Displacement assay methodology for pseudorotaxane formation in the millisecond time-scale

Abstract

Rotaxanes, formed by an axis through the cavity of a macrocycle, are promising systems for the construction of molecular machines. A very limited number of experimental techniques are available for mechanistic studies since only mechanical bonds are formed, being NMR one of the most widely used. The major inconvenience derived from NMR use is the time-scale for threading/dethreading processes lasting a few minutes in the case of faster processes. In the present manuscript, we report the application of a new kinetic methodology based on a displacement assay for cyclodextrin-based pseudorotaxane formation. By coupling a very fast (microseconds time-scale) binding/dissociation of nitrophenol to α-CD with a dicationic axle threading/dethreading process, we have been able to study kinetic processes taking place in the millisecond time-scale.

Use of dye complexation dynamics to determine α‐cyclodextrin host:guest stability constants

“…Application of this methodology has focused on steady‐state conditions where the equilibrium has been fully established before spectroscopic determination. Dye displacement methodology allows not just binding constant determination but also analysis of the inclusion dynamics as have been shown for pseudorotaxane formation . Experimental design requirement is host:guest association being much slower than dye inclusion dynamics.…”

“…Dye displacement methodology allows not just binding constant determination but also analysis of the inclusion dynamics as have been shown for pseudorotaxane formation. [26][27][28] Experimental design requirement is host:guest association being much slower than dye inclusion dynamics. Consequently, host:dye recognition is in equilibrium at all times during the dynamics of guest inclusion.…”

Complexation Kinetics of Cyclodextrins with Bile Salt Anions: Energy Barriers for the Threading of Ionic Groups

“…However, the kinetics of the complexation and dissociation processes have only been determined for relatively few complexes, probably less than a hundred. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Of these, most are with the small αCD, fewer with the wider βCD and its derivatives, and rate constants have only been reported for a few complexes with γCD, [23][24][25][26] which has the largest diameter of the natural CDs.…”

“…Most of the applications rely on the binding affinity of the guest moiety for the CD host, and binding constants for thousands of CD complexes with predominantly small guest molecules have been reported. However, the kinetics of the complexation and dissociation processes have only been determined for relatively few complexes, probably less than a hundred. − Of these, most are with the small αCD and fewer with the wider βCD and its derivatives; rate constants have only been reported for a few complexes with γCD, − which has the largest diameter of the natural CDs. With time scales ranging from nanoseconds to seconds for the vast majority of complexes, the dynamics are sufficiently fast to be of negligible importance for many practical applications but may be crucial for understanding the properties of some supramolecular systems .…”

Synthesis of Bottlebrush Copolymers Using a Polypseudorotaxane Intermediate

“…Several dethreading rate constants at room temperature are reported to be in the 10 −5 s. −1 range. 69,70,73 Given the length of the terminal units (7 carbon and 1 oxygen atoms) and the bulky end groups of guest 2, it is likely that the room temperature rate constant in the present system would be very low, as low as 10 −31 s −1 ; for a comparison of the end groups of 2 with other studied systems and k dethr values predicted from molecular volumes, see the Supporting Information. Additionally formation of styrene oligomers with a degree of polymerization of 5 is shown to drive the dethreading rates to extremely low levels, essentially preventing dethreading on the laboratory time scale.…”