Stimuli-Responsive Molecular Duplexes Displaying Duplex-to-Duplex Switching.

Synthetic duplexes with high stabilities have promising potential for mimicking biomolecular functions and developing supramolecular smart materials. Herein, we describe the synthesis and stimuli-responsive properties of molecular duplexes derived from indolocarbazole-pyridine (I-P) oligomers. These duplexes adopt nonclassical helical structures, stabilized by I-P hydrogen-bonding pairs in anhydrous chlorinated solvents. Notably, the longest duplex 62 (11-mer)2 displays remarkable stability, forming twenty hydrogen bonds; its exchange energy barrier was determined to be ΔG≠=22.0 kcal ⋅ mol-1 at 75 °C in anhydrous (CDCl2)2. Upon the addition of water, a hydrated duplex 62 (11-mer)2⊃10H2O was formed, with one water molecule inserted between each I-P hydrogen-bonding pair. The Hill coefficient (n) for this process is 6.1, demonstrating extremely positive cooperativity. Conversely, the hydrated duplex 62 (11-mer)2⊃10H2O was completely converted into the original anhydrous duplex 62 (11-mer)2 when the temperature was increased. Interconversion between these two distinct duplexes can be repeatedly carried out by varying the temperature. Furthermore, reversible switching between hetero-duplexes and homo-duplexes was also demonstrated by controlling the temperature, with concomitant changes in the characteristic emission signals.

Template-Directed Quantitative One-Pot Synthesis of Homochiral Helical Receptors Enabling Enantioselective Binding.

Template-directed synthesis and dynamic covalent chemistry were implemented to achieve quantitative one-pot syntheses of homochiral helical cavities inside aromatic foldamers. One-handed helical receptors P-1, M-1, P-2 and M-2 were assembled from their precursors in the presence of appropriate templates (d- and l-tartaric acid, and d- and l-sorbitol, respectively) via three sequential steps in one pot: imine-linked chain elongation, template-induced folding and [4+2] cycloaddition between helical turns. These helical receptors were proven to enantioselectively bind chiral guests used as the templates, and the differences between the association constants of enantiomeric guests were up to more than two orders of magnitude. The structures and binding modes of the receptors were fully characterized by single-crystal X-ray crystallography and 1 H NMR spectroscopy.

Complexation-driven assembly of imine-linked helical receptors showing adaptive folding and temperature-dependent guest selection.

The development of synthetic receptors capable of selectively binding guests with diverse structures and multiple functional groups poses a significant challenge. Here, we present the efficient assembly of foldamer-based receptors for monosaccharides, utilising the principles of complexation-induced equilibrium shifting and adaptive folding. Diimine 4 can be quantitatively assembled from smaller components when D-galactose is added as a guest among monosaccharides we examined. During this assembly, dual complexation-induced equilibrium shifts toward both the formation of diimine 4 and the conversion of D-galactose into α-D-galactofuranose are observed. Diimine 6 is quantitatively assembled in the presence of two different guests, methyl ß-D-glucopyranoside and methyl ß-D-galactopyranoside, resulting in the formation of two dimeric complexes: (6-MP)2⊃(methyl ß-D-glucopyranoside)2 and (6-MM)2⊃(methyl ß-D-galactopyranoside∙2H2O)2, respectively. These two complexes exhibit distinct folding structures with domain-swapping cavities depending on the bound guest and temperature. Interestingly, (6-MM)2⊃(methyl ß-D-galactopyranoside∙2H2O)2 is exclusively formed at lower temperatures, while (6-MP)2⊃(methyl ß-D-glucopyranoside)2 is only formed at higher temperatures.

Tweezer-type binding cavity formed by the helical folding of a carbazole-pyridine oligomer.

We have synthesised a new aromatic foldamer based on the carbazole-pyridine oligomers that adopt helical conformations via dipole-dipole interactions and π-stacking between two ethynyl bond-linked monomers. This foldamer scaffold has been further modified into a synthetic receptor with a tweezer-type binding cavity outside the helical backbone upon folding, in contrast to most aromatic foldamers with internal binding cavities. The tweezer-type cavity is composed of two parallel pyrenyl planes, allowing for the intercalation of a naphthalenediimide guest via π-stacking and CH⋯O interactions, as demonstrated using its 1H NMR spectra and X-ray crystal structure.

Subtle Modification of Imine-linked Helical Receptors to Significantly Alter their Binding Affinities and Selectivities for Chiral Guests.

Aromatic helical receptors P-1 and P-2 were slightly modified by aerobic oxidation to afford new receptors P-7 and P-8 with right-handed helical cavities. This subtle modification induced significant changes in the binding properties for chiral guests. Specifically, P-1 was reported to bind d-tartaric acid (Ka =35500 M-1 ), used as a template, much strongly than l-tartaric acid (326 M-1 ). In contrast, its modified receptor P-7 exhibited significantly reduced affinities for d-tartaric acid (3600 M-1 ) and l-tartaric acid (125 M-1 ). More dramatic changes in the affinities and selectivities were observed for P-2 and P-8 upon binding of polyol guests. P-2 was determined to selectively bind d-sorbitol (52000 M-1 ) over analogous guests, but P-8 showed no binding selectivity: d-sorbitol (1890 M-1 ), l-sorbitol (3330 M-1 ), d-arabitol (959 M-1 ), l-arabitol (4970 M-1 ) and xylitol (4960 M-1 ) in 5% (v/v) DMSO/CH2 Cl2 at 25±1 °C. These results clearly demonstrate that even subtle post-modifications of synthetic receptors may significantly alter their binding affinities and selectivities, in particular for guests of long and flexible chains.

Aromatic Helical Foldamers as Nucleophilic Catalysts for the Regioselective Acetylation of Octyl ß-d-Glucopyranoside.

Two indolocarbazole-naphthyridine foldamers 2 and 3 that fold into helical conformations were prepared. The 4-(N,N-dimethylamino)pyridine (DMAP) moiety was introduced at one end of the foldamer strands to develop foldamer-based catalysts for the site-selective acylation of polyols. These foldamers adopt helical conformations containing internal cavities capable of binding octyl ß-d-glucopyranoside. The association constants were determined to be 1.9 (±0.1)×105  M-1 for 2 and 2.1 (±0.1)×105  M-1 for 3 in CH2 Cl2 at 25 °C. In the presence of DMAP, 2 or 3 as the catalysts, octyl ß-d-glucopyranoside was subjected to acetylation under identical reaction conditions. The DMAP-catalysed reaction afforded the random distribution of the monoacetylates (6-OAc : 4-OAc : 3-OAc : 2-OAc=33 : 24 : 41 : 2). In contrast, foldamers 2 and 3 led to the predominant formation of 6-OAc. The relative distributions were estimated to be 6-OAc : 4-OAc : 3-OAc=88 : 4 : 6 : ∼0 with 2 and 6-OAc : 4-OAc : 3-OAc : 2-OAc=90 : 3 : 6 : 1 with 3.