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.