Correlation

Principal technique(s)

Comments

2D 1H-¹H COSY

Proton J-coupling typically over 2 or 3 bonds.

2D ¹H-¹H TOCSY

Relayed proton J-couplings within a coupled spin system. Remote protons may be correlated provided there is a continuous coupling network in between them.

2D ¹H-X HMQC

2D ¹H-X HSQC

One-bond heteronuclear couplings with proton observation.

HSQC provides for greater X-spin resolution

2D ¹H-X HMBC

Long-range heteronuclear couplings with proton observation.
Typically over 2 or 3 bonds when X= ¹³C.

2D X-X COSY

2D X-X INADEQUATE

2D H-X-X-H ADEQUATE

COSY only used when X–spin natural abundance > 20 %.
INADEQUATE sensitivity can be problematic when X has low natural abundance eg ¹³C; this can be improved with proton detection methods (ADEQUATE)

Homonuclear NOEs

1D ¹H-¹H NOE difference

1/2D NOESY

1/2D ROESY

Through-space correlations.
NOE difference only applicable to “small” molecules. 1D NOESY can often provide higher quality data in less time.

NOESY may be used for small and large molecules whereas ROESY is applicable to “mid-sized” molecules with masses of ca. 1-2 kDa.

Heteronuclear NOEs

1D ¹H-X NOE difference

2D HOESY

Sensitivity usually limited by X-spin observation so rarely used. Care required to make NOEs specific in presence of broadband proton decoupling.

2D heteronuclear NOESY eg ¹H-¹⁹F. Proton detection can aid sensitivity.

1D saturation or inversion transfer

2D EXSY

Interchange of spins at chemically distinct locations.
Exchange must be slow on NMR timescale for separate resonances to be observed. Intermediate to fast exchange requires lineshape analysis.

2D experiment maps exchange.

Spin-echo or Stimulated-echo methods

2D DOSY

Measurement of molecular self-diffusion using pulsed field gradient technology. Used mainly in studies of molecular associations.

2D experiment separates species according to their diffusion propoerties.