Isosterism steric effects

J. Xiao, B. Weisbium, P. Wipf, Electrostatic versus steric effects in peptidomimicry Synthesis and secondary structure analysis of gramicidin S analogues with ( )-alkene peptide isosteres, J. Am. Chem. Soc. 127 (2005) 5742-5743. 

For the characterization of the electronic and steric effects of substituents on the catalytic properties of tertiary aliphatic amines, Bogatkov et al. 71,72) proposed a correlation between the steric hindrance of R1R2R3N amines by means of the En(En) constants which are identical with steric constants ES(E9) according to Taft for isosteric hydrocarbon substrates R1 R2R3C. On this basis, they proposed the following linear correlation for the nucleophilic activity of amines ... 

Although fluorine does not have the same valency as hydrogen, it is often considered an isostere of that atom since it is virtually the same size. Replacement of a hydrogen atom with a fluorine atom will therefore have little steric effect, but since the fluorine is strongly electronegative, the electronic effect may be dramatic. 

For example, substitution of the vinyl sulfone 13 by primary, secondary, and teriary amines (equation 3) obeys a single equation (equation 4) (56), where 2a is the sum of the inductive effects of the amine substituents, and En is an isosteric parameter where the steric effect of an amine R1R2NH is taken as similar to Es of CHR 2. Twenty-two amines obeyed the equation with p = —4.8 and 8 = 1.70 where p and 8 are the sensitivity parameters to the inductive and steric effects, respectively. As a demonstration of the electronic effects, fccyciohexyUmin Aniline 10 in sPite of their similar size, whereas steric effects are reflected in the Et2NH i-Pr2NH °f approximately 3000 in spite of the similar basicities. Similar LFERs were observed in other reactions (Table IX) (29). 

Any modification of a complex, in order to increase or decrease its reactivity towards a substrate for catalytic purposes, can be easily accomplished by modulating the steric effects, even though modification of the electronic properties of the reactive site may also be necessary to render the catalyst more efficient. The evaluation of such electronic influence requires a comparison of complexes bearing ligands of the same size (isosteric ligands) but different in their chemical nature. The organometallic chemistry of the hard lanthanide elements is dominated by the soft cyclopentadienyl type ligands, while the number of non cyclopentadienyl hydrides is really modest. Due to the paucity of the published syntheses of... 

QSAR 48 was derived [ 14] for the antiviral data of hydroxyethylene isostere derivatives (40) for inhibition of HIV protease in H9 human T-lymphocytes cells, reported by De Solms et al. [160]. One of the prototype pentapeptides (L-682,679) was modified at the carboxy terminus and mostly variations of the P2 amino acid and the elimination/replacement of the P3 amino acid were studied [160]. This model showed that overall bulky molecules would favor the activity. However, the X-substituents would have a negative steric effect. 

The pertinent thermodynamic variable to quantitatively describe the thermal effects in the exo(endo) thermic gas ad(de)sorption process is called the iso-steric heat of adsorption.The isosteric heat of adsorption of component i of an ideal gas mixture (q/) at adsorbate loading of rii and temperature T is given by the following thermodynamic relationship... 

The infrared (IR) data quoted for 5-hydroxythieno[2,3-6]pyridinel (the isostere of 3-hydroxyisoquinoline) implies no contribution from the keto tautomer, and in numerous reports on studies of pyridoxine-type analogs,69, 11-73,92-94 which contain a 7-hydroxy-thieno[3,4-c]pyridine system, the oxygen function /3 to the nitrogen is invariably represented as a normal hydroxy group. In a paper devoted to ketoenol equilibria in l,3-dihydro-5-hydroxythieno[3,2-6 pyridine derivatives42 (72-73), it was reported that the keto farms were exclusively present in the solid state, but in dioxane the ratios 72 73 and 74 75 were 0.43 1 and 1.09 1, respectively. These facts were interpreted in terms of steric and electronic effects. 

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