Fusing the Nagano’s and the Anslyn’s chemistry for lyso-specific NO detection

Abstract The biorelevance of nitric oxide (NO) has attracted intensive efforts in their in situ detection. Fluorescence-based methods have been established as the benchmark due to their sensitivity. The high stability and radical nature of NO contributed to the difficulties of their sensitive detection. Direct detection of NO has either involved the use of a heavy transition metal complex, or a sluggish cheletropic reaction with a diene. Therefore, detection of nitrosonium species, generated upon a formal one-electron oxidation of NO, has become the routine practice as a surrogate of biological NO. Amongst all, the Nagano chemistry using ortho-phenylenediamine and the Anslyn chemistry using 2-amino-3′-dialkylaminobiphenyl are the two predominant approaches. They differ from each in that a nitrogen-based or a carbon-based diazo-coupling occurs upon nitrosation of the primary amino group. Presumably, their cyclization kinetics are expected to differ and further impact the time required to turn-on the fluorescence. To address this mechanistic curiosity, we designed model molecular scaffolds (NOP1−3), via hybriding the Nagano and the Anslyn NO sensing chemistry, and showcased that the Anslyn chemistry exhibits a relatively higher cyclization kinetics. Based on that the detection product becomes fluorescent in lyso-relevent pH, we found that NOP3 have potentials for lyso-specific NO detection.