Nanospaces within enzymes play a crucial role in chemical reactions in biological systems, garnering significant attention from supramolecular chemists. Inspired by the highly efficient catalysis of enzymes, artificial supramolecular hosts have been developed and widely employed in various reactions, paving the way for innovative and selective catalytic processes and offering new insights into enzymatic catalytic mechanisms. In supramolecular macrocycle systems, weak non-covalent interactions are exploited to enhance substrate solubility, increase local concentration, and stabilize the transition state, ultimately accelerating reaction rates and improving product selectivity. In this review, we will focus on the opportunities and challenges associated with the catalysis of chemical reactions by supramolecular macrocycles in the aqueous phase. Key issues to be discussed include limitations in molecular interaction efficiency in aqueous media, product inhibition, and the incompatibility of catalysts or conditions in "one-pot" reactions.
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