Skip to main content
NCBI home page
ACS Omega logoLink to ACS Omega
. 2021 Dec 30;7(1):293–298. doi: 10.1021/acsomega.1c04679

TfNN15N: A γ-15N-Labeled Diazo-Transfer Reagent for the Synthesis of β-15N-Labeled Azides

Hyeok-Jun Kwon †, Sungduk Gwak †, Jun Young Park †,‡, Minhaeng Cho †,‡, Hogyu Han †,*
PMCID: PMC8757338  PMID: 35036700

Abstract

graphic file with name ao1c04679_0008.jpg

Azides are infrared (IR) probes that are important for structure and dynamics studies of proteins. However, they often display complex IR spectra owing to Fermi resonances and multiple conformers. Isotopic substitution of azides weakens the Fermi resonance, allowing more accurate IR spectral analysis. Site-specifically 15N-labeled aromatic azides, but not aliphatic azides, are synthesized through nitrosation. Both 15N-labeled aromatic and aliphatic azides are synthesized through nucleophilic substitution or diazo-transfer reaction but as an isotopomeric mixture. We present the synthesis of TfNN15N, a γ-15N-labeled diazo-transfer reagent, and its use to prepare β-15N-labeled aliphatic as well as aromatic azides.

Introduction

Various spectroscopic techniques have been used to study the structures and dynamics of proteins. Fluorophores are widely used probes for studying changes in the protein structure.1 However, the introduction of relatively large fluorophores significantly disturbs the native structure.

Infrared (IR) probes, such as CO,2 CN,3 and SCN,4 which directly convey intramolecular bonding vibrations, are relatively small, thus minimizing native structure disturbance. IR probes have been used as site-specific probes of biomolecules because of their sensitivity to the local environment. However, IR spectral analysis of biomolecules is difficult because their IR signals often overlap with those of peptides. Therefore, IR probes with isotopic labels or a signal in the transparent window region between 1800 and 2500 cm–1 are used.5

Azides have considerable potential as vibration probes of biomolecules due to their IR absorption in the transparent window region of the spectrum.6 In addition, the molar extinction coefficient of the azide probe is approximately 5–19 times larger than that of the CN probe. Therefore, azide probes may be used for low-concentration peptides or proteins. Azides are also used in site-specific “click chemistry”.7

However, short vibrational lifetimes and Fermi resonance are disadvantages in the IR spectral analysis of azide.8 In the presence of Fermi resonance, the IR absorption spectrum is complex, which hampers the spectral analysis for probing structural changes in proteins or surrounding solvents. Furthermore, whether the IR spectrum is complicated by Fermi resonance or multiple conformation is unclear.

Accidental Fermi resonance can be detected by FTIR absorption and 2DIR spectroscopies.9 However, the complex spectra, due to Fermi resonance, are challenging to analyze. Generally, isotopic substitution overcomes spectral interference by Fermi resonance because its effect is reduced by increasing the energy difference between the fundamental and overtone (or combination) modes.10

Three synthetic routes are known for preparing 15N-labeled azides (Scheme 1).10,11 First, nucleophilic substitution reaction, wherein halides or good leaving groups are substituted with 15N3–, is the most commonly used method for the synthesis of 15N-labeled aliphatic azides. This method was used by Brewer and co-workers to prepare azido isotopomers of 2′-azido-2′-deoxyuridine (dU-NNN) as a mixture of dU-15NNN and dU-NN15N.11 Although there was a slight frequency red-shift of dU-15NNN (2111 cm–1) and dU-NN15N (2089 cm–1) relative to dU-NNN (2111 cm–1), IR spectral analysis of the two-isotopomer mixture was still difficult because their IR spectra overlapped.

Scheme 1. (a–d) Syntheses of Site-Specifically 15N-Labeled Azides.

Scheme 1

Open in a new tab

Second, nitrosation of aryl hydrazine with Na15NO2 is useful for the synthesis of site-specifically 15N-labeled aromatic azides. This method was used by Brewer and co-workers to prepare azido isotopomers of 3-azidopyridine (PyrNNN) in a site-specific manner.10 In the IR spectrum of PyrNNN, a complex band containing the Fermi resonance was observed at 2075–2150 cm–1. The IR bands of Pyr15NNN, PyrNN15N, and PyrN15NN were observed at 2121, 2080, and 2067 cm–1, respectively. The IR spectrum of PyrNN15N was still complex, due to Fermi resonance, but those of Pyr15NNN and PyrN15NN revealed one band. However, unlike aryl or carbonyl hydrazine, alkyl hydrazine has the limitation that it cannot be rearranged through nitrosation to produce azides.12

Finally, the diazo-transfer reaction of primary amines is an efficient method for the syntheses of both 15N-labeled aromatic and aliphatic azides.11,13 Diazo-transfer occurs via nucleophilic attack of amine on the azido group of the reagent at its terminal γ-N atom as suggested by Wong’s mechanism.14 Accordingly, the α-, β-, and γ-15N-labeled diazo-transfer reagents furnish the unlabeled, γ-, and β-15N-labeled azides, respectively. Brewer and co-workers synthesized azido isotopomers of trifluoromethanesulfonyl azides (TfNNN), a diazo-transfer reagent, as a mixture of Tf15NNN and TfNN15N (α- and γ-15N-labeled ones) by the nucleophilic substitution reaction of trifluoromethanesulfonic anhydride (Tf2O) with Na15NNN.11 That mixture was then used to prepare a mixture of dU-NNN and dU-N15NN. The IR spectrum of dU-N15NN (2069 cm–1) exhibited a red-shift of 42 cm–1 from that of dU-NNN. Such frequency difference is greater than those for dU-15NNN and dU-NN15N. Therefore, the β-15N-labeled azide modulated the accidental Fermi resonance occurring in the unlabeled azide by the largest frequency shift among the single-labeled azides, but its IR spectrum still overlapped with that of the unlabeled azide. Azido isotopomers of other diazo-transfer reagents such as imidazole-1-sulfonyl azide (ImSO2N3) and 2-azido-1,3-dimethylimidazolinium hexafluorophosphate (ADMP) were also synthesized as an isotopomeric mixture. A mixture of α- and γ-15N-labeled azido isotopomers of ImSO2N3 was synthesized by nucleophilic substitution using Na15NNN.13 Recently, we found that a 1:1 mixture of α- and γ-15N-labeled azido isotopomers of ADMP was synthesized by nitrosation of 1,3-dimethylimidazolidinone hydrazone with Na15NO2.15 Such a mixture was also obtained by the nucleophilic substitution reaction of 2-chloro-1,3-dimethylimidazolinium chloride with Na15NNN.

Taken together, site-specifically 15N-labeled aromatic azides, but not aliphatic azides, can be synthesized through nitrosation. Both 15N-labeled aromatic and aliphatic azides can be synthesized by nucleophilic substitution or diazo-transfer reaction but as an isotopomeric mixture (-15NNN, -NN15N- or -N15NN, -NNN). That is, a synthetic method for preparing site-specifically 15N-labeled aliphatic azides has not been established yet. In particular, β-15N-labeled azides are demanded to facilitate the IR spectral analysis of the azide probe by decreasing the Fermi resonance effect. Herein, we report the synthesis of TfNN15N, a γ-15N-labeled diazo-transfer reagent, via nitrosation of TfNHNH2 with Na15NO2, and its use to prepare β-15N-labeled aliphatic as well as aromatic azides.

Results and Discussion

A γ-15N-labeled diazo-transfer reagent was designed based on TfN3, an early model diazo-transfer reagent.16 Like aryl or carbonyl hydrazine, sulfonyl hydrazine may rearrange to produce γ-15N-labeled azides upon nitrosation with Na15NO2.17

TfNN15N 1 (or TfNNN 1′) was synthesized by nitrosation of in situ generated TfNHNH21″ with Na15NO2 (or NaNO2) (Scheme 2). TfNHNH2 could not be obtained upon treatment of Tf2O with NH2NH2.18,19 Instead, it was generated in situ from TfNHNHBoc 1‴,20,21 which was synthesized using Tf2O and NH2NHBoc. Hydrazine precursor 1‴ is a more stable and easier-to-use solid than its derived hydrazine 1″. After the removal of Boc in 1‴ with trifluoroacetic acid (TFA), it was subjected without purification to direct reaction with Na15NO2 to afford the desired product 1. This indicates that nitrosation occurs under acidic conditions without being severely affected by the cleavage product of Boc. TfNN15N present in the organic layer (CH2Cl2) obtained through the work-up process was used without further purification for subsequent spectral analyses and diazo-transfer reactions because of its low boiling point.22 Currently, the yields in the preparation of TfNN15N are inconsistent. However, hydrazine is easily obtained via its precursor for TfN3 but not for ImSO2N3.

Scheme 2. Synthesis of TfNN15N 1.

Scheme 2

Open in a new tab

The synthesis of TfNN15N was confirmed by 15N NMR and IR spectroscopies. Nitrosation usually occurs at the β-N of hydrazine, forming the γ-15N-labeled azide. Occasionally, however, nitrosation occurs at the α-N of hydrazine, forming not only γ-15N-labeled but also β-15N-labeled azide.23 The 15N NMR spectrum of TfNN15N shows only one peak at −139.08 ppm, confirming the synthesis of the γ-15N-labeled azide via nitrosation at the β-N of hydrazine. The IR spectrum of TfNN15N shows a strong, broad band at 2126 cm–1, confirming the synthesis of the γ-15N-labeled azide (Figure 1). The IR band of TfNNN appears at 2154 cm–1, which is blue-shifted by approximately 28 cm–1 from that of TfNN15N. Note that TfNN15N and TfNNN show the shoulder peaks at 2155 and 2128 cm–1, respectively, which arise from Fermi resonance. Although site-specific isotopic substitutions are confirmed through the observed frequency shift, accurate analysis of the IR spectrum is difficult because of Fermi resonance.

Figure 1.

Figure 1

Open in a new tab

IR spectra of TfNN15N 1 and TfNNN 1′ in CH2Cl2 at 20 °C.

With TfNN15N in hand, we then explored the diazo-transfer reaction of various amines (Scheme 3). Three representative amines used were Ac-DAP-NHMe·TFA 2a,6a H-Phe-OtBu·HCl 2b, and Ac-Phe(p-NH2)-OMe 2c, which are aliphatic amines bonded to primary and secondary carbons, and aromatic amines, respectively. Upon the reaction with TfNN15N, they were converted to the β-15N-labeled aliphatic and aromatic azides 3a–3c in moderate yields.24

Scheme 3. Syntheses of Azides 3 by Diazo-Transfer Reactions of Amines 2 with TfNN15N 1.

Scheme 3

Open in a new tab

The syntheses of the β-15N-labeled aliphatic and aromatic azides were confirmed by 1H NMR, 13C NMR, and IR spectroscopies. First, the 1H NMR spectra of AlaN15NN (Ac-Ala(N15NN)-NHMe, 3a) and AlaNNN (Ac-Ala(NNN)-NHMe,6b3a′) revealed that the splitting pattern of the signal for two Hβs, Hβ1 and Hβ2, at 3.45–3.80 ppm was different between 3a and 3a′ (Figure 2). The signal for the two Hβs in 3a and 3a′ is split into 16 and 8 peaks, respectively, which can be explained as follows. Each of the two Hβs exhibits a different signal, which appear at 3.73 and 3.53 ppm for 3a and 3.72 and 3.54 ppm for 3a′. Each of these two signals is further split into eight and four peaks for 3a and 3a′, which is due to the coupling of Hβ1 with Hβ2, Hα, and β-15Nβ for 3a but with Hβ2 and Hα for 3a′. Thus, the 1H NMR spectrum confirms the presence of β-15Nβ in 3a. The 13C NMR spectrum of 3a shows the 2J and 3J couplings of β-15Nβ with adjacent Cβ (2J(β-15Nβ,Cβ) = 1.9 Hz) and Cα (3J(β-15Nβ,Cα) = 1.9 Hz), which also confirms the presence of β-15Nβ in 3a. The IR spectra of 3a and 3a′ exhibit one band at 2061 and 2104 cm–1, respectively (Figure 3). A red-shift of 43 cm–1 is due to replacing β-Nβ with β-15Nβ. Thus, the IR spectrum also confirms the presence of β-15Nβ in 3a. The same patterns were also observed in the 1H NMR, 13C NMR, and IR spectra of other azides 3b, 3b′, 3c, and 3c′ (Figures S1–S6 of the Supporting Information): 1H NMR spectra (500 MHz, CDCl3) of 3b, δ 3.91 (ddd, J = 8.5, 6.0, 5.0 Hz, 1H); 3b′, δ 3.91 (dd, J = 8.0, 6.0 Hz, 1H); 13C NMR spectra (125 MHz, CDCl3) of 3b, 2J(β-15Nα,Cα) = 1.9 Hz, 3J(β-15Nα,Cβ) = 1.8 Hz; 3c, 2J(β-15Np,Cp) = 2.8 Hz; IR spectra of 3b, 2062 cm–1; 3b′, 2112 cm–1; 3c, 2090 cm–1; 3c′, 2143 cm–1.

Figure 2.

Figure 2

Open in a new tab

1H NMR spectra (500 MHz, CDCl3) of AlaN15NN 3a and AlaNNN 3a′ in the β-proton region: 3a, δ 3.73 (ddd, J = 12.4, 5.1, 3.6 Hz, 1H), 3.53 (ddd, J = 12.3, 6.3, 3.8 Hz, 1H); 3a′, δ 3.72 (dd, J = 12.3, 4.8 Hz, 1H), 3.54 (dd, J = 12.3, 6.3 Hz, 1H).

Figure 3.

Figure 3

Open in a new tab

IR spectra of AlaN15NN 3a and AlaNNN 3a′ in DMF at 20 °C.

Conclusions

In conclusion, we synthesized TfNN15N, a γ-15N-labeled diazo-transfer reagent, via nitrosation of TfNHNH2 with Na15NO2. We then demonstrated that it could be used to prepare both β-15N-labeled aliphatic and aromatic azides. TfNN15N is the first example of a site-specifically 15N-labeled diazo-transfer reagent, which can provide site-specifically 15N-labeled aliphatic azides for the first time. β-15N-Labeled azides display a larger frequency red-shift than α- and γ-15N-labeled azides compared to the unlabeled one. Thus, β-15N-labeled azides render the IR spectral analysis of azide probes much easier because a more significant decrease in the Fermi resonance effect is attained.25,26

Experimental Section

General

1H and 13C NMR spectra were recorded on a Bruker Ascend 500 NMR spectrometer. 15N NMR spectra were recorded on an Agilent DD2 700 NMR spectrometer. Chemical shifts (δ) and coupling constants (J) are reported in parts per million (ppm) and hertz (Hz), respectively. 1H NMR spectra are referenced to TMS (0.03% v/v tetramethylsilane in CDCl3) as an internal standard. 13C NMR spectra are referenced to the solvent (13C: CDCl3, δ 77.00 ppm) as an internal standard. High-resolution mass spectra (HRMS) were recorded on a JEOL JMS-700 mass spectrometer using the fast atom bombardment (FAB) technique. IR spectra were measured on a Bruker VERTEX 70 FTIR spectrometer equipped with a HgCdTe detector. The samples 1 and 3 were dissolved in DMF at 0.3 M. IR spectra were measured with a frequency resolution of 1 cm–1 in 12 scans using a CaF2 cell (2 mm thickness) confined with a Teflon spacer (25 μm thickness). Thin-layer chromatography (TLC) was performed on silica gel 60 F254 precoated plates (0.25 mm thickness, Merck, Darmstadt). Flash chromatography was carried out on silica gel 60 (230–400 mesh, Merck). Reagent-grade chemicals were purchased from Sigma-Aldrich, Alfa Aesar, and TCI and used as received unless otherwise specified. Amino acids (H-DAP(Boc)-OMe·HCl, H-Phe-OtBu·HCl 2b, and Ac-p-amino-Phe-OMe 2c) were purchased from BACHEM. Sodium nitrite (15N, 98%+) was purchased from Cambridge Isotope Laboratories. TfNHNHBoc 1‴(21) and Ac-Dap-NHMe·TFA 2a(6a) were prepared as reported previously.

Preparation of γ-15N-Labeled Trifluoromethanesulfonyl Azide (TfNN15N, 1)

To a cooled (0 °C) and stirred solution of TfNHNHBoc 1‴(21) (2.38 g, 9.00 mmol) in CH2Cl2 (40 mL) was added trifluoroacetic acid (15 mL). After stirring at 0 °C for 1 h, a solution of Na15NO2 (931 mg, 13.3 mmol) in H2O (10 mL) was added. After stirring at 0 °C for a further 1 h, the reaction mixture was treated with saturated aqueous Na2CO3 solution (200 mL). The organic layer was collected and used without further purification.

General Procedure for the Preparation of β-15N-Labeled Azides 3

To a stirred solution of amine 2 (1.0 mmol) in H2O/MeOH (1:2, 15 mL) were added CuSO4·5H2O (10 mg, 40 μmol), K2CO3 (691 + x mg, 5.0 + n mmol),a and then a solution of TfNN15N 1 (∼3 mmol) in CH2Cl2 (15 mL). After stirring vigorously at room temperature for 12 h, the reaction mixture was concentrated in vacuo. The residue was purified by flash chromatography to give azide 3.

Ac-Ala(N15NN)-NHMe (3a)

Ac-Dap-NHMe·TFA 2a(6a) (273 mg, 1.0 mmol) was treated according to the general procedure (flash chromatography, MeOH/CH2Cl2 = 1:50) to give 3a (155 mg, 83%) as a white solid. TLC (MeOH/CH2Cl2 = 1:15) Rf = 0.38; 1H NMR (500 MHz, CDCl3) δ 6.69 (brs, 1H), 6.63 (d, J = 7.5 Hz, 1H), 4.62 (ddd, J = 7.6, 6.4, 5.1 Hz, 1H), 3.73 (ddd, J = 12.4, 5.1, 3.6 Hz, 1H), 3.53 (ddd, J = 12.3, 6.3, 3.8 Hz, 1H), 2.84 (d, J = 4.5 Hz, 3H), 2.06 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 170.55, 169.69, 52.24 (d, J = 1.9 Hz), 51.88 (d, J = 1.9 Hz), 26.43, 23.13; 15N NMR (70 MHz, CDCl3) δ −133.45; HRMS (FAB+) for C6H12N415NO2 (MH+), calcd 187.0961, found 187.0966.

N15NN-Phe-OtBu (3b)

H-Phe-OtBu·HCl 2b (258 mg, 1.0 mmol) was treated according to the general procedure (flash chromatography, CH2Cl2/n-hexene = 1:6) to give 3b (189 mg, 76%) as a colorless oil. TLC (CH2Cl2/n-hexene = 1:3) Rf = 0.32; 1H NMR (500 MHz, CDCl3) δ 7.34–7.23 (m, 5H), 3.91 (ddd, J = 8.5, 6.0, 5.0 Hz, 1H), 3.13 (dd, J = 14.0, 6.0 Hz, 1H), 2.99 (dd, J = 14.0, 8.5 Hz, 1H), 1.45 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 168.99, 136.18, 129.26, 128.56, 127.11, 83.00, 63.60 (d, J = 1.9 Hz), 37.55 (d, J = 1.8 Hz), 27.94; 15N NMR (70 MHz, CDCl3) δ −135.09; HRMS (FAB+) for C13H18N215NO2 (MH+), calcd 249.1369, found 249.1371.

Ac-Phe(p-N15NN)-OMe (3c)

Ac-Phe(p-NH2)-OMe 2c (236 mg, 1.0 mmol) was treated according to the general procedure (flash chromatography, EtOAc/n-hexene = 1:1) to give 3c (91.1 mg, 35%) as a yellow solid. TLC (EtOAc/n-hexene = 3:1) Rf = 0.41; 1H NMR (500 MHz, CDCl3) δ 7.08 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 5.93 (d, J = 7.0 Hz, 1H), 4.87 (q, J = 6.5 Hz, 1H), 3.74 (s, 3H), 3.14 (dd, J = 13.5, 6.0 Hz, 1H), 3.06 (dd, J = 14.0, 5.5 Hz, 1H), 1.99 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 171.93, 169.50, 138.97, 132.57, 130.59, 119.15 (d, J = 2.8 Hz), 53.11, 52.39, 37.29, 23.14; 15N NMR (70 MHz, CDCl3) δ −137.72; HRMS (FAB+) for C12H15N315NO3 (MH+), calcd 264.1115, found 264.1110.

Acknowledgments

H.H. is grateful for financial support from the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (NRF2021R1A2C1094754). M.C. thanks financial support from the Institute for Basic Science (IBS-R023-D1).

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.1c04679.

  • NMR and IR spectra of compounds (PDF)

Author Contributions

# H.-J.K. and S.G. contributed equally to this work.

The authors declare no competing financial interest.

This paper was original published ASAP on December 30, 2021. Additional minor corrections were made to the Results and Discussion section, and a revised Supporting Information file was uploaded. The corrected version was reposted on January 3, 2022. Additional corrections were made and the paper was reposted January 11, 2022.

Footnotes

a

Additional quantities (x, n) should be added when the reaction does not reach completion. For example, the reaction of TfNN15N 1 and Ac-Phe(p-NH2)-OMe 2c required x = 691 mg, n = 5.0 mmol.

Supplementary Material

ao1c04679_si_001.pdf (635.2KB, pdf)

References

  1. a Lockhart D. J.; Kim P. S. Internal Stark effect measurement of the electric field at the amino terminus of an α helix. Science 1992, 257, 947–951. 10.1126/science.1502559. [DOI] [PubMed] [Google Scholar]; b Lockhart D. J.; Kim P. S. Electrostatic screening of charge and dipole interactions with the helix backbone. Science 1993, 260, 198–202. 10.1126/science.8469972. [DOI] [PubMed] [Google Scholar]; c Giaimo J. M.; Gusev A. V.; Wasielewski M. R. Excited-state symmetry breaking in cofacial and linear dimers of a green perylenediimide chlorophyll analogue leading to ultrafast charge separation. J. Am. Chem. Soc. 2002, 124, 8530–8531. 10.1021/ja026422l. [DOI] [PubMed] [Google Scholar]; d Miyawaki A.; Llopis J.; Heim R.; McCaffery J. M.; Adams J. A.; Ikural M.; Tsien R. Y. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 1997, 388, 882–887. 10.1038/42264. [DOI] [PubMed] [Google Scholar]; e Tsien R. Y. The green fluorescent protein. Annu. Rev. Biochem. 1998, 67, 509–544. 10.1146/annurev.biochem.67.1.509. [DOI] [PubMed] [Google Scholar]
  2. a Park E. S.; Boxer S. G. Origins of the sensitivity of molecular vibrations to electric fields: Carbonyl and nitrosyl stretches in model compounds and proteins. J. Phys. Chem. B 2002, 106, 5800–5806. 10.1021/jp0203043. [DOI] [Google Scholar]; b Stavrov S. S.; Wright W. W.; Vanderkooi J. M.; Fidy J.; Kaposi A. D. Optical and IR absorption as probe of dynamics of heme proteins. Biopolymers 2002, 67, 255–258. 10.1002/bip.10103. [DOI] [PubMed] [Google Scholar]
  3. a Chattopadhyay A.; Boxer S. G. Vibrational Stark effect spectroscopy. J. Am. Chem. Soc. 1995, 117, 1449–1450. 10.1021/ja00109a038. [DOI] [Google Scholar]; b Schultz K. C.; Supekova L.; Ryu Y.; Xie J.; Perera R.; Schultz P. G. A genetically encoded infrared probe. J. Am. Chem. Soc. 2006, 128, 13984–13985. 10.1021/ja0636690. [DOI] [PubMed] [Google Scholar]
  4. a Fafarman A. T.; Webb L. J.; Chuang J. I.; Boxer S. G. Site-specific conversion of cysteine thiols into thiocyanate creates an IR probe for electric fields in proteins. J. Am. Chem. Soc. 2006, 128, 13356–13357. 10.1021/ja0650403. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Park K.-H.; Jeon J.; Park Y.; Lee S.; Kwon H.-J.; Joo C.; Park S.; Han H.; Cho M. Infrared probes based on nitrile-derivatized prolines: Thermal insulation effect and enhanced dynamic range. J. Phys. Chem. Lett. 2013, 4, 2105–2110. 10.1021/jz400954r. [DOI] [Google Scholar]
  5. a Adhikary R.; Zimmermann J.; Romesberg F. E. Transparent window vibrational probes for the characterization of proteins with high structural and temporal resolution. Chem. Rev. 2017, 117, 1927–1969. 10.1021/acs.chemrev.6b00625. [DOI] [PubMed] [Google Scholar]; b Chin J. K.; Jimenez R.; Romesberg F. E. Direct observation of protein vibrations by selective incorporation of spectroscopically observable carbon-deuterium bonds in cytochrome c. J. Am. Chem. Soc. 2001, 123, 2426–2427. 10.1021/ja0033741. [DOI] [PubMed] [Google Scholar]; c Romesberg F. E. Multidisciplinary experimental approaches to characterizing biomolecular dynamics. ChemBioChem 2003, 4, 563–571. 10.1002/cbic.200300572. [DOI] [PubMed] [Google Scholar]
  6. a Oh K.-I.; Lee J.-H.; Joo C.; Han H.; Cho M. β-Azidoalanine as an IR probe: Application to amyloid Aβ(16-22) aggregation. J. Phys. Chem. B 2008, 112, 10352–10357. 10.1021/jp801558k. [DOI] [PubMed] [Google Scholar]; b Oh K.-I.; Kim W.; Joo C.; Yoo D.-G.; Han H.; Hwang G.-S.; Cho M. Azido gauche effect on the backbone conformation of β-azidoalanine peptides. J. Phys. Chem. B 2010, 114, 13021–13029. 10.1021/jp107359m. [DOI] [PubMed] [Google Scholar]; c Lee K.-K.; Park K.-H.; Joo C.; Kwon H.-J.; Han H.; Ha J.-H.; Park S.; Cho M. Ultrafast internal rotational dynamics of the azido group in (4S)-azidoproline: Chemical exchange 2DIR spectroscopic investigations. Chem. Phys. 2012, 396, 23–29. 10.1016/j.chemphys.2011.04.024. [DOI] [Google Scholar]; d Lee K.-K.; Park K.-H.; Joo C.; Kwon H.-J.; Jeon J.; Jung H.-I.; Park S.; Han H.; Cho M. Infrared probing of 4-azidoproline conformations modulated by azido configurations. J. Phys. Chem. B 2012, 116, 5097–5110. 10.1021/jp1085119. [DOI] [PubMed] [Google Scholar]; e Schmitz A. J.; Hogle D. G.; Gai X. S.; Fenlon E. E.; Brewer S. H.; Tucker M. J. Two-dimensional infrared study of vibrational coupling between azide and nitrile reporters in a RNA nucleoside. J. Phys. Chem. B 2016, 120, 9387–9394. 10.1021/acs.jpcb.6b07212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. a Kolb H. C.; Finn M. G.; Sharpless K. B. Click chemistry: Diverse chemical function from a few good reactions. Angew. Chem., Int. Ed. 2001, 40, 2004–2021. . [DOI] [PubMed] [Google Scholar]; b Díez-González S.; Nolan S. P. [(NHC)2Cu]X complexes as efficient catalysts for azide–alkyne click chemistry at low catalyst loadings. Angew. Chem., Int. Ed. 2008, 47, 8881–8884. 10.1002/ange.200803289. [DOI] [PubMed] [Google Scholar]; c Amblard F.; Cho J. H.; Schinazi R. F. Cu(I)-catalyzed Huisgen azide–alkyne 1,3-dipolar cycloaddition reaction in nucleoside, nucleotide, and oligonucleotide chemistry. Chem. Rev. 2009, 109, 4207–4220. 10.1021/cr9001462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. a Bertran J. F.; Ballester L.; Dobrihalova L.; Sánchez N.; Arrieta R. Study of Fermi resonance by the method of solvent variation. Spectrochim. Acta, Part A 1968, 24, 1765–1776. 10.1016/0584-8539(68)80232-6. [DOI] [Google Scholar]; b Duncan J. L. The determination of vibrational anharmonicity in molecules from spectroscopic observations. Spectrochim. Acta, Part A 1991, 47, 1–27. 10.1016/0584-8539(91)80174-H. [DOI] [Google Scholar]; c Reimers J. R.; Hall L. E. The solvation of acetonitrile. J. Am. Chem. Soc. 1999, 121, 3730–3744. 10.1021/ja983878n. [DOI] [Google Scholar]; d Kondratyuk P. Analytical formulas for Fermi resonance interactions in continuous distributions of states. Spectrochim. Acta, Part A 2005, 61, 589–593. 10.1016/j.saa.2004.05.010. [DOI] [PubMed] [Google Scholar]
  9. Nydegger M. W.; Dutta S.; Cheatum C. M. Two-dimensional infrared study of 3-azidopyridine as a potential spectroscopic reporter of protonation state. J. Chem. Phys. 2010, 133, 134506. 10.1063/1.3483688. [DOI] [PubMed] [Google Scholar]
  10. a Lipkin J. S.; Song R.; Fenlon E. E.; Brewer S. H. Modulating accidental Fermi resonance: What a difference a neutron makes. J. Phys. Chem. Lett. 2011, 2, 1672–1676. 10.1021/jz2006447. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Lešsetický L.; Barth R.; Němec I.; Štícha M.; Tišlerová I. Synthesis and spectra of N-15 labelled phenylazides. Czech. J. Phys. 2003, 53, A777–A782. 10.1007/s10582-003-0101-0. [DOI] [Google Scholar]
  11. Gai X. S.; Fenlon E. E.; Brewer S. H. A sensitive multispectroscopic probe for nucleic acids. J. Phys. Chem. B 2010, 114, 7958–7966. 10.1021/jp101367s. [DOI] [PubMed] [Google Scholar]
  12. a Smith P. A. S.; Clegg J. M.; Lakritz J. Preparation of alkyl azides from hydrazine derivatives. J. Org. Chem. 1958, 23, 1595–1599. 10.1021/jo01105a001. [DOI] [Google Scholar]; b Laszlo P.; Polla E. Efficient conversion of hydrazines to azides with clay-supported ferric nitrate. Tetrahedron Lett. 1984, 25, 3701–3704. 10.1016/0040-4039(84)80109-4. [DOI] [Google Scholar]
  13. a Pandiakumar A. K.; Sarma S. P.; Samuelson A. G. Mechanistic studies on the diazo transfer reaction. Tetrahedron Lett. 2014, 55, 2917–2920. 10.1016/j.tetlet.2014.03.057. [DOI] [Google Scholar]; b Goddard-Borger E. D.; Stick R. V. An efficient, inexpensive, and shelf-stable diazotransfer reagent: Imidazole-1-sulfonyl azide hydrochloride. Org. Lett. 2007, 9, 3797–3800. 10.1021/ol701581g. [DOI] [PubMed] [Google Scholar]; c Stevens M. Y.; Sawant R. T.; Odell L. R. Synthesis of sulfonyl azides via diazotransfer using an imidazole-1-sulfonyl azide salt: Scope and 15N NMR labeling experiments. J. Org. Chem. 2014, 79, 4826–4831. 10.1021/jo500553q. [DOI] [PubMed] [Google Scholar]
  14. a Nyffeler P. T.; Liang C.-H.; Koeller K. M.; Wong C.-H. The chemistry of amine–azide interconversion: Catalytic diazotransfer and regioselective azide reduction. J. Am. Chem. Soc. 2002, 124, 10773–10778. 10.1021/ja0264605. [DOI] [PubMed] [Google Scholar]; b Alper P. B.; Hung S.-C.; Wong C.-H. Metal catalyzed diazo transfer for the synthesis of azides from amines. Tetrahedron Lett. 1996, 37, 6029–6032. 10.1016/0040-4039(96)01307-X. [DOI] [Google Scholar]
  15. Kitamura M.; Tashiro N.; Miyagawa S.; Okauchi T. 2-Azido-1,3-dimethylimidazolinium salts: Efficient diazo-transfer reagents for 1,3-dicarbonyl compounds. Synthesis 2011, 1037–1044. 10.1055/s-0030-1258457. [DOI] [Google Scholar]
  16. a Cavender C. J.; Shiner V. J. Jr. Trifluoromethanesulfonyl azide. Its reaction with alkyl amines to form alkyl azides. J. Org. Chem. 1972, 37, 3567–3569. 10.1021/jo00795a052. [DOI] [Google Scholar]; b Zaloom J.; Roberts D. C. Preparation of azido derivatives from amino acids and peptides by diazo transfer. J. Org. Chem. 1981, 46, 5173–5176. 10.1021/jo00338a022. [DOI] [Google Scholar]
  17. Azeez S.; Chaudhary P.; Sureshbabu P.; Sabiah S.; Kandasamy J. tert-Butyl nitrite mediated nitrogen transfer reactions: Synthesis of benzotriazoles and azides at room temperature. Org. Biomol. Chem. 2018, 16, 8280–8285. 10.1039/C8OB01950A. [DOI] [PubMed] [Google Scholar]
  18. a Roezky H. W. Perfluoroalkanesulfinic acids. Angew. Chem., Int. Ed. 1971, 10, 810–811. 10.1002/anie.197108102. [DOI] [Google Scholar]; b Shainyan B. A.; Tolstikova L. L.; Meshcheryakov V. I.; Danilevich Y. S. Trifluoromethanesulfonic hydrazides. Russ. J. Org. Chem. 2004, 40, 1071–1075. 10.1023/B:RUJO.0000045884.87574.ec. [DOI] [Google Scholar]; c Guo J.-Y.; Wu R.-X.; Jin J.-K.; Tian S.-K. TfNHNHBoc as a trifluoromethylating agent for vicinal difunctionalization of terminal alkenes. Org. Lett. 2016, 18, 3850–3853. 10.1021/acs.orglett.6b01862. [DOI] [PubMed] [Google Scholar]
  19. Shainyan B. A.; Tolstikova L. L. Trifluoromethanesulfonamides and related compounds. Chem. Rev. 2013, 113, 699–733. 10.1021/cr300220h. [DOI] [PubMed] [Google Scholar]
  20. Ragnarsson U.; Grehn L.; Koppel J.; Loog O.; Tšubrik O.; Bredikhin A.; Mäeorg U.; Koppel I. Acidity of di- and triprotected hydrazine derivatives in dimethyl sulfoxide and aspects of their alkylation. J. Org. Chem. 2005, 70, 5916–5921. 10.1021/jo050680u. [DOI] [PubMed] [Google Scholar]
  21. Hendrickson J. B.; Sternbach D. D. A mild oxidation of alkyl halides to aldehyde derivatives. J. Org. Chem. 1975, 40, 3450–3452. 10.1021/jo00911a036. [DOI] [Google Scholar]
  22. Bernet B.; Vasella A.; Liu Q.; Tor Y. Trifluoromethanesulfonyl azide. e-EROS Encycl. reagents org. synth. 2009, 10.1002/047084289X.rn00114.pub2. [DOI] [Google Scholar]
  23. Clusius K.; Schwarzenbach K. 81. Reaktionen mit l5N XXXII. Bildung und abbau von nitrosophenylhydrazin. Helv. Chim. Acta 1959, 42, 739–748. 10.1002/hlca.19590420315. [DOI] [Google Scholar]
  24. Liu Q.; Tor Y. Simple conversion of aromatic amines into azides. Org. Lett. 2003, 5, 2571–2572. 10.1021/ol034919+. [DOI] [PubMed] [Google Scholar]
  25. a Park J. Y.; Kwon H.-J.; Mondal S.; Han H.; Kwak K.; Cho M. Two-dimensional IR spectroscopy reveals a hidden Fermi resonance band in the azido stretch spectrum of β-azidoalanine. Phys. Chem. Chem. Phys. 2020, 22, 19223–19229. 10.1039/D0CP02693J. [DOI] [PubMed] [Google Scholar]; b Park J. Y.; Mondal S.; Kwon H.-J.; Sahu P. K.; Han H.; Kwak K.; Cho M. Effect of isotope substitution on the Fermi resonance and vibrational lifetime of unnatural amino acids modified with IR probe: A 2D-IR and pump-probe study of 4-azido-L-phenyl alanine. J. Chem. Phys. 2020, 153, 164309. 10.1063/5.0025289. [DOI] [PubMed] [Google Scholar]
  26. Shi L.; Liu X.; Shi L.; Stinson H. T.; Rowlette J.; Kahl L. J.; Evans C. R.; Zheng C.; Dietrich L. E. P.; Min W. Mid-infrared metabolic imaging with vibrational probes. Nat. Methods 2020, 17, 844–851. 10.1038/s41592-020-0883-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao1c04679_si_001.pdf (635.2KB, pdf)

Articles from ACS Omega are provided here courtesy of American Chemical Society

RESOURCES