Hydrophobicity substituent parameters

Hansch-Leo hydrophobic substituent parameter Hammett sigma constants Modtried Swam Lupton constants... 

In Eq. 27, is the equilibrium constant (M-1). The four N-substituents are classified as E (R ) E (R2) E,(R3) E (R4). Hydrophobic substituent parameter, n, is evaluated by taking the H substituent as the reference, and summed for component four substituents. Since the steric effect of bulkiest R4 substituents is not significant, the ion-pairing is perhaps achieved in such a manner that the counter anion must approach from the least hindered side of the ammonium ions (11). 

A number of o- and ir values for substituents which were present within our set of compounds were missing in the published compilations. We calculated them from the regression equations in Figures 4 and 5. An interesting feature of both equations is that the substituent R at the carbonyl group of the hydrazones contributes in a very different way from that of the substituents in the aromatic ring to pK as well as to log P. Rm values from reversed-phase thin-layer chromatography (TLC) correlated poorly with the w constants and thus cannot be used in this case to derive hydrophobic substituent parameters (18). 

A new class of water-soluble materials [10,11], was developed as a result of such design parameters that will be referred to as double substituted cationic cellulose ethers (DCEs). These materials contain both a cationic substituent and a hydrophobic substituent, attached to a cellulose ether backbone. The use of a double-substituted hydrophobe modified cationic polysaccharide is fundamentally different from current commercial vaginal formulations, which rely exclusively on nonionic or anionic vehicles. 

The distribution coefficient refers to the hydrophobicity of the entire molecule. Within a family of organic compounds it is sometimes useful to deal with hydrophobic substituent constants that relate the hydrophobicity of a derivative, log Px, to that of the parent molecule, log P. Therefore, a substituent parameter, n, has been defined [21] as... 

Similarly, the partitioning of nitroimidazoles into octanol-water, log Poet and into four liposome preparations with different lipid composition, log KM, was determined and regression equations were derived to explain the observed variation in the pharmacokinetic parameters of these drugs [85]. The log fCM ranged from 1.5 to 0.5 and was at least two- to threefold greater than log Poct (Table 4.24). In addition, the hydrophobic substituent constants of functional groups in various partitioning systems... 

Based on the earlier work of Meyer and Overton, who showed that the narcotic effect of anesthetics was related to their oil/water partition coefficients, Hansch and his co-workers have demonstrated unequivocally the importance of hydrophobic parameters such as log P (where P is, usually, the octanol/water partition coefficient) in QSAR analysis.28 The so-called classical QSAR approach, pioneered by Hansch, involves stepwise multiple regression analysis (MRA) in the generation of activity correlations with structural descriptors, such as physicochemical parameters (log P, molar refractivity, etc.) or substituent constants such as ir, a, and Es (where these represent hydrophobic, electronic, and steric effects, respectively). The Hansch approach has been very successful in accurately predicting effects in many biological systems, some of which have been subsequently rationalized by inspection of the three-dimensional structures of receptor proteins.28 The use of log P (and its associated substituent parameter, tr) is very important in toxicity,29-32 as well as in other forms of bioactivity, because of the role of hydrophobicity in molecular transport across cell membranes and other biological barriers. 

This parameter is often used as a substituent steric constant in - Hansch analysis. In order to put the molar refractivities of the substituents on approximately the same scale as the - hydrophobic substituent constants Jt, the substituent MR values are often scaled down by the factor 0.1. 

The most popular substituent constants are electronic substituent constants, - Hansch-Fujita hydrophobic substituent constants and -> steric substituent constants such as - Taft steric constant, - Charton steric constant, -> substituent front strain, and - steric density parameter. 

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. 

The analysis of the parameters representing the effect of the medium in terms of extrathermodynamical relations has shown (see above, section A.2) that the hydrophobic substituent constant it depends on the molecules from which it is derived. For example, hydrophobic constants derived from the octanol/water partition coefficients of aromatic molecules differ from those obtained from aliphatic molecules (112). Collander s equation (111) provides the empirical basis for the evaluation of logP values for the same molecule in different solvents. However, solvents with markedly different solvation properties (e.g., hydrogen bonding ability) do not conform to Collander s equation (see below, section C.3). 

Classical Quantitative Structure-Activity Relationship Techniques The early QSAR models for calcium channel ligands were based on classical Hansch analysis and elucidated the structural requirements for the binding of molecules to their receptors [111-115], It was found that various steric (Bl, L), electronic (a), and hydrophobic (n) parameters or their combination correlated well with the potency of various DHPs [111]. QSAR analysis of another set of DHPs revealed good correlations between electronic properties (F-constants) of the phenyl ring substituents and binding affinities or functional potency [112] lipophilicity as well as ortho- and meta-substituents inductivity... 

The MR parameter has the dimensions of volume and can correlate with the hydrophobic substituent constant n it can be used as a crude measure of bulk. However, the parameter has a component proportional to polarisability. These potential complications can be avoided by careful experimental design so that the chosen substituents have tc values which are not linear with their MR parameters. The coefficient of MR in the free energy equation can be used to indicate a steric interaction (-ve) coefficient or an interaction involving dispersion forces (+ve coefficient). 

The preliminary results showed a correlation between physicochemical characteristics of inhibitor (activator) molecules and changes in kinetic parameters of bioluminescent reaction. For example the comparison of the effects of the quinones and phenols on three bacterial bioluminescence systems of different complexity indicates that the influence of the compounds on the bioluminescence intensity depends on the structure and redox characteristics. The inhibitory activity of quinones depends on their hydrophobic substituents and the size of the aromatic part. Such correlations are closely related to the physical mechanism of bioluminescence they are the biophysical basis for bioluminescent ecological monitoring. 

Examining 18 substituted 3-phenylthio-1,1,1-trlfluoro-2-propanones, regression equations were obtained between the inhibitory activities and the Hammett (ct), Taft (E ) steric and Hansch (ir) hydrophobicity constants (H). In the fiope of increasing the significance of these equations and to better distinguish between the Importance of various substituent positions, several new compounds of the related structure were synthesized, a much larger set of substituent parameters was applied, and instead of the arbitrary choice of these values, the variables were selected into the equations by a more sophisticated tool, linear stepwise regression analysis. 

A broad range of different electronic, hydrophobic and steric substituent parameters are available in the literature (30). In the present study 11 physicochemical parameters were... 

MR still is the chameleon [91] amongst the physicochemical parameters, despite its broad application in QSAR studies. It has been correlated with lipophilicity, molar volume, and steric bulk. Of course, due to its MW/q component it is indeed related to volume and size of a substituent. But two recent statements that MR is only based on these properties [91, 291] cannot be accepted. The refractive index-related correction term in MR accounts for the polarizability and thus for the size and the polarity of a certain group [158, 173, 286]. The larger the polar part of a molecule is, the larger its MR value will be. Even hydrophobic substituents have a weak enthalpic interaction due to dispersion forces, in addition to their entropic... 

In eqn (1.3) three substituent parameters n, cj, and E, are used to describe the hydrophobic, electronic, and steric properties of substituents. The substituent constant E, due to Taft (1956), is based on the measurement of rate constants for the acid hydrolysis of esters of the following type... 

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