Measurement of the absolute rate of 1,2-hydrogen migration in benzylchlorocarbene

Jackson, James E.; Soundararajan, Ν.; White, Walter P.; Liu, Michael T. H.; Bonneau, Roland; Platz, Matthew S.

doi:10.1021/ja00199a076

Cited by 48 publications

(26 citation statements)

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“…Although this result should not be over-interpreted because of the potentially uneven backbone fragmentation of the peptide complex ion, it nevertheless points to the realistic representation of the peptide dynamics in the complex. It is also consistent with the previously postulated extremely low activation energies for carbene insertion [9][10][11][12], justifying the assumption that covalent bond formation occurs with high probability upon close contact between the carbene and the X−H bond. The overall conclusion of this theoretical analysis Figure S8b, c), it appears that each laser pulse creates a reactive carbene at only one of the L* residues.…”

Section: Molecular Dynamics Simulationssupporting

confidence: 90%

“…We selected 25 lowest-energy complex structures from DFT optimizations and ran trajectory calculations for 100 ps at 310 K corresponding to the experimental ion trap temperature. The 100 ps time frame is compatible with the half-life of a carbene intermediate, which is expected to be in the 0.1-5 ns range [9][10][11][12].…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 87%

“…Photon absorption causes N 2 elimination, creating a highly reactive singlet carbene that undergoes insertion into proximate X−H bonds (X = C, N, O) to form new covalent H−C−X bonds [8]. Competing with insertion, the carbene can undergo fast intramolecular isomerization by 1,2-hydrogen shift to form a nonreactive olefin in the photoactive component [9][10][11][12], which can no longer covalently bind to the complex counterpart. This side reaction provides an internal clock that limits the time scale for carbene-X-H bond interactions to within 10 -7 s. The photochemical crosslinking (Bstitching^) can be readily detected by mass spectrometry, and the position of the new covalent link can be located by tandem mass spectrometry sequencing of gas-phase adduct ions [7].…”

Section: Introductionmentioning

confidence: 99%

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Efficient Covalent Bond Formation in Gas-Phase Peptide–Peptide Ion Complexes with the Photoleucine Stapler

Shaffer

Andrikopoulos

Řezáč

et al. 2016

J. Am. Soc. Mass Spectrom.

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Abstract. Noncovalent complexes of hydrophobic peptides GLLLG and GLLLK with photoleucine (L*) tagged peptides G(L* n L m )K (n = 1,3, m = 2,0) were generated as singly charged ions in the gas phase and probed by photodissociation at 355 nm. Carbene intermediates produced by photodissociative loss of N 2 from the L* diazirine rings underwent insertion into X−H bonds of the target peptide moiety, forming covalent adducts with yields reaching 30%. Gas-phase sequencing of the covalent adducts revealed preferred bond formation at the C-terminal residue of the target peptide. Site-selective carbene insertion was achieved by placing the L* residue in different positions along the photopeptide chain, and the residues in the target peptide undergoing carbene insertion were identified by gas-phase ion sequencing that was aided by specific 13 C labeling. Density functional theory calculations indicated that noncovalent binding to GL*L*L*K resulted in substantial changes of the (GLLLK + H) + ground state conformation. The peptide moieties in [GL*L*LK + GLLLK + H] + ion complexes were held together by hydrogen bonds, whereas dispersion interactions of the nonpolar groups were only secondary in ground-state 0 K structures. Born-Oppenheimer molecular dynamics for 100 ps trajectories of several different conformers at the 310 K laboratory temperature showed that noncovalent complexes developed multiple, residue-specific contacts between the diazirine carbons and GLLLK residues. The calculations pointed to the substantial fluidity of the nonpolar side chains in the complexes. Diazirine photochemistry in combination with Born-Oppenheimer molecular dynamics is a promising tool for investigations of peptide-peptide ion interactions in the gas phase.

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Section: Molecular Dynamics Simulationssupporting

confidence: 90%

Section: Molecular Dynamics Simulationsmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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Efficient Covalent Bond Formation in Gas-Phase Peptide–Peptide Ion Complexes with the Photoleucine Stapler

Shaffer

Andrikopoulos

Řezáč

et al. 2016

J. Am. Soc. Mass Spectrom.

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“…9 s −1 range [32][33][34], and so the peptide carbene is too short-lived to be collisionally cooled. The dominant formation upon UVPD of small fragments, such as (a 2 -N 2 ) + , (b 2 − N 2 ) + and y 2 , is consistent with UVPD being more energetic than CID.…”

Section: Discussionmentioning

confidence: 99%

Photoleucine Survives Backbone Cleavage by Electron Transfer Dissociation. A Near-UV Photodissociation and Infrared Multiphoton Dissociation Action Spectroscopy Study

Shaffer

Martens

Marek

et al. 2016

J. Am. Soc. Mass Spectrom.

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Abstract. We report a combined experimental and computational study aimed at elucidating the structure of N-terminal fragment ions of the c type produced by electron transfer dissociation of photo-leucine (L*) peptide ions GL*GGKX. The c 4 ion from GL*GGK is found to retain an intact diazirine ring that undergoes selective photodissociation at 355 nm, followed by backbone cleavage. Infrared multiphoton dissociation action spectra point to the absence in the c 4 ion of a diazoalkane group that could be produced by thermal isomerization of vibrationally hot ions. The c 4 ion from ETD of GL*GGK is assigned an amide structure by a close match of the IRMPD action spectrum and calculated IR absorption. The energetics and kinetics of c 4 ion dissociations are discussed.

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“…However, substituents directly attached to the carbenic carbon can have a dramatic influence on the activation barriers for the 1,2-H shift to this centre (7,8). Thus, substitution of a methoxy group at the carbenic carbon of an alkylcarbene suppresses the characteristic 1,2-H migration (9) and the direct spectroscopic observation of methylmethoxycarbene in solution has been reported (10).…”

Section: Resultsmentioning

confidence: 99%

Intramolecular 1,2-alkyl shifts in unsymmetric dialkoxycarbenes studied by very low vapour pressure (VLVP) pyroiysis – mass spectrometry

Suh¹,

Pole²,

Warkentin³

et al. 1996

Can. J. Chem.

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Methoxy-(2,2,2-trifluoroethoxy)carbene radical cations, CH,O-C-OCH,CF,'+, I", are cleanly generated by the dissociative electron ionization (EI) of 2-methoxy-5,5-dimethyl-2-(2,2,2-trifluoroethoxy)-~-1 ,3,4-oxadiazoline I. Neutralization-reionization (NR) mass spectrometry of the neutral carbene 1, generated by one-electron reduction of I'+, shows no recovery ion signal and thus 1 is not a viable species within the ks time scale of the experiment. Very low vapour pressure (VLVP) pyrolysis -mass spectrometry of I in conjunction with (multiple) collision experiments shows that 1 completely isomerizes, via a 1,2-trifluoroethyl shift, into methyl 3,3,3-trifluoropropionate, CF,CH,C(=O)OCH,, l a . This technique was also used to study the related dialkoxycarbenes C,H,O-C-OCH,CF,, 2, CH,O-C-0C2H,, 3, and CH,O-C-OCH(CH,),, 4, generated from the corresponding 2,2-dialkoxy-5,5-dimethyl-A3-1 ,3,4-oxadiazolines. The pyrolytically generated carbene 2 behaves analogously to 1 and completely isomerizes to ethyl 3,3,3-trifluoropropionate, 2a. The neutral carbenes 3 and 4 undergo only a partial isomerization via 1,2-alkyl shifts in which the ethyl and isopropyl groups show a slightly greater migratory aptitude, respectively, than the methyl group. The differences in migratory aptitude are explained in terms of a transition state model similar to that of a 1,2-H shift in carbenes, with development of negative charge in the migrating group. The greater migratory aptitude of CF,CH,, as compared to CH, and CH,CH2, is attributed to the stabilization of negative charge in the transition state by strongly electron-withdrawing p-fluorines whereas the differences in migratory aptitude between the alkyl groups in 3 and 4 are largely due to the greater polarizability of isopropyl and ethyl groups, as compared to the methyl group.Key words: dialkoxycarbenes, pyrolysis, tandem mass spectrometry.Resume : On peut gCnCrer proprement les cations radicaux mtthoxy-(2.2.2-trifluoroCthoxy)carbknes, CH30-C-0CH2CF,'+, 1'+, en procCdant ? I une ionisation Clectronique (IE) dissociative de la 2-mCthoxy-5,5-dim~thyl-2-(2,2,2-trifluoroCthoxy)-~3-1 ,3,4-oxadiazoline, I. La spectroscopie par neutralisation-rkionisation (NR) du carbkne neutre, 1, gCnCrC par une rCduction un electron du 1". ne prksente pas de signal correspondant ii de la rCcupCration d'ion et le composC 1 n'est donc pas une espkce approprike ii I'tchelle de temps, ks, de I'expCrience: La spectromCtrie de masse du composC I avec pyrolyse ii trks basse tension de vapeur (VLVP), rCalisCe de concert avec des expkriences de (multiples) collisions ont montrC que le composC 1 s'isomkrise complktement, par le biais d'un dCplacement-1,2 d'un groupe trifluoroCthyle, en un 3,3,3-trifluoropropionate de mCthyle, CF,CH,C(=O)OCH,, la. On a aussi utilisk cette technique pour Ctudier des dialkoxycarbknes apparentis : C2HjO-C-OCH,CF,, 2, CH,O-C-OC,H,, 3, et CH,O-C-OCH(CH,),, 4, gCnCrCs a parti des 2,2-dialko~~-5,5-dirnCth~l-~~-1,3,4-oxadiazolines correspondantes. Le carbkne 2 prCparC d'une f a~o n py...

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Measurement of the absolute rate of 1,2-hydrogen migration in benzylchlorocarbene

Cited by 48 publications

References 0 publications

Efficient Covalent Bond Formation in Gas-Phase Peptide–Peptide Ion Complexes with the Photoleucine Stapler

Efficient Covalent Bond Formation in Gas-Phase Peptide–Peptide Ion Complexes with the Photoleucine Stapler

Photoleucine Survives Backbone Cleavage by Electron Transfer Dissociation. A Near-UV Photodissociation and Infrared Multiphoton Dissociation Action Spectroscopy Study

Intramolecular 1,2-alkyl shifts in unsymmetric dialkoxycarbenes studied by very low vapour pressure (VLVP) pyroiysis – mass spectrometry

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