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

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.