Cucurbit[8]uril Controls the Folding of Cationic Diaryl Ureas in Water

Abstract

The ability of cucurbit [8]uril (CB[8]) to control the folding of diaryl ureas 1 and 2 in water was investigated. Compounds 1 and 2 contain two ureidyl C-N bonds which can each populate two conformational states resulting in a conformational ensemble comprising at least three states. We find that the presence of CB[8] results in the selective population of the (E,E)-2 conformer by the formation of CB[8]·(E,E)-2 complex at CB[8]:2 stoichiometries of 1: < 1; at higher stoichiometries, an unfolding process takes place during the formation of CB[8]·(Z,Z)-2 2 . In contrast, compound 1 forms the 2:2 complex CB[8] 2 ·(Z,Z)-1 2 over a broad range of CB[8]:2 stoichiometries. The absolute stoichiometries of these complexes were established by diffusion ordered spectroscopic methods (DOSY). The folding of 2 into the (E,E)-2 conformer under the formation of CB[8]·(E,E)-2 is responsive to the presence of guests in its environment. For example, the addition of 8 results in the expulsion of (E,E)-2 from the cavity of CB[8] followed by its unfolding to the thermally preferred mixture of (Z,Z)-and (Z,E)-2 conformers. These results suggest that complexation within synthetic molecular containers-just like their natural counterparts the chaperones-may be an efficient route to control the folding behaviour of non-natural oligomers in aqueous solution.

2:2 Complexes from Diphenylpyridiniums and Cucurbit[8]uril: Encapsulation‐Promoted Dimerization of Electrostatically Repulsing Pyridiniums

“…Previous studies by Zhao and co-workers established that CB [8] encapsulatedt wo PhPy + units to form an antiparallel 1:2 complex. [3b] We, and others, have utilized this bindingm otif to generate an umber of two-and three-dimensional supramolecular organic frameworks.…”

“…The crystal structures of the complexes formed between compounds G3-G5 andC B [8] are provided in Figure 1. All three complexesd isplayed 2:1b inding stoichiometry,w ith the antiparallel dimer of the PhPy + unit of the guest encapsulated in the cavity of CB [8],a sr evealed previously by Zhao andc oworkers.…”

“…Cucurbit[n]urils (CB[n]) represent af amily of rigid macrocycles that can bind discrete aliphatic and/or aromatic molecules driven mainly by hydrophobicity in water. [1] Among others, CB [8] has been revealed to encapsulate homo-orheterodimers of aromaticu nits. [2,3] Currently,t his unique 1:2b inding motif has found wide applicationsi nt he construction of av ariety of supramolecular polymers, gels, and frameworks.…”

“…In this context, severale legant examples have been reported. [7][8][9] However,a ll complexes have been investigated only in solution,a nd X-ray crystal structures have never been available, although they are crucially important for providing direct evidencef or the binding stoichiometry and refined structuralp arameters in the solid state.…”

“…To gain an insight into this potentially useful higher degree of binding pattern and to expand the scope of the linear building blocks, we have prepared rigid compounds G1 and G2, which contained two 4-phenylpyridinium (PhPy + )u nits. X-ray crystal structures revealed that both compounds formed new quaternary 2:2c omplexes with CB [8] in the solid state. In particular,f or the first time, the crystal structure of the complex of G2 and CB [8] disclosed the parallel-stacked dimerizationo f two electrostatically repulsing pyridinium (Py + )u nits through the encapsulationo fC B [8].I sothermal titrationc alorimetry (ITC) experiments showed that both complexes possessed highly stable binding in water,w hereas 1 HNMR spectroscopy experiments indicated that parallel-stacked dimerization of Py + units of G2 could also occur in solution.…”