Swain-Lupton resonance

MR molar refractivity it hydrophobic substituent constant and Op overall electronic constants for meta- and para-position K and p Swain-Lupton resonance and field constants L Sterimol length parameter B1 and B5 Sterimol B parameters SD Dash-Behera steric density parameter. 

Swain-Lupton resonance constant resonance constant -> electronic substituent constants (O field/resonance effect separation)... 

Figure 16. The AD values of the meta-substituted triplet diradicals 10 versus the Swain Lupton resonance parameter R.

Table 4.5 Examples of the different electronic substitution constants used in QSAR studies. Inductive substituent constants (crO are the contribution the inductive effect makes to Hammett constants and can be used for aliphatic compounds. Taft substitution constants (cr ) refer to aliphatic substituents but use propanoic acid (the 2-methyl derivative of ethanoic acid) as the reference point. The Swain-Lupton constants represent the contributions due to the inductive (.F) and mesomeric or resonance (R) components of Hammett constants. Adapted from An Introduction to the Principles of Drug Design and Action by Smith and Williams 3rd Ed. (1998) Ed. H.J.Smith. Reproduced by permission of Harwood Academic Publishers.

Swain-Lupton equation A dual-parameter approach to the correlation analysis of substituent effects, which involves a field constant (F) and a resonance constant (R). The original treatment was modified later. The procedure has been considerably applied, but also much criticized. 

The Swain-Lupton treatment was a reaction against the proliferation of scales of polar substituent constants. The authors maintained that the polar effect of any given substituent could be adequately expressed in terms of just two basic characteristics a field constant and a fixed resonance constant Swain and Lupton maintained that the correlation analysis of chemical reactivity data and spectroscopic data of aromatic systems could be carried out satisfactorily in terms of and 9. cf the four cri -type parameters introduced for the DSP equation), meta and para series being dealt with separately, as in the case of the DSP equation. The assumptions involved in establishing the and 9 . scales provoked much criticism. Nevertheless, the treatment achieved fair success when applied to chemical reactivity data and some spectroscopic data, particularly The most... 

The fact that two cr-constants are needed to explain the substituent elfects led to the proposal that each a value is a dilferent linear combination of two separate factors field and resonance elfects, for example, the Swain-Lupton Tand R (see Table 3.1), as shown in equation (3.4). 

The successful decomposition of a values into field and resonance components could eliminate the need for several sets of o values. The Swain-Lupton system must treat meta- and para-substituted compounds as separate reaction series, with differing values for r and / for a meta versus para placement of the substituent. The reason is that resonance interactions are usually stronger in the para series. There must also be an additional parameter for each reaction, since the relative sensitivity to resonance and field effects differs from reaction to reaction. Swain and Lupton have observed satisfactory correlation for over forty reaction series using and This treatment also provides an indication of the relative importance of resonance and field interactions. The mathematical manipulations are, of course, more complex than in the simple Hammett equation. The Swain-Lupton correlations are carried out by a computer program that provides a best-fit correlation in terms of /, r, and The computation also yields percent resonance by comparing the magnitude of/ andr. 

Gj/ Gp Taft inductive and mesomeric F,R Swain-Lupton field and resonance constants (F14)... 

In SAR work, the biological activity of compounds is usually expressed by the values of IC50 or ED50. Physico-chemical properties used in SAR can be broadly classified into three general tjq)es electronic parameters, steric parameters and hydrophobic parameters. Electronic parameters include Hammett constants o ,(7, <7 ), Swain and Lupton field parameter (F), Swain and Lupton resonance parameter (R), etc. Steric parameters include Taft s steric parameter (Eg), molecular volume (Vm), molecular surface area (Area), molecular weight (MW), van der Waals radius (r), molar refractivity (MR), parachor (Pr), etc. Hydrophobic parameters include partition coefficient (LogP), distribution coefficient (LogD), substituent constant ( ), solubility... 

Swain C G and E C Lupton 1968. Field and Resonance Components of Substituent Effects. Journal of tl American Chemical Society 90 4328-4337. 

Here we will not discuss these problems and the intriguing observation that am and strong correlation which is, however, difficult to explain (reviews Charton, 1981 Cook et al., 1989 Hansch et al., 1991). These questions were intensively studied in the 1970s and 1980s, leading gradually to the development of field and resonance parameters denoted by F and R respectively (after an original proposal of Swain and Lupton, 1968), which can be considered as independent of each other. The secondary parameters R + and R reflect the potential for an additional mesomeric donor-acceptor interaction (as in 7.7, and the opposite type with a donor instead of NQ2 and the reaction site as acceptor). 

The only groups in Table 9.5 with negative values of CT/ are the alkyl groups methyl and tert-butyl. There has been some controversy on this point. One opinion is that CT/ values decrease in the series methyl, ethyl, isopropyl, /ert-butyl (respectively, — 0.046, —0.057, —0.065, —0.074). Other evidence, however, has led to the belief that all alkyl groups have approximately the same field effect and that the a/ values are invalid as a measure of the intrinsic field effects of alkyl groups. Another attempt to divide ct values into resonance and field contributions is that of Swain and Lupton, who have shown that the large number of sets of ct values (cTm, <3p, a, a+, CT/, csp etc., as well as others we have not mentioned) are not entirely independent and that linear combinations of two sets of new values F (which expresses the field-effect contribution) and R (the resonance contribution) satisfactorily express 43 sets of values. Each set is expressed as... 

A rival analysis of substituent effects into field (equivalent to inductive) and resonance components was proposed many years ago by Swain and Lupton °, was later slightly corrected by Hansch and colleagues and fairly recently has been substantially modified... 

A table of correlations between seven physicochemical substituent parameters for 90 chemical substituent groups has been reported by Hansch et al. [39]. The parameters include lipophilicity (log P), molar refractivity MR), molecular weight MW), Hammett s electronic parameters (a and o ), and the field and resonance parameters of Swain and Lupton F and R). 

There are several systematic nuclear magnetic resonance studies of the interaction between the substituents and the protons and ring atoms of five-membered heterocycles. In some 2-substituted furans, thiophenes, selenophenes, and tellurophenes there is a linear correlation between the electronegativity of the chalcogen and several of the NMR parameters.28 As there also is a good correlation between the shifts of the corresponding protons and carbons in the four heterocycles, the shifts of unknown selenophene and tellurophene derivatives can be predicted when those of thiophene are known. This is of special interest for the tellurophene derivatives, since they are difficult to synthesize. In the selenophene series, where a representative set of substituents can be introduced in the 2- as well as in the 3-position, the correlation between the H and 13C shifts and the reactivity parameters according to Swain and Lupton s two-parameter equation... 

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