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For some host-guest pairs with incomplete complementarity, addition of polar cosolvent makes the binding tight. See ref 22.
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a, were -0.04 (guest = Ala-OMe, Phe-OMe, and Trp-OMe) and -0.49 (guest = pyridine, butylamine, benzylamine, Ala-OMe, Leu-OMe, PhGly-OMe, Phe-OMe, and Trp-OMe) for 1a and 3a, respectively. For instance, amines are bound less tightly to 1a-3a than amino esters. These negative correlation coefficients can be rationalized by the existence of pre-equilibrium in which more basic amines are more easily protonated and to be deactivated as a Lewis base for zinc.
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