Dynamic multi-component covalent assembly for the reversible binding of secondary alcohols and chirality sensing

Abstract

Reversible covalent bonding is often employed for the creation of novel supramolecular structures, multi-component assemblies, and sensing ensembles. In spite of remarkable success of dynamic covalent systems, the reversible binding of a mono-alcohol with high strength is challenging. Here we show that a strategy of carbonyl activation and hemiaminal ether stabilization can be embodied in a four-component reversible assembly that creates a tetradentate ligand and incorporates secondary alcohols with exceptionally high affinity. Evidence is presented that the intermediate leading to binding and exchange of alcohols is an iminium ion. Further, to demonstrate the use of this assembly process we explored chirality sensing and enantiomeric excess determinations. An induced twist in the ligand by a chiral mono-ol results in large Cotton effects in the circular dichroism spectra indicative of the alcohol’s handedness. The strategy revealed in this study should prove broadly applicable for the incorporation of alcohols into supramolecular architecture construction.

Supramolecular Chirality in Self-Assembled Systems

“…This chiral sensor can be used for determination of the enantiomeric excess of mixed chiral alcohols with different ee values ( Figure 131B). 373 A chiral sensor with the ability to differentiate many different chiral molecules, such as amino acids, peptides, proteins, and even some aromatic drugs, has been developed by Biedermann and Nau. These systems are based on ternary complexes formed between the macrocyclic host cucurbit [8]uril, dicationic dyes, and chiral aromatic analytes ( Figure 132A).…”

Unassisted formation of hemiaminal ether from 4-aminopyridine and o-vanillin - experimental and theoretical study

“…However, quite unexpectedly, the reaction between 4AP and OV that has not been earlier reported in the literature led exclusively to hemiaminal ether or undefined polymeric products. In the last few years, direct formation of aminoethers was observed for the reactions of pyridyl aldehydes and/or pyridylamines, but these reactions were usually performed in the presence of metal cations and the products were isolated as metal complexes [26][27][28]. Formation of hemiaminal ethers was also observed in the presence of molecular sieves [29].…”

From substituent effects to applications: enhancing the optical response of a four-component assembly for reporting ee values

“…For example, various stereodynamic systems that utilize circular dichroism (CD) for ee determination have been published 12,13,17. Recently, our group developed a chiral alcohol sensor involving a multicomponent assembly that incorporates the alcohol into a hemiaminal ether ( 1 ) under equilibrium conditions13–15 (Fig. 1).…”

“…2, Y ) was expected to similarly alter the dr values due to different interactions with the axial metal ligand ( L ). Because we have previously found that larger dr values result in larger CD signals and lower errors in ee determination,13–15 the goal of our substitutent effect studies was to enhance the dr's.…”