Macrocyclic host structures

The process of combining cyanine and squaraine dyes by encapsulation, or covalent or noncovalent attachment with macrocyclic hosts, macromolecules, and micro- or nano-particles is a promising way to design novel probes and labels with substantially improved properties and for the development of advanced fluorescence-based assays. Nevertheless, the physicochemical properties of these dye-compositions are strongly dependent on the dye structure as well as the nature of the host macrocycle, macromolecule, or particle. Finally, development of new methods to synthesize these tracers can also be considered a challenging task. 

A biomembrane is an excellent example of supramolecular assemblies, in which various functional molecules are structurally organized for molecular recognition. In order to develop artificial supramolecular systems capable of mimicking biomembrane functions, it seems important to investigate molecular recognition by macrocyclic hosts embedded in synthetic bilayer membranes. 

Very recently, nice recognition of free and AT-acetylated amino acids (Gly, Ala, Phe) and some structurally related guests by a dicationic cyclophane-type A/,Ar -dibenzylated chiral derivative (4) of a bisisoquinoline alkaloid S,S-(+)-tetrandine (3 DBT) has been studied by NMR titration in water [31]. In contrast to other macrocyclic hosts, DBT shows high affinity and large enan-tioselectivity (K(S)/K(R)> 10) toward the smaller N-acetylalanine and binds the larger phenylalanine more weakly and nonselectively. The binding specificity of DBT was rationalized on the basis of molecular mechanics calculations. 

Calixarenes provided the main inspiration for the artifidal receptors studied in my group. We wanted to develop a new class of macrocyclic host with binding properties and structural variability similar to calixarenes but a closer relationship to natural systems. The obvious choice was, of course, to base such receptors on cyclopeptides, macrocydic compounds that are composed of the same subunits as the natural systems. 

Cram, D. Trueblood, K. In Host Guest Complex Chemistry Macrocycles Synthesis, Structures, Application Vogtle, F. Webber E., Ed. Springer-Verley Berlin Heiddberg New York Tokyo, 1985. 

Calixarene-A Versatile Host Calixarenes are macrocyclic host molecules made from phenol units finked through methylene bridges. The great freedom to structurally modify calixarenes allows us to create various types of host structures. 

F, Fogtle and E. Weber, eds., Host Guest Complex Chemistry. Macrocycles Synthesis, Structures, Applications. Springer-Verlag, Berlin, 1985. 

Newcomb s group has developed MM2 parameters for organotin compounds. The parameters were based on IR, ab initio, and crystal structure data. They developed these parameters so that they could treat the following Lewis acidic macrocyclic hosts.It was found that the experimental structures were well reproduced. The major deviations from the crystal structure came from regions with a high disorder. 

A particularly interesting family of host-guest systems [1] is that in which a linear guest is threaded through the cavity of a macrocyclic host (Figure 1). A compound which exhibits such a supramolecular structure is usually called pseudorotaxane [2], with reference to the name rotaxane (see Volume III, Part 2, Chapter 7) used to indicate the species in which the ring is prevented to dethread by the presence of bulky stoppers at the ends of the linear guest. 

Figure 1. Schematic representation of a pseudorotaxane structure formed from a macrocyclic host and a linear guest.

Host-Guest Complex Chemistry Macrocycles. Synthesis, Structures, Apphcation / Ed. by F.Vogtle and E. Weber, Springer Verlag, Heidelberg, 1985. 

H.J. Choi and M.P. Suh, Self-assemhly of Molecular Brick wall and Molecular Honeycomb from Nickel(II) Macrocycle and 1,3,5-Benzenetricarboxylate Guest-dependent Host Structures. J. Am. Chem. Soc., 1998, 120, 10622-10628. 

These results are so far comparable to those of Schmidtchen (25), who also observed strong anion binding preferentially with the smaller host I. In contrast to the small kinetic effect reported for I, however, we find a large rate decrease in the reaction of VI with nitrite after adding the host IX (Figure 4), which levels off after the macrocycle has taken up to two molecules of anion. Preliminary NMR titrations support the view that the complex contains more than one anion. The use of smaller charged host structures thus opens up the possibility for a selective inhibition of nucleophilic substitution. 

The basic study of intermolecular interactions is facilitated by one-bead-one-structure libraries which can be powerfnl tools for the discovery of ligands to synthetic receptors and vice versa. Encoded combinatorial libraries have been useful for disclosing ligands for well-designed macrocyclic host molecnles and to elucidate their specificities for peptide sequences. These stndies led via receptors with more flexibility to simple host molecules without elaborate design that are accessible to combinatorial synthesis. One application is the development of chemical sensors for analytes that are otherwise difficult to detect or only non-specifically detected. Snch hbraries have been nsed to find new catalysts and enzyme mimics. 

The free macrocyclic host 10 was prepared by the reaction of its diiodide 13 with silver acetate.In a similar fashion, a series of substituted derivatives of 10 was obtained from the corresponding dihalide complexes and silver acetate. The structure o/10 in a form of the 10-(THF)4-(H20)2 adduct was established by an x-ray diffraction study. A treatment o/lO with 1 regenerates the initial 13. 

A structural modification of organocobalt-containing receptors was achieved by introduction of cyclopentadienylcobalt moieties attached to dithiolene-crown ethers, 82 ]134. The electrochemical behavior of this new type of macrocyclic host has been investigated by cyclic voltammetry. 

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