¹⁹F NMR matrix‐assisted DOSY: a versatile tool for differentiating fluorinated species in mixtures

Abstract

NMR is the most versatile tool for the analysis of organic compounds and, in combination with Diffusion-Ordered Spectroscopy ('DOSY'), can give information on compounds in complex mixtures without the need for physical separation. In mixtures where the components' diffusion coefficients are nearly identical, for example because of similar sizes, Matrix-Assisted DOSY ('MAD') can help separate the signals of different constituents, resolving their spectra. Unfortunately, DOSY (including MAD) typically fails where signals overlap, as is common in H NMR. Using F NMR avoids such problems, because the great sensitivity of the F chemical shift to local environment leads to very well-dispersed spectra. Another advantage is the absence of any F background signals from the matrices typically used, avoiding interference with the analyte signals. In this study, differentiation among fluorophenol and fluoroaniline isomers was evaluated using normal and reverse micelles-of sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB) and dioctyl sodium sulfosuccinate (AOT)-as matrices. These surfactants provide useful diffusion separation in these difficult mixtures, with all the solutes interacting with the matrices to different extents, in some cases leading to differences in diffusion coefficient of more than 30%. The best matrices for separating the signals of both acid and basic species were shown to be AOT and CTAB, which are useful over a wide range of surfactant concentration. Copyright © 2016 John Wiley & Sons, Ltd.

Ligand-Based Fluorine NMR Screening: Principles and Applications in Drug Discovery Projects

“…While the method predicts with accuracy the 19 F chemical shifts of molecules 8 and 9 , the unambiguous assignment is not possible. The use of 2D 19 F NMR DOSY experiments ,− is capable of distinguishing the two molecules based on their different diffusion coefficients that depend on the molecular weights of the molecules, as shown in Figure . The pulse sequence of the 2D 19 F NMR DOSY was modified in order to cover a large spectral bandwidth that is often encountered with fragments having different fingerprints.…”

Matrix-assisted DOSY

“…The combination of CHORUS and the Oneshot DOSY experiment has resulted in CHORUS-Oneshot allowing 19 F diffusion NMR to be performed on mixtures of fluorinated species containing a range of fluorine functional groups [131]. Effective separation of rosuvastatin, a precursor, fluticasone aqueous SDS or CTAB micelles and AOT in CDCl3 reverse micelles as matrices 43 [132]. Some of these species had previously been used when developing 19 F DOSY in the presence of large 19 F- 19 F homonuclear couplings [130].…”

“…Some of these species had previously been used when developing 19 F DOSY in the presence of large 19 F- 19 F homonuclear couplings [130]. Separation of the isomers of fluorophenol or fluoroaniline was achieved using all of the micelle systems, with small differences in the effects attributed to differences in binding strength between the analytes and the micellar surfaces [132]. The use of 19 F MAD allows much clearer separation of a mixture of all six fluorophenol and fluoroaniline species using 50 mM CTAB micelles than the corresponding 1 H DOSY spectrum as there is significantly less spectral crowding in the frequency dimension, due to the greater chemical shift dispersion observed in the 19 F frequency dimension, and simpler spectra due to the lack of numerous homonuclear couplings [132].…”

Copper(i) activation of C–X bonds: bimolecularvs.unimolecular reaction mechanism

“…ln of molecular weight (ln(Mw)) produce linear representations in which the average Mw of the mixture can be read. 17–19 We have previously found that the measurement of diffusion rates by 19 F NMR of copper and palladium complexes with fluoroaryl ligands provides linear representations of molecular weight vs. D. 11 b Applying this methodology we have obtained the data shown in Fig. 1 (details in ESI†).…”