Chiral recognition in complexation of guests by designed host molecules

Abstract

Host molecules have been designed and synthesized to selectively complex and lipophilize guest molecules. Examples of the use of the following binding interactions are given: hydrogen bonding, ion pairing, cation to n-electrons, carbonyl to n-electrons and pi-pi bonding. Multiheteromacrocycles have been prepared whose association constants with tert-butylammonium salts in chloroform range from <50 to 106 M . Host molecules with built-in counterions have been prepared that selectively complex and lipophilize metal and alkylammonium cations. Locations of complementary binding sites and noncomplementary steric barriers provide for selective binding by host molecules of candidate guest molecules. Locations of appropriate chiral barriers and multiple complexing sites in guest compounds have led to the complete optical resolution of host compounds by optically active amino acids, and of amino acid esters by optically active host compounds. Ratios of association constants for diastereomeric complexes in excess of ten have been obtained. A molecular basis for designing an amino acid resolving machine has been developed.Central to nature's enzyme, transport and regulatory systems are highly structured molecular complexes. Large host molecules bind smaller guest molecules, and the chemical and physical properties of each are vastly altered. Nature's complexes are characterized by a high degree of structure, very high rates of formation and decomposition, and mutual structural recognition of host and guest. In enzymic catalysis, the rate-limiting transition state energies are lowered by complexation and orientation. In transport mechanisms, selection and lipophilization of polar entities are frequently accomplished by complexation. In regulatory systems, competitive complexation between inhibitor and substrate for sites of host molecules control *

Chiral separation of enantiomers via selector/selectand hydrogen bondings

“…46 Chiral recognition and separation of racemic ammonium-substituted guest-molecules by complexation with designed host-molecules is of particular interest. 47 The association constants in chloroform of tertbutylammonium thiocyanate and 6-crown-18, the mono-(dinaphthyl) and the bis(binaphthyl) described in Figure 10, are 750,000, 420, and <50, respectively. The decrease in the association factors expresses the reduced basicity of the oxygen atoms conjugated to the aromatic rings and the steric factors imposed by the bi-naphthyl moiety on the formation of the H-bonds.…”

Macrocyclic receptor molecules: aspects of chemical reactivity. Investigations into molecular catalysis and transport processes

“…Chiral derivatives (Ref. 5,6), especially those containing a binaphthyl group as chiral unit inserted into the macrocycles (Ref. x ~~ ·x…”

Enantiomeric Separation of trans‐2‐Aminocyclohexanol on a Crown Ether Stationary Phase Using Evaporative Light Scattering Detection

“…As a result, the chiral separation of trans-2-aminocyclohexanol is critical to the process. [12][13][14][15][16][17] It was discovered that bulky groups, such as binaphthyl groups grafted onto the crown ether, could provide steric barriers and induce enantioselective interactions with the guest molecule. 2,4-dinitrobenzoyl chloride) followed by separation on a chiral column.…”

“…Because TACH possesses no chromophore, the analysis of this compound usually involves derivatization with a UV absorption moiety (e.g. [12] The use of crown ethers for enantioseparations with liquid chromatography was introduced later by Cram and co-workers. The derivatization reaction incorporates a rigid phenyl moiety into the structure, thus, not only enhances the UV absorbance, but also facilitates the chiral recognition due to the steric hindrance of the phenyl group.…”