Quaternary 2:2 Complexes as Kinetic Intermediates: Unveiling an Overlooked Pathway in Cucurbit[8]uril-Mediated Assembly

Abstract

Molecular assembly is typically viewed as a stepwise process from lower- to higher-order structures. Here, we uncovered an alternative kinetic pathway in the cucurbit[8]uril (CB[8])-mediated assembly, where a transient quaternary (2:2) complex formed before the thermodynamically favored ternary (2:1) product. Stopped-flow spectroscopy and structural analysis confirmed the 2:2 intermediate, which formed 36-fold faster than the direct 1:1 → 2:1 pathway at 298 K. The system thus accumulated in the 2:2 state before relaxing to the 2:1 product. These findings revise the conventional binary-to-ternary model and highlight the mechanistic relevance of higher-order intermediates. It also refines our understanding of apparent cooperativity within a complex assembly network. Recognizing such kinetic complexity opens new avenues for dynamic control in the design of high-performance functional and structural materials.

Tianyi Yang

PhD graduate (2021)

PhD alumna; defended her doctoral dissertation on March 13, 2026.

Yuanchen Shen

Bachelor’s graduate (2019)

Alumnus; graduated in June 2023 and returned in 2025 to share research on heteroatom-modified polycyclic aromatic hydrocarbons.

Haoyuan Qu

PhD Candidate (2022)

This student is a genuine Changchun native, friendly and approachable.

Yibin Sun

Assistant Professor

Research interests: catassembly, assembly kinetics, protein-protein assembly, and protein engineering

Guanglu Wu

Professor

Research interests: multi-component functional assemblies, noncovalent dimerization, supramolecular catalysis, and smart soft matter