Chemical shifts methods

If the spin-spin information was being transmitted by the normal through-bond mechanism the upfield three proton signal would be expected to occur as a doublet because these protons are the only ones which can assume the required planar zig-zag conformation 77>78h Preliminary results, using the change in chemical shift method 79>, indicates that the energy barrier to rotation is of the order of 20 k.cal.mole O. As expected the silicon compound (39) shows a nine proton doublet... 

By combining this method with the previously discussed chemical shift method, which is sensitive in the 0.05-20 range for the ionization ratio, the acidity could be measured over more than 5 Hq units with the same indicator. Figure 1.8 shows the complementarity of both methods. 

There has recently been increasing interest in mixed solvation using either the chemical shift (29, 36-43) or the relaxation (27, 44-49) as an experimental variable. Either method bears the potential to provide information on preferential solvation as a function of solvent composition. The chemical shift method is based on the assumptions (a) that the shielding of the solvated ionic nucleus varies linearly with the composition of the solvation sheath and (b) that outer-sphere... 

To predict proton chemical shifts, methods had been developed using theoretically derived formulae with an empirical parametrization (see Section 4.6). Despite the relatively large scatter of the predictions when plotted versus the experimental values, it was found that the deviations were reduced when calculating the shifts from better refined structures. Proton chemical shifts were thus included as target functions into force field calculations. Kuszewski et included a harmonic pseudo-energy term into XI LOR. " The ll... 

Fig. 9. Graph of temperature rise vs. time as a function of microwave heating (and subsequent cooling periods), in a tumour induced in a rat. The temperature was measured using a Co chemical shift method. The error bars correspond to one standard deviation. (Fig. from ref. 113, Copyright 1996 by Academic Press, reproduced by permission of the publisher.)...

Powder as well as MAS studies are available for several r/ -bonded olefins. The spans of the chemical-shift tensors are reduced with respect to the free olefins, which is discussed in terms of the Dewar-Chatt-Duncanson model of fx-donation and tt- back-bonding." " " The bond lengths and the orientations of the shielding tensor elements are available from dipolar-chemical shift methods and 2-D spin-echo experiments on the doubly labelled oleflns." " 77 -cyclopentadienyl and 77 -benzene ligands of transition-metal complexes, but also some derivatives of alkali or main-group elements," exhibit single resonances and shielding tensors of axial symmetry at room temperature. Both observations point to relatively fast rotations around the respective 5- and 6-fold local rotor axis. ... 

The chemical shift method for the determination of equilibrium isotope effects is based on the chemical shift difference (the equilibrium isotope shift) between nmr signals for nuclei which are time-averaged to equivalence in the absence of the isotopic perturbation (Saunders, 1979). 

Both diastereoisomeric 4-t-butyl>A -methylpiperidine A -oxides have been prepared and separated by alumina chromatography.2 By comparison with the n.m.r. spectra of model compounds the authors show that an equatorial AT-methyl group resonates at lower field, leading to stereochemical assignments. The conformational equilibrium in //-methylpiperidine A -oxide, (20a) (20b), was then investigated by Eliel s chemical-shift method. 

In parallel with the differential UV absorption method mentioned previously, a differential chemical shift method had been designed and employed experimentally. For example, to find the binding site of a compound-ascomysin, a slightly modified compound-3 l-keto-32-desoxyascomysin is synthesized. Comparison between the chemical shifts of the two compounds clearly indicates that the cyclohexyl ring is the binding site ... 

Cheng HN and Ellingsen SJ (1983) Carbon-13 nuclear magnetic resonance spectral interpretation by a computerized substituent chemical shift method. Journal of Chemical Information and Computer Science 23 197. 

A useful empirical method for the prediction of chemical shifts and coupling constants relies on the information contained in databases of structures with the corresponding NMR data. Large databases with hundred-thousands of chemical shifts are commercially available and are linked to predictive systems, which basically rely on database searching [35], Protons are internally represented by their structural environments, usually their HOSE codes [9]. When a query structure is submitted, a search is performed to find the protons belonging to similar (overlapping) substructures. These are the protons with the same HOSE codes as the protons in the query molecule. The prediction of the chemical shift is calculated as the average chemical shift of the retrieved protons. 

The similarity of the retrieved protons to those of the query structure, and the distribution of chemical shifts among protons with the same HOSE codes, can be used as measures of prediction reliability. When common substructures cannot be found for a given proton (within a predefined number of bond spheres) interpolations are applied to obtain a prediction proprietary methods are often used in commercial programs. 

In such tables, typical chemical shifts are assigned to standard structure fragments (e.g., protons in a benzene ring). Substituents in these blocks (e.g., substituents in ortho, meta, or para positions) are assumed to make independent additive contributions to the chemical shift. These additive contributions are listed in a second series of tables. Once the tables are defined, the method is easy to implement, does not require databases, and is extremely fast. Predictions for a molecule with 50 atoms can be made in less than a second. On the other hand, it requires that the parent structure and the substituents are tabulated, and it considers no interaction... 

Counterpropagation neural networks (CFG NN) were then used to establish relationships between protons and their H NMR chemical shifts. A detailed description of this method is given in the Tools Section 10,2.4.2,... 

After selection of descriptors/NN training, the best networks were applied to the prediction of 259 chemical shifts from 31 molecules (prediction set), which were not used for training. The mean absolute error obtained for the whole prediction set was 0.25 ppm, and for 90% of the cases the mean absolute error was 0.19 ppm. Some stereochemical effects could be correctly predicted. In terms of speed, the neural network method is very fast - the whole process to predict the NMR shifts of 30 protons in a molecule with 56 atoms, starting from an MDL Molfile, took less than 2 s on a common workstation. 

An example of the neural network prediction of NMR chemical shifts for a natural product is illustrated in Figure 10.2-7 together with the calculations from other methods. This molecule was chosen as it had been discovered [47]... 

Semiempirical methods are parameterized to reproduce various results. Most often, geometry and energy (usually the heat of formation) are used. Some researchers have extended this by including dipole moments, heats of reaction, and ionization potentials in the parameterization set. A few methods have been parameterized to reproduce a specific property, such as electronic spectra or NMR chemical shifts. Semiempirical calculations can be used to compute properties other than those in the parameterization set. 

The typed neglect of differential overlap (TNDO) method is a semiempirical method parameterized specifically to reproduce NMR chemical shifts. This... 

The methods listed thus far can be used for the reliable prediction of NMR chemical shifts for small organic compounds in the gas phase, which are often reasonably close to the liquid-phase results. Heavy elements, such as transition metals and lanthanides, present a much more dilficult problem. Mass defect and spin-coupling terms have been found to be significant for the description of the NMR shielding tensors for these elements. Since NMR is a nuclear effect, core potentials should not be used. 

There is one semiempirical program, called HyperNMR, that computes NMR chemical shifts. This program goes one step further than other semiempiricals by defining different parameters for the various hybridizations, such as sp carbon vs. sp carbon. This method is called the typed neglect of differential overlap method (TNDO/1 and TNDO/2). As with any semiempirical method, the results are better for species with functional groups similar to those in the set of molecules used to parameterize the method. 

Another semiempirical method, incorporated in the VAMP program, combines a semiempirical calculation with a neural network for predicting the chemical shifts. Semiempirical calculations are useful for large molecules, but are not generally as accurate as ah initio calculations. 

In general, the computation of absolute chemical shifts is a very difficult task. Computing shifts relative to a standard, such as TMS, can be done more accurately. With some of the more approximate methods, it is sometimes more reliable to compare the shifts relative to the other shifts in the compound, rather than relative to a standard compound. It is always advisable to verify at least one representative compound against the experimental spectra when choosing a method. The following rules of thumb can be drawn from a review of the literature ... 

Ah initio methods are applicable to the widest variety of property calculations. Many typical organic molecules can now be modeled with ah initio methods, such as Flartree-Fock, density functional theory, and Moller Plesset perturbation theory. Organic molecule calculations are made easier by the fact that most organic molecules have singlet spin ground states. Organics are the systems for which sophisticated properties, such as NMR chemical shifts and nonlinear optical properties, can be calculated most accurately. 

LORG (localized orbital-local origin) technique for removing dependence on the coordinate system when computing NMR chemical shifts LSDA (local spin-density approximation) approximation used in more approximate DFT methods for open-shell systems LSER (linear solvent energy relationships) method for computing solvation energy... 

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