Creating a suprazyme: integrating a molecular enzyme mimic with a nanozyme for enhanced catalysis

Abstract

Enzyme mimics, due to their limited complexity, traditionally display low catalytic efficiency. Herein we present a strategy that enables the transformation of a slow-acting catalyst into a highly active one by creating a non-covalent suprastructure, termed "suprazyme". We show that cucurbit[7]uril macrocycles, rudimentary molecular enzyme mimics, embedded within an anionic monolayer on the surface of gold nanoparticles, outperform individual cucurbit[7]urils as well as nanoparticles, which also exhibit catalytic enzyme-like activity and thus act as nanozymes, by over 50 times, showcasing a 1044-fold acceleration in a model oxime formation reaction. The superior performance of such a suprazyme is attributed to a synergistic interplay between the organic monolayer and macrocycles, which is accompanied by a decreased local polarity and pH that favors the acid-catalyzed condensation process. The proposed approach holds promise for developing diverse suprazymes, contingent upon achieving a complementary structure and mechanism of action between the molecular catalyst and nanoparticles.

Fig. 1. (A) Chemical structure and cartoon representation of cucurbit[7]uril (CB7); (B) oxime formation reaction; (C) titration of CB7 with the substrate, water, pH = 6 (adjusted with HCl/NaOH), 298 K; (D) kinetic traces for the reaction progress at various amounts of CB7, [S] = 0.01 mM, water, pH = 6 (adjusted with HCl/NaOH), 298 K.

Fig. 2. (A) Chemical structure and cartoon representation of anionic ligands and gold nanoparticles covered by them; (B) titration of AuMUS with the substrate, water, pH = 6 (adjusted with HCl/NaOH), 298 K; (C) titration of AuMUS with 4-aminobenzylamine, water, 298 K; (D) kinetic traces for the reaction progress at various amounts of AuMUS, [S] = 0.01 mM, water, pH = 6 (adjusted with HCl/NaOH), 298 K.

Fig. 3. (A) Kinetic traces for the reaction progress in water (blank), in the presence of the macrocycle (1 equiv.), AuMUS (4 equiv.), and their mixture (1 : 4), [S] = 0.01 mM, water, pH = 6 (adjusted with HCl/NaOH), 298 K; (B) initial rates for CB7–AuMUS (1 : 4) at varying substrate concentrations; (C) titration of AuMUS with CB7, water, pH = 6 (adjusted with HCl/NaOH), 298 K; (D) the particle size distribution before (d = 6.41 ± 0.17 nm) and after the addition of CB7 (d = 6.86 ± 0.10 nm).

Fig. 4. Location of CB7 molecules (red) at the onset (CB7@B1) (A, left) and at the late stage of binding (CB7@B2) (A, right) with AuMUS NPs (white). Structures are extracted from MD calculations at increasing CB7 content. CB7@B1 denotes binding occurrences prior to monolayer structure's reorganization, whereas CB7@B2 refers to those after; (B) zoom views of the AuMUS/CB7 complex highlighting the chemical space around the macrocyclic cavity in CB7@B1 (left) and CB7@B2 (right) modes; (C) comparison of molecular features and local environments pertaining to CB7@B1 and CB7@B2. Descriptors (from left to right): solvent accessible surface area (SASA, Ų), number of water molecules, number of C atoms belonging to MUS ligands, orientation of the macrocycle's central axis with respect to the direction connecting the center-of-mass of CB7 and NPs (ω, °), number of S/O atoms of SO₃⁻ groups, and number of heavy atoms of another CB7 molecule. Environments are assigned for each CB7 accounting for all atoms within the first peak of the radial distribution function from the center of the macrocycle.