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Preorganization plays a critical role in supramolecular chemistry by minimizing the entropic cost associated with host–guest complex formation. In a typical binding event, the host and guest molecules must adopt complementary conformations to fit together, which often requires a reduction in their rotational and translational freedom, leading to a significant entropic penalty. Preorganized hosts, however, are designed in such a __________ ____ ________ ____ ______ _____ ______ ____.
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