Improved 1H Resolution with 14N Decoupling

The J coupling between ¹³C and quadrupolar nuclides can be resolved, for example, in the cases of the ¹³C NMR spectra of deuterated compounds, some cobalt complexes and some tetraalkyl ammonium salts.  The ability to resolve the coupling depends on the relaxation rates among the Zeeman levels of the quadrupolar nuclide with respect to the reciprocal coupling constant.  When the relaxation is slow, the J coupling can be resolved and when it is very fast, the ¹³C is a sharp singlet and said to be "self decoupled".  When the relaxation rates among the Zeeman levels of the quadrupolar nuclide are on the same order of the coupling constant, the NMR resonance of the ¹³C will be broadened.  This is a very common observation for the ¹³C resonances of nitrogen bearing carbons.  It is also possible to see broadened ¹H or ¹⁹F resonances due to coupling to ¹⁴N.  Such is the case for the resonances of the proton on C6 and the fluorine on C2 in 2,3-difluoropyridine as can be seen from the figure below which clearly shows these resonances broadened compared to the resonances of ¹H or ¹⁹F further removed from the nitrogen.

The broadening of the resonance of the ¹H on C6 can be reduced by applying ¹⁴N decoupling during the acquisition time, thus providing much improved resolution.  This is  demonstrated in the figure below.

PSYCHE to Evaluate 1H-19F Coupling Constants

Even small molecules can yield very complex ¹H NMR spectra as the result of spin - spin coupling.  This is particularly true for small molecules that contain fluorine.  It can sometimes be challenging to determine which splittings are due to ¹H-¹H coupling and which are due to ¹H-¹⁹F coupling.  One can collect a ¹H spectrum with ¹⁹F decoupling to give a spectrum with only ¹H-¹H coupling present.  Even with this data, it may be difficult to evaluate the ¹H-¹⁹F coupling constants by comparing the ¹H[¹⁹F] spectrum to the ¹H spectrum due to the complexity of the multiplets.  The ¹H-¹⁹F coupling constants can however be read directly from a ¹H PSYCHE spectrum.  The PSYCHE spectrum provides a ¹H decoupled ¹H spectrum, leaving only the ¹H-¹⁹F coupling behind.  The bottom trace of the figure below shows the 300 MHz ¹H NMR spectrum of 2,3-difluoro pyridine.  The spectrum is quite complex, making it difficult to assign ¹H-¹H and ¹H-¹⁹F couplings.  The middle trace shows the ¹H[¹⁹F] spectrum which allows the evaluation of all of the ¹H-¹H coupling constants (³J_H5-H4 = 4.8 Hz, ⁴J_H5-H3 = 1.6 Hz and ³J_H4-H3 = 8.0 Hz.  The top trace shows the ¹H PSYCHE spectrum which allows one to evaluate all of the ¹H-¹⁹F coupling constants.  For this compound, ⁴J_H3-F1 = ³J_H3-F2 = 9.8 Hz, ⁴J_H4-F2 = 3.2 Hz and ⁴J_H5-F1 = 1.8 Hz.

Pure Shift 1H NMR - PSYCHE

Much effort has been directed to obtain broadband ¹H decoupled ¹H NMR spectra.  The subject has been reviewed recently.¹  One technique used to obtain such spectra is the pseudo-2D Zangger - Sterk method^2,3 based on a selective refocusing pulse applied simultaneously with a weak field gradient centered in the t1 evolution period allowing all chemical shifts to be measured at the same time but from different slices of the column of sample in the NMR tube.  For each resonance, the coupling from all of the coupling partners is refocused.  The data are collected in a conventional 2D matrix however, a single FID is constructed by concatenating a chunk from each of the individual 2D time domain signals.  The Fourier transform of the reconstructed FID is a pure shift, ¹H decoupled ¹H NMR spectrum.  The PSYCHE (Pure Shift Yielded by CHirp Excitation) modification⁴ of the Zangger - Sterk method uses a pair of small flip angle, frequency swept chirp pulses rather than a selective 180° pulse applied simultaneously with the weak spatially selective field gradient.  This modification offers improved sensitivity.  The details of implementing this technique are kindly provided on-line by the Manchester NMR Methodology Group.  As an example, the figure below shows the 600 MHz PSYCHE spectrum of sucrose in in DMSO-d6, collected in less than 3 minutes.  One can observe the collapse of all multiplets into singlets.

The PSYCHE technique can dramatically simplify complex ¹H NMR spectra as shown in the figures below. The second figure is an expansion of the low frequency region of the first.

1.  Castañar and Parella. Mag. Res. Chem. 53, 399 (2015).
2.  Zangger and Sterk. J. Mag. Reson. 124, 486 (1997).
3.  Aguilar, Faulkner, Nilsson and Morris. Angew. Chem. Int. Ed. 49, 3901 (2010)
4.  Foroozandeh, Adams, Meharry, Jeannerat, Nilsson, Morris. Angew. Chem. Int. Ed. 53, 6990 (2014).

Exchange Effects in HSQC Spectra

The effects of chemical or dynamic exchange on NMR spectra are very well known.  Exchange is often studied by observing line shape changes as a function of temperature, by 2d EXSY, inversion transfer or saturation transfer methods.  Effects due to exchange can also be observed in ¹H - ¹³C HSQC spectra.  The HSQC method works by transferring ¹H magnetization to ¹³C magnetization via an INEPT transfer through the one-bond J coupling across the ¹H - ¹³C chemical bond.  The ¹³C magnetization evolves during the incremented delay, t1, of the 2D pulse sequence according to its chemical shift.  The ¹³C magnetization is then transferred back to ¹H magnetization where is observed during t2.  HSQC spectra thus exhibit cross peaks between ¹H resonances and the resonances of their attached carbons.  If there is exchange between nonequivalent carbon sites during t1, some ¹H resonances may appear to be correlated to two carbon resonances.  An example of this is shown in the figure below.

The ¹³C spectrum of cannabidiol has equally intense broad, resolved aromatic resonances for non-protonated carbons 2 and 6 (not shown) as well as for the protonated carbons 3 and 5.  The ¹H spectrum has broad resolved resonances for both aromatic protons.  This indicates that either the aromatic ring undergoes 180° flips about the 1 - 4 axis or it has two equally probable rotomers defined by a rotation about the 1 - 4 axis.  In either case, the dynamic exchange is slow enough on the NMR time scale to produce resolved resonances yet fast enough to cause significant line broadening.  For each of the two aromatic protons, the HSQC spectrum shows correlations to both C3 and C5; a strong correlation to the carbon to which it is chemically bonded and a weaker correlation to the carbon site in exchange with its attached carbon.