Toward Precision Measurement and Manipulation of Single‐Molecule Reactions by a Confined Space

Abstract All chemical reactions can be divided into a series of single molecule reactions (SMRs), the elementary steps that involve only isomerization of, dissociation from, and addition to an individual molecule. Analyzing SMRs is of paramount importance to identify the intrinsic molecular mechanism of a complex chemical reaction, which is otherwise implausible to reveal in an ensemble fashion, owing to the significant static and dynamic heterogeneity of real‐world chemical systems. The single‐molecule measurement and manipulation methods developed recently are playing an increasingly irreplaceable role to detect and recognize short‐lived intermediates, visualize their transient existence, and determinate the kinetics and dynamics of single bond breaking and formation. Notably, none of the above SMRs characterizations can be realized without the aid of a confined space. Therefore, this Review aims to highlight the recent progress in the development of confined space enabled single‐molecule sensing, imaging, and tuning methods to study chemical reactions. Future prospects of SMRs research are also included, including a push toward the physical limit on transduction of information to signals and vice versa, transmission and recording of signals, computational modeling and simulation, and rational design of a confined space for precise SMRs.