Predicting δ

Predicting Chemical Shifts

How can you predict the chemical shift of hydrogen with a molecule?

Chemical shifts result from the differential electron shielding of ¹H nuclei in molecules. Nuclei that are less shielded have larger chemical shifts (higher values of δ). The degree of shielding can be estimated by looking at the electronegativity of nearby molecular groups, especially proximity to oxygen (O) atoms, double bonds, and aromatic rings. These concepts are illustrated in the diagram below and explained more completely in the sections that follow.

Tetramethylsilane (TMS), δ = 0

Tetramethylsilane (TMS)

Tetramethylsilane (TMS) serves as the reference standard for ¹H NMR spectroscopy, being arbitrarily assigned the value δ = 0. TMS was chosen for this role because its ¹H nuclei are highly shielded by electron clouds. The central Si and C atoms have low electronegativities and the molecule is symmetric. The ¹H nuclei of nearly all other organic molecules will be less shielded than those of TMS, and hence have larger chemical shifts.

Aliphatic protons, δ = 1 − 2

Most aliphatic protons, such as those contained in fat (triglycerides), are covalently bonded to carbon atoms in relatively long (16-20 atom) chains. Carbon is only weakly electronegative, and the covalently bonded -(CH2)- groups possess electron clouds that effectively shield the protons from externally applied fields. Most aliphatic lipids, therefore, have chemical shifts not too far removed from the tetramethylsilane (TMS) reference, usually in the δ = 1.0-1.5 range.

Water protons, δ = 4.65

Deshielding of ¹H nuclei due to the highly electronegative oxygen atom in water.

Unlike the ¹H nuclei of fats and simple alkanes, water protons are bonded to highly electronegative oxygen atoms. The electron clouds are pulled toward the oxygen atom, and the ¹H protons are deshielded. Unlike fat protons nestled in long covalent carbon-containing chains, water protons are more "exposed" to the externally applied field. They thus experience a higher local field and resonate faster than aliphatic protons. The exact chemical shift of water will vary by temperature, pH, hydrogen bonding, and presence of dissolved solutes and gases.

Aromatic protons, δ = 6 − 8

Aromatic (phenolic) protons, such as those found in cholesterol and other compounds containing benzene rings, have even larger chemical shifts, in the range of 6-8 ppm. The reason for this large chemical shift relates to the circulation of the delocalized (π) electrons around the aromatic ring. The local field induced by circulation of these electrons serves to augment the applied field for benzylic protons along the plane of the ring, causing them to experience a higher local field than would otherwise be expected.

Accentuated local fields experienced by benzylic hydrogens due to circulation of π-electrons

Carboxylic acids and aldehydes, δ = 9 − 12

Carbonyl groups (C=O) are magnetically anisotropic and electronegative. They induce strong deshielding of nearby ¹H nuclei lying within their plane. This explains the relatively large δ values for carboxylic acids (R-COOH) and aldehydes (R-COH).

Metallo-proteins (large ±δ's)

Very large chemical shifts (below −50 to over +100 ppm) may be observed for ¹H nuclei in close proximity to paramagnetic ions such as Fe⁺³ in metallo-proteins such as deoxyhemoglobin. This results from the so-called hyperfine shift mechanism arising from scalar and dipolar interactions between the proton and unpaired electrons near the metallic centers. Depending on geometry the shifts may be either positive or negative. These large-shifted peaks are generally quite small, since the overwhelming majority of protons are not near the paramagnetic centers and continue to exhibit δ-values in the "normal" range (0 - 12 ppm).

Advanced Discussion (show/hide)»

Experienced chemists are able to predict ¹H δ-values for most organic molecules to within about 0.3 ppm by considering such factors as sp-hybridization and proximity to electronegative atoms (O, N, halogens) or magnetically anisotropic species (phenolic groups, double bonds, carbonyl groups). Chemical shifts of thousands of molecules have been measured and substituent tables (e.g., Curphy-Morrison) are widely available. The most sophisticated and accurate predictions of chemical shifts come from the use of modern quantum chemistry software programs (e.g., Gaussian, GAMESS) that take into account 3-dimensional configurations, magnetic anisotropy, lone-pair interactions, and steric compression effects.

In theory, the chemical shift of a completely deshielded ("naked") proton would be about +40 ppm, a value approximated in so-called "superacids" such as HF-SbF₅. Even larger (positive and negative) chemical shifts may occur when the molecule contains a metallic center.

The hyperfine shift between delocalized electrons and protons described for metallo-proteins results from both scalar (Fermi) contact contributions via chemical bonds and dipolar (pseudo-contact, "through space") interactions with angular and 1/r³ distance dependence. Both contributions are proportional to S(S+1), where S is the spin state. The effect is thus not seen in oxyhemoglobin (where S=0), but is present in deoxyhemoglobin (S=1/2) and to an even greater degree in methemoglobin (S=5/2).

Oxyhemoglobin, for example, which is weakly diamagnetic, has nearly all of its resonances in the 0 to +10 ppm range, typical for most non-metal-containing organic molecules. The spectrum for deoxyhemoglobin remains dominated by these core resonances, but also exhibits a number of additional small peaks from +10 to +20 as well as negative shifts down to as low as −20, all arising from protons near the heme center. Two very tiny broad peaks at δ = +75 and +63 ppm have been determined to arise from arise from hyperfine-shifed NH protons of the proximal histidyl residues. These peaks have been used in experimentally to monitor O₂ binding. Methemoglobin, which has a stronger paramagnetic center than deoxyhemoglobin, displays even more resonances in outside the "standard" range, with the highest shift occurring at δ = +87.

The presence of paramagnetic centers near ¹H nuclei can also cause less dramatic chemical shifts of just a few ppm from their expected locations. For example, degraded silicone fragments that have leaked from breast implants have been recorded to have δ-values in the 0 to −3 range (rather than the expected 0 to +0.5 range). This unexpected negative shift has been ascribed to conglomeration with iron and other paramagnetic ions in tissue.

It should be noted that all paramagnetic ions do not cause hyperfine shifts. Gd⁺³, for example, has a very short electron-spin relaxation time (T1_e) and functions as a spectral line "broadener" than a line "shifter".

References
Meyer LH, Saika A, Gutowsky HS. Electron distribution in molecules. III. The proton magnetic spectra of simple organic groups. J Am Chem Soc 1953; 75:4567-73. (First large published table of NMR chemical shifts of organic molecules)
Reich HJ. Chemical shifts. Lecture Notes from Chem 605, Structure Determination Using Spectroscopic Methods. University of Wisconsin-Madison, 2014. Excellent on-line resource for structural NMR, available at this link.

Related Questions
How are proton chemical shifts measured on the δ scale?

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