The doubly-selective ge-1D NOESY-TOCSY (NOTO) experiment permit to obtain high-quality artefact-free 1D TOCSY 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 NOESY-TOCSY experiment consists basically of a selective NOESY experiment  experiment followed by a selective ge-1D TOCSY. The following steps must be considered:

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

Mixing period consisting of the basic 90º(1H)-delay-90º(1H) block  for in-phase polarization transfer to other spins via NOE. Purging gradients are usually applied during the mixing period in order to remove any residual tranverse magnetization (see NOESY Block).

Selective inversion on the relayed resonance.

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).

Proton detection as usual.

Gradients can be incorporated only to suppress unwanted magnetization and, therefore, there is no sensitivity losses due to coherence selection ( 97JMR248-126 ). Excellent spectral quality is obtained using a four-step phase cycle.

The selective ge-1D NOESY-TOCSY 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 NOESY block.

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

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