Review
Bis–Calix[4]pyrroles: Preparation, structure, complexation properties and beyond

https://doi.org/10.1016/j.ccr.2020.213528Get rights and content

Highlights

  • Summarizes the preparation and properties of bis–calix[4]pyrroles, specifically various linked dimers.

  • Details how bis–calix[4]pyrroles exhibit relatively enhanced binding affinities and selectivities.

  • Provides an overview of the ion recognition chemistry displayed by bis–calix[4]pyrroles.

Abstract

Calix[4]pyrrole and its derivatives are key members of the supramolecular Parthenon along with other well-recognized receptor systems, such as crown ethers, cyclodextrins (CDs), cucurbiturils, calixarenes and pillararenes. Calix[4]pyrroles are relatively easy–to–make and widely recognized for their ability to bind anions and ion pairs. Many review papers relating to aspects of calix[4]pyrrole chemistry have been published within the past decades. These reviews have focused primarily on monomeric calix[4]pyrroles. The emergent area of bis–calix[4]pyrroles, species wherein two calix[4]pyrrole subunits are linked by one or more “walls”, has not benefited from such treatment, even though the species in question often exhibit enhanced binding affinities and selectivities relative to their single calix[4[pyrrole congeners. This review is designed to summarize recent progress involving bis–calix[4]pyrroles. Advances in the design, synthesis, and coordination chemistry of bis–calix[4]pyrroles containing “one wall”, “two walls”, “three walls”, and “four walls”, as well as their possible application in ion recognition, sensing and logic gate construction, will be detailed. The hope is that this review will provide a guide for the design and preparation of new multi-component calix[4]pyrrole receptors possessing improved recognition properties, thereby advancing host–guest chemistry in new and useful directions.

Introduction

Molecular recognition processes that serve to bring together two or more molecules or ions through non–covalent bonding are ubiquitous in nature and underlie a range of biological processes [1]. They play vital roles in information processing and have allowed for the preparation of a number of supramolecular devices that exploit changes in the electrical, optical, magnetic properties, chemical properties, etc. [2]. Not surprisingly, molecular recognition (also referred to as supramolecular and host–guest chemistry) has attracted increasing attention across the scientific community in recent decades.

Macrocyclic chemistry is one of the central topics within the cadre of host–guest chemistry. With well–defined recognition pockets and enhanced preorganization and substrate complementarity, macrocycles such as crown ethers [3], [4], cyclodextrins (CDs) [5], [6], [7], cucurbiturils [8], calixarenes and pillararenes [9], [10], [11], [12], have enjoyed wide-spread use as receptors for guest species or as building blocks for supramolecular assembly. In addition, considerable effort continues to be devoted to the development of new functional macrocycles that can complement these well-studied receptor systems in terms of their substrate selectivities or inherent binding affinities.

Calix[4]pyrrole (1) represents an “old-but-new” receptor system. The parent form dates back to 1886 when it was first synthesized by Baeyer via the acid–catalyzed condensation of pyrrole with acetone (Fig. 1) [13]. However, the utility of calix[4]pyrroles as receptors for anions and ion pair recognition was only recognized in the mid-1990s due to the pioneering work of Sessler and collaborators [14], [15]. Calix[4]pyrrole is a conformationally flexible molecule and can exist in four main conformations, namely 1,3-alternate, cone, partial cone, and 1,2-alternate [16]. The first of these conformations generally dominates in the absence of a substrate, whereas near-complete conversion to the cone form is typically seen in the presence of a strongly bound anion (e.g., fluoride, chloride, dihydrogen phosphate, etc.). In addition to anions, it was appreciated early on that calix[4]pyrroles could form complexes with small polar neutral guests; in such instances the partial cone 1,2-alternate conformations could be stabilized [17].

These inherent recognition features, coupled with the fact that calix[4]pyrroles are both simple to prepare and easy to modify synthetically, has led to a blossoming of calix[4]pyrrole-related research over the last 20 years or so. Indeed, at present a large number of calix[4]pyrrole derivatives are known. Collectively, they have seen use in ion sensing, extraction, transportation, as well as building blocks for the construction of chemical switches and logic gates [18], [19], [20]. Much of this work has been covered in recent reviews [17], [18], [19], [21], [22], [23]. Largely excluded from these prior reviews are so-called bis–calix[4]pyrrole systems, constructs that contain two parent calix[4]pyrroles subunits linked through one or more bridging “walls”. The present review is designed to summarize the chemistry and potential applications of these latter bis–calix[4]pyrrole systems.

Section snippets

Mono–walled bis–calix[4]pyrroles

In the absence of a bound anion, the parent form calix[4]pyrrole 1 exists primarily in the so-called 1,3-alternate conformation. However, at room temperature equilibration between forms is rapid in most organic media making the four pyrrolic NHs identical, as well as the eight β–pyrrolic CHs and eight meso methyl groups. Anion binding, typically mediated via pyrrole NH–anion hydrogen bonding interactions, generally serves to lock the calix[4]pyrrole into the symmetric cone conformation.

Double–walled bis–calix[4]pyrroles

Double–walled bis–calix[4]pyrroles are linked through two tethers, which serve to restrict the relative degrees of freedom. That is to say, the preorganization of bis–calix[4]pyrrole derivatives is typically higher than ostensibly similar mono–walled calix[4]pyrroles. In principle, there exist several ways to link two calix[4]pyrrole subunits. However, so far only bis–calix[4]pyrroles with double walls and high symmetry have been explored, although both covalent linkers and noncovalent bridges

Triple– and quadruple–walled bis–calix[4]pyrroles

As the number of “walls” serving to bridge two calix[4]pyrrole units increases, the degree of preorganization is expected to increase in a commensurate manner. It thus might be expected that both the inherent anion selectivity and the thermodynamics of binding for appropriately sized anionic substrates would be enhanced. However, the preparation of these systems is expected to be rather challenging. Perhaps as the result of the latter perceived limitation, to date only few examples of triple–

Conclusions and perspectives

Bis–calix[4]pyrroles may be defined as being calix[4]pyrrole derivatives that contain two calix[4]pyrrole units linked through one or more bridging “walls”. By considering the numbers of linkers involved, these “walled” bis–calix[4]pyrroles are organized into four classes: mono–walled bis–calix[4]pyrroles; double–walled bis–calix[4]pyrroles; triple–walled bis–calix[4]pyrroles; and quadruple–walled bis–calix[4]pyrroles. As a general rule, synthetic access to the targets becomes increasingly

CRediT authorship contribution statement

Zhenzhen Lai: Methodology, Writing - original draft, Software, Validation. Tian Zhao: Writing - original draft. Jonathan L. Sessler: Supervision, Writing - review & editing. Qing He: Conceptualization, Writing - review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This research was supported by the National Natural Science Foundation of China (21901069 to Q.H.), the Special Funds for Hunan's Plan on Innovative Province Construction (2019RS1018 to Q.H.), and the Fundamental Research Funds for the Central Universities (Startup Funds to Q.H.). Further support for this work was provided by the U.S. Department of Energy, Office of Basic Energy Sciences under Award Number (DE–FG02–01ER15186 to J.L.S.) and the Robert A. Welch Foundation (F–0018 to J.L.S.).

References (134)

  • I. Saha et al.

    Eur. J. Org. Chem.

    (2015)
  • H. Miyaji et al.

    Tetrahedron Lett.

    (2000)
  • W. Sato et al.

    Tetrahedron Lett.

    (2000)
  • L. Shao et al.

    Polym. Chem.

    (2018)
  • K.G. Yager et al.

    J. Photochem. Photobiol. A Chem.

    (2006)
  • Q. He

    Chem

    (2017)
  • A. Caballero et al.

    Coord. Chem. Rev.

    (2013)
  • M.K. Chae et al.

    Tetrahedron Lett.

    (2010)
  • R. Molina-Muriel et al.

    J. Org. Chem.

    (2018)
  • M.C. Merckel et al.

    Structure

    (2001)
  • S.L. Xiong et al.

    Org. Lett.

    (2020)
  • P.D. Beer et al.

    Angew. Chem. Int. Ed.

    (2001)
  • J.-M. Lehn

    Supramolecular Chemistry: Concepts and Perspectives

    (1995)
  • S. Shinkai et al.

    J. Am. Chem. Soc.

    (1981)
  • M. Natali et al.

    Chem. Soc. Rev.

    (2012)
  • A. Ueno et al.

    J. Chem. Soc., Chem. Commun.

    (1980)
  • Y. Wang et al.

    Angew. Chem. Int. Ed.

    (2007)
  • Y. Liu et al.

    J. Org. Chem.

    (2008)
  • S.J. Barrow et al.

    Chem. Rev.

    (2015)
  • S. Wiktorowicz et al.

    Macromolecules

    (2013)
  • S. Wiktorowicz et al.

    Polym. Chem.

    (2013)
  • H.C. Zhang et al.

    Chem. Soc. Rev.

    (2018)
  • G.C. Yu et al.

    Chem. Rev.

    (2015)
  • A. Baeyer

    Berichte der deutschen chemischen Gesellschaft

    (1886)
  • P.A. Gale et al.

    J. Am. Chem. Soc.

    (1996)
  • R. Custelcean et al.

    Angew. Chem. Int. Ed.

    (2005)
  • J.R. Blas et al.

    J. Am. Chem. Soc.

    (2002)
  • P.A. Gale et al.

    Chem. Commun.

    (1998)
  • S.K. Kim et al.

    Acc. Chem. Res.

    (2014)
  • D.S. Kim et al.

    Chem. Soc. Rev.

    (2015)
  • J.L. Sessler et al.

    Angew. Chem. Int. Ed.

    (2003)
  • G.M. Mamardashvili et al.

    Russ. Chem. Rev.

    (2015)
  • S.S. Peng et al.

    Chem. Soc. Rev.

    (2020)
  • H. Miyaji et al.

    Angew. Chem. Int. Ed.

    (2000)
  • A. Loudet et al.

    Chem. Rev.

    (2007)
  • G. Ulrich et al.

    Angew. Chem. Int. Ed.

    (2008)
  • A. Treibs et al.

    Justus Liebigs Annalen der Chemie

    (1968)
  • K. Rurack et al.

    Angew. Chem. Int. Ed.

    (2001)
  • N. Boens et al.

    Chem. Soc. Rev.

    (2012)
  • Y. Lv et al.

    Chem. Pap.

    (2011)
  • R. Gotor et al.

    Eur. J. Org. Chem.

    (2013)
  • J.L. Sessler et al.

    Pure Appl. Chem.

    (1998)
  • J.L. Sessler et al.

    Ind. Eng. Chem. Res.

    (2000)
  • N. Saki et al.

    J. Incl. Phenom. Macrocycl. Chem.

    (2005)
  • S.L. Wiskur et al.

    Acc. Chem. Res.

    (2001)
  • L. Fabbrizzi et al.

    Angew. Chem. Int. Ed.

    (2002)
  • M. Wenzel et al.

    Chem. Soc. Rev.

    (2012)
  • Z.-M. Shi et al.

    Org. Biomol. Chem.

    (2011)
  • C.-H. Lee et al.

    J. Org. Chem.

    (2005)
  • G. Cafeo et al.

    Chem. Eur. J.

    (2014)
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