Solvents suppression

The goal of solvent suppression is therefore to reduce the magnitude of the solvent resonance before the NMR signal reaches the receiver. This seemingly simple requirement has generated an enormous research area [67, 68], which is still on-going, emphasising the fact that this is by no means a trivial exercise. The more widely used approaches can be broadly classified into three areas  

The simplest and the most robust technique is presaturation of the solvent [70]. This is simple to implement, may be readily added to existing experiments and leaves (nonexchangeable) resonances away from the presaturation frequency unperturbed. It involves the application of continuous, weak rf irradiation at the solvent frequency prior to excitation and acquisition (Fig. 10.30a), rendering the solvent spins saturated and therefore unobservable (Fig. 10.31). Resonances invariably close to the solvent frequency also experience some loss in intensity, with weaker irradiation leading to less spillover but reduced saturation of the solvent. Longer presaturation periods improve the suppression at the expense of extended experiments, so a compromise is required and typically 1-3 s are used trial and error usually represents the best approach to optimisation. Wherever possible, the same rf channel should be used for both presaturation and subsequent proton pulsing, with appropriate transmitter power switching. 

A more recent approach [73] to cancelling the solvent signal arising from peripheral regions of the sample that minimises the loss of solute signal intensity employs an 

The principal disadvantage of all presaturation schemes is that they also lead to the suppression of exchangeable protons by the process of saturation transfer. In favourable cases, solution conditions may be altered (temperature and pH) to slow the exchange sufficiently to reduce signal attenuation, but this approach has limited applicability. The methods presented below largely avoid such losses. 

The principal reason to suppress a large solvent resonance in the presence of far smaller solute resonances is so that the dynamic range of the NMR signals 

The following sections illustrate examples from these areas that have proved most popular but represent only a small subsection of available methods (see, for example. Chapter 2 of reference [61]). All schemes inevitably involve some loss of signal intensity for those resonances close to that of the solvent, and careful adjustment of solution conditions, the simplest being sample temperature, can prove useful in avoiding signal loses by shifting the water resonance relative to solute signals (Fig. 9.22). 

A feature of simple presaturation in protonated solutions (particularly with older probes whieh may also lack appropriate shielding of the coil leads [63]) is a residual hump in the ID spectrum that originates from peripheral regions 

Some methods take advantage of a difference in a particular property between water and the molecule to be studied. In particular, a macromolecule usually has a shorter value for proton Tt than water and a much lower diffusion coefficient. One of the oldest methods for water signal suppression is WEFT (water elimination Fourier transform), in which an inversion recovery sequence is applied (see Fig. 2.12) with r chosen to be the time that the water signal goes through zero (Tj In 2), just as in the BIRD pulse sequence. Another method makes use of the technique described in Section 9.3 to measure diffusion coefficients. 

The increased solvent requirements for LC-NMR over tube NMR make the technique expensive if fully deuterated solvents are used. D2O is usually substituted for H2O in the eluent, mainly because of its low cost ( 150 per 1), but also because it provides a lock solvent for the NMR. Fully deuterated organic modifiers such as 3-acetonitrile may not be absolutely required, but in practice they are often also used in many pharmaceutical laboratories as they give reduced solvent signals. This reduces the need for solvent suppression, which lessens the risk that diagnostic resonances are also suppressed in error. 

The implementation of solvent suppression was a major step in the development of LC-NMR [66]. The use of non-deuterated organic solvents gives rise to 

Other even more cunning methods have been devised to suppress the water signal in samples that have a large water content (e.g., bio-fluid samples) such as the WET and the WATERGATE pulse sequences. Other sequences have been devised to cope with signals from carbon-bound hydrogens. Some of these actually collapse the 13C satellites into the main 12C peak prior to suppression. Such a sequence would be useful if you were forced to acquire a spectrum in a nondeuterated solvent. 

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MHz H NMR spectra were measured on solutions of ca 25 mg pectin/0.5 ml D2O on a Bruker AMX600 NMR spectrometer. The temperature was 350 K to diminish the viscosity of these solutions and 32 scans were measured. Solvent suppression was performed using presaturation during the recycle delay. 

On-line coupling of separation techniques to NMR has recently been reviewed [459,651-653], and solvent suppression methods in NMR spectroscopy in particular [654],... 

In this chapter we illustrate a direct method of characterisation of polymer/additive dissolutions by means of (500 MHz) NMR, which takes advantage of selective signal suppression allowing elimination of unwanted signals, such as the ca. 105 x more intensive PE signal. The most effective approach to solvent suppression is the destruction of the net solvent magnetisation by pulsed... 

The ketone 15 was eventually prepared by Grignard addition to Weinreb amide 21, as shown in Scheme 5.5. The Weinreb amide 21 was prepared from p-iodobenzoic acid (20). The phenol of readily available 3-hydroxybenzaldehyde (22) was first protected with a benzyl group, then the aldehyde was converted to chloride 24 via alcohol 23 under standard conditions. Preparation of the Grignard reagent 25 from chloride 24 was initially problematic. A large proportion of the homo-coupling side product 26 was observed in THF. The use of a 3 1 mixture of toluene THF as the reaction solvent suppressed this side reaction [7]. The iodoketone 15 was isolated as a crystalline solid and this sequence was scaled up to pilot plant scale to make around 50 kg of 15. 

Solvent suppression Suppression of a dominant and unwanted signal (usually a solvent) either directly by saturation or by use of a more subtle method such as the WATERGATE sequence. 

A solvent-suppression method is normally required in NMR applications because the solvent signals, if not suppressed, may saturate the receiver and hinder... 

The development of simple, multiple-frequency solvent suppression techniques has greatly improved the quality of data that can be obtained using LC-NMR. One of the most useful methods for multiple resonance solvent suppression in LC-NMR is... 

SFC-NMR was used for the separation and identification of a mixture of five vitamin A acetate isomers using supercritical CO2 as the eluent [74], An advantage pointed out in this report is the lack of a solvent resonance, eliminating the need for solvent suppression and allowing unrestricted observation of the entire... 

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