Programmable Synthesis of Organic Cages with Reduced Symmetry

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 May 3

PMID 38699263

Authors

Keith G Andrews

Peter N Horton

Simon J Coles

Affiliations

Soon will be listed here.

Abstract

Integrating symmetry-reducing methods into self-assembly methodology is desirable to efficiently realise the full potential of molecular cages as hosts and catalysts. Although techniques have been explored for metal organic (coordination) cages, rational strategies to develop low symmetry organic cages remain limited. In this article, we describe rules to program the shape and symmetry of organic cage cavities by designing edge pieces that bias the orientation of the amide linkages. We apply the rules to synthesise cages with well-defined cavities, supported by evidence from crystallography, spectroscopy and modelling. Access to low-symmetry, self-assembled organic cages such as those presented, will widen the current bottleneck preventing study of organic enzyme mimics, and provide synthetic tools for novel functional material design.

Citing Articles

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References

Berardo E, Greenaway R, Turcani L, Alston B, Bennison M, Miklitz M . Computationally-inspired discovery of an unsymmetrical porous organic cage. Nanoscale. 2018; 10(47):22381-22388. DOI: 10.1039/c8nr06868b. View

Mastalerz M . Porous Shape-Persistent Organic Cage Compounds of Different Size, Geometry, and Function. Acc Chem Res. 2018; 51(10):2411-2422. DOI: 10.1021/acs.accounts.8b00298. View

Mitra T, Jelfs K, Schmidtmann M, Ahmed A, Chong S, Adams D . Molecular shape sorting using molecular organic cages. Nat Chem. 2013; 5(4):276-81. DOI: 10.1038/nchem.1550. View

Serrano-Molina D, Montoro-Garcia C, Mayoral M, de Juan A, Gonzalez-Rodriguez D . Self-Sorting Governed by Chelate Cooperativity. J Am Chem Soc. 2022; 144(12):5450-5460. PMC: 8972263. DOI: 10.1021/jacs.1c13295. View

Rebek Jr J . Molecular behavior in small spaces. Acc Chem Res. 2009; 42(10):1660-8. DOI: 10.1021/ar9001203. View

Saraogi I, Incarvito C, Hamilton A . Controlling curvature in a family of oligoamide alpha-helix mimetics. Angew Chem Int Ed Engl. 2008; 47(50):9691-4. DOI: 10.1002/anie.200803778. View

Berardo E, Turcani L, Miklitz M, Jelfs K . An evolutionary algorithm for the discovery of porous organic cages. Chem Sci. 2018; 9(45):8513-8527. PMC: 6251339. DOI: 10.1039/c8sc03560a. View

Lewis J, Crowley J . Metallo-Supramolecular Self-Assembly with Reduced-Symmetry Ligands. Chempluschem. 2020; 85(5):815-827. DOI: 10.1002/cplu.202000153. View

Manor Armon A, Bedi A, Borin V, Schapiro I, Gidron O . Bending versus Twisting Acenes - A Computational Study. European J Org Chem. 2021; 2021(39):5424-5429. PMC: 8597036. DOI: 10.1002/ejoc.202100865. View

10.

Lewis J . Pseudo-heterolepticity in Low-Symmetry Metal-Organic Cages. Angew Chem Int Ed Engl. 2022; 61(44):e202212392. PMC: 9828238. DOI: 10.1002/anie.202212392. View

11.

Zhang Q, Catti L, Tiefenbacher K . Catalysis inside the Hexameric Resorcinarene Capsule. Acc Chem Res. 2018; 51(9):2107-2114. DOI: 10.1021/acs.accounts.8b00320. View

12.

Hardy M, Lutzen A . Better Together: Functional Heterobimetallic Macrocyclic and Cage-like Assemblies. Chemistry. 2020; 26(59):13332-13346. PMC: 7693062. DOI: 10.1002/chem.202001602. View

13.

Ollerton K, Greenaway R, Slater A . Enabling Technology for Supramolecular Chemistry. Front Chem. 2021; 9:774987. PMC: 8634592. DOI: 10.3389/fchem.2021.774987. View

14.

Schneider M, Oppel I, Mastalerz M . Exo-functionalized shape-persistent [2+3] cage compounds: influence of molecular rigidity on formation and permanent porosity. Chemistry. 2012; 18(14):4156-60. DOI: 10.1002/chem.201200032. View

15.

Ahmad N, Younus H, Chughtai A, Verpoort F . Metal-organic molecular cages: applications of biochemical implications. Chem Soc Rev. 2014; 44(1):9-25. DOI: 10.1039/c4cs00222a. View

16.

Santolini V, Miklitz M, Berardo E, Jelfs K . Topological landscapes of porous organic cages. Nanoscale. 2017; 9(16):5280-5298. DOI: 10.1039/c7nr00703e. View

17.

Zhang L, Jin Y, Tao G, Gong Y, Hu Y, He L . Desymmetrized Vertex Design toward a Molecular Cage with Unusual Topology. Angew Chem Int Ed Engl. 2020; 59(47):20846-20851. DOI: 10.1002/anie.202007454. View

18.

Mishra S, Kompella S, Krishnaswamy S, Balasubramanian S, Chand D . Low-Symmetry Self-Assembled Coordination Complexes with Exclusive Diastereoselectivity: Experimental and Computational Studies. Inorg Chem. 2020; 59(17):12884-12894. DOI: 10.1021/acs.inorgchem.0c01964. View

19.

Dasary H, Jagan R, Chand D . Ligand Isomerism in Coordination Cages. Inorg Chem. 2018; 57(19):12222-12231. DOI: 10.1021/acs.inorgchem.8b01884. View

20.

Jin Y, Yu C, Denman R, Zhang W . Recent advances in dynamic covalent chemistry. Chem Soc Rev. 2013; 42(16):6634-54. DOI: 10.1039/c3cs60044k. View