Hammet constants

Halterman et al. agreed with this proposal to show the selectivity of 5-aryl-5-phenylcyclopentadiene favoring the reactions on the anti side of a more electron rich aromatic system with significant correlation between the Hammet constants for the aromatic substituents and the facial selectivity [19] (Scheme 29). 

The substituent hydrophobicity constant, based on partition coefficients analogs to Hammet constants ... 

Regression analysis is currently the most widely used correlative method in drug design. This is because it simplifies problems within a set of compounds by using a limited number of descriptors, notably the Hansch hydrophobic constant n, Hammet constants, or other electronic characteristics of substituents, and the Taft steric constant Eg. 

The same situation is encountered with a,/ -alkynic phosphonium salts in which C(a) carbons are strongly shielded vs C p) carbons 47.8-73.0 vs 119-127 ppm36,97. The linear correlation of the C(a) and C(P) chemical shifts with a para Hammet constant was illustrative of the polarization of the 7r-electron system in the C=C triple bond (Figure 8). In the same sense, the observed C(flt) and C(/J) chemical shifts were used to argue for the existence of either resonance hybrid structures as in the case of enaminophosphonium salts98,99 or incipient ylide contribution40. 

This was investigated by Schott and Langecker for the case of the hydrolysis of tetraalkyl and tetraaryldisilanes565 Substitution on the phenyl group changes the reaction rate. A relation between the rate constants and the Hammet constants was observed, but for linearity the Hammet constants have to be reduced to take into account a mesomeric factor. Special aSj constants are therefore necessary (there are similar differences in the a constants of other Si compounds16, 6281. 

For illustrative purposes. Table 3.10 lists a few representative values of Hammet constants for substituents in benzoic acid. 

Table 3.10. Hammet Constants for Substituents in Benzoic Acids"...

Thiazole exhibits a H NMR spectrum of first order. Table 3 lists the relevant chemical shifts for which a relationship exists with the calculated 7t-electron densities on the respective carbon atoms (to which the protons are bonded). Simple correlations were observed in other cases. For instance, a satisfactory linear relationship between the experimental S values and the calculated 7t-electron densities was found for bromothiazoles <84H(22)1077>. Correlations between the experimental d values of some substituted thiazoles and the Cp Hammet constants have been also reported <85SUL17>. 

A study of the electrochemical behavior of derivatives of ebselen was carried out. The presence of a substituent at the C-7 position, adjacent to the selenium atom, enhances the glutathione peroxidase-like activity. A Hammet relationship was observed between the oxidation potential and the Hammet constant values of the C-7 substituent <90MI 307-01,9iMl 307-01 >. 

However, 54 are much better quenchers than would be predicted on the basis of Hammet constants for these type of parasubstltuted anilines. 

Examination of O chemical shifts of several 2-substituted and 2,5-disubstituted furans <85MRC985> has demonstrated the additivity of substituent effects by plotting the O chemical shifts of 2,5-disubstituted furans versus those of the 2-substituted analogues. Failure of the electronic character of substituents in determining O chemical shifts is found, because they do not correlate with Hammet constants. Such a lack of correlation is known for C ortho chemical shifts in aromatic systems. A good correlation is obtained by plotting O chemical shifts versus a parameter Q of the substituent—a parameter which accounts for the paramagnetic contributions and is a function of the polarizability and ionization potential of the substituent. The cyano- and methylfurans, however, do not follow the Q relationship. 

This enables us to introduce a concept of polar effects in homological reactions, seen in the kinetics of radical polymerisation and homolytic arylation of p-substituted benzenes. Combination of heterogroups with different electronegativity in the PSF structure - strong electron-acceptor sulfonyl (the Hammet constant = + 0.7) and electron-donor ether (o = -0.32) groups, as well as weak electron-donor isopropylydene group (o = -0.197), causes alternation of electron density on aromatic carbon atoms, which is naturally displayed in values of chemical shears of NMR (see Figure 7.3). 

In ion-pair chromatography, Tomlinson and Riley [9] have estimated the ion retention factors using functional group values, t, related to the Hammet constants. This shows that the hydrophobic part of the ionic solutes is responsible for file retention as well as its ionic part. The later part may be pH and ionic strength dependent. 

Fig. 7A,B. Inhibition of uridine incorporation by 10 rM benzamides vs (A) inhibition of poly-(ADP-ribose)synthetase or (B) Hammet constant...

It has clearly been shown that inhibition of poly(ADP-ribose) synthetase was responsible for the cytotoxicity exhibited by five of the six benzamides tested. 3-Nitrobenz-amide was markedly more cytotoxic than would be expected on the basis of its K,. Nitro-compounds have been shown to be cytotoxic and genotoxic. This is thought to arise by reduction to reactive intermediates which can then modify DNA [3]. When uridine incorporation was correlated with the Hammet constant, 3-nitrobenzamide fitted very well. The shorter exposure time in this assay minimises any metabolite effects. 

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