Improving the accuracy of ¹H–¹⁹F internuclear distance measurement using 2D ¹H–¹⁹F HOESY

Abstract

With the rise in fluorinated pharmaceuticals, it is becoming increasingly important to develop new 19 F NMR-based methods to assist in their analysis. Crucially, obtaining information regarding the conformational dynamics of a molecule in solution can aid the design of strongly binding therapeutics. Herein, we report the development of a 2D 1 H-19 F Heteronuclear Overhauser Spectroscopy (HOESY) experiment to measure 1 H-19 F internuclear distances, with accuracies of~5% when compared with 1 H-19 F internuclear distances calculated by quantum chemical methods. We demonstrate that correcting for cross-relaxation of 1 H, using the diagonal peaks from the 2D 1 H-1 H Nuclear Overhauser Enhancement Spectroscopy (NOESY), is critical in obtaining accurate values for 1 H-19 F internuclear distances. Finally, we show that by using the proposed method to measure 1 H-19 F internuclear distances, we are able to determine the relative stereochemistry of two fluorinated pharmaceuticals.

How to write a research article for MRC

“…Examples of these different formats can be found throughout the pages of MRC, for example, IMRaD see Peroza, et al, Joubert, et al, and Araújo, et al. [19][20][21] IRDaM see Blechta and Sýkora, Lomas, and Dewis, et al [22][23][24]…”

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