2H{19F} REDOR for distance measurements in biological solids using a double resonance spectrometer

Application of REDOR NMR in natural product chemistry

“…To avoid signal overlap from the background, it is preferable to use rare isotopes in biological systems, such as 19 F and 2 H. Considering both distance limit and background suppression, utilization of a ligand labeled with 19 F, which has large g and no background in a biological system, is a good strategy for REDOR experiments of biological solids. 17 The major and information-rich NMR active isotopes in biological samples are 13 C and 15 N. These nuclei have large background signals, due to the natural abundances of 1.1% and 0.37%, respectively. To suppress the large background of these nuclei, coherence filtering techniques are combined with REDOR.…”

Solid state 19F NMR methods for studying biomembranes

“…More established than CPMG are MAS-based dipolar recoupling schemes for measuring distances, such as the homonuclear rotational resonance (RR) and radio-frequency driven recoupling (RFDR) experiments [8,27], as well as the heteronuclear rotational-echo double resonance (REDOR) [46,[76][77][78][79][80][81][82][83][84][85]. In these types of experiment, the data analysis is based on the time-dependent evolution of signal intensities as a function of rotor period.…”

“…RR and RFDR measurements have been a challenge for 19 F NMR in view of the fast signal decay that needs to be suppressed by 1 H-decoupling, but they have been successfully applied to 19 F-labeled organic compounds to pick up long-range distances up to 12 Å [27]. In REDOR experiments, it has been preferable to observe the low-g partners such as 13 C, 31 P, 15 N, which tend to give much narrower lines than 19 F. Even the quadrupolar deuterium nucleus has been used as a REDOR partner for 19 F, yielding distances of over 5 Å [83,84]. Fig.…”

The Application of REDOR NMR to Understand the Conformation of Epothilone B

“…Although a trifluoromethyl group (–CF 3 ) was widely used as the label for REDOR distance measurements [ 4 , 35 ], and for orientation-dependent NMR studies of membrane associated protein, as well [ 36 , 37 ], earlier work had shown that the labeling of fluorine atoms could affect the tubulin-binding affinity of paclitaxel by as much as two orders of magnitude [ 7 ]. A monofluoromethyl group (–CH 2 F) was also successfully employed as the REDOR label for measuring the relatively long intermolecular distances (~8 Å) of a membrane-bound antimicrobial peptide [ 38 ].…”

“…Among these, rotational-echo double-resonance (REDOR) is a well-established technique used for precise measurements of interatomic distances by exploiting stable isotopes of the nuclei abundant in biological solids, such as 13 C, 15 N, and 2 H to avoid structural modification [ 3 ]. Pharmaceutical compounds often contain fluorine and use of the high-γ nucleus 19 F is helpful to enhance the sensitivity and range of measurable interatomic distances by compensating the low sensitivity and small range of dipolar interactions of other isotopes [ 4 , 5 ]. For example, REDOR was successfully applied to determine the conformation of microtubule-bound paclitaxel on a lyophilized sample of microtubules loaded with the fluorine-labeled analog of the ligand [ 6 , 7 ], which led to the synthesis and development of a novel compounds [ 8 , 9 ].…”