Calculation of proton chemical shifts

If we use the ligand-specific parameters for the calculations of proton chemical shifts of allenes from Table 8, the proton chemical shifts of ketene imines (89,92) mfiy be estimated to a good approximation by Equation 75, which takes into consideration that the substituent effects in ketene imines are generally larger than those in allenes. 

Calculations of proton chemical shifts that used several common density functionals and basis sets on a test set of compounds together with Unear scaling of the results recommended WP04/cc-pVDZ(rms error 0.115 ppm, m = 1.020, ft = 31.84), WP04/6-31G (rms error 0.12 ppm, m = 1.033, ft = 32.02), B3LYP/6-31G (rms error 0.13 ppm. 

Abraham, R. J. (1999) A model for the calculation of proton chemical shifts in non-conjugated organic compounds. Prog. NMR Spectrosc., 35, 85-152. 

With the advances in experimental solid-state NMR and computational resources (both software and computing power), it is now possible to use both the experimental and computational results (sometimes in a complementary way) to study biologically important macromolecules such as proteins. The quantum-chemical computation (particularly by density functional theory) of NMR parameters in solids has found important application in protein structure determination.30-36 Tesche and Haeberlen37 calculated the proton chemical shift tensor of the methyl groups in dimethyl terephthalate and found the theoretical results were in good agreement with the multiple pulse experiment. 

Jain, R. Bally, T. Rablen, P. R. Calculating accurate proton chemical shifts of organic molecules with density functional methods and modest basis sets, J. Org. Chem. 2009, 74,4017-4023. 

Though both NH and CH2 are ortho, para-directing, we should expect NH to win as it has a Icr. pair of electrons. This would favour the first structure, but is not evidence. Calculation of > expected chemical shifts of protons in the two structures gives a more reliable answer. For exampi the two marked hydrogen atoms are predicted to come at ... 

This result is in stark contrast to a study of Moyna et alf who applied nearly the same formalism for calculating the proton chemical shifts [Eq. (40)]. For the tripeptide under investigation only a limited set of intra-residue proton distances was available. The definition of structure was therefore greatly improved when the proton chemical shift constraints were switched on. The chemical shift refinement reduced the rmsd for the backbone atoms from 1.2 A to 0.2 A, and it revealed a single set of conformers with both peptide bonds in trans conformation. The shift constraints drove the molecule energetically uphill by 3.9 kcal/mol but produced a well-defined minimum within the energy hyper-surface. Obviously, chemical shift constraints will produce well-defined structures when other constraints are not available from experiment. 

The first measurements of the dependence of proton chemical shifts 8 on temperature were performed using ethanol, and observing the shift of the OH proton with respect to the methyl and methylene protons. The first extensive study" of hydrogen-bonding mediated chemical shifts showed that, in the gas phase at very low pressures, the chemical shift measured at a particular temperature is essentially liquid phase, two factors alter the chemical shift from the value measured in the gas phase. The first factor is the change in bulk susceptibility caused by the change in density. The second factor is the association shift , which is the difference between the calculated and measured chemical shifts. The calculated value is given by ... 

L. F. Pacios and P. C. Gomez, Dependence of calculated NMR proton chemical shifts on electron density properties in proton-transfer processes on short strong hydrogen bonds, J. Phys. Chem. A 108, 11783-11792 (2004). 

Summary The -l-cyclopropyl-2-(triisopropylsilyl)ethyl cation is formed by protonation of -l-(triisopropylsilyl)ethenyl-cyclopropane with FSOsH/SbFs at -135°C and was characterized by H- and C-NMR spectra in SO2F2/SO2CIF solution at -105°C. Quantum chemical DFT ab initio calculations of NMR chemical shifts and spin-spin coupling constants were performed for the model structures E- and Z-1-cyclopropyl-2-(trimethylsilyl)ethyl cations. The calculated NMR data of the -l-cyclopropyl-2-(trimethylsilyl)ethyl cation are in good agreement with the experimental data and show that this p-silyl-substituted secondary cyclopropylmethyl carbocation is static on the NMR time scale in the observed temperature range. 

Basic data obtained from NMR studies consist of distance and torsion angle restraints. Once resonances have been assigned, nuclear Overhauser effect (NOE) contacts are selected and their intensities are used to calculate interproton distances. Information on torsion angles are based on the measurement of coupling constants and analysis of proton chemical shifts. Together, this information is used to formulate a nonlinear optimization problem, the solution of which should provide the correct protein structure. Typically, a hybrid energy function of the following form is employed ... 

The relationship between ring proton chemical shifts and 7r-electron densities of aromatic molecules and ions is important. S.C.F. molecular orbital calculations have been used to evaluate ring currents and associated chemical shifts for pyridine and other heterocycles 276a. When corrections are made for polar solvent effects and ring current effects, a roughly linear relationship between chemical shift and electron density is obtained for pyridine and other heterocycles 276 With 4-substituted pyridines, a simple additivity relationship of substituent contribution to the proton shieldings in these compounds can be applied, as for substituted benzenesi277 Correlations of proton chemical shifts and 7r-electron densities have been made for a... 

In general, the factors that affect the chemical shifts of carbons are the same as for protons (i.e. electron density around the nucleus in question, and anisotropy effects). Carbon chemical shifts can be readily calculated from tables of shift effects found in many texts. However, unlike protons attached to sp carbons, sp carbons attached to sp carbons exhibit only a small shift difference. There are also few good substituent parameters available for calculating the chemical shifts of alkene carbons bearing polar groups, unlike the calculation of NMR chemical shifts near polar groups. However, in systems where resonance is present, some predictions can be made of relative shift differences in the carbons (see Figure 1). 

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. 

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