Invited
Entropy-driven hydrophobic assembly of 1,2-diols within a porous nanocapsule

We have used porous icosahedral-symmetry metal-oxide capsules, [{Mo^VI₆O₂₁(H₂O)₆}₁₂{Mo^V₂O₄(L)}₃₀]^42– {Mo₁₃₂} (L = an endohedrally coordinated η²-bound carboxylate anion), to investigate organic reactions within nano-confined domains in water, including: 1) diffusion through flexible pores [1], 2) catalysis [2-3], and 3) self-assembly [4-5]. In the latter, a {Mo₁₃₂} capsule was used to reveal the energetics of individual steps in the formation of a “micelle”-like aggregate of n-butyrate ions [4] and the population of distinct host domains by differently sized alkanes [5]. We now show that the large (unfavorable) entropic cost of hydrating 1,2-diol functionalized ligands can be used to drive their uptake and assembly. Highly soluble in water, alcohols are viewed as consummate hydrophiles. Nevertheless, the H-bonding behind their favorable solvation enthalpies imposes substantial entropic costs. Thus, like hydrocarbons, the sequestration of alcohols from water is entropically favorable. This "hydrophobic" effect is demonstrated using a {Mo₁₃₂} capsule and variable-temperature ¹H NMR to investigate the one-to-one exchange of endohedrally-bound formate ligands (HCO₂^–) by a 1,2-hydroxyl-functionalized ligand, L-glycerate (L-HOCH₂(HO)CHCO₂^–) in D₂O. At pH 5, van`t Hoff analysis reveals that ΔH^o, -TΔS^o and ΔG^o for the exchange reaction are +33.7, -33.0 and 0.7 kcal mol^-1, respectively, giving K = 0.29. When the unfavorable enthalpy change is attenuated by co-sequestration of protons by the alcoholic environment created by encapsulated L-glycerate ligands, -TΔS^o (-26.5 kcal mol^-1) dominates over ΔH^o (+23.4 kcal mol^-1) and K increases by 200-fold, triggering the spontaneous uptake of 24 L-glycerate ligands via an entropically-driven hydrophobic effect.

[1] Weinstock, I. A., et. al., JACS. 2009, 131, 6380.

[2] Weinstock, I. A., et. al., JACS. 2012, 134, 13082.

[3] Weinstock, I. A., et. al., JACS. 2015, 137, 12740.

[4] Weinstock, I. A., et. al., Angew. Chem. Int. Ed. 2013, 52, 8358.

[5] Weinstock, I. A., et. al., Ang. Chem. Int. Ed., 2016, 55, 4476