pH-Controlled selection between one of three guests from a mixture using a coordination cage host

Cullen, William; Thomas, Katie A.; Hunter, Christopher A.; Ward, Michael D.

doi:10.1039/c5sc01475a

Cited by 33 publications

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“…An important point is that at the pD of the reaction, the product 2-cyanophenolate (pKa = 6.9) is deprotonated and therefore hydrophilic and shows no sign of binding to the cage by NMR spectroscopy. 27,28 Thus, the anionic product of the reaction is expelled from the cavity, facilitating catalytic turnover and we did not observe the reaction rate decreasing with time: the reaction was not being inhibited by accumulation of product.To confirm that the reaction is indeed associated with the benzisoxazole being bound in the cage cavity, we added an excess of a strongly-binding competing guest (20 mM cycloundecanone, K = 1.2 ! 10 6 M -1 ).…”

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“…Importantly, only neutral guests bind strongly: cationic (protonated amines) or anionic (carboxylate) guests bind much more weakly as they are hydrophilic and preferentially solvated by bulk water, which means that pH can be used to control uptake and release of ionisable guests. 27,28 In the catalytic system we report here, conversion of a neutral starting material to an anionic product is the basis of product release and catalytic turnover.The reaction that is catalysed is the Kemp elimination (Fig. 2) in which benzisoxazole undergoes a ring-opening reaction with hydroxide to afford 2-cyanophenolate.…”

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confidence: 99%

“…The interior of the cage therefore provides a poorer medium than water for the reaction because of preferential solvation of the developing negative charge by water, and the weak binding of the product anion underlines this. 27,28 In these terms, binding the substrate is anti-catalytic.Secondly, what is the reason for the pD-independence of kcat? As there are no basic sites associated with the cage, the rate invariance in the pD 8.5 -11.4 range could be explained by the use of water as the base for the reaction rather than hydroxide.…”

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Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage

et al. 2016

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The hollow cavities of coordination cages can provide an environment for enzyme-like catalytic reactions of small-molecule guests . We report here a new example (catalysis of the Kemp elimination -reaction of benzisoxazole with hydroxide to form 2-cyanophenolate) in the cavity of a water-soluble M8L12 coordination cage, with two features of particular interest. Firstly, the rate enhancement is amongst the largest so far observed: at pD 8.3, kcat/kuncat is 2 x 10 5 , due to the accumulation of a high concentration of partially desolvated hydroxide ions around the bound guest arising from ion-pairing with the 16+ cage. Secondly, the catalysis is based on two orthogonal interactions: (i) hydrophobic binding of benzisoxazole in the cavity, and (ii) polar binding of hydroxide ions to sites on the cage surface, both of which were established by competition experiments. Hundreds of turnovers occur with no loss of activity due to expulsion of the hydrophilic, anionic product. 2Since the realisation that hollow molecular container molecules can accommodate guest molecules in their central cavities, 1-3 their ability to modify the reactivity of their bound guests has been of great interest. [4][5][6][7][8] Well known examples include Cram's stabilisation of highly-reactive cyclobutadiene; 4 Fujita's 'ship-in-a-bottle' synthesis of cyclic silanol oligomers; 5 Nitschke's stabilisation of P4 in a tetrahedral cage; 6 and the demonstration of unusual regioselectivity in a Diels-Alder reaction when the two reacting molecules are co-confined in a host cavity. 7 The ultimate expression of this behaviour is efficient catalysis of a reaction occurring in the cavity of a container molecule. 8 These synthetic systems have the potential to achieve the selectivity and catalytic rate enhancements displayed by biological systems. For example, artificial container molecules provide relatively rigid and hydrophobic central cavities that may mimic binding pockets in enzymes. These containers may be purely organic hydrogen-bonded assemblies (such as Rebek's 'softball' dimer) 9 or may be metal-ligand polyhedral coordination cages [such as Fujita's Pd6/tris(pyridyl)triazine cage]. 10 Coordination cages offer particular promise in this field because of the ease with which they can be formed by a self-assembly process from very simple component parts, using the predictable coordination geometries of metal ions to provide the three-dimensional ordering of the components which generates the necessary cavity. [1][2][3]8,11,12 In order for a container molecule to act as an efficient catalyst it needs to (i) recognise and bind the guest(s); (ii) accelerate the reaction by increasing the local concentration of reactants and/or stabilising the transition state; and (iii) expel the product to allow catalytic turnover. 8 Guest binding in cage cavities has been very well studied and is becoming a mature field, 1 to the extent that a modeling tool for quantitative prediction of guest binding has recently been reported by us. 13 For a reaction of t...

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Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage

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“…The paramagnetism of the cage complexes greatly facilitates this by dispersing the individual 1 H resonances over a range of nearly 200 ppm, with the Co II ions acting as excellent shift agents 10, 11, 13, 22. This allows similar but slightly different signals for a particular 1 H environment associated with empty and guest‐containing cages to be distinguished and integrated separately (Figure 4 a).…”

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Binding of Hydrophobic Guests in a Coordination Cage Cavity is Driven by Liberation of “High‐Energy” Water

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Williams

et al. 2017

Chemistry A European J

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The cavity of an M8L12 cubic coordination cage can accommodate a cluster of ten water molecules in which the average number of hydrogen bonds per water molecule is 0.5 H‐bonds less than it would be in the bulk solution. The presence of these “hydrogen‐bond frustrated” or “high‐energy” water molecules in the cavity results in the hydrophobic effect associated with guest binding being predominantly enthalpy‐based, as these water molecules can improve their hydrogen‐bonding environment on release. This contrasts with the classical form of the hydrophobic effect in which the favourable entropy change associated with release of ordered molecules from hydrophobic surfaces dominates. For several guests Van't Hoff plots showed that the free energy of binding in water is primarily enthalpy driven. For five homologous pairs of guests related by the presence or absence of a CH2 group, the incremental changes to ΔH and TΔS for guest binding—that is, ΔΔH and TΔΔS, the difference in contributions arising from the CH2 group—are consistently 5(±1) kJ mol−1 for ΔΔH and 0(±1) kJ mol−1 for TΔΔS. This systematic dominance of ΔH in the binding of hydrophobic guests is consistent with the view that guest binding is dominated by release of “high energy” water molecules into a more favourable solvation environment, as has been demonstrated recently for some members of the cucurbituril family.

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“…510 In addition, binding of a guest in the cavity results in the 1 H NMR signals from the guest being shifted to the region ¹5 to ¹10 ppm, again making analysis of the guest binding simple. 6,9,10 However, individual analyses like this are time-consuming and inefficient.…”

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Guest Binding and Catalysis in the Cavity of a Cubic Coordination Cage

2017

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Mike Ward studied in Cambridge for his BA and Ph.D. before a post-doc position in Strasbourg with Jean-Pierre Sauvage. His independent academic career started with a lectureship in Bristol from 1990, and he remained there for 13 years before moving to Sheffield as a Professor of Inorganic Chemistry in 2003. His research interests cover many aspects of transition-metal and lanthanide ion coordination and supramolecular chemistry.Chris Hunter is the Herchel Smith Professor of Organic Chemistry at the University of Cambridge. After a BA and then Ph.D. in Cambridge, he started his academic career as a lecturer at the University of Otago in New Zealand and then worked at the University of Sheffield for 23 years before taking up his current post in 2014. He has research interests in various aspects of supramolecular and physical organic chemistry.Nick Williams did his BA, Ph.D., and early post-doctoral work in Cambridge. In 1994 he went to McGill University in Montréal as a RS/NSERC Research Fellow, working with Prof. J. Chin. In 1996 he was appointed to a lectureship at the University of Sheffield, where he has remained. His interests are in physical organic chemistry, working on understanding reactivity, mechanism, and catalysis in a range of contexts from organic surfaces to biological catalysis. These insights have underpinned the creation and understanding of a variety of biomimetic and supramolecular systems. AbstractAn M 8 L 12 coordination cage, which is water-soluble but has a hydrophobic interior cavity, is an effective host for a wide range of small organic guests; the factors responsible for guest binding have been investigated in detail. Benzisoxazole is a competent guest and, when bound, undergoes the Kemp elimination reaction with a rate acceleration of up to 2 © 10 5 times compared to the reaction of unbound benzisoxazole; the reasons for this have been analyzed.

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pH-Controlled selection between one of three guests from a mixture using a coordination cage host

Abstract: We demonstrate the use of a simple pH swing to control the selection of one of three different guests from aqueous solution by a coordination cage host.

Cited by 33 publications

References 32 publications

Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage

Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage

Binding of Hydrophobic Guests in a Coordination Cage Cavity is Driven by Liberation of “High‐Energy” Water

Guest Binding and Catalysis in the Cavity of a Cubic Coordination Cage

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