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Effective Recognition of Caffeine by Diaminocarbazolic Receptors
Author(s) -
Francesconi Oscar,
Ienco Andrea,
Nativi Cristina,
Roelens Stefano
Publication year - 2020
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.202000114
Subject(s) - theobromine , caffeine , isothermal titration calorimetry , chemistry , theophylline , molecular recognition , receptor , selectivity , affinities , adenosine receptor , stereochemistry , hydrogen bond , allosteric regulation , titration , combinatorial chemistry , biophysics , biochemistry , molecule , organic chemistry , agonist , pharmacology , biology , endocrinology , catalysis
Caffeine is a competitive inhibitor of adenosine receptors and possesses wide pharmacological activity. Artificial receptors recognizing caffeine potentially have a wide range of biomedical and industrial applications. Herein, we describe two structurally related and readily available artificial receptors: 1) a macrocyclic receptor, which binds caffeine with the unprecedented affinity of 9.3 μM, though with poor selectivity; and 2) a tweezers‐like structure, showing an affinity of 26 μM and a 4.5‐fold and 6‐fold selectivity compared to theophylline and theobromine, respectively. Binding affinities were measured by 1 H NMR titrations and were confirmed by isothermal titration calorimetry. The X‐ray structure of the complex between caffeine and the acyclic receptor revealed the origin of the recognition, explained the selectivity, and shed light on the role of hydrogen bonding and CH−π/π–π interactions.