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Comprehensive Characterization of the Self-Folding Cavitand Dynamics

preprint
revised on 01.02.2021, 22:12 and posted on 03.02.2021, 07:53 by Ricard López-Coll, Rubén Álvarez-Yebra, Ferran Feixas, Agustí Lledó
The conformational equilibria and guest exchange process of a resorcin[4]arene derived self-folding cavitand receptor have been characterized in detail by molecular dynamics simulations (MD) and 1H EXSY experiments. A multi-timescale strategy for exploring the fluxional behavior of this system has been constructed, exploiting conventional MD and accelerated MD (aMD) techniques. The use of aMD allows the reconstruction of the folding/unfolding process of the receptor by sampling high-energy barrier processes unattainable by conventional MD simulations. We obtained MD trajectories sampling events occurring at different timescales from ns to s: 1) rearrangement of the directional hydrogen bond seam stabilizing the receptor, 2) folding/unfolding of the structure transiting partially open intermediates, and c) guest departure from different folding stages. Most remarkably, reweighing of the biased aMD simulations provided kinetic barriers that are in very good agreement with those determined experimentally by 1H NMR. These results constitute the first comprehensive computational characterization of the complex dynamic features of cavitand receptors. Our approach emerges as a valuable rational design tool for synthetic host-guest systems.

Funding

RYC2012‐11112

CTQ2017‐83587‐P

RTI2018‐101032‐J‐I00

MSCA‐IF‐2014‐EF‐661160‐ MetAccembly

History

Email Address of Submitting Author

agusti.lledo@udg.edu

Institution

Universitat de Girona

Country

Spain

ORCID For Submitting Author

0000-0003-3681-6688

Declaration of Conflict of Interest

No conflict of interest

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