Chirality is a key property in chemistry and biology because many biomolecules, such as amino acids and sugars, exist in left- or right-handed forms, which can exhibit drastically different biological activities. Single-molecule chiral recognition is the ability to detect and distinguish their specific interactions with a chiral probe or surface at the most fundamental, single-molecule level. The electrochemical activity of chiral self-assembled monolayers (SAMs) has been previously investigated, but their use as a method for introducing stereoselectivity in electron transfer at the electrode-protein interface remains limited. In this study, we first employed single-entity collision electrochemistry techniques to investigate the interfacial behavior of microperoxidase-11 (MP-11) on gold electrodes modified with chiral L-cysteine and D-cysteine SAMs. These electrochemical measurements revealed distinct transient catalytic differences in collision frequency, current amplitude, and event duration, which indicated that surface chirality dynamically influences both molecular recognition and electron transfer at the single-molecule level. Subsequently, using Raman analysis and molecular docking simulations, we discovered the critical role that hydrogen bonds play in the differential binding of L-cysteine and D-cysteine to MP-11. Our findings reveal that the unique arrangement of hydrogen bonds significantly influences the interaction between the chiral cysteine and MP-11, contributing to the distinct electron transfer rates and adsorption efficiencies observed on chiral electrode surfaces. This study enhanced our understanding of the molecular interactions at the chiral interface not only sheds light on the underlying mechanisms of chiral recognition but also provides valuable insights for designing new effective chiral biosensors and catalysts.
References:
[1]. N. Kong, J. He., W. Yang, “Formation of molecular junctions by single-entity collision electrochemistry,” J. Phys. Chemi. Lett., (2023), 38(14), 8513-8524.
[2]. J. Liu, H. Zhou, W. Yang, K. Ariga, “Soft nanoarchitectonics for enantioselective biosensing,” Acc. Chem. Res., (2020), 53(3), 644-653.
[3]. F. Yang, N. Kong, X. A. Conlan, H. Wang, C. J. Barrow, F. Yan, J. Guo, W. Yang, “Electrochemical evidence of chiral molecule recognition using L/D-cysteine modified gold electrodes,” Electrochim. Acta, (2017), 237, 22-28.