Solid pulse-sequences

Figure Bl.12.15. Some double-resonance pulse sequences for providing distance infomiation in solids (a) SEDOR, (b) REDOR, (c) TEDOR and (d) TRAPDOR. In all sequences the narrow pulses are 90° and the wide pulses 180°. For sequences that employ MAS the luimber of rotor cycles N is shown along the bottom.

Figure Bl.14.9. Imaging pulse sequence including flow and/or diflfiision encoding. Gradient pulses before and after the inversion pulse are supplemented in any of the spatial dimensions of the standard spin-echo imaging sequence. Motion weighting is achieved by switching a strong gradient pulse pair G, (see solid black line). The steady-state distribution of flow (coherent motion) as well as diffusion (spatially...

Fig. 6. The generalized Jeener-Broekaert three pulse sequence. Note that FT of the solid echo and the alignment echo starts at times delayed by the pulse separation r, after the second and third pulse, respectively...

Wideline NMR spectra were collected using a Bruker CXP 200 NMR spectrometer, operating at u>o/2n ( H) = 30.7 MHz. To obtain spectra void of spectrometer artifacts, the solid spin echo pulse sequence, n/2) -T-n/2) -x-echo, was used. Unless otherwise noted, the delay between pulses, X, was set at 30 Js. 

In addition to sample rotation, a particular solid state NMR experiment is further characterized by the pulse sequence used. As in solution NMR, a multitude of such sequences exist for solids many exploit through-space dipolar couplings for either signal enhancement, spectral assignment, interauclear distance determination or full correlation of the spectra of different nuclei. The most commonly applied solid state NMR experiments are concerned with the measurement of spectra in which intensities relate to the numbers of spins in different environments and the resonance frequencies are dominated by isotropic chemical shifts, much like NMR spectra of solutions. Even so, there is considerable room for useful elaboration the observed signal may be obtained by direct excitation, cross polarization from other nuclei or other means, and irradiation may be applied during observation or in echo periods prior to... 

The slice selection procedure can be combined with a number of pulse sequences to spatially resolve NMR parameters or to contrast the profiles with a variety of filters. The most commonly used acquisition schemes implemented to sample echo train decays are the CPMG [(jt/2)0—(Jt)90] or a multi-solid echo sequence [(jt/ 2)0-(jt/2)9o]. In these instances, the complete echo train can be fitted to determine... 

Using the OPENCORE NMR spectrometer, standard solid-state NMR experiments have been demonstrated in Ref. 2. They include 1H-13C CPMAS with TPPM decoupling, 13C-15N dipolar recoupling under MAS, 1H FSLG, 13C-13C 2D exchange, and so on. Here we show two more examples, where the spectrometer was used to implement standard pulse sequences, but in somewhat demanding circumstances in terms of sensitivity. 

It is clear that pulse sequences may not only be designed by analytical means, they may also be designed numerically (see, e.g., reviews on numerical aspects of solid-state NMR in [54, 65, 66]) using standard nonlinear optimization to well-defined analytical expressions [67, 68], by optimizing pulse sequences directly on the spectrometer [69], or by optimal control procedures [70-72] to name but a few of the possibilities. We will in this review restrict ourselves to optimal control design procedures that recently in analytical and numerical form have formed a new basis for efficient NMR experiment design. 

Up to now, neither this method nor STARTMAS has been used by researchers other than their authors, especially because they are subjected to many imperfections of the pulse sequence. Still, it may be anticipated that they will open up new possibilities in a variety of applications, including studies on unstable systems, in-situ high-temperature experiments, hyperpolarized solids, or measurements on very slowly relaxing spins. 

Fig. 21 HMQC pulse sequences for (a) 14N-13C and (b) 14N- H correlations under rotor-synchronized MAS. In (b), dipolar recoupling is usually applied during time intervals Texc and Trec. (c) Coherence transfer pathways for the observation of SQ (solid lines) and DQ (dashed lines) in the 14N dimension...

Throughout the cross-polarization pulse sequence, a number of competing relaxation processes are occurring simultaneously. The recognition and understanding of these relaxation processes are critical in order to apply CP pulse sequences for quantitative solid state NMR data acquisition or ascertaining molecular motions occurring in the solid state. 

Fig. 9 Examples of simplifying solid state NMR spectra by the TOSS and delayed decoupling pulse sequences. Shown is a comparison of the 31P CP/MAS NMR spectrum of fosinopril sodium utilizing the standard pulse sequence (A) and the TOSS routine (B). Also shown is the full 13C CP/MAS NMR spectrum of fosinopril sodium (C) and the nonprotonated carbon spectrum (D) obtained from the delayed decoupling pulse sequence utilizing a 80 /us delay time. Signals due to the methyl carbon resonances (0-30 ppm) are not completely eliminated due to the rapid methyl group rotation, which reduces the carbon-proton dipolar couplings.

In addition to measuring TCH for the polymorphic system in question, the proton T value must be determined since the repetition rate of a CP experiment is dependent upon the recovery of the proton magnetization. Common convention states that a delay time between successive pulses of 1-5 X T, must be used. Figure 10B outlines the pulse sequence for measuring the proton Tx through the carbon intensity. One advantage to solids NMR work is that a common proton Tx value will be measured, since protons communicate through a spin-diffusion process. An example of spectral results obtained from this pulse sequence is displayed in Fig. 12. 

Within various pharmaceutical laboratories (industrial and academic), the mul-tinuclear technique of solid state NMR has primarily been applied to the study of polymorphism at the qualitative and quantitative levels. Although the technique ideally lends itself to the structure determination of drug compounds in the solid state, it is anticipated that in the future, solid state NMR will become routinely used for method development and problem solving activities in the analytical/materials science/physical pharmacy area of the pharmaceutical sciences. During the past few years, an increasing number of publications have emerged in which solid state NMR has become an invaluable technique. With the continuing development of solid state NMR pulse sequences and hardware improvements (increased sensitivity), solid state NMR will provide a wealth of information for the physical characterization of pharmaceutical solids. 

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