Spatial Confinement Mechanism for Developing Versatile Nonionic Guest-in-CD-MOF-1 Complexes to Generate Transparent Nonionic Guest in Aqueous Dispersion

Understanding the universal encapsulation mechanism of nonionic guests in CD-MOF-1 is important to develop various stable nanosized nonionic guest-in-CD-MOF-1 complexes for improving the aqueous dispersity of hydrophobic nonionic guests. Herein, typal nonionic guests with different sizes and van der Waals volumes were encapsulated into CD-MOF-1. We found that urolithin A (Uro-A) could be effectively encapsulated into CD-MOF-1 compared to other guests. The long edge size of Uro-A (1.06 nm) exceeds the aperture size of CD-MOF-1 (0.78 nm), while its short edge size (0.62 nm) is slightly smaller than the aperture size. The van der Waals volume of Uro-A is 193.07 ų, smaller than the A and B pore volumes of CD-MOF-1 (i.e., 2571.14 ų and 381.51 ų). Consequently, Uro-A can easily enter into the pores of CD-MOF-1 via free diffusion, while the noncovalent spatial confinement prevents the encapsulated Uro-A against escaping. Ellagic acid (EA) and caffeic acid phenethyl ester (CAPE) share similar molecular dimensions and van der Waals volumes compared to Uro-A, resulting in a reasonable loading capacity and are effectively difficult to escape from CD-MOF-1. However, the van der Waals volumes of Vitamin K1 (VK1) and coenzyme Q₁₀ (CoQ₁₀) are significantly larger than the B pore volume of CD-MOF-1, stopping them from diffusing into CD-MOF-1. Alternatively, carvacrol, geranyl acetate, and nerol have excessively small dimensions and van der Waals volumes and thus are prone to escape from CD-MOF-1 during the washing process. Furthermore, the developed Uro-A-in-CD-MOF-1 presented desirable hydrolysis characteristics without significant residual nanostructures. This work provides a universal mechanism for developing nonionic guest-in-CD-MOF-1 to improve aqueous dispersibility of hydrophobic guests, providing potential applications in food, cosmetics, and pharmaceutical development.