Shortening measurement time by multiple acquisition experiments

① NOAH method

NOAH (NMR by Ordered Acquisition using ¹H-detection) is a useful method which can acquire multiple 2D spectra at once even without using multiple receivers. Fig. 1 shows a NOAH pulse sequence which acquires 2D ¹H-¹³C HSQC, ¹H-¹³C HMBC and ¹H-¹H COSY spectra altogether.
All the 2D spectra are generated simultaneously after the experiment has finished. Fig. 2 shows results of NOAH-3 of 10% cinnamic acid cis-3-hexen-1-yl ester in CDCl₃. These spectra can be obtained within 5 minutes by using NUS.
A dedicated automation was made for NOAH to improve its usability (Fig. 3). User sets the spectrum width, number of Y points, number of scans, and selects/unselects the NUS option. As individual filenames and process lists are automatically set for each data file after the measurement has completed, these data can be analyzed in the same way as traditionally acquired data.

Fig. 1: Pulse sequence of NOAH-3

Fig. 2: NOAH-3: a) HSQC, b) HMBC, c) COSY

Number of scans: 1, Y points: 256, NUS density: 25%, exp. time: 5 min

Fig. 3: Setting screen of NOAH automation

Instrument

• JNM-ECZ400S
• ROYALPROBE™ HFX

Reference

• Eriks. Kupce and Tim D.W. Claridge, Angew. Chem. Int. Ed. Eng., vol.56 (39), pp. 11779-11783 (2017).
• JEOL Application Note NM190005E "NOAH-NMR Supersequences with Nested Acquisition for Small Molecules"

② Interleaved method

Interleaved experiments also have multiple acquisition blocks during one experiment. However, when compared to NOAH experiments, interleaved experiments detect different nuclei by means of multiple receivers.
Fig. 4 shows a pulse sequence of interleaved COSY. One receiver observes ¹H-¹H COSY and the second receiver observes ¹⁹F-¹⁹F COSY. Therefore, ¹H-¹H COSY and ¹⁹F-¹⁹F COSY spectra are recorded at the same time.
Fig. 5 shows results of interleaved COSY collected on 10 mg voriconazole in DMSO-d6. These spectra can be obtained within 3 minutes with NUS.

Fig. 4: Pulse sequence of Interleaved COSY

Fig. 5: Interleaved COSY: a) ¹H-¹H COSY, b) ¹⁹F-¹⁹F COSY

Number of scans: 1, Y points: 256, NUS density: 25%, exp. time: 3 min

Instrument

• JNM-ECZ500R with HF2 extension
• ROYALPROBE™ HFX

③ PANSY method

PANSY (Parallel Acquisition Nmr SpectroscopY) experiments usually acquire two FID data in parallel. These techniques also observe signal of different nuclei using multiple receivers as in the Interleaved method. On the other hand, acquisition blocks are executed at the same time, i.e. in parallel, in PANSY. Fig. 6 shows a pulse sequence of PANSY COSY which acquires ¹H-¹H COSY and ¹⁹F-¹H HETCOR spectra.
Fig. 7 shows the results of PANSY COSY on 15 mg 1-ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)benzene in CDCl₃.
Fig. 8 shows a pulse sequence of PANSY HMBC which collects ¹H-¹³C HMBC and ¹⁹F-¹³C HMBC spectra.
Fig. 9 shows the results of PANSY HMBC of the same sample. These measurements time were reduced by NUS.

Fig. 6: Pulse sequence of PANSY COSY

Fig. 7: PANSY COSY: a) ¹H-¹H COSY, b) ¹⁹F-¹H HETCOR

Number of scans: 1, Y points: 256, NUS density: 25%,　exp. time: 3 min

Fig. 8: Pulse sequence of PANSY HMBC

Fig. 9: PANSY HMBC: a) ¹H-¹³C HMBC, b) ¹⁹F-¹³C HMBC

Number of scans: 4, Y points: 256, NUS density: 25%,　exp. time: 8 min

Instrument

• JNM-ECZ500R with HF2 extension
• ROYALPROBE™ HFX

Reference of Interleaved and PANSY:

• Helena Kovacs and Eriks Kupce, Magn. Reson. Chem. 2016, 54, 544-560.