Thermodynamic Analysis of Allosteric and Chelate Cooperativity in Di- and Trivalent Ammonium/Crown-Ether Pseudorotaxanes

Abstract

A detailed thermodynamic analysis of the axle-wheel binding in di- and trivalent secondary ammonium/[24]crown-8 pseudorotaxanes is presented. Isothermal titration calorimetry (ITC) data and double mutant cycle analyses reveal an interesting interplay of positive as well as negative allosteric and positive chelate cooperativity thus providing profound insight into the effects governing multivalent binding in these pseudorotaxanes.

Allosteric and Chelate Cooperativity in Divalent Crown Ether/Ammonium Complexes with Strong Binding Enhancement

“…From the data in Table , it is apparent that both factors increase with increasing methanol content. This indicates that ion‐pair formation causes negative allosteric cooperativity here . As reported earlier by Gibson et al., ion‐pair formation is important for the free ammonium ions, whereas it does not play an important role for the crown ether complexes.…”

“…It is the factor in the association constant of the divalent complex that accounts for the intramolecular ring closure in the second binding step (Figure 1, complex a). However,E Mc annot be measured directly.T oq uantify EM, ad ouble-mutant cycle (DMC) analysis [18,23,24,[32][33][34][35][36][37][38] (Figure 1, top) can be used (for ad etailed description including the determination of statistical factors, see the Supporting Information). Briefly,m utation 1, which corresponds to acut through the host spacer,leads from a to b.This step contains the effects on divalent binding that are due to the host spacer.…”

“…Herein, we present a thorough analysis of allosteric and chelate cooperativity of divalent crown ether/ammonium complexes by a combination of experimental thermochemical analysis with small‐scale (DFT) and large‐scale (molecular dynamics (MD) simulations) calculations. We use simple divalent crown/ammonium complexes as model systems.…”

“…Herein, we present at horough analysis of allosteric [15,16] and chelate cooperativity [17][18][19][20][21][22][23][24] of divalentc rown ether/ammonium complexes by ac ombination of experimental thermochemical analysisw ith small-scale (DFT) and large-scale (molecular dynamics( MD) simulations) calculations. We use simple divalent crown/ammonium complexesa smodel systems.These binding motifsa re widely used tool kits for the generation of complex, programmed structures in supramolecular chemistry.…”

“…We use simple divalent crown/ammonium complexesa smodel systems.These binding motifsa re widely used tool kits for the generation of complex, programmed structures in supramolecular chemistry. [23][24][25][26][27][28][29][30] Their advantages for our purposes are 1) easy synthetic accessibility, 2) solubility in ar ange of organic solvents of different polarity, 3) relatively strong binding interactions, 4) al imited molecular size suitable for computational analysis [29,31] by DFT and molecular dynamics simulations, and 5) aw ell-understood monovalent binding motif.…”