Double rosettes

Vieekamp RH, van Duynhoven JPM, Hubert M, Verboom W, Reinhoudt DN. Molecular boxes based on calix[4]arene double rosettes. Angew Chem Int Ed Engl 1996 35 1215-1218. 

We wanted to explore the limits of the self-assembly approach for the synthesis of well-defined structures with nanoscale dimensions by further increasing the size of the assemblies. Our group has shown that calix[4]arenes diametrically substituted with two melamine units at the upper rim are very good platforms for the formation of double rosette assemblies. 

In the presence of two equivalents of 5,5-diethylbarbiturate (DEB) or isocyanuric acid derivatives (CYA), dimelamines la-d form stable double rosette assemblies la-d3 (DEB) 6 in apolar solvents such as chloroform, benzene or toluene even at 10 4 M concentration (Figure 4.2).9,10 They consist of 9 different components held together by 36 hydrogen bonds. X-ray diffraction studies of lb3 (DEB)6 showed that the two rosette layers are tightly stacked on top of each other with an interatomic separation of 3.5 A at the edges and... 

FIGURE 4.2. Formation of the double rosette assemblies l3 (DEB)6, from its building blocks calix[4]arene dimelamine 1 and DEB. 

These double rosettes can be easily extended to tetrarosettes by connecting two calix[4]arene dimelamines by a flexible linker unit X (Figure 4.3).11,12 A tetrarosette assembly consists of fifteen components, three tetramelamines 2 and twelve barbiturate/cyanurate derivatives held together by 72 hydrogen bonds and it has a size of 3.0 x 3.1 x 2.7 nm. The thermodynamic equilibrium for the assembly 23 (DEB)i2 is reached within seconds after mixing the two different components. Similarly, hexarosettes 33 (DEB)ig are prepared... 

FIGURE 4.5. Conformational isomers of the double rosette assembly. 

Furthermore, CD was used to assess the stability of assemblies having the same /Tm but with slightly different chemical structure. CD titrations with THF of chiral double rosette assemblies lc 3(l)EB)6 and 1c 3(BuCYA)6 in CHC13 showed values of xthf = 10% and xthf = 95%, respectively, as predicted taking in account the higher strength of the cyanurate H-bonds when compared with barbiturates. 

We have carried out the study of the adsorption on surfaces of finite double rosette l3 (DEB)6 assemblies and the polymeric nanostructures [ 13 631, (Figure 4.6)35 by means of atomic force microscopy.36-41... 

More detailed information about the characterization of double rosette assemblies can be found in D. N. Reinhoudt, P. Timmerman, F. Cardullo, and M. Crego-Calama, in Supramolecular Science Where it is and Where it is Going, edited by R. Ungaro and E. Dalcanale (Kluwer Academic Publishers, Dordrecht, 1999), pp. 181-195. 

Fig. 6 Schematic representation of double rosette assemblies with three constitutional isomers with different symmetry. The D3 symmetric assembly is chiral and exists as a racemic mixture...

Chiral calix[4]arene dimelamines are weakly CD active, while on the contrary chiral double rosettes show strong absorptions with Aemax ... 

Fig. 7 Schematic representation of highly diastereoselective non-covalent synthesis A (RJt) chiral dimelamine and achiral barbiturate components lead only to the (M) double rosettes with very high d.e. B Achiral hindered dimelamine and chiral barbiturate leads to highly solvent dependent asymmetric induction, while C achiral alkyl dimelamine and chiral barbiturate components lead instead to all the isomeric double rosettes with different symmetry...

Similar chiral supramolecular assemblies are also observed from achiral calix[4]arene dimelamine derivatives with chiral cyanurates thus leading to D3 symmetry species [21]. Analogously to chiral dimelamines, predominantly one of the two possible diastereomeric double-rosette assemblies was observed in most cases and it is noteworthy that the same (R) chiral moiety when mounted in the dimelamine is located on the left-hand side of the calix[4]arene and induces (M) chirality, while when implemented in the cya-nurate is placed on the right-hand side and therefore promotes P chirality (Fig. 8). 

Fig. 8 Schematic representation of highly diastereoselective non-covalent synthesis achiral dimelamine calix[4]arene with enantiopure chiral cyanurate components lead to chiral double rosettes with d.e. as high as 96% (R)-cyanurate induces complete (P) chirality, while (S) favors only (M) chirality...

Fig. 24 Enantioselective non covalent synthesis of double rosettes exploiting the chiral memory effect. Exchange of chiral barbiturate with the achiral cyanurate occurs faster then racemization by dissociation of the supramolecular structure and allows temporary preservation of the asymmetry instructed in the first diastereoselective step...

Exploiting the same concept, Reinhoudt and Shinkai were able to obtain another example of enantioenriched chiral double-rosette made of achiral components. In this case achiral calix[4]arene bearing dimelamine moieties with pyridine functionalities were assembled with achiral cyanurate leading to racemic chiral double rosettes. The latter are perfect counterparts for chiral D-dibenzoyl tartaric acid via two-point hydrogen-bonding interactions thus... 

The imbalance between the two diastereoisomers is prolonged when the chiral D-tartrate is removed by precipitation with ethylendiamine thus leading to an enantioenriched chiral double-rosette made of achiral components with 90% e.e. The memory effect in this case is even stronger then in the former example with activation energy towards racemization as high as 119 KJ/mol and a half-life time of one week at room temperature. 

Figure 3.4 Origin of chirality in Reinhoudt s double rosettes.

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