Allosteric initiation and regulation of catalysis with a molecular knot

Marcos, Vanesa; Stephens, Alexander J.; Jaramillo‐García, Javier; Nussbaumer, Alina L.; Woltering, Steffen L.; Valero, Alberto; Lemonnier, Jean‐François; Vitórica-Yrezábal, Iñigo J.; Leigh, David A.

doi:10.1126/science.aaf3673

Cited by 228 publications

(177 citation statements)

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“…Accordingly, extrapolating knot properties between such disparate length scales, as with machine mechanisms,1 will not always be valid 2. Although a number of small‐molecule knots have been synthesized,3, 4 to date the knotting of a strand has only been exploited in functions that have no macroscopic counterpart (anion binding5a,5b and allosterically regulated5c and asymmetric5d catalysis) 1, 5, 6. In our everyday world, “stopper knots”7 are tied to prevent unreeving (that is, to prevent a strand from passing through a narrow aperture or slipping through another knot8).…”

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confidence: 99%

Securing a Supramolecular Architecture by Tying a Stopper Knot

et al. 2018

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We report on a rotaxane‐like architecture secured by the in situ tying of an overhand knot in the tris(2,6‐pyridyldicarboxamide) region of the axle through complexation with a lanthanide ion (Lu3+). The increase in steric bulk caused by the knotting locks a crown ether onto the thread. Removal of the lutetium ion unties the knot, and when the axle binding site for the ring is deactivated, the macrocycle spontaneously dethreads. When the binding interaction is switched on again, the crown ether rethreads over the 10 nm length of the untangled strand. The overhand knot can be retied, relocking the threaded structure, by once again adding lutetium ions.

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Securing a Supramolecular Architecture by Tying a Stopper Knot

et al. 2018

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“…For these reasons, MIMs can be regarded as appealing systems for investigating allosteric communication mechanisms and implementing them within synthetic species to achieve functions (11). Nevertheless, studies of allosteric effects in rotaxanes and catenanes are rare (12) and have been limited so far to a pioneering work by Sauvage and coworkers (13) and, more recently, to the realization of stimuli-responsive switches (14, 15) for controlling catalytic functions (16)(17)(18)(19)(20).In a recent investigation of a family of [2]rotaxanes (21) we showed quantitatively that the acidity of an ammonium ion on the axle is strongly depressed when it is surrounded by a crown ether ring, for which it is an efficient recognition motif (8). Such a phenomenon, that can be rationalized with both thermodynamic and kinetic arguments, is in line with earlier observations (22-26) that deprotonation of ammonium axles in crown etherbased rotaxanes is extremely difficult to achieve.…”

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Remote electrochemical modulation of pK _a in a rotaxane by co-conformational allostery

Ragazzon

Schäfer

Franchi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Allosteric control, one of Nature's most effective ways to regulate functions in biomolecular machinery, involves the transfer of information between distant sites. The mechanistic details of such a transfer are still an object of intensive investigation and debate, and the idea that intramolecular communication could be enabled by dynamic processes is gaining attention as a complement to traditional explanations. Mechanically interlocked molecules, owing to the particular kind of connection between their components and the resulting dynamic behavior, are attractive systems to investigate allosteric mechanisms and exploit them to develop functionalities with artificial species. We show that the pK a of an ammonium site located on the axle component of a [2]rotaxane can be reversibly modulated by changing the affinity of a remote recognition site for the interlocked crown ether ring through electrochemical stimulation. The use of a reversible ternary redox switch enables us to set the pK a to three different values, encompassing more than seven units. Our results demonstrate that in the axle the two sites do not communicate, and that in the rotaxane the transfer of information between them is made possible by the shuttling of the ring, that is, by a dynamic intramolecular process. The investigated coupling of electron-and proton-transfer reactions is reminiscent of the operation of the protein complex I of the respiratory chain.acid-base processes | electrochemistry | free energy change | molecular machine | molecular switch A llostery-the process by which a chemical transformation at one site causes a change at a distant site within the same molecule or molecular assembly-is a key phenomenon for the regulation of biological activity (1, 2). A most important example is the long-range coupling of redox-active and acid-basesensitive sites, a crucial element of electron transport chains, as exemplified by the respiratory complex I (3). Although allosteric effects are usually described in terms of conformational changes induced by binding at one site directly affecting the affinity of the other site (4), the idea that the transmission of information at the basis of allostery could take place through dynamic mechanisms is receiving increasing attention (5-7). Indeed, despite its importance for life, allosteric regulation remains an elusive biochemical phenomenon.Mechanically interlocked molecules (MIMs) (8) such as rotaxanes and catenanes, because of the lack of strong chemical bonds between their molecular parts, are characterized by a rich dynamic behavior that involves changes of the relative position of the components (co-conformation). Indeed, in appropriately designed MIMs co-conformational rearrangements can be precisely controlled by modulating the noncovalent intercomponent interactions through external stimulation (9, 10). For these reasons, MIMs can be regarded as appealing systems for investigating allosteric communication mechanisms and implementing them within synthetic species to achieve functions (11)....

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“…Moreover, anion templating with chloride and careful use of stereoelectronic effects, symmetry and linker length, were all needed in order to form this complicated structure. In very recent work, 10 More generally, once molecular knots have been created, they can then be derivatised, either to allow for the synthesis of higher assemblies of knots (see Section 2.2) or to alter or study the properties of the system itself. For example, an amide-based trefoil knot has been mono, di-and tri-dendronised to form molecules known as "dendroknots".…”

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Knot theory in modern chemistry

et al. 2016

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(2016) 'Knot theory in modern chemistry.', Chemical society reviews., 45 (23). pp. 6432-6448. Further information on publisher's website:https://doi.org/10.1039/C6CS00448BPublisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. Knot theory is a branch of pure mathematics, but it is increasingly being applied in a variety of sciences. Knots appear in chemistry, not only in synthetic molecular design, but also in an array of materials and media, including some not traditionally associated with knots. Mathematics and chemistry can now be used synergistically to identify, characterise and create knots, as well as to understand and predict their physical properties. This tutorial r eview provides a brief introduction to the mathematics of knots and related topological concepts in the context of the chemical sciences. We then survey the broad range of applications of the theory to contemporary research in the field. Key Learning Points Some fundamentals of knot theory.  Knot theory and closely related ideas in topology can be applied to modern chemistry.  Knots can be formed in single molecules as well as in materials and biological fibres using a mixture of selfassembly, metal templating and optical manipulation. The inclusion of knots in molecular structures can alter chemical and physical properties.  Knots are surprisingly ubiquitous in the chemical sciences.

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Allosteric initiation and regulation of catalysis with a molecular knot

Cited by 228 publications

References 43 publications

Securing a Supramolecular Architecture by Tying a Stopper Knot

Securing a Supramolecular Architecture by Tying a Stopper Knot

Remote electrochemical modulation of pK _a in a rotaxane by co-conformational allostery

Knot theory in modern chemistry

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Allosteric initiation and regulation of catalysis with a molecular knot

Cited by 228 publications

References 43 publications

Securing a Supramolecular Architecture by Tying a Stopper Knot

Securing a Supramolecular Architecture by Tying a Stopper Knot

Remote electrochemical modulation of pK a in a rotaxane by co-conformational allostery

Knot theory in modern chemistry

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Remote electrochemical modulation of pK _a in a rotaxane by co-conformational allostery