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We also characterized the association of control guest N1 with M2 in water. The naphthalene core of N1 has two attached oxygen atoms with similar spacing as the two oxygens in S3 and F1, but with much weaker hydrogen bond accepting ability. 1H NMR chemical shift data indicated threading of N1 by M2 (Figure S8), and ITC titration studies in water at 27 °C determined that a 1:1 complex was formed with K a = 7.7 ×103 M-1 δ H = -5.9 kcal/mol, and T δS = 0.8 kcal/mol (Figure S27). The change in guest from S3 (or F1) to N1 thus lowers the enthalpic driving force by ∼6 kcal/mol. It seems likely that part of this is due to the weaker hydrogen bonding of N1 with the four NH residues inside M2, although other factors presumably contribute since the structures of S3, F1, and N1 have different hydrophobic surface areas and hydration shells. For a recent discussion of these factors, see
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