A Subtle Twist on Sensor Design: NO-Induced Nitration-Triggered C–C Bond Cleavage

Abstract A benzochromene-dihydropyridine-based probe (CQME) undergoes carbon–carbon bond cleavage upon exposure to NO, producing a bright fluorescent compound (PYNO2) and a nonfluorescent compound (PYMAA), resulting in an enhancement of fluorescence intensity by about 29 times at 615 nm when excited at 470 nm along with a huge Stokes shift (∼145 nm) that reduces interference from autofluorescence, making it advantageous for in vivo applications. The most striking observation in this context is the C–C bond cleavage between benzochromene and dihydropyridine moieties (DIPY) for both CQME and CQET which is facilitated by NO mediated nitration at the C2* atom. Both the probe (CQME) and the product (PYNO2) were structurally characterized by a single-crystal X-ray diffraction method. Extension of this study to a simple chromene-DIPY based probe (SALDPY) gives dimethyl 4-(2H-chromen-3-yl)-2,6-dimethylpyridine-3,5-dicarboxylate (SALPY) as the major product (∼50%) with a very small amount (∼3%) of C-nitrated product (SALNO2) and the origin of these different reactivities was investigated computationally. Again, the cell permeability, notable selectivity, sensitivity (LOD ∼ 42 nM), and pH independent fluorescence properties of CQME make it an outstanding candidate for monitoring endogenous and exogenous NO in the nanomolar range.