Choline Esterase Inhibitors and Synthetic Oxalic Acid Receptors Based on Calix[4]arene Derivatives

Abstract

New reversible butyrylcholine esterase inhibitors based on calix[4]arene derivatives were suggested. A series of new distally disubstituted calix [4]arenes were prepared in 60 380% yields. Some of these compounds showed properties of reversible choline esterase effectors, activating it at low concentrations and inhibiting at high concentrations. The macrocycles prepared were tested in extraction of d,l-tartaric, glycolic, d,l-mandelic, d,l-glutamic, malonic, oxalic, and succinic acids and of sodium acetate. Oxalic acid is efficiently transferred through a liquid impregnated membrane under the action of calix[4]arenes with nitrogen-containing substituents.Various biochemical processes such as recognition, reaction, active and selective transport, and reception [1] are based on intermolecular interactions. Transformation of the genetic information into such cell functions as growth activation and regulation of enzymes [1] is based on recognition and selective binding of the protein surface with biopolymers. Active studies made in the past decade are aimed at development of synthetic small molecules whose target is protein3 protein interaction [2, 3].Relatively simple and synthetically accessible molecules capable to reversibly [switch] various functions of proteins are interesting as potential components of drugs enhancing the specificity of the active component and its selective transport in patient's body [4]. However, the high degree of solvation and large area of the protein surface complicate the designing of molecules capable to reversibly alter the protein function. Calixarenes, being low-toxic and containing several functionalization centers, show promise for development of new highly effective drugs.We have shown recently that some distally substituted calix[4]arenes inhibit the hydrolysis of indophenyl acetate with butyrylcholine esterase, which is due to formation of host3guest complexes of calixarene with indophenyl acetate and localization of the resulting supramolecule near the active center of the enzyme [3].To examine the influence of structural factors on the interaction of calix[4]arenes with a model protein, butyrylcholine esterase, we prepared a series of new 1,3-disubstituted (at the lower rim) p-tert-butylcalix-[4]arenes containing proton-donor (I), proton-acceptor (II), and electron-acceptor (III, IV) groups. Dicarboxylic acid I was prepared by hydrolysis of the corresponding ester. Compounds II3IV were prepared by selective alkylation of p-tert-butylcalix [4]arene with the corresponding halo derivatives in acetonitrile in the presence of potassium carbonate.

Nuclearity control in calix[4]arene-based zinc(ii) coordination complexes

“…Ligand (3-4H) has been designed as a tweezer for binding the zinc cations and presents a disubstituted calix [4]arene derivative bearing two carboxylic groups connected to macrocyclic platform via benzyl moieties. The synthesis of (3-4H) was achieved in high yield following a slightly modified procedure described for preparation of its p-tert-butyl analogue 39 , 40 following a two steps procedure (Figure 2). Firstly, two appended substituents containing ester junction have been successfully grafted to the macrocyclic platform using nucleophilic substitution reaction between p-H-calix [4]arene (CA) 41 and methyl 4-(bromomethyl)benzoate in the presence of potassium carbonate acting as a base, leading to 3'.…”

“…The synthesis of (4-4H) was adapted from previously reported procedures. 39,40 Synthesis of (3-4H) The synthesis of 3-4H was achieved in two steps starting from p-H-calix [4]arene 41 as initial compound.…”