The doubly-selective ge-1D COSY-NOESY (CONO) experiment permit to obtain high-quality artefact-free 1D NOESY spectra  on specific protons resonating in overlapped regions and in which 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 COSY-NOESY experiment consists basically of a refocused selective ge-1D COSY 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.

Evolution of homonuclear J-couplings during an optimized delay followed by a mixing pulse for anti-phase polarization transfer to other spins (see COSY Block). A final refocusing period allows to obtain in-phase magnetization of the desired relayed spin.

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

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 ).

The selective ge-1D COSY-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 J-coupling delays in the COSY block, as a function of 1/(2*J(HH)), in order to get the in-phase magnetization of the relayed proton suitable for NOE transfer.

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 COSY-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 COSY experiment could be applied.