Through-space effects

Despite having been the earliest attempted prediction, proton prediction remains relatively poor. The reasons for this have been alluded to earlier but to summarise the proton chemical shift is often highly dependant on through-space effects (anisotropy) and has a very small distribution. There are four main commercial approaches to proton prediction currently Incremental parameters, HOSE code databases, semi-empirical and cib initio methods. 

The aziridine-coupling reaction had the ability to introduce bridge-substituents X or Y on either side of the iV-bridge in fused 7-azanorbomanes 87 and allowed a rare opportunity to study through-space effects on A-bridge hybridisation and JV-alkyl invertomerisation in fused 7-aza norbomanes. 

In aliphatic compounds, 3JCC is related to the dihedral angle according to a Karplus cosine function as portrayed in Fig. 3.18. Similar to 3JHH, the maximum at = 180° is larger than that at 4> — 0° for carboxylic acids. A reversed pattern is found for aldehydes and alcohols, due to heteroatom through-space effects [129]. 

Enolization of cationic ketones is accelerated by electrostatic stabilization of the enolate anion. Rate constants for water-, acetate-, and hydroxide ion-catalysed enolization of 2-acetyl- 1-methylpyridinium ion (94) have been measured13811 and compared with a 2-acetylthiazolium ion (95), a simple analogue of 2-acetylthiamine pyrophosphate.13811 For (94), qh = 1.9 x 102 M-1 s 1, about 1.1 x 106 times that for a typical methyl ketone such as acetone. Thermodynamically, it is >108 times more acidic (pAa values of 11.1 vs 19.3). These increases in kinetic and thermodynamic acidity are derived from through-bond and through-space effects, and the implications for enzymatic catalytic sites with proximal, protonatable nitrogen are discussed. The results for (94) suggest a pAa value of 8.8 for (95), a value that cannot be measured directly due to competing hydrolysis. 

The hyperfine paramagnetic contribution (LIS, Spara) corresponding to the sum of contact (through-bond) and pseudo-contact (through-space) effects is easily obtained from the experimental NMR data ... 

The adsorption of CO on a site is also accompanied by backrelaxation of the surrounding ions. This is a through-solid effect, which must be added to the through-space effects (static dipole-dipole interactions, etc.) to explain the larger Avstat shift (53, 499, 500). 

C chemical shifts are more sensitive to steric crowding effects and less sensitive to through-space effects of double bonds than 1H chemical shifts. Increasing the substitution of a carbon (CH3 to CH2 to CH to C) leads to downfield shifts of about 10 ppm in each step. 

Figure 12.9 displays graphically the proton chemical shifts of all 20 amino acids in an unstructured peptide context. These are called random coil chemical shifts because they are not influenced by the through-space effects observed in specifically folded proteins. In this environment, there is not much chemical-shift dispersion Hn falls between 8 and 9 ppm, Ha between 4 ppm and the water resonance ( 4.8 ppm), and the side-chain Hn resonances... 

Inductive (through o-bonds) and field (through space) effects arise from a highly polar bond (—lo-), resulting in electron withdrawal to fluorine (Figure 1.11). 

The utilization of metal /3-diketonate complexes as organic-soluble NMR shift reagents was first explored in the mid-sixties with Ni(II) and Co(II) complexes of 2,4-pentanedione [(Ni(acac)2 and Co(acac)2] . Donor ligands such as triarylphosphines, isonitriles, pyridine V-oxides and picoline V-oxides bind to the metal ion. Relatively small shifts were observed in the NMR spectrum of the bound donor groups. These shifts were the results of contact (through-bond) and pseudocontact (dipolar or through-space) effects. 

As we see, the pattern of non-bonded group interactions may change dramatically, depending upon the particular shape of the given cage system. Thus far it has been impossible to account for the observed phenomena of the through-space effects in terms of a unified description. 

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