Ultra-Tight Host-Guest Binding with Exceptionally Strong Positive Cooperativity.

Cooperativity plays a critical role in self-assembly and molecular recognition. A rigid aromatic oligoamide macrocycle with a cyclodirectional backbone binds with DABCO-based cationic guests in a 2 : 1 ratio in high affinities (Ktotal ≈1013  M-2 ) in the highly polar DMF. The host-guest binding also exhibits exceptionally strong positive cooperativity quantified by interaction factors α that are among the largest for synthetic host-guest systems. The unusually strong positive cooperativity, revealed by isothermal titration calorimetry (ITC) and fully corroborated by mass spectrometry, NMR and computational studies, is driven by guest-induced stacking of the macrocycles and stabilization from the alkyl end chains of the guests, interactions that appear upon binding the second macrocycle. With its tight binding driven by extraordinary positive cooperativity, this host-guest system provides a tunable platform for studying molecular interactions and for constructing stable supramolecular assemblies.

Stable pseudo[3]rotaxanes with strong positive binding cooperativity based on shape-persistent aromatic oligoamide macrocycles.

New aromatic oligoamide macrocycles with C3-symmetry bind a bipyridinium guest (G) to form compact pseudo[3]rotaxanes involving interesting enthalpic and entropic contributions. The observed high stabilities and strong positive binding cooperativity are found in few other host-guest systems.

Dipropinonates of Sugar Alcohols as Water-Soluble, Nontoxic CPAs for DMSO-Free Cell Cryopreservation.

Sorbitol, mannitol, xylitol, and erythritol, four readily available sugar alcohols with poor or no membrane permeability, are converted into their corresponding dipropionates by acylating their primary hydroxyl groups. With enhanced membrane permeability, these diesters are expected to permeate the cell membranes and, upon their hydrolysis, release the corresponding sugar alcohols inside the cells. NIH-3T3 cells incubated with these diesters before being frozen at -80 °C exhibited considerably higher total recovery over those incubated with the free sugar alcohols or media only. Among the four diesters, those of sorbitol, especially mannitol, showed cryoprotective effects comparable to that shown by 5% DMSO. This work has demonstrated the feasibility of converting readily available, naturally occurring compounds into membrane-permeable derivatives that serve as water-soluble, nontoxic alternatives to DMSO.