Fluorine labeling is a versatile and powerful tool for NMR structural investigation of nucleic acids. The fluorine nucleus offers several attractive properties for NMR spectroscopy: high NMR sensitivity (0.83 of ¹H), 100% natural abundance, and a chemical shift that responds to its local chemical environment. In addition, fluorine’s virtual absence in biological systems enables measurements that are free of background signals making it an ideal candidate for in vivo NMR applications.

¹⁹F-¹³C labelling results in very favourable spectroscopic behaviour

Recently, Haribabu Arthanari and co-workers showed that an aromatic labeling scheme with a [¹⁹F-¹³C] spin pair has a very favourable spectroscopic behaviour in an NMR-TROSY experiment alleviating the size problem in nucleic acid NMR.

The figure [1] shows the labelling patterns and the NMR-TROSY spectra at 25°C and at 0°C of Heron hepatitis B virus (hHBV) RNA with [6-D, 5-¹⁹F, 5-¹³C] uridine labels (highlighted in green) on the left and the [5-D, 6-¹³C] uridine labels on the right (highlighted in brown).

Both stable isotope labelling schemes gave well resolved correlation peaks at 25°C. At 0°C however, when the slowed down molecular mobility leads to a higher molecular weight like behavior, the superior spectral properties of the ¹⁹F/¹³C spin pair is manifested.

Conclusion of Haribabu Arthanaris study:

All five [6-D, 5-¹⁹F, 5-¹³C]-U labels were observed,
but only two of five ¹H-¹³C uridine resonances were found.

The favorable spectral behaviour of labelled fluorine presents new opportunities for characterizing the structure, dynamics, and interactions of nucleic acids with the help of appropriate fluorine NMR hardware.

Silantes offers a range of ¹⁹F-labelled rNTP standards

Silantes offers suitable isotope labelled rNTP standards for your fluorine NMR project: (please see at the bottom of this page)

Further references: 

1. Synthesis of 5-fluoropyrimidine nucleotides as sensitive NMR probes of RNA structure. Hennig M, Scott LG, Sperling E, Bermel W, Williamson JR. J Am Chem Soc. 2007 Dec 5;129(48):14911-21. doi: 10.1021/ja073825i.
2. Enzymatic synthesis and ¹⁹F NMR studies of 2-fluoroadenine-substituted RNA. Scott LG, Geierstanger BH, Williamson JR, Hennig M. J Am Chem Soc. 2004 Sep 29;126(38):11776-7. doi: 10.1021/ja047556
3. Sochor, F., R. Silvers, D. Müller, C. Richter, B. Fürtig, and H. Schwalbe. "19F-labeling of the Adenine H2-site to Study Large RNAs by NMR Spectroscopy." Journal of Biomolecular NMR 64.1 (2015): 63-74. Web.
4. Aromatic ¹⁹F-¹³C TROSY: a background-free approach to probe biomolecular structure, function, and dynamics. Boeszoermenyi A, Chhabra S, Dubey A, Radeva DL, Burdzhiev NT, Chanev CD, Petrov OI, Gelev VM, Zhang M, Anklin C, Kovacs H, Wagner G, Kuprov I, Takeuchi K, Arthanari H. Nat Methods. 2019 Apr;16(4):333-340. doi: 10.1038/s41592-019-0334-x.
5. Solution NMR readily reveals distinct structural folds and interactions in doubly ¹³C- and ¹⁹F-labeled RNAs. Becette OB, Zong G, Chen B, Taiwo KM, Case DA, Dayie TK. Sci Adv. 2020 Oct 7;6(41):eabc6572. doi: 10.1126/sciadv.abc6572.

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