Unlocking a Diazirine Long-Lived Nuclear Singlet State via Photochemistry: NMR Detection and Lifetime of an Unstabilized Diazo-Compound

Procacci, Barbara; Roy, Soumya Singha; Norcott, Philip; Turner, Norman; Duckett, Simon B.

doi:10.1021/jacs.8b10923

Cited by 28 publications

(32 citation statements)

References 60 publications

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“…14,48 Conversely, products resulting from labeling through the diazo are more-likely to represent weaker binding interactions, since the lifetime of the diazo is above the rate of diffusion. 49 There are relatively few chemistries that have been used to selectively label carboxylic acids in whole cells, [50][51][52] and fewer photoactivatable chemistries, 27 suggesting that this chemistry could be intentionally utilized to profile carboxylic acids in cells as a method that senses the protonation state of the acids.…”

Section: Discussionmentioning

confidence: 99%

Labeling Preferences of Diazirines with Protein Biomolecules

West¹,

Muncipinto²,

Wu³

et al. 2020

Preprint

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<p>Diazirines are widely used in photoaffinity labeling (PAL) to trap non-covalent interactions with biomolecules. However, design and interpretation of PAL experiments is challenging without a molecular understanding of the reactivity of diazirines with protein biomolecules. Here, we report a systematic evaluation of the labeling preferences of alkyl and aryl diazirines with individual amino acids, single proteins, and in the whole cell proteome. We find that aryl-fluorodiazirines react primarily through a carbene intermediate, while alkyl diazirines generate a reactive alkyl diazo intermediate on route to the carbene. The generation of a reactive diazo intermediate leads to preferential labeling of acidic amino acids in a pH-dependent manner. From a survey of 32 alkyl diazirine probes, we use this reactivity profile to rationalize why these probes preferentially enrich highly acidic proteins or those embedded in membranes and why probes with a net positive-charge tend to produce higher labeling yields. These results indicate that alkyl diazirines are an especially effective chemistry for surveying the membrane proteome, and will facilitate probe design and interpretation of biomolecular labeling experiments with diazirines.<b></b></p>

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Section: Discussionmentioning

confidence: 99%

Labeling Preferences of Diazirines with Protein Biomolecules

West¹,

Muncipinto²,

Wu³

et al. 2020

Preprint

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“…[22][23][24][25] The iridium complex [Ir(IMes)(H)2(Py)3] + Cl -(1) is extensively used for SABRE hyperpolarization. [18][19][20][21] Recently, experimental evidence has suggested that the evolution of hydrogen spin states in organometallic complexes is strongly influenced by the formation of shortlived intermediates. [26][27][28] In particular, it has been suggested that parahydrogen in solution suffers a rapid loss of coherence possibly due to the presence of, until now, unknown reaction intermediates.…”

mentioning

confidence: 99%

Indirect Detection of Short-Lived Hydride Intermediates of Iridium N-Heterocyclic Carbene Complexes via Chemical Exchange Saturation Transfer Spectroscopy

et al. 2019

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For the first time, chemical exchange saturation transfer (CEST) nuclear magnetic resonance (NMR) is utilized to study short-lived hydride intermediates in the catalytic cycle of an organometallic complex [Ir(IMes)(Py) 3 (H) 2 ]Cl. These complexes are typically not observable by other NMR techniques because they are low concentrated and undergo reversible ligand exchange with the main complex. The intermediate complexes [Ir(Cl)(IMes)(Py) 2 (H) 2 ] and [Ir(CD 3 OD)(IMes)(Py) 2 (H) 2 ] are detected, assigned, and characterized in solution, in situ and at room temperature. Understanding the spin dynamics in these complexes is necessary for enhancing the performance of the nuclear spin hyperpolarization technique signal amplification by reversible exchange. By eliminating [Ir(Cl)(IMes)(Py) 2 (H) 2 ] and manipulating the spin system by radiofrequency irradiation, the nuclear spin singlet lifetime of the hydride protons was increased by more than an order of magnitude, from 2.2 ± 0.1 to 27.2 ± 1.2 s. Because of its simplicity and ability to unravel unobservable chemical species, the utilized CEST NMR approach has a large application potential for studying short-lived hydride intermediates in catalytic reactions.

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“…Singlet states in 15 N 2 -diazirines are also enriched well at fields between 0.5 and 50 G. Subsequent UV irradiation releases the p-15 N 2 .Note that, in Figure 5b,UVirradiation of the diazirine can lead to the carbene and nitrogen directly,o ri ndirectly through formation of an intermediate diazo compound. [78]…”

Section: Production Of Paranitrogen Via Sabre Hyperpolarization Of 15mentioning

confidence: 99%

Parahydrogen‐Induced Hyperpolarization of Gases

et al. 2020

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Imaging of gases is a major challenge for any modality including MRI. NMR and MRI signals are directly proportional to the nuclear spin density and the degree of alignment of nuclear spins with applied static magnetic field, which is called nuclear spin polarization. The level of nuclear spin polarization is typically very low, i.e., one hundred thousandth of the potential maximum at 1.5 T and a physiologically relevant temperature. As a result, MRI typically focusses on imaging highly concentrated tissue water. Hyperpolarization methods transiently increase nuclear spin polarizations up to unity, yielding corresponding gains in MRI signal level of several orders of magnitude that enable the 3D imaging of dilute biomolecules including gases. Parahydrogen‐induced polarization is a fast, highly scalable, and low‐cost hyperpolarization technique. The focus of this Minireview is to highlight selected advances in the field of parahydrogen‐induced polarization for the production of hyperpolarized compounds, which can be potentially employed as inhalable contrast agents.

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Unlocking a Diazirine Long-Lived Nuclear Singlet State via Photochemistry: NMR Detection and Lifetime of an Unstabilized Diazo-Compound

Cited by 28 publications

References 60 publications

Labeling Preferences of Diazirines with Protein Biomolecules

Labeling Preferences of Diazirines with Protein Biomolecules

Indirect Detection of Short-Lived Hydride Intermediates of Iridium N-Heterocyclic Carbene Complexes via Chemical Exchange Saturation Transfer Spectroscopy

Parahydrogen‐Induced Hyperpolarization of Gases

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