QSAR based modeling on a series of α-hydroxy amides as a novel class of bradykinin B1 selective antagonists

G-protein coupled receptors like Bradykinin (BK) B₁ represent a potential treatment route for chronic pain and inflammation. Quantitative structure activity relationship has been performed on a series of α-hydroxy amides as a novel class of bradykinin B₁ selective antagonists, using different physicochemical parameters along with appropriate indicator variables. It has been found that physicochemical parameters such as connectivity indices ³χ, ⁴χ and ⁵χ, molecular weight, molar refractivity, density along with indicator variables are significantly correlated with activity. In this paper best results were obtained by using multiple regression analysis. Different models were generated with high values of R² and low values of PRESS/SSY ratio. The significant equations were statistically tested by using leave one out (LOO) technique and cross validation methods.     

Synthesis and reactions of p-vinylbenzyltris(trimethylsilyl)methane

Benzyl chloride was treated with (Me₃Si)₃CLi to give (Me₃Si)₃CCH₂Ph (1). A new styrene derivative, (Me₃Si)₃CCH₂C₆H₄(CHCH₂-p) (2), was synthesized by reaction of p-vinylbenzyl chloride with (Me₃Si)₃CLi in the presence of CuCl. Addition and oxidation reactions on 2 gave a series of new compounds (Me₃Si)₃CCH₂C₆H₄X-p (X = CH₂CH₃, CHBrCH₂Br, CHClCH₂I, CHBrCH₂I, cyclo-C₃H₃Cl₂, CHOHCH₂OH, COOH, CH₂OH).     

Studies on the synthesis of a hindered analogue of the antitumour agent CC-1065

Studies on the synthesis of a sterically congested analogue of CC-1065 (2) are described. Interesting steric effects in the reactivity of intermediates and the rare predominance of keto tautomers in some phenols were observed.     

Energetic study of diastereoselective thio-Claisen rearrangement

Molecular simulation is applied to explain the diastereoselective thio-Claisen rearrangement results of various S-allyl γ-hydroxy ketene dithioacetals. We show that the experimental results of Sreekumar et al. in the absence and in the presence of zeolite catalyst can be rationalized in terms of the energetics of the steric of the reactant and the transition-state structure and of the non-bonding interactions of zeolite–reactant and zeolite–transition-state structure. The procedures used can successfully identify optimum products for a given diastereoselective thio-Claisen rearrangement.     

Replacement of N-heterocyclic carbenes by N-heterocyclic silylenes at a Pd(0) center: Experiment and theory

Via NMR-spectroscopy the relative reactivity of N-heterocyclic silylenes (NHSi) and carbenes (NHC) was studied. Reaction of sterically crowded bis-N-heterocyclic Pd(0) carbene complexes with free N-heterocyclic silylenes led to complete displacement of the N-heterocyclic carbene, which is unexpected knowing that usually a silylene is a weaker bound ligand compared to a carbene. High-level DFT calculations on a small model system and the experimentally used complexes confirm the experimental findings and indicate that steric interactions play an important role in the substitution reaction.     

Molecular mechanisms of aqueous boundary lubrication by mucinous glycoproteins

Mucins have long been recognized as instrumental to biolubrication but the molecular details of their lubrication mechanisms have only been explored relatively recently. The glycoprotein PRG4, also known as lubricin, shares many features with mucins and appears to lubricate through similar mechanisms. A number of studies have contributed to a more in-depth understanding of mucin adsorption and layer formation on surfaces and the mechanisms by which these layers lubricate. Although mucinous glycoproteins differ in their aggregation properties, their adsorption behaviors on surfaces, and in their ability to reduce friction, they share important similarities favorable for lubrication. They are highly hydrated, they adsorb strongly to a broad range of surfaces, and the layers they form are both sterically and electrostatically repulsive, all attributes thought to contribute to boundary lubrication. They also hydrophilize hydrophobic surfaces, promoting the formation of aqueous fluid films that can lower friction at already relatively low sliding speeds. In this paper we briefly review current knowledge of mucin adsorption and lubrication, with a focus on recent advances.     

On study of sterically controlled regioselective lithiation of meta-halopyridocarboxamides derivatives

Sterically controlled regioselective lithiation of meta-halopyridocarboxamides derivatives using deuterated probes is described. A first experimental demonstration that the nitrogen is the main chelating-base approach site onto the oxazoline and N-alkoxyamide DMGs is reported.     

Differential nitrogen–carbon bond cleavages in architecturally complex molecular scaffolds containing a bridge-head nitrogen atom

Application of an N–C bond cleavage reaction in various structurally complex molecular frameworks containing bridge-head nitrogen atom offered differential outcomes that were attempted to rationalize invoking both steric and electronic factors.     

‘Counter-intuitive’ regioselectivity, subtle steric and solvation effects in lithiation of cyclic tertiary aralkylamines

Lithiation of a series of cyclic aralkyl tertiary amines with sec-BuLi in various solvents has been studied. There is a subtle sensitivity to steric factors and lithium coordinating solvents/additives have an adverse effect. ortho-Lithiation is observed only in the case of an eight-membered cyclic amine and the ease of benzylic lithiation with respect to nitrogen is in the surprising order γ > β ? α, δ. These observations are discussed in the context of nitrogen coordination promoted lithiation.     

Steric Interactions in Organic Chemistry: Spatial Requirements of Substituents

From the very extensive factual material available on steric interactions in organic chemistry, the present paper reviews the investigations that provide information about the “size” (“spatial requirement”) of the substituents. After an introductory section on the results obtained with the aid of spectroscopic data and by analysis of chemical reactions, attention is turned to conformational processes, including hindered rotation in ethanes, in the biphenyl system, in butadienes, multiply substituted arenes, molecular propellers, and triptycenes. The main emphasis is placed on the explanation of sterically hindered ring inversions in bridged arenes, a class of compounds particularly suitable for the study of steric interactions. The results obtained by variation of the parameters in this system are also discussed with respect to the spatial requirements of organic substituents.