Stabilization of Imines and Hemiaminals in Water by an Endo‐Functionalized Container Molecule

Abstract

Stabilizing water-sensitive reaction intermediates is challenging but desirable for guiding reactions to desired products in water. Herein, we report that labile imine and hemiaminal functional groups can be stabilized inside a synthetic container compound, a watersoluble naphthotube. The naphthotube features a primary amine group anchored in a cavity with both hydrogen bonding sites and hydrophobic surfaces. Aldehydes in bulk aqueous solution are trapped in the cavity by the amine to form hemiaminals stabilized through hydrogen bonding and hydrophobic effects. Dehydration of the hemiaminal to the imine is favored by the release of water from the hydrophobic microenvironment. Both the hemiaminals and imines can be detected at room temperature by NMR spectroscopy and mass spectrometry.

Enantioselective Recognition of Functional Organic Molecules in Water by Biomimetic Macrocyclic Hosts

“…According to our experience with chiral naphthotubes 1 , the five enantiomeric pairs of guests 4 – 8 (Figure a) should also be enantioselectively differentiated by chiral naphthotubes 3 . The association constants between all possible combinations of hosts and guests were determined by fluorescence titrations (Figures S21–S30) and are listed in Figure c.…”

“…In addition, the solvent isotope effect may also contribute more or less to the different enantioselectivities. 41 These numbers are comparable to or higher than those achieved by bioreceptors for chiral drug molecules, for example, the enantioselective recognition (S e = 16.3) of crizotinib by MTH1. 52 In particular, such a wide scope of guests with such high enantioselectivities has not been reported for both synthetic chiral hosts and bioreceptors in water before.…”

“…To be effective in water, noncovalent interactions should be located in a hydrophobic microenvironment such as the hydrophobic cavity of bioreceptors . Over the past years, we reported a series of water-soluble and achiral hosts with an endo -functionalized cavity, namely, naphthotubes. − These hosts are able to achieve the selective recognition of polar groups/molecules in water. They share cavity features similar to those of bioreceptors, except that they are not chiral.…”

Supramolecular multivalency effects enhance imine formation in aqueous medium allowing for dynamic modification of enzymatic activity

“…, micelles and molecular containers) led to remarkable results. 23–25 The synthesis of complex 3D-architectures has also been achieved by exploiting multivalency. 26–28 In these cases, the simultaneous cleavage of multiple dynamic covalent bonds – clearly more challenging than breaking a single bond – further decreases the tendency of imines to hydrolyze in aqueous medium (Fig.…”

“…[20][21][22] This approach has been further exploited by performing imine condensations in conned apolar arrangements, in which the hydrophobic environments generated within molecular microreactors (e.g., micelles and molecular containers) led to remarkable results. [23][24][25] The synthesis of complex 3Darchitectures has also been achieved by exploiting multivalency. [26][27][28] In these cases, the simultaneous cleavage of multiple dynamic covalent bondsclearly more challenging than breaking a single bondfurther decreases the tendency of imines to hydrolyze in aqueous medium (Fig.…”