A supramolecular system that strictly follows the binding mechanism of conformational selection

Abstract

Induced fit and conformational selection are two dominant binding mechanisms in biology. Although induced fit has been widely accepted by supramolecular chemists, conformational selection is rarely studied with synthetic systems. In the present research, we report a macrocyclic host whose binding mechanism is unambiguously assigned to conformational selection. The kinetic and thermodynamic aspects of this system are studied in great detail. It reveals that the kinetic equation commonly used for conformational selection is strictly followed here. In addition, two mathematical models are developed to determine the association constants of the same guest to the two host conformations. A “conformational selectivity factor” is defined to quantify the fidelity of conformational selection. Many details about the kinetic and thermodynamic aspects of conformational selection are revealed by this synthetic system. The conclusion and the mathematical models reported here should be helpful in understanding complex molecular recognition in both biological and synthetic systems.

Multiple Stimuli-Responsive Conformational Exchanges of Biphen[3]arene Macrocycle

“…and synthesis of molecular machines and devices [2,[7][8][9][10] but also function as an important tool for host-guest binding mechanism analysis [37]. The assignment of the binding mechanism is often inconclusive in synthetic supramolecular systems because of the fast exchange kinetics [38,39].…”

“…This result also suggests that the exchange kinetics of host-guest complex is faster than the conformational exchange. NMR titration experiments were employed to measure the association constants (K 1 , K 2 ) between two conformers of MeBP3 and 1 + [37]. When we gradually titrated 1 + into a CDCl 3 solution of MeBP3 (1.0 mM, Figures S17 and S18), the obvious shifts were observed in both two conformers' 1 H NMR signals, showing that 1 + can be recognized by both MeBP3-I and MeBP3-II.…”

“…Although conformational interconversions of macrocyclic acceptors can be observed in molecular recognition processes [29][30][31][32][33][34][35][36], slow exchanges of coexisting conformations of macrocycles have been rarely reported [37]. Developing slow conformational exchange systems of macrocycles can not only apply in the design and synthesis of molecular machines and devices [2,[7][8][9][10] but also function as an important tool for host-guest binding mechanism analysis [37]. The assignment of the binding mechanism is often inconclusive 2 of 10 in synthetic supramolecular systems because of the fast exchange kinetics [38,39].…”

“…The assignment of the binding mechanism is often inconclusive 2 of 10 in synthetic supramolecular systems because of the fast exchange kinetics [38,39]. Very recently, Jiang et al demonstrated the strict analysis of the binding mechanism based on a macrocycle with slow conformational exchange [37].…”

Ternary Cocrystals with Large Soft Cavities: A 1,4‐diiodotetrafluorobenzene (DITFB)⋅4‐Biphenylpyridine N‐oxide (BPNO) Host Assembled by Inclusion of Planar Aromatic Guests

“…Supramolecular host-guest chemistry has attracted significant interest in the fields of material science, molecular recognition, gas storage, drug delivery, and biomedical engineering. [1][2][3][4][5][6][7][8] At present, hosts with an intrinsic cavity, capsule or cage-type structure have been constructed based on various noncovalent interactions to recognize or capture guest molecules among various other applications. [9][10][11] Such hosts include metal-organic, covalent-organic, hydrogen-bonded organic, and halogenbonded organic frameworks, as well as porous organic polymers and inclusion crystals.…”