Solvents play an extremely important role in chemical reactions and life processes. A complete understanding of solvent effects can guide us to decipher the intrinsic mechanism of chemical reactions and life processes, and further to optimize synthetic conditions and regulate the driving force of the biological processes. For a long time, the understanding and characterization of the solvents can be summarized as (1) intrinsic properties: chemical potential, dipole moment, and dielectric properties; (2) interaction mode (static disorder): hydrogen bond, π−π stacking, hydrophobic interaction, and electrostatic interaction; (3) dynamic properties: diffusion, transfer of charge and energy, etc. These properties have been described by a series of macroscopic-scale solvent experiments, such as solvent thermodynamics, diffraction images, etc. However, the most intrinsic characteristics, including solute−solute, solute−solvent, and solvent−solvent interactions, are averaged in these observed macroscopic properties. More local structural features and detailed pictures have never been obtained because of the formidable challenges of direct characterization from a microscopic perspective. Recently, Prof. Xuefeng Guo group from Peking University developed a new method based on the single-molecule electrical platform to analyze the microstructures and interactions in solvents—a real-time single-molecule event spectroscopy, which shed light on the microscopic heterogeneity and reveals the dynamic characteristics of segregated phase and intermolecular interactions in solvents (Fig. 1).
Fig.1 Schematic of a single-molecule indicator
Xuefeng Guo’s group from Peking University has long been committed to the study of single-molecule reaction dynamics. Together with their collaborators, they have revealed new mechanisms and novel phenomena that are covered by ensemble averages. In one of their previous works, they integrated the molecular bridge with fluorenone functional center to graphene point electrodes, using the nucleophilic addition of fluorenone and hydroxylamine (Sci. Adv. 2018, 4, eaar2177) as an indicator to detect subtle changes in the external environment. Through reverse thinking, the label-free, high time resolution electrical monitoring platform was in turn applied to detected the homogeneity and heterogeneity of solvents at the single-molecule level. The thermodynamics and kinetics characterization of the model reaction indicated that the micro-heterogeneity of alcohol−water and alcohol−n-hexane solutions, and an approximately ideal mixing of alcohol−carbon tetrachloride solution (Fig. 2). In addition, they have also developed the single-molecule event spectroscopy to monitor the single-molecule solvation events, which demonstrated the dynamic characteristics of the microscopic segregated phases and the intermolecular interactions in the solvent. The development of the unique high-resolution indicator with single-molecule and single-event accuracy provides infinite opportunities for in-depth interpretation of solvent effects and optimization of chemical reactions and biological processes in solution.
Fig. 2 Anomalous kinetics and corresponding schematic of the microscopic structure in mixed solvents.
The label-free single-molecule electrical detection platform with ultra-high spatial-temporal resolution can be used to measure the microstructure and interaction of complex solutions accurately, providing a new idea for revealing the principle of chemical reactions and life processes in solutions. This work was published online in JACS Au on November 18th with the title "Accurate single-molecule indicator of solvent effects" (JACS Au 2021, https://doi.org/10.1021/jacsau.1c00400). The co-first authors are Yilin Guo and Chen Yang from College of Chemistry and Molecular Engineering. The research was supported by the National Key R&D Program of China, the National Natural Science Foundation of China and Beijing National Laboratory for Molecular Sciences.
Original link: https://pubs.acs.org/doi/abs/10.1021/jacsau.1c00400
