DOSY NMR experiments

Giuseppone N, Schmitt J-L, Allouche L, Lehn J-M (2008) DOSY NMR experiments as a tool for the analysis of constitutional and motional dynamic processes implementation for the driven evolution of dynamic combinatorial libraries of helical strands. Angew Chem Int Ed 47 2235-2239... 

There has also been a recent assessment of different methods for the processing of diffusion ordered spectroscopy (DOSY) NMR experiments. This included the evaluation of iterative single channel methods including single channel methods such as... 

DOSY is a useful tool to analyze mixtures by providing valuable information about molecular size and shape [32]. In a typical DOSY experiment, a series of spectra are collected at different gradient pulse amplitudes various processing methods are then used to produce a 2D spectrum with chemical shift in the dimension and diffusion coefficients in the/i dimension. Generally, the larger the molecular size, the smaller the diffusion coefficient. It is known that synthetic polymers consist of polymer chains with a distribution of molecular weights (MWs). The use of DOSY to determine the MW distributions of polydispersed polymers has been reported by Chen et al. [33]. Therefore, the DOSY NMR experiment has the potential to distinguish between the resonances of the chain ends and branch ends in polymers. 

DOSY NMR experiments are popular for analysing diffusional properties of mixtures. Quality of the results is affected by experimental factors such as baseline drift, peak shift and phase shift. Huo et al proposed a series of pre-processing operations to reduce the experimental distortions, including baseline correction and reference deconvolution to remove frequency and phase shifts. The corrected data can be successfully analysed with a combination of multivariate curve resolution with non-linear least square regression. 

As follows from DOSY NMR experiments, supramolecular interactions of these anionic guests within the cavities of capsules 526 and 527 with neutral pendant substituents are substantially weaker [30]. 

DOSY is a technique that may prove successful in the determination of additives in mixtures [279]. Using different field gradients it is possible to distinguish components in a mixture on the basis of their diffusion coefficients. Morris and Johnson [271] have developed diffusion-ordered 2D NMR experiments for the analysis of mixtures. PFG-NMR can thus be used to identify those components in a mixture that have similar (or overlapping) chemical shifts but different diffusional properties. Multivariate curve resolution (MCR) analysis of DOSY data allows generation of pure spectra of the individual components for identification. The pure spin-echo diffusion decays that are obtained for the individual components may be used to determine the diffusion coefficient/distribution [281]. Mixtures of molecules of very similar sizes can readily be analysed by DOSY. Diffusion-ordered spectroscopy [273,282], which does not require prior separation, is a viable competitor for techniques such as HPLC-NMR that are based on chemical separation. 

Diffusions NMR spectroscopy (e.g. PGSE = Pulsed Gradient Spin Echo STE = Stimulated Echo DOSY = Diffusion Ordered Spectroscopy) is a straightforward and accurate method for determination of the self-diffusion coefficient of a molecule. Its principal use in dendrimer chemistry is for size determination of dissolved dendrimers since the self-diffusion coefficient is directly correlated with the hydrodynamic radius of the molecule via the Stokes-Einstein equation [24]. Although one-dimensional and multidimensional diffusion NMR experiments can thus make an important contribution to structural characterisation of dendrimers, they have been used comparatively rarely until recently [25, 26]. 

All the spectroscopic approaches applied for structural characterization of mixtures derive from methods originally developed for screening libraries for their biological activities. They include diffusion-ordered spectroscopy [15-18], relaxation-edited spectroscopy [19], isotope-filtered affinity NMR [20] and SAR-by-NMR [21]. These applications will be discussed in the last part of this chapter. As usually most of the components show very similar molecular weight, their spectroscopic parameters, such as relaxation rates or selfdiffusion coefficients, are not very different and application of these methodologies for chemical characterization is not straightforward. An exception is diffusion-edited spectroscopy, which can be a feasible way to analyze the structure of compounds within a mixture without the need of prior separation. This was the case for the analysis of a mixture of five esters (propyl acetate, butyl acetate, ethyl butyrate, isopropyl butyrate and butyl levulinate) [18]. By the combined use of diffusion-edited NMR and 2-D NMR methods such as Total Correlation Spectroscopy (TOCSY), it was possible to elucidate the structure of the components of this mixture. This strategy was called diffusion encoded spectroscopy DECODES. Another example of combination between diffusion-edited spectroscopy and traditional 2-D NMR experiment is the DOSY-NOESY experiment [22]. The use of these experiments have proven to be useful in the identification of compounds from small split and mix synthetic pools. 

Silver ( Ag) (f=l/2, 1/2). Silver-containing layered networks [Ag(L)] (L = 4-pyridinesulfonate or p-toluenesulfonate) were treated with primary amines in different ratios. Solid-state ° Ag, and CP/ MAS NMR experiments were used to study the interactions between the primary amines and the parent materials. Ag chemical shift tensor parameters are extremely sensitive to changes in silver environments. Reaction of Ag20 with the A-heterocyclic carbene precursors 3,5-bis[3-(2,4,6-tri-methylphenyl)imidazolium-l-ylmethyl]-lH-pyrazole bishexafluorophosphate and 3,5-bis[3-(2,6-diisopropylphenyl)imidazolium-l-ylmethyl]-lH-pyrazole bishexafluorophosphate yielded silver(I) complexes 2 and 3, respectively The identity of those species could be elucidated by detailed NMR spectroscopic studies ( H, C, N, Ag and DOSY experiments). 

Pulsed-Field Gradient Spin-Echo NMR Diffusion NMR experiments resolve different compounds in a mixture based on their diffusion coefficients, depending on physical parameters such as size and shape of the molecules, temperature, and viscosity. The diffusion NMR technique is often referred to as diffusion-ordered spectroscopy (DOSY) or pulsed-field gradient spin-echo (PGSE) NMR. A series of NMR diffusion spectra are acquired as a function of the gradient strength G (Fig. 2.19) [56], and the slope of the peak decay is used to obtain the diffusion coefficient D. Furthermore, the hydrodynamic radius can be obtained from the Stokes-Einstein equation (Eq. 2.3). 

ID and 2D NMR experiments, such as ROESY and DOSY allowed us to define the conformation assumed by macrocycle 22 and by the model Suc-AAPF-pNA substrate in solution. In the latter case, the coexistence of trans and cis stereoisomers due to the constrained rotation around the Pro-Ala peptide bond was pointed out, with a large prevalence of the trans one (namely, 90 10). Notably, any of the two species (22 and Suc-AAPF-pNA) showed propensity to self-assemble, which could, instead, compete with aggregation processes with the enzyme. In this respect, the determination of diffusion coefficients by DOSY in progressively diluted solutions was fundamental. 

The study of molecular diffusion in solution by NMR methods offers insights into a range of physical molecular properties. Different mobility rates or diffusion coefficients may also be the basis for the separation of the spectra of mixtures of small molecules in solution, this procedure being referred to as diffusion-ordered spectroscopy (DOSY) [271] (Figure 5.11). In this 2D experiment, the acquired FID is transformed with respect to 2 (the acquisition time). 

An important technical development of the PFG and STD experiments was introduced at the beginning of the 1990s the Diffusion Ordered Spectroscopy, that is DOSY.69 70 It provides a convenient way of displaying the molecular self-diffusion information in a bi-dimensional array, with the NMR spectrum in one dimension and the self-diffusion coefficient in the other. While the chemical-shift information is obtained by Fast Fourier Transformation (FFT) of the time domain data, the diffusion information is obtained by an Inverse Laplace Transformation (ILT) of the signal decay data. The goal of DOSY experiment is to separate species spectroscopically (not physically) present in a mixture of compounds for this reason, DOSY is also known as "NMR chromatography."... 

More recently, three-dimensional (3D) pulse sequences with DOSY have been presented where a diffusion coordinate is added to the conventional 2D map. As in the conventional 2D spectra, these experiments reduce the probability of signal overlap by spreading the NMR frequency of the same species over a 2D plane, and distribute the diffusion coefficient. 

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