Enantioselective synthesis of chiral porphyrin macrocyclic hosts and kinetic enantiorecognition of viologen guests.

Pieter J Gilissen,Jiangkun Ouyang,Roeland J M Nolte,Johannes A A W Elemans,Annemiek D Slootbeek,Rob Bakker,Nicolas Vanthuyne

doi:10.1039/d0sc05233g

Pieter J Gilissen, Jiangkun Ouyang + Show 5 more

Open Access

https://doi.org/10.1039/d0sc05233g

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Abstract

The construction of macromolecular hosts that are able to thread chiral guests in a stereoselective fashion is a big challenge. We herein describe the asymmetric synthesis of two enantiomeric C2-symmetric porphyrin macrocyclic hosts that thread and bind different viologen guests. Time-resolved fluorescence studies show that these hosts display a factor 3 kinetic preference (ΔΔG‡on = 3 kJ mol−1) for threading onto the different enantiomers of a viologen guest appended with bulky chiral 1-phenylethoxy termini. A smaller kinetic selectivity (ΔΔG‡on = 1 kJ mol−1) is observed for viologens equipped with small chiral sec-butoxy termini. Kinetic selectivity is absent when the C2-symmetric hosts are threaded onto chiral viologens appended with chiral tails in which the chiral moieties are located in the centers of the chains, rather than at the chain termini. The reason is that the termini of the latter guests, which engage in the initial stages of the threading process (entron effect), cannot discriminate because they are achiral, in contrast to the chiral termini of the former guests. Finally, our experiments show that the threading and de-threading rates are balanced in such a way that the observed binding constants are highly similar for all the investigated host–guest complexes, i.e. there is no thermodynamic selectivity.

Highlights

Chiral recognition and selection of substrate molecules are well-established features of enzymes and natural receptors.[1,2] Inspired by these naturally occurring chiral hosts, chemists have developed a variety of synthetic chiral macromolecular architectures that function as receptors
In this paper we report an alternative approach to synthesize a chiral C2-symmetric porphyrin cage compound, i.e. a host in which the porphyrin macrocycle is linked to the glycoluril framework via chiral linkers (H23, Fig. 1)
We show that the enantiomers of H23 display a kinetic preference for the threading and binding of viologen guests equipped with a chiral head group

Summary

Introduction

Chiral recognition and selection of substrate (guest) molecules are well-established features of enzymes and natural receptors.[1,2] Inspired by these naturally occurring chiral hosts, chemists have developed a variety of synthetic chiral macromolecular architectures that function as receptors. Examples include macrocyclic arenes,[3,4,5,6,7,8] cyclodextrins,[9] and metal– organic cages.[10,11,12,13] Calixarenes have been reported that display enantiorecognition towards chiral carboxylates[3] and chiral amines.[4,5,6] Amino acid recognition has been achieved with calixarenes,[4] cyclodextrins,[9] and metal–organic cages.[10] Chiral metal–organic cages have been used for the enantioseparation of small alcohols and carboxylic acids,[11,12] and for the separation of atropisomeric compounds, such as 1,10-bi-2naphthol (BINOL) derivatives.[11] Triptycene-based hosts have been developed for the recognition of chiral trimethylammonium compounds.[14] The reported receptors showed different degrees of thermodynamic enantiorecognition (up to 12-fold difference in binding constant Kassoc for the binding of the two enantiomers). Studies on kinetic enantiorecognition, such as differences in threading rate constants (kon-values), have rarely been reported.[15]

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