Multiple-pulse sequence robustness

As demonstrated by Hartmann and Hahn (1962), energy-matched conditions can be created with the help of rf irradiation that generates matched effective fields (see Section IV). Although Hartmann and Hahn focused on applications in the solid state in their seminal paper, they also reported the first heteronuclear polarization-transfer experiments in the liquid state that were based on matched rf fields. A detailed analysis of heteronuclear Hartmann-Hahn transfer between scalar coupled spins was given by Muller and Ernst (1979) and by Chingas et al. (1981). Homonuclear Hartmann-Hahn transfer in liquids was first demonstrated by Braunschweiler and Ernst (1983). However, Hartmann-Hahn-type polarization-transfer experiments only found widespread application when robust multiple-pulse sequences for homonuclear and heteronuclear Hartmann-Hahn experiments became available (Bax and Davis, 1985b Shaka et al., 1988 Glaser and Drobny, 1990 Brown and Sanctuary, 1991 Ernst et al., 1991 Kadkhodaei et al., 1991) also see Sections X and XI). 

Since the first description of the Hartmann-Hahn transfer in liquids, spectroscopists have been fascinated by this technique. Many theoretical and practical aspects have been thoroughly investigated by several groups. With the development of robust multiple-pulse sequences, homonuclear and heteronuclear Hartmann-Hahn transfer has become one of the most useful experimental building blocks in high-resolution NMR. 

The APT sequence was the first experiment to decode the sign of the signal amplitude as a function of I S multiplicity. Because of the hardware restrictions in early NMR spectrometers, particularly applying simultaneous pulses on both the acquisition and second channel, emphasis was made on making the pulse sequence as simple as possible. The sequence only requires a 90° pulse and 180° pulse on the acquisition channel, which may be easily determined, and a simple decoupler switch-on/off on the second channel. Nevertheless the experiment is still included in modern pulse program libraries the experiment seems to be very robust and in contract to DEPT or INEPT type experiments quaternary carbon atoms can also be detected by the same experiment. 

Calibrations and tolerance Now we add one more level of complication. Not only will the sequence need the characteristics described above (i.e. powerful, selective, quick, and clean), but we also seek methods that are easy to use and tolerant of mistakes. All NMR users, regardless of experience, would imdoubt-edly appreciate a pulse sequence that is easy to conceptualize, requires the least number of experimental parameters to be optimized, and yields simple reproducible results for efficient optimization. If a pulse sequence takes hours to optimize (e.g. full equilibrium must be reached between transients) with multiple interdependent parameters and must subsequently be re-optimized for each sample, then the sequence will need exceptional performance in every other aspect of evaluation to be adopted. Alternatively, a pulse sequence that gives only average suppression but requires little or no optimization will likely receive enthusiastic usage even though the overall performance may not meet that of other suppression choices. While neither extreme is likely we are often faced with several comparable choices and must evaluate the experimental needs and the robustness of the chosen suppression method(s). 

Most of the sequences performed well even on this short and moderately shimmed sample. Despite not optimizing the shims, almost every sequence was able to suppress sufficiently to acquire useful spectra with minimal baseline distortions even close to the solvent. The exception occurred for the WET style sequences. The WET family did not suppress nearly as well and required the gain to be reduced by 6 dB (vertical scale in the figure was increased to compensate) to prevent a receiver overflow and ADC error. However, WET and SWET are very easy to include in pulse sequences (e.g. during the recycle delay or mixing periods) and allow simple suppression of multiple frequencies using composite shaped pulses. The poor results may come from several sources (e.g. coding error, optimization error, etc.) and therefore may not represent a limitation of the pulse sequences. Alternatively, as a real world example, some sequences simply perform better on some spectrometers and users must be prepared to adapt when necessary. We have t)q)ically found WET to be extremely reliable and robust, but certainly not on this particular sample. 

The D-HMQC (dipolar heteronuclear multiple-quantum coherence) technique is a recently developed NMR pulse sequence particularly suitable for the investigation of spatial proximity between quadrupolar and spin-1/2 nuclei. Compared to the crosspolarisation magic-angle spinning technique applied to a quadrupolar nucleus, D-HMQC does not require time-consuming optimisations and exhibits on the quadrupolar spin a better robustness to irradiation offset and to Cq values and... 

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