Hydrophobic substructures

The work by Hammett and Taft in the 1950s had been dedicated to the separation and quantification of steric and electronic influences on chemical reactivity. Building on this, from 1964 onwards Hansch started to quantify the steric, electrostatic, and hydrophobic effects and their influences on a variety of properties, not least on the biological activity of drugs. In 1964, the Free-Wilson analysis was introduced to relate biological activity to the presence or absence of certain substructures in a molecule. 

Reconsidering the past, many attempts have been made to enhance the hydrolytic stability of these products. The trials were based upon the variation of both the alkyl spacer part or similar hydrophobic moieties in order to protect the hydrolytically sensitive Si-O-Si substructure. These experiments lead to substances which show improved stability at neutral, slightly acid or alkaline pH. However, totally stable materials could not be obtained that way [2]. 

Two of the three conserved a helices are fastened together by disulfide bridges to form a highly stable substructure that contributes many of the active site residues. Four (class III), five (class I), or six (class II) of the disulfide bridges found in sPLAgS incorporate half-cystines derived from this substructure. Conserved side chains arising from these helices assist in the coordination of the primary calcium ion (Asp-49/35), form the deeper contours of the hydrophobic channel (Cys-45, Ala-102, Ala-103, Phe-106), and create the catalytic network (His-48/34, Asp-99/64, Tyr-52/87). 

Synthesis of functionalized hydrophobic ionic liquids bearing the 2-hydroxyben-zylamine substructure, and their application in partitioning of metal ions from water have been described (Scheme 15) [94],... 

The chemical structure representation in Apex-3D is based on the concept of a descriptor center that represents a part of the hypothetical biophore. Descriptor centers can be atoms, sets of atoms, pseudo-atoms, or substructures that participate in ligand-receptor interactions. The interaction is derived from electrostatic, hydrophobic, dispersion force, and charge-transfer information that comes from quantum-chemical calculations or from atomic conkibutions to hydrophobicity or molar refractivity. 

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