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## Steric Parameters (steric + parameter)
## Selected Abstracts## Strain Energies as a Steric Descriptor in QSAR Calculations MOLECULAR INFORMATICS, Issue 7 2004CatherineAbstract The difference between the calculated heats of formation of gauche and anti conformers of monosubstituted propanes was determined and used as a new steric parameter (AG60 value) in QSAR calculations. The dihedral angle of the gauche conformation was fixed at 60° during the calculation to force interaction of the gauche groups. AG60 values are a thermodynamically determined steric measure in contrast to the Taft steric parameter, which is based upon kinetic measurements of ester hydrolyses. In comparisons to published QSAR studies, AG60 values correlated steric effects and biological activities very similarly to the Taft parameter. The average of r2 values from five QSAR studies for the Taft parameter was 0.887, while AG60 values averaged 0.883. Direct comparison of the Taft parameter and AG60 values showed a poor correlation (r2=0.300), indicating the two parameters are fundamentally different methods of measuring steric bulk. [source] ## Pentiptycene-Derived Light-Driven Molecular Brakes: Substituent Effects of the Brake Component CHEMISTRY - A EUROPEAN JOURNAL, Issue 38 2010Wei-Ting SunAbstract Five pentiptycene-derived stilbene systems (1,R; R=H, OM, NO, Pr, and Bu) have been prepared and investigated as light-driven molecular brakes that have different-sized brake components (1,H<1,OM<1,NO<1,Pr<1,Bu). At room temperature (298,K), rotation of the pentiptycene rotor is fast (krot=108,109,s,1) with little interaction with the brake component in the trans form ((E)- 1,R), which corresponds to the brake-off state. When the brake is turned on by photoisomerization to the cis form ((Z)- 1,R), the pentiptycene rotation can be arrested on the NMR spectroscopic timescale at temperatures that depend on the brake component. In the cases of (Z)- 1,NO, (Z)- 1,Pr, and (Z)- 1,Bu, the rotation is nearly blocked (krot=2,6,s,1) at 298,K. It is also demonstrated that the rotation is slower in [D6]DMSO than in CD2Cl2. A linear relationship between the free energies of the rotational barrier and the steric parameter A values is present only for (Z)- 1,H, (Z)- 1,OM, and (Z)- 1,NO, and it levels off on going from (Z)- 1,NO to (Z)- 1,Pr and (Z)- 1,Bu. DFT calculations provide insights into the substituent effects in the rotational ground and transition states. The molar reversibility of the E,Z photoswitching is up to 46,%, and both the E and Z isomers are stable under the irradiation conditions. [source] ## Global physicochemical properties as activity discriminants for the mGluR1 subtype of metabotropic glutamate receptors JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 16 2001Marta FilizolaAbstract Metabotropic glutamate receptors (mGluRs) are important as candidate therapeutic targets for many neurological disorders. In the present work, the focus has been on the mGluR1 subtype, where agonists have a proconvulsant profile while antagonists exert anticonvulsant activity. Identification of molecular determinants for the inhibition of mGluR1 provides a new avenue for the discovery and development of novel anticonvulsant drugs. Spatial configuration of key groups alone cannot explain activation selectivity at this specific receptor subtype. In fact, all known agonists and antagonists acting at mGluR1 can accommodate the same critical moieties in a similar geometric arrangement that corresponds to the extended conformation of glutamate. Therefore, other factors must account for the differences in activation. This study presents the results of an analysis of a large suite of steric, topological, electrostatic, and thermodynamic molecular properties calculated for a representative set of potent mGluR1 agonists and antagonists. Global steric parameters and the total nonpolar area provide discrimination between the mGluR1 agonists and antagonists considered in the present work. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 2018,2027, 2001 [source] ## Mechanism and structure,reactivity correlation in the homogeneous, unimolecular elimination kinetics of 2-substituted ethyl methylcarbonates in the gas phase JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2003Gabriel ChuchaniAbstract The gas-phase elimination kinetics of 2-substituted ethyl methylcarbonates were determined in a static reaction system over the temperature range of 323,435°C and pressure range 28.5,242 Torr. The reactions are homogeneous, unimolecular and follow a first-order rate law. The kinetic and thermodynamic parameters are reported. The 2-substituents of the ethyl methylcarbonate (CH3OCOOCH2CH2Z, Z=substituent) give an approximate linear correlation when using the Taft,Topsom method, log(kZ/kH)=,(0.57±0.19),,+(1.34±0.49),R, (r=0.9256; SD=0.16) at 400°C. This result implies the elimination process to be sensitive to steric factors, while the electronic effect is unimportant. However, the resonance factor has the greatest influence for a favorable abstraction of the ,-hydrogen of the C,,H bond by the oxygen carbonyl. Because ,, is significant, a good correlation of the alkyl substituents of carbonates with Hancock's steric parameters was obtained: log(kR/kH) versus ESC for CH3OCOOCH2CH2R at 400°C, R=alkyl, ,=,0.17 (r=0.9993, SD=0.01). An approximate straight line was obtained on plotting these data with the reported Hancock's correlation of 2-alkyl ethylacetates. This result leads to evidence for the ,-hydrogen abstraction by the oxygen carbonyl and not by the alkoxy oxygen at the opposite side of the carbonate. The carbonate decompostion is best described in terms of a concerted six-membered cyclic transition state type of mechanism. Copyright © 2003 John Wiley & Sons, Ltd. [source] ## Exploring QSAR for Substituted 2-Sulfonyl-Phenyl-Indol Derivatives as Potent and Selective COX-2 Inhibitors Using Different Chemometrics Tools CHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2008Mehdi KhoshneviszadehSelective inhibition of cyclooxygenase-2 inhibitors is an important strategy in designing of potent anti-inflammatory compounds with significantly reduced side effects. The present quantitative structure,activity relationship study, attempts to explore the structural and physicochemical requirements of 2-sulfonyl,phenyl,indol derivatives (n = 30) for COX-2 inhibitory activity using chemical, topological, geometrical, and quantum descriptors. Some statistical techniques like stepwise regression, multiple linear regression with factor analysis as the data preprocessing (FA-MLR), principal component regression analysis, and genetic algorithms partial least squares analysis were applied to derive the quantitative structure,activity relationship models. The generated equations were statistically validated using cross-validation and external test set. The quality of equations obtained from stepwise multiple linear regression, FA-MLR, principal component regression analysis and PLS were in the acceptable statistical range. The best multiple linear regression equation obtained from factor analysis (FA-MLR) as the preprocessing step could predict 77.5% of the variance of the cyclooxygenase-2 inhibitory activity whereas that derived from genetic algorithms partial least squares could predict 84.2% of variances. The results of quantitative structure,activity relationship models suggested the importance of lipophilicity, electronegativity, molecular area and steric parameters on the cyclooxygenase-2 inhibitory activity. [source] |