A chemoselective and enantioselective fluorescent probe for D-Histidine in aqueous solution and living cells

D-Histidine (D-His) holds clinical relevance in the pathogenesis of various diseases, including neurological disorders and chronic kidney disease. The specific detection of D-His within biological systems holds profound significance for the early diagnosis of associated ailments. However, the design of probes targeting D-His is inherently challenging due to the presence of its enantiomers. Herein, we introduce a novel D-His fluorescence probe, designated as (S)-1, based on the 1,1'-bi-2-naphthol (BINOL) framework. Remarkably, (S)-1 demonstrates exceptional chemoselectivity and enantioselectivity towards D-His, achieving a remarkable detection limit of 4.896 nM. Moreover, the low cytotoxicity and superior biocompatibility of (S)-1 facilitate fluorescence imaging of D-His within living cellular environments. NMR analysis and theoretical calculations have substantiated the reaction products and elucidated the recognition mechanism. To our knowledge, (S)-1 stands as the inaugural BINOL-based fluorescence probe for the specific detection of D-His among the 20 common amino acids. These findings provide pivotal groundwork for the development of chiral fluorescence probes targeting amino acids.