Arene-based Ligand Research Articles

Designed calix[8]arene-based ligands for selective tryptase surface recognition

Basic amino acid calix[8]arene receptors for tryptase surface recognition have been synthesized. The tetrameric arrangement and the negative charge distribution close to the active sites of the enzyme, have suggested the design of complementary multifunctional receptors that might bind to the active region of the protein blocking the approach of the substrate. Kinetic inhibition analysis on recombinant lung tryptase have showed a time-dependent competitive inhibition with both initial and steady-state rate constants in the nanomolar range.

Selective functionalization at the small rim of calix[6]arene. Synthesis of novel non-symmetrical N3, N4 and N3Ar O biomimetic ligands

Eight novel calix[6]arene-based biomimetic ligands for transition metal ions have been synthesized. They display a non-symmetrical N 3, N 4 or N 3Ar O binding core that mimics enzyme active sites presenting histidine and tyrosine residues. The key step for their synthesis is the mono-alkylation at the small rim of the C 3v symmetrical trimethyl ether derivative of tBu-calix[6]arene with N-Boc-2-chloroethylamine to yield a novel calix[6]arene synthon. Its combined O-alkylation with a chloromethyl aromatic amine and N-deprotection or alkylation or reductive alkylation with a salicylaldehyde derivative yielded the calix[6]arene-based ligands with mixed N/ O donors.

Modulation of a Supramolecular Bowl and Pot by Changing Solvent Systems and/or Metal/Ligand Ratios

A resorcin[4]arene-based ligand 2 a with four pyrimidine substituents at the upper rim was synthesized, and the generation of different metal-mediated superstructures from the same ligand and metal ions utilizing the unfavorable incorporation of the third and fourth Pd(II) ions to ligand 2 a was investigated. The supramolecular bowl 3 a, which comes from a 1:2 combination of ligand 2 a and [Pd(en)(NO(3))(2)], was obtained in water even though excess of Pd(II) complexes were employed. By adding methanol, the supramolecular pot 4 gradually formed, which was the major product when the ratio of mixed solvent reached methanol/water=5:1 (v/v). Host-guest complexation phenomena of 3 a toward several aromatic carboxylates were demonstrated by isothermal titration calorimetry (ITC) and by (1)H NMR spectroscopy; both the enthalpy gain from electrostatic and hydrophobic interactions, and the entropy gain from desolvation cooperatively contribute to the binding of anionically charged guests. The crystal structure of supramolecular pot 4 shows direct evidence for the hydrogen bonding between water and the aromatic pi electrons in the solid state. The modulation between supramolecular bowl 3 a and pot 4 was also made possible by changing the metal/ligand ratios in aqueous methanol solution as well as by varying the water content of the mixed solvent.

Molecular recognition of alkylamines: conformational and binding properties of calix[6]arene-based ester ligands

A series of alkyl 15,35,55,75,95,115-hexa-tert-butyl-1,3,5,7,9,11-hexa[1,3]benzenacyclododecaphane esters have been prepared that selectively bind to alkylammonium cations. Ester ligands showed extraction efficiency toward alkylamines in the sequence of ammonium Pr > Pri > Bu > Bui≃ Bus > tert-butylammonium guests. Single and competitive transport experiments of butylamines also confirmed the binding properties obtained with extraction experiments and the transport selectivity for Bu/But pair exceeds 25. Conformational properties, such as Tc and ΔGc‡, of ester ligands were investigated by means of temperature-dependent 1H NMR spectroscopy. Conformational freedom was generally found to decrease as the size of substituent of ester side chain increased. 1H NMR complexation studies of ethyl ester 2 with caesium tetraphenylborate and butylammonium picrate guests suggest that the conformational reorganization into a cone conformation has provoked complex formation.

Molecular design of calixarene-based ion-selective electrodes

In order to obtain insights into relationships between the calix[4]arene structure and the ion selectivity in the electrode system, 20 ionophoric calix[4]arenes were synthesized and their ion selectivity (with Na+ as a standard) estimated. Among these ionophoric calix[4]arenes, 25,26,27,28-tetrakis[(ethoxycarbonyl)methoxy]-p-t-octylcalix[4]arene afforded the highest logKNA,Mpot value (−3.1) in the presence of 2-fluorophenyl-2′-nitrophenylether (10) as the best of 13 plasticizers. This is the first example in which the Na+/K+ selectivity exceeds a factor of 103 in the electrode system based on the neutral carrier. The high Na+ selectivity is attributed to modification of the upper rim which ostensibly has no relation with the component of the cavity. This paper demonstrates the potential relationships between the unique structure of the calix[4]arene-based ligands and selectivity performance for the design of ion-selective electrodes.