Nuclear magnetic resonance decoupling (NMR decoupling for short) is a special method used innuclear magnetic resonance (NMR) spectroscopy where a sample to beanalyzed is irradiated at a certainfrequency or frequency range to eliminate or partially the effect ofcoupling between certainnuclei. NMR coupling refers to the effect of nuclei on each other in atoms within a couple of bonds distance of each other in molecules. This effect causes NMR signals in a spectrum to be split into multiple peaks. Decoupling fully or partially eliminates splitting of the signal between the nuclei irradiated and other nuclei such as the nuclei being analyzed in a certain spectrum. NMR spectroscopy and sometimes decoupling can helpdeterminestructures ofchemical compounds.

NMR spectroscopy of a sample produces an NMR spectrum, which is essentially agraph of signal intensity on the vertical axis vs.chemical shift for a certain isotope on the horizontal axis. The signal intensity is dependent on the number of exactly equivalent nuclei in the sample at that chemical shift. NMR spectra are taken to analyze oneisotope of nuclei at a time. Only certain types of isotopes of certainelements show up in NMR spectra. Only these isotopes cause NMR coupling. Nuclei of atoms having the same equivalent positions within a molecule also do not couple with each other.¹H (proton) NMR spectroscopy and¹³C NMR spectroscopy analyze¹H and¹³C nuclei, respectively, and are the most common types (most common analyte isotopes which show signals) of NMR spectroscopy.

Homonuclear decoupling is when the nuclei beingradio frequency (rf) irradiated are the same isotope as the nuclei being observed (analyzed) in the spectrum.Heteronuclear decoupling is when the nuclei being rf irradiated are of a different isotope than the nuclei being observed in the spectrum.^[1] For a given isotope, the entire range for all nuclei of that isotope can be irradiated inbroad band decoupling,^[2] or only a select range for certain nuclei of that isotope can be irradiated.

Practically all naturally occurringhydrogen (H) atoms have¹H nuclei, which show up in¹H NMR spectra. These¹H nuclei are often coupled with nearby non-equivalent¹H atomic nuclei within the same molecule. H atoms are most commonly bonded tocarbon (C) atoms inorganic compounds. About 99% of naturally occurring C atoms have¹²C nuclei, which neither show up in NMR spectroscopy nor couple with other nuclei which do show signals. About 1% of naturally occurring C atoms have¹³C nuclei, which do show signals in¹³C NMR spectroscopy and do couple with other active nuclei such as¹H. Since the percentage of¹³C is so low innatural isotopic abundance samples, the¹³C coupling effects on other carbons and on¹H are usually negligible, and for all practical purposes splitting of¹H signals due to coupling with natural isotopic abundance carbon does not show up in¹H NMR spectra. In real life, however, the¹³C coupling effect does show up on non-¹³C decoupled spectra of other magnetic nuclei, causingsatellite signals.

Similarly for all practical purposes,¹³C signal splitting due to coupling with nearby natural isotopic abundance carbons is negligible in¹³C NMR spectra. However, practically all hydrogen bonded to carbon atoms is¹H in natural isotopic abundance samples, including any¹³C nuclei bonded to H atoms. In a¹³C spectrum with no decoupling at all, each of the¹³C signals is split according to how many H atoms that C atom is next to. In order to simplify the spectrum,¹³C NMR spectroscopy is most often runfully proton decoupled, meaning¹H nuclei in the sample are broadly irradiated to fully decouple them from the¹³C nuclei being analyzed. This full proton decoupling eliminates all coupling with H atoms and thus splitting due to H atoms in natural isotopic abundance compounds. Since coupling between other carbons in natural isotopic abundance samples is negligible, signals in fully proton decoupled¹³C spectra inhydrocarbons and most signals from other organic compounds are single peaks. This way, the number of equivalent sets of carbon atoms in achemical structure can be counted by counting singlet peaks, which in¹³C spectra tend to be very narrow (thin). Other information about the carbon atoms can usually be determined from thechemical shift, such as whether the atom is part of acarbonyl group or anaromatic ring, etc. Such full proton decoupling can also help increase the intensity of¹³C signals.

There can also beoff-resonance decoupling of¹H from¹³C nuclei in¹³C NMR spectroscopy, where weaker rf irradiation results in what can be thought of as partial decoupling. In such an off-resonance decoupled spectrum, only¹H atoms bonded to a carbon atom will split its¹³C signal. The coupling constant, indicating a small frequency difference between split signal peaks, would be smaller than in an undecoupled spectrum.^[1] Looking at a compound's off-resonance proton-decoupled¹³C spectrum can show how many hydrogens are bonded to the carbon atoms to further helpelucidate the chemical structure. For most organic compounds, carbons bonded to 3 hydrogens (methyls) would appear as quartets (4-peak signals), carbons bonded to 2 equivalent hydrogens would appear as triplets (3-peak signals), carbons bonded to 1 hydrogen would be doublets (2-peak signals), and carbons not bonded directly to any hydrogens would be singlets (1-peak signals).^[2]

Another decoupling method isspecific proton decoupling (also called band-selective or narrowband). Here the selected "narrow"¹H frequency band of the (soft) decoupling RF pulse covers only a certain part of all¹H signals present in the spectrum. This can serve two purposes: (1) decreasing the deposited energy through additionally adjusting the RF pulse shapes/using composite pulses, (2) elucidating connectivities of NMR nuclei (applicable with both heteronuclear and homonuclear decoupling). Point 2 can be accomplished via decoupling e.g. of a single¹H signal which then leads to the collapse of the J coupling pattern of only those observed heteronuclear or non-decoupled¹H signals which are J coupled to the irradiated¹H signal. Other parts of the spectrum remain unaffected. In other words this specific decoupling method is useful for signal assignments which is a crucial step for further analyses e.g. with the aim of solving a molecular structure.Note that more complex phenomena might be observed when for example the decoupled¹H nuclei are exchanging with non-decoupled¹H nuclei in the sample with the exchange process taking place on the NMR time scale. This is exploited e.g. with chemical exchange saturation transfer (CEST) contrast agents inin vivo magnetic resonance spectroscopy.^[3]

• Nuclear magnetic resonance