Physics:Nuclear magnetic resonance decoupling

Nuclear magnetic resonance decoupling (NMR decoupling for short) is a special method used in nuclear magnetic resonance (NMR) spectroscopy where a sample to be analyzed is irradiated at a certain frequency or frequency range to eliminate fully or partially the effect of coupling between certain nuclei. 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 help determine structures of chemical compounds.

Explanation

NMR spectroscopy of a sample produces an NMR spectrum, which is essentially a graph 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 one isotope of nuclei at a time. Only certain types of isotopes of certain elements 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 and ¹³C NMR spectroscopy analyze ¹H and ¹³C nuclei, respectively, and are the most common types (most common analyte isotopes which show signals) of NMR spectroscopy.

Homonuclear decoupling is when the nuclei being radio 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. For a given isotope, the entire range for all nuclei of that isotope can be irradiated in broad band decoupling, or only a select range for certain nuclei of that isotope can be irradiated.

Practically all naturally occurring hydrogen (H) atoms have ¹H nuclei, which show up in ¹H NMR spectra. These ¹H nuclei are often coupled with nearby non-equivalent ¹H atomic nuclei within the same molecule. H atoms are most commonly bonded to carbon (C) atoms in organic compounds. About 99% of naturally occurring C atoms have ¹²C nuclei, which neither show up in NMR spectroscopy nor couple with other nuclei which do show signals. About 1% of naturally occurring C atoms have ¹³C nuclei, which do show signals in ¹³C NMR spectroscopy and do couple with other active nuclei such as ¹H. Since the percentage of ¹³C is so low in natural isotopic abundance samples, the ¹³C coupling effects on other carbons and on ¹H are usually negligible, and for all practical purposes splitting of ¹H signals due to coupling with natural isotopic abundance carbon does not show up in ¹H NMR spectra. In real life, however, the ¹³C coupling effect does show up on non-¹³C decoupled spectra of other magnetic nuclei, causing satellite signals.

Similarly for all practical purposes, ¹³C signal splitting due to coupling with nearby natural isotopic abundance carbons is negligible in ¹³C NMR spectra. However, practically all hydrogen bonded to carbon atoms is ¹H in natural isotopic abundance samples, including any ¹³C nuclei bonded to H atoms. In a ¹³C spectrum with no decoupling at all, each of the ¹³C 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 run fully proton decoupled, meaning ¹H nuclei in the sample are broadly irradiated to fully decouple them from the ¹³C 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 decoupled ¹³C spectra in hydrocarbons and most signals from other organic compounds are single peaks. This way, the number of equivalent sets of carbon atoms in a chemical structure can be counted by counting singlet peaks, which in ¹³C spectra tend to be very narrow (thin). Other information about the carbon atoms can usually be determined from the chemical shift, such as whether the atom is part of a carbonyl group or an aromatic ring, etc. Such full proton decoupling can also help increase the intensity of ¹³C signals.

There can also be off-resonance decoupling of ¹H from ¹³C nuclei in ¹³C NMR spectroscopy, where weaker rf irradiation results in what can be thought of as partial decoupling. In such an off-resonance decoupled spectrum, only ¹H atoms bonded to a carbon atom will split its ¹³C signal. The coupling constant, indicating a small frequency difference between split signal peaks, would be smaller than in an undecoupled spectrum. Looking at a compound's off-resonance proton-decoupled ¹³C spectrum can show how many hydrogens are bonded to the carbon atoms to further help elucidate 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).

Another decoupling method is specific 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 all ¹H 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 single ¹H signal which then leads to the collapse of the J coupling pattern of only those observed heteronuclear or non-decoupled ¹H signals which are J coupled to the irradiated ¹H 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 decoupled ¹H nuclei are exchanging with non-decoupled ¹H 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 in in vivo magnetic resonance spectroscopy.