10.1021/acs.nanolett.8b00949.s001 Chunhui Gu Chunhui Gu Chen Hu Chen Hu Ying Wei Ying Wei Dongqing Lin Dongqing Lin Chuancheng Jia Chuancheng Jia Mingzhi Li Mingzhi Li Dingkai Su Dingkai Su Jianxin Guan Jianxin Guan Andong Xia Andong Xia Linghai Xie Linghai Xie Abraham Nitzan Abraham Nitzan Hong Guo Hong Guo Xuefeng Guo Xuefeng Guo Label-Free Dynamic Detection of Single-Molecule Nucleophilic-Substitution Reactions American Chemical Society 2018 biophysics investigations nucleophilic-substitution reaction single-molecule approach elucidating time trajectories 9- phenyl -9-fluorenol bromide species Label-Free Dynamic Detection mechanism single-molecule level reaction chemistry equilibrium conditions non-equilibrated systems single-molecule dynamics formation dynamics chemical reactions single-molecule junctions Single-Molecule Nucleophilic-Substitution Reactions nanogapped graphene electrodes carbocation intermediates transformation pathways 2018-06-06 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Label-Free_Dynamic_Detection_of_Single-Molecule_Nucleophilic-Substitution_Reactions/6463106 The mechanisms of chemical reactions, including the transformation pathways of the electronic and geometric structures of molecules, are crucial for comprehending the essence and developing new chemistry. However, it is extremely difficult to realize at the single-molecule level. Here, we report a single-molecule approach capable of electrically probing stochastic fluctuations under equilibrium conditions and elucidating time trajectories of single species in non-equilibrated systems. Through molecular engineering, a single molecular wire containing a functional center of 9-phenyl-9-fluorenol was covalently wired into nanogapped graphene electrodes to form stable single-molecule junctions. Both experimental and theoretical studies consistently demonstrate and interpret the direct measurement of the formation dynamics of individual carbocation intermediates with a strong solvent dependence in a nucleophilic-substitution reaction. We also show the kinetic process of competitive transitions between acetate and bromide species, which is inevitable through a carbocation intermediate, confirming the classical mechanism. This unique method creates plenty of opportunities for carrying out single-molecule dynamics or biophysics investigations in broad fields beyond reaction chemistry through molecular design and engineering.