Complexation Properties of Preorganized Receptor Molecules for Large, Neutral Guests

Abstract

Receptor molecules with a preorganized cavity were synthesized by combining two resorcin [4]arene and one calix[4]-arene building block. Based on predictions from a computational study which matches hosts and guests, several steroids, sugar derivatives, and alkaloids were selected for complexation studies. Experimentally the complexation of such guests by these receptor molecules was proven by 'H-NMR spectroscopy (association constants of 1.0-6.0 X 10' M-' in CDC1,). One of these receptors with four hydroxyl groups forms a dimeric capsule (Kdlmer = 11 M -~ in CDC13). Evidence for this dimerization comes from 'H-NMR, FAB MS spectroscopy, and molecular mechanics and dynamics calculations.Nowadays a large variety of synthetic hosts for relatively small guest species e.g. cations, anions, and small neutral molecules are described in the literature. In most cases the general strategy focuses on the complementarity of functional groups in receptor and guest; this approach is always guest-directed and requires for each individual guest a new synthetic pathway. With increasing size and structural complexity of the guest species, this approach becomes increasingly demanding in terms of design and the number of steps in the synthesis of a complementary host (or receptor) molecule.An alternative approach to the synthesis of such receptor molecules is based on the proper combination of (different) molecular building blocks to which functional groups can be attached, giving rise to molecules with large well-defined cavities and hydrophobic surfaces. Most likely, the complexation of large guest molecules requires preorganized host molecules because otherwise the entropy might be too high to form an appropriate cavity. On the other hand, some flexibility gives the host molecules the possibility for structural adaption that might be necessary for complexation. Computational methods for matching the shape of host and guest are nowadays available ['].More or less planar building blocks that have recently been used in the design of receptor for the complexation of small neutral molecules and spherical anions are porphyrin~ [~] andIn our own work we use mainly non-planar building blocks that have a molecular cavity and a variety of functional groups e.g. calix [4] ["]. A systematic search for suitable guests using the computer simulation program DOCK['] revealed among others a good fit for different steroids, aromatic compounds, sugar derivatives, and fused ring systems. Unfortunately, in CDC13 solution complexation could not be detected probably because the cavity is too well solvated. Therefore, we have synthesized the more flexible combination of two upper rim 1,2-difunctionalized calix[4]arenes coupled to one resorcin[4]arene (1, 2, and 3, see Scheme 1). These compounds complex steroids (corticosteroids) in non-uqueous media with association constants of 0.9-9.5 X 102 M -~ in CDC13 ['21.In this paper we describe the synthesis of molecules 4 and 5 (see Scheme 2) that are constructed by the combination of two resorcin [4]

Molecular Recognition of Pyranosides by a Family of Trimeric, 1,1′-Binaphthalene-Derived Cyclophane Receptors

“…Both molecules, in particular the one which is not shown (molecule 2), exhibit severe disorder as a result of the flexible BnO and MOM residues. The torsion angle for rotation about the chirality axis, C(6)ÀC(1)ÀC(23)ÀC (24), in molecule 1 adopts a value of 878, whereas it is significantly narrowed to 658 in molecule 2, illustrating the well-known conformational flexibility of the 1,1'-binaphthalene moiety [60]. A satisfactory yield of ( S )-22 (up to 66%) was finally obtained by treatment of ( S )-21 with 5 equiv.…”

Resorcarenes: Hollow Building Blocks for the Host-Guest Chemistry

“…In the example 60 (Chart 30), four strong intramolecular hydrogen bonds between the linking acetamide and the oxygens of the acetal bridging were found to significantly rigidify the structure [112]. In the example 60 (Chart 30), four strong intramolecular hydrogen bonds between the linking acetamide and the oxygens of the acetal bridging were found to significantly rigidify the structure [112].…”

“…Studies in many different solvents and solvent mixtures revealed that carcerand formation is templated by the solvent and no empty carcerands are formed [112,114]. Studies in many different solvents and solvent mixtures revealed that carcerand formation is templated by the solvent and no empty carcerands are formed [112,114].…”

The Modular Approach in Supramolecular Chemistry

“…U-shaped receptor molecules 16 and 17, composed of either two calix [4]arenes and one resorcin [4]arene [43] or of one calix [4]arene and two resorcin [4]arenes [44] , have a cavity similar to that of holand 15, but are more flexible than holand 15. This allows them to accommodate the structural deformations probably necessary for complexation.…”

“…The stereochemistry of these 1:2-calix-resorcin [4]arenes is perhaps influenced by intramolecular interactions leading exclusively to endo-endo isomers. Receptor molecule 17 (R ϭ ϪH) is selective for acylated five-membered sugars and quinine deriva-According to 1 H-NMR spectroscopy, these 1:2-calix-resorcin [4]arene receptor molecules selectively complex cer-tives [44] . From a dilution experiment a dimerization constant of K dimer of 11 tain corticosteroids, sugar derivatives, and alkaloids with association constants of (1.0Ϫ6.0) ϫ 10 2  Ϫ1 in CDCl 3 .…”