The doubly-selective ge-1D TOCSY-NOESY (TONO) experiment permit to obtain high-quality artefact-free 1D NOESY spectra  on specific protons resonating in overlapped regions where typical on-resonance selective excitation is not possible.
 

Easy implementation on AVANCE spectrometers equipped with pulsed field gradients and selective excitation using shaped pulses.

The basic scheme of the selective ge-1D TOCSY-NOESY experiment consists basically of a selective ge-1D TOCSY experiment followed by a selective NOESY experiment.  In this second step, the first 90º pulse before the mixing time is made selective on the relayed spin. The following steps must be considered:

Selective excitation of the selected resonance using the SPFGE block or the DPFGE block.

Mixing period to achieve in-phase polarization transfer to other spins. This is usually achieved applying some isotropic mixing sequence like MLEV, WALTZ or DIPSI pulse trains (see TOCSY Block).

Selective excitation on the relayed resonance. The corresponding z-magnetization is allowed to evolve during the mixing time as a typical NOESY experiment. Purging gradients can be included during the mixing time. A final 90º pulse creates the desired transverse magnetization (see NOESY Block).

Proton detection as usual.

Gradients can be incorporated in this basic scheme in two different ways depending if a refocusing gradient is inserted before acquisition. If is is not incorporated, EXORCYCLE must be applied on a selective 180º pulse of the SPFGE or DPFGE scheme. If it is incorporated, ultra clean 1D spectra are obtained without need of phase cycling but sensitivity is lost with compared to a non-refocused experiment (selection of N- or P-type data as a function of the intensity of this refocusing gradient). Coherence selection was used in the original experiment ( 95JMRA124-113 ). Excellent spectral quality without sensitivity losses can also be obtained using purged gradients ( 97JMR248-126 ) using a four-step phase cycle.

The selective ge-1D TOCSY-NOESY experiment can be run with minor changes from a predefined parameter set. The best option is the version which uses a SPFGE or DPFGE scheme as a selective excitation and the refocusing gradient is omitted. Important parameters to consider are:

Selectivity of the first selective inversion pulse: the user must define the shape, the duration and the power level needed for a defined excitation profile.

Optimization of the mixing time in the TOCSY block (as a function of 1/(J(HH)). When long mixing times are employed, magnetization is transferred to the whole spin subsystem.

Selectivity of the second selective excitation pulse: the user must define the shape, the duration and the power level needed for a defined excitation profile.

Optimization of the mixing time in the NOESY block.

The final spectrum of a doubly-selective ge-1D TOCSY-NOESY experiment is a clean NOESY spectrum of a specific relayed resonance appearing in a overlapped region of a 1H spectrum. It is needed that this relayed proton is J-coupled to another well-isolated proton on which a previous selective 1D TOCSY experiment could be applied.