title: A comparison of chemical shift sensitivity of trifluoromethyl tags: optimizing resolution in ¹⁹F NMR studies of proteins.
abstract: The elucidation of distinct protein conformers or states by fluorine ((19)F) NMR requires fluorinated moieties whose chemical shifts are most sensitive to subtle changes in the local dielectric and magnetic shielding environment. In this study we evaluate the effective chemical shift dispersion of a number of thiol-reactive trifluoromethyl probes [i.e. 2-bromo-N-(4-(trifluoromethyl)phenyl)acetamide (BTFMA), N-(4-bromo-3-(trifluoromethyl)phenyl)acetamide (3-BTFMA), 3-bromo-1,1,1-trifluoropropan-2-ol (BTFP), 1-bromo-3,3,4,4,4-pentafluorobutan-2-one (BPFB), 3-bromo-1,1,1-trifluoropropan-2-one (BTFA), and 2,2,2-trifluoroethyl-1-thiol (TFET)] under conditions of varying polarity. In considering the sensitivity of the (19)F NMR chemical shift to the local environment, a series of methanol/water mixtures were prepared, ranging from relatively non-polar (MeOH:H2O = 4) to polar (MeOH:H2O = 0.25). (19)F NMR spectra of the tripeptide, glutathione ((2S)-2-amino-4-{[(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl]carbamoyl}butanoic acid), conjugated to each of the above trifluoromethyl probes, revealed that the BTFMA tag exhibited a significantly greater range of chemical shift as a function of solvent polarity than did either BTFA or TFET. DFT calculations using the B3LYP hybrid functional and the 6-31G(d,p) basis set, confirmed the observed trend in chemical shift dispersion with solvent polarity.
authors: Department of Chemistry, University of Toronto, UTM, 3359 Mississauga Road North, Mississauga, ON, L5L 1C6, Canada.
authors: Libin
authors: L
authors: Ye
authors: Sacha Thierry
authors: ST
authors: Larda
authors: Yi Feng
authors: YF
authors: Frank Li
authors: Aashish
authors: A
authors: Manglik
authors: R Scott
authors: RS
authors: Prosser
mesh_terms: D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011506:Proteins / Q000737:chemistry*; D012680:Sensitivity and Specificity; D012997:Solvents
chemical_list: D011506:Proteins; D012997:Solvents