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Review
. 2019 Dec 5;11(2):324-332.
doi: 10.1039/c9sc05482k. eCollection 2020 Jan 14.

Shapeshifting molecules: the story so far and the shape of things to come

Aisha N Bismillah  1 , Brette M Chapin  1 , Burhan A Hussein  1 , Paul R McGonigal  1
Affiliations
Review

Shapeshifting molecules: the story so far and the shape of things to come

Aisha N Bismillah et al. Chem Sci. .

Abstract

Shapeshifting molecules exhibit rapid constitutional dynamics while remaining stable, isolable molecules, making them promising artificial scaffolds from which to explore complex biological systems and create new functional materials. However, their structural complexity presents challenges for designing their syntheses and understanding their equilibria. This minireview showcases (1) recent applications of highly dynamic shapeshifting molecules in sensing and distinguishing complex small molecules and (2) detailed insights into the adaptation of tractable bistable systems to changes in their local environment. The current status of this field is summarised and its future prospects are discussed.

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Figures

Fig. 1
Fig. 1. Structural formulas of fluxional carbon cages BV, BB+, BB˙, BB, BVO, BBO, and SBV. The number of degenerate isomers they each access is given below the structures.
Scheme 1
Scheme 1. (a) BV and five of its valence isomers accessed through Cope rearrangements, where coloured squares and numbers show the movement of the cyclopropane carbon atoms from the initial structure. (b) Comparison of BV and a functionalised derivative, which can isomerise between nondegenerate regioisomers. A schematic representation illustrates changes in the degeneracy of the potential energy surfaces. (c) A substituted barbaralane and its Cope rearrangement demonstrating dynamic constitutional isomerism, where coloured squares illustrate carbon atoms remaining in the same sequence in space. Blue and orange circles represent different functional groups.
Scheme 2
Scheme 2. Serratosa's stepwise BV synthesis. Reagents and conditions: (i) CuSO4, PhSMe, xylene, 140 °C, ∼2%; (ii) (1) TsNHNH2, (2) MeLi, 20%.
Scheme 3
Scheme 3. Fallon's concise synthesis of BV (R1 = R2 = H) and a variety of mono- and disubstituted analogues 2. Reagents and conditions: (i) CoBr2(dppe) (10 mol%), ZnI2 (20 mol%), Zn dust (30 mol%), 1,2-dichloroethane, 25 °C or 55 °C, 16–24 h, 63–100%; (ii) hν, Me2CO, 25 °C, 16–24 h, 35–81%.
Fig. 2
Fig. 2. An isomer coding system for network analysis and the computationally predicted isomeric ratios for three monosubstituted BV derivatives.
Fig. 3
Fig. 3. The equilibrium distribution of isomers of shapeshifting molecules 3 are perturbed upon addition of a guest (illustrated with C60), favouring structures that form the most stable supramolecular complexes. Coloured dots represent pendant groups connected to the BV cores.
Fig. 4
Fig. 4. (a) Bode's bisporphyrin-bullvalene 4, which was prepared with natural isotopic abundance (4a), enriched in 13C at one position (4b) of the dynamic C10 core, and functionalised with a photocleavable group (4c). (b) The complex 13C NMR spectra of the dynamic mixtures are converted to simplified representations, showing that the 13C NMR spectrum of a 4b mixture at equilibrium changes in the presence of fullerene guests. NMR data (150 MHz, solutions in CS2 with 3% CD2Cl2) shown for samples of: (4b) 2.8 mM 4b; (4b + C60) 2.8 mM 4b with 2 equiv. C60; (4b + derC60) 2.8 mM 4b with 4 equiv. derC60. The representations of NMR spectra correspond to two trials overlaid. NV = o-nitroveratryl. Adapted from ref. 7e with permission from The Royal Society of Chemistry.
Fig. 5
Fig. 5. The equilibrium distribution of 13C-labelled bisboronic acid 5, which can be monitored by its NMR ‘barcode’, which changes in a characteristic manner upon interaction with polyols. Even structurally similar polyols 6 and 7 cause distinctive changes in the barcode. The 13C NMR resonance of 6 at 129.1 ppm and of 7 at 129.8 ppm are omitted from the respective barcodes. Conditions: 2.5 μmol 5 and 5.0 μmol of the corresponding analyte were dissolved in 0.6 mL of a 9 : 1 mixture of (CD3)2SO/phosphate buffer (0.05 M, pH = 7.2), followed by equilibration for 1 h at rt and analysis by 13C NMR (typically 14 500 scans). Adapted with permission from J. F. Teichert, D. Mazunin and J. W. Bode, J. Am. Chem. Soc., 2013, 135, 11314. Copyright 2013 American Chemical Society.
Scheme 4
Scheme 4. Dihalogenated BB synthesis from norbornadiene. Reagents and conditions: (i) CHCl3, Cetrimide®, NaOH, H2O, 30 °C, 2 h, 18%; (ii) Zn, Me2CO, 56 °C, 6.5 h, 90%.
Scheme 5
Scheme 5. Gold-catalysed transformation of alkynyl cycloheptatrienes 8 into a barbaralyl methyl ether 10 or barbaralones 11. X-ray crystal structures of each product are shown. Reagents and conditions: (i) 8, R = 2-naphthyl, [JohnPhosAu(MeCN)][SbF6] (5 mol%), CH2Cl2–MeOH (1 : 1), rt, 2 h, 40%; (ii) 8, [IPrAu(MeCN)][SbF6] (5 mol%), Ph2SO, CH2Cl2, 1.5–12 h, rt, 35–97%. L = ancillary ligand, JohnPhos = (2-biphenyl)di-tert-butylphosphine, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene.
Fig. 6
Fig. 6. McGonigal reported a series of disubstituted BB derivatives, 12/12′, that crystallise in a manner controlled by their shapes, preferring valence isomers that pack effectively in a crystal lattice. In each case, the same isomer 12 is present as the major species in solution, but small changes in the aromatic substituent, R, favour different solid-state structures. In some cases, the minor solution-state valence isomer is the one observed in the solid state.
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Aisha N. Bismillah
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Brette M. Chapin
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Burhan A. Hussein
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Paul R. McGonigal
See this image and copyright information in PMC

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