The concept of preorganization in molecular assembly has been well established, and its impact on synthetic supramolecular chemistry is profound.1 Many natural systems thrive on the ability of inherently flexible molecules to self-organize. This process is promoted by a well-defined surrounding architecture and culminates in self-assembly.2 The ability of a protein to find its thermodynamically most stable tertiary structure from a linear sequence of amino acids is an example. Also related is the ability of two flexible, complementary polynucleotide strands to form a double helix. In this paper we demonstrate how flexible molecules can reversibly self-assemble to give a well-defined receptor caVity. The calix[4]arene skeleton3 was chosen as a vehicle for modeling such phenomena. The calixarene platform has recently been exploited for assembly by several laboratories.4,5 Research in our group has explored a unique dimeric binding mode for the calix[4]arene framework which provides for the encapsulation of small molecule guests.5,6 Specifically, urea functions placed on the upper rim of the calix[4]arene permit dimerization to occur through a head-to-tail hydrogen bonding pattern (Figure 1). It is well-known that the calix[4]arenes interconvert between four discrete conformations in solution.3,7 This conformational flexibility can be controlled by alkylation of the phenolic oxygens with substituents larger than ethyl, i.e. reaction of the parent phenol with n-PrBr to give the tetrapropoxy derivative allows the isolation of three stable conformations: the cone (42%), partial cone (55%), and 1,3-alternate (3%).7b We have recently explored derivative 1-1, which uses benzyl ether substituents for such control. In calixarene derivative 1-2 much smaller lower rim substituents are present. The tetramethoxy calix[4]arene has been wellstudied and is defined as a “flexible” system.7,8 It freely interconverts between all four conformations, but the partial cone is the thermodynamically most favorable one.8 Specifically, in the parent tert-butyl system the difference in energy between the partial cone/cone isomers is ∼1.5 kcal/mol, and the barrier to interconversion is on the order of 13 kcal.8c We have found that intermolecular hydrogen bonding through dimerization can be used to driVe the conformational equilibrium exclusiVely to the cone conformer. Since substitution on the upper rim of the calixarene is not known to substantially bias the conformational equilibria,3 the observed conformational selection (self-organization) can be attributed solely to hydrogen bonding effects.
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Oct 2, 2001
Kei Goto + 4
Open Access