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. 2022 Jul:340:107227.
doi: 10.1016/j.jmr.2022.107227. Epub 2022 Apr 26.

Determination of accurate 19F chemical shift tensors with R-symmetry recoupling at high MAS frequencies (60-100 kHz)

Gal Porat-Dahlerbruch  1 , Jochem Struppe  2 , Caitlin M Quinn  1 , Angela M Gronenborn  3 , Tatyana Polenova  4
Affiliations

Determination of accurate 19F chemical shift tensors with R-symmetry recoupling at high MAS frequencies (60-100 kHz)

Gal Porat-Dahlerbruch et al. J Magn Reson. 2022 Jul.

Abstract

Fluorination is a versatile and valuable modification for numerous systems, and 19F NMR spectroscopy is the premier method for their structural characterization. 19F chemical shift anisotropy is a sensitive probe of structure and dynamics, even though 19F chemical shift tensors have been reported for only a handful of systems to date. Here, we explore γ-encoded R-symmetry based recoupling sequences for the determination of 19F chemical shift tensors in fully protonated organic solids at high, 60-100 kHz MAS frequencies. We show that the performance of 19F-RNCSA experiments improves with increasing MAS frequencies, and that 1H decoupling is required to determine accurate chemical shift tensor parameters. In addition, these sequences are tolerant to B1-field inhomogeneity making them suitable for a wide range of systems and experimental conditions.

Keywords: R-symmetry recoupling; chemical shift anisotropy; high-frequency (19)F MAS NMR.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Schematic depiction of 19F RNCSA pulse sequences used. (a) One R1485 block. (b) Conversion of a single π-pulse to a 270°–90° composite pulse [37]. (c) One composite (270°–90°) R1485 block. (d) CP-based 19F RNCSA with a short spin echo prior to acquisition for suppression of ring-down and baseline distortion. (e) DP-based 19F RNCSA experiment with either (f) spin echo or (g) triple pulse excitation [38] prior to acquisition for suppression of ring-down and baseline distortion. The spin echo-based 19F RNCSA phase cycle is: . The triple-pulse excitation phase cycle φ11,φ12,φ13,φrec is as described in [38].
Figure 2.
Figure 2.
Spectrum and 19F CSA line shapes of Atorvastatin calcium (a) recorded with CP-excitation at the MAS frequency of 10 kHz (b) and R1254 RNCSA sequence at the MAS frequency of 60 kHz (c, d) and 100 kHz (e, f). 1H π-decoupling was applied to remove 1H-19F dipolar couplings. The experimental spectra and the fits are shown in black solid lines and red dotted lines, respectively. R1254 spectra were recorded with 19 (60 kHz MAS) and 32 (100 kHz MAS) t1 transients, respectively, resulting in approximately the same CSA evolution period.
Figure 3.
Figure 3.
Spectrum and 19F CSA line shapes of 5F-L-Trp (a) recorded with 1H-19F CP at the MAS frequency of 10 kHz (b) and R1254 RNCSA acquired at 60 kHz MAS (c). 1H π-decoupling was applied to remove 1H-19F dipolar couplings. The experimental spectra and the fits are shown in black solid and red dotted lines, respectively. The R1254 spectrum was collected with 38 t1 transients.
Figure 4.
Figure 4.
19F spectrum and CSA line shapes of Mefloquine (a) recorded with single-pulse excitation at the MAS frequency of 10 kHz (b) and R1254 RNCSA acquired at 60 kHz (c, d) and 100 kHz (e, f). 1H π-decoupling was applied to remove 1H-19F dipolar couplings. The experimental spectra and the fits are shown in black solid and red dotted lines, respectively. R1254 spectra were collected with 38 (MAS frequency of 60 kHz) and 64 (MAS frequency of 100 kHz) t1 transients, respectively, resulting in approximately the same CSA evolution period.
Figure 5.
Figure 5.
Effect of 1H decoupling on Mefloquine 19F RNCSA line shapes recorded at a MAS frequency of 100 kHz. Left and right are line shapes recorded with R1254 and R1453 sequences, respectively. Top and bottom are line shapes extracted for peaks with isotropic chemical shifts of 16.2 and 8.8 ppm, respectively. Line shapes recorded without and with π- and CW-decoupling are depicted in black, purple, and blue, respectively. R1254 and R1453 spectra were collected with 64 and 32 t1 transients, respectively.
Figure 6.
Figure 6.
1H-decoupled Mefloquine 19F RNCSA line shapes recorded at MAS frequencies of 100 kHz (purple), 80 kHz (blue), and 60 kHz (black). Left and right are R1254 and R1453 line shapes, respectively, and top and bottom are peaks with isotropic chemical shifts of 16.2 and 8.8 ppm, respectively. π-pulse 1H decoupling was applied in all experiments. R1254 spectra were collected with 38 (MAS frequency of 60 kHz), 51 (MAS frequency of 80 kHz), and 64 (MAS frequency of 100 kHz) t1 transients, respectively, resulting in approximately the same CSA evolution period. R1453 spectra were collected with 19 (MAS frequency of 60 kHz), 26 (MAS frequency of 80 kHz), and 32 (MAS frequency of 100 kHz) t1 transients, respectively, resulting in approximately the same CSA evolution period.
Figure 7.
Figure 7.
19F RNCSA line shapes of Mefloquine and 5F-L-Trp at a MAS frequency of 60 kHz MAS using different R-symmetry sequences. The line shapes for two Mefloquine peaks at isotropic shifts 16.2 ppm (left) and 8.8 ppm (middle) as well as the line shapes for 5F-L-Trp (right) are shown. The R-symmetry numbers are indicated on the left and the corresponding RF power is indicated on the right. All spectra were collected with 38 t1 transients, except for cR1093 and cR1485, which were collected with 48 and 24 t1 transients, respectively. 1H π-decoupling was used during t1 evolution period of all sequences, but R1453 and cR1485, for which by 1H CW-decoupling was employed.
Figure 8.
Figure 8.
Effect of RF field mismatch on the 19F reduced anisotropy in RNCSA experiments of Mefloquine (peaks at 16.2 (a) and 8.8 (b) ppm) and microcrystalline 5F-L-Trp (c). All experiments were performed at a MAS frequency of 60 kHz. δσ values extracted from R1274, R1485, R1465, R1254, and R1453 experiments are shown as squares, stars, circles, triangles, and diamonds, respectively. The number of t1 transients and 1H decoupling schemes are as described in the legend of Fig. 7. RF field mismatch effect was measured by recollecting the 19F-RNCSA experiment with an adjusted 19F RF field during the CSA recoupling period (t1), followed by fitting of the obtained line shapes.
Figure 9.
Figure 9.
Off-resonance effects on the recoupled line shape in 19F RNCSA experiments of Mefloquine at a MAS frequency of 60 kHz. R1254 (a-f) and cR1485 (g-l) line shapes of Mefloquine peaks with isotropic shifts 16.2 ppm (a-c, g-i) and 8.8 ppm (d-f, j-l) with on-resonance irradiation at 13 ppm (a, d, g, j), 40 ppm off-resonance irradiation (b, e, h, k), and 80 ppm off-resonance irradiation (c, f, i, l).
Figure 10.
Figure 10.
1H-decoupled 19F cR1485 line shapes of Mefloquine at MAS frequencies of 60 kHz (black) and 100 kHz (purple) for peaks with isotropic chemical shifts of 16.2 (left) and 8.8 ppm (right), respectively. cR1485 spectra were recorded with 24 (MAS frequency of 60 kHz and CW 1H decoupling) and 40 (MAS frequency of 100 kHz and π-pulse 1H decoupling) t1 transients, respectively, resulting in the same CSA evolution period.
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