Switching between Anion-Binding Catalysis and Aminocatalysis with a Rotaxane Dual-Function Catalyst

Abstract

ABSTRACT:The 'off' state for aminocatalysis by a switchable [2]rotaxane is shown to correspond to an 'on' state for anion-binding catalysis. Conversely, the aminocatalysis 'on' state of the dual-function rotaxane is inactive in anion-binding catalysis. Switching between the different states is achieved through the stimuli-induced change of position of the macrocycle on the rotaxane thread. The anion-binding catalysis results from a pair of triazolium groups that act together to CHhydrogen bond to halide anions when the macrocycle is located on an alternative (ammonium) binding site, stabilizing the in situ generation of benzhydryl cation and oxonium ion intermediates from activated alkyl halides. The aminocatalysis and anion-binding catalysis sites of the dual-function rotaxane catalyst can be sequentially concealed or revealed, enabling catalysis of both steps of a tandem reaction process.

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

“…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.…”

“…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).…”

Driving Smart Molecular Systems by Artificial Molecular Machines

“…Most of these systems regulate the host macrocycle to slide across the axle to bind with different recognition sites and thus leave the catalytic groups exposed (on‐state) or concealed (off‐state). Over the past two decades, various controllably manipulatable rotaxane‐based catalysts have been designed . In 2012, Leigh and coworkers designed a switchable organocatalyst comprising a host DB24C8 ring and two different binding sites (DBA and MTA), using the Michael addition of an aliphatic thiol to trans ‐cinnamaldehyde as a model reaction to study catalytic efficiency.…”

Acid‐Regulated Switching of Metal Cation and Anion Guest Binding in Halogen‐Bonding Rotaxanes

“…This occurs primarily by changing the affinity of the enzyme to its target guest species, which can be achieved by either allosteric or orthosteric regulation, and hence are both attractive targets for drug development . Allosteric regulation, the process by which ligand binding at a site distinct from the guest binding cavity modulates the latter's guest affinity by changing its size and shape, has been demonstrated in numerous artificial biomimetic systems in recent years, enabling applications such as controlled guest release in changing chemical media and switchable catalysis . The alternative orthosteric regulation mechanism, where direct ligand coordination within the original binding site itself changes its native guest affinity and selectivity, by comparison, has received scant attention in the design of abiotic host systems.…”

“…[3,4] Allosteric regulation,t he process by which ligand binding at as ite distinct from the guest binding cavity modulates the latter's guest affinity by changingi ts size and shape, has been demonstrated in numerousa rtificial biomimetic systems in recent years, [5][6][7] enablinga pplicationss uch as controlled guest release in changing chemical media [8,9] and switchable catalysis. [10][11][12] The alternative orthosteric regulation mechanism,w here direct ligand coordination within the original binding site itself changes its nativeg uest affinity and selectivity,b yc omparison, has received scant attention in the design of abiotich ost systems. Partly due to the significant challenges in designing receptors containing binding cavities capable of such chemical stimuli-responsiveb ehaviour,e xisting systemsc apable of orthosteric regulatory binding are limited to pH-induced modulation of anion selectivity of acyclicp yridyl thioureas [13] and quaternary ammonium guest orientationw ithin ac avitand host binding pocket.…”