeled glycine (13Cα) it was determined that loss of the imine is from the same residue as that from which water was initially lost. The collision-induced dissociation spectra of ion III derived from both I and II were identical, and their energy-resolved curves were also very similar. Ion III fragments by losses of a glycine molecule (the dominant channel), a water molecule, and a glycine residue (57 Da), giving ions IV, V, and VII, respectively. Isotopic labeling established the origins of each of the neutral molecules that are lost. Using glycine (2,2 D2), rapid deuterium exchange was observed for both ions I and II for the α-hydrogens that are from the same residue as that from which the water had been eliminated.

Hydrogen atom transfer in the radical cations of tryptophan-containing peptides AW and WA studied by mass spectrometry, infrared multiple-photon dissociation spectroscopy, and theoretical calculations

Two types of radical cations of tryptophan—the π-radical cation and the protonated tryptophan-N radical—have been studied in dipeptides AW and WA. The π-radical cation produced by removal of an electron during collision-induced dissociation of a ternary Cu(II) complex was only observed for the AW peptide. In the case of WA, only the ion corresponding to the loss of ammonia, [WA–NH3] •+, was observed from the copper complex. Both protonated tryptophan-N radicals were produced by N-nitrosylation of the neutral peptides followed by transfer to the gas phase via electrospray ionization and subsequent collision-induced dissociation. The regiospecifically formed N• species were characterized by infrared multiple-photon dissociation spectroscopy which revealed that the WA tryptophan-N• radical remains the nitrogen radical, while the AW nitrogen radical rearranges into the π-radical cation. These findings are supported by the density functional theory calculations that suggest a relatively high barrier for the radical rearrangement (N• to π) in WA (156.3 kJ mol−1) and a very low barrier in AW (6.1 kJ mol−1). The facile hydrogen atom migration in the AW system is also supported by the collision-induced dissociation of the tryptophan-N radical species that produces fragments characteristic of the tryptophan π-radical cation. Gas-phase ion–molecule reactions with n-propyl thiol have also been used to differentiate between the π-radical cations (react by hydrogen abstraction) and the tryptophan-N• species (unreactive) of AW.

Erratum to: Structure and Reactivity of the Distonic and Aromatic Radical Cations of Tryptophan

Andrii Piatkivskyi, Sandra Osburn, Kendall Jaderberg, Josipa Grzetic, Jeffrey D. Steill, Jos Oomens, Junfang Zhao, Justin Kai-Chi Lau, Udo H. Verkerk, Alan C. Hopkinson, K. W. Michael Siu, Victor Ryzhov Department of Chemistry and Biochemistry, and Center for Biochemical and Biophysical Studies, Northern Illinois University, DeKalb, IL 60115, USA FOM Institute for Plasma Physics, Rijnhuizen 14, 3439 MN Nieuwegein, The Netherlands University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands Institute for Molecules and Materials (IMM), FELIX facility, Radboud University Nijmegen, Heyendaalseweg 135, 6525AJ Nijmegen, The Netherlands Department of Chemistry and Centre for Research in Mass Spectrometry, York University, Toronto, ON, Canada Sandia National Laboratories, Livermore, CA 94550-0969, USA