A Nuclear-Localized Naphthalimide-Based Fluorescent Light-Up Probe for Selective Detection of Carbon Monoxide in Living Cells

Abstract

A nuclear-localized fluorescent light-up probe, NucFP-NO 2 , was designed and synthesized that can detect CO selectively in an aqueous buffer (pH 7.4, 37 °C) through the CO-mediated transformation of the nitro group into an amino-functionalized moiety. This probe triggered a more than 55-fold "turn-on" fluorescence response to CO without using any metal ions, e.g., Pd, Rh, Fe, etc. The enhanced response is highly selective over a variety of relevant reactive oxygen, nitrogen, and sulfur species and also various biologically important cationic, anionic, and neutral species. The detection limit of this probe for CO is as low as 0.18 μM with a linear range of 0−70 μM. Also, this fluorogenic probe is an efficient candidate for monitoring intracellular CO in living cells (RAW 264.7, A549 cells), and the fluorescence signals predominantly localize in the nuclear region.

Recent Advances in Fluorescence Light‐Up Endogenous and Exogenous Carbon Monoxide Detection in Biology

“…Also, the fluorogenic probe efficiently monitored intracellular CO in living cells (Raw 264.7, and A549 cells), predominantly localize in the nuclear-region by confocal laser scanning fluorescence microscopy ( Figure 31). [1] Both the reports are unique till date showing significant enhancement of fluorescence without using any heavy transition metals for the detection of CO. Thus, these probes are not only cost effective, but also devoid of heavy metal toxicity and…”

“…CO poisoning renders reduction of O 2 concentration in cells of living organism as it binds readily with hemoglobin to produce carboxy-hemoglobin and makes it unavailable for carrying O 2 , causing even death by affecting the central nervous system (permissible limit 10-300 ppm). [1] But the twist in the story lies on the fact that at very low concentration CO acts as a cell-signalling agents thus carry positive influence in biological systems as well. [2][3][4][5] However, abnormal metabolism of CO is the reason for several diseases like hypertension, inflammation, Alzheimer's disease, heart failure, etc.…”

“…[6][7][8] Recently it has been observed that CO act as (i) gasotransmitter, (ii) repair and control cardiovascular system by inhibiting platelet aggregation, (iii) through the stimulation of soluble guanylate cyclase reduces derogatory effect of chronic hypertension, (iv) protect against hypoxia and ischemic lung injury by inhibiting growth of human airway smooth muscle cell which prevent endothelial cell apoptosis. [1,[9][10][11][12][13] Research, clinical trials and also treatment for the prevention and cure of these diseases are highly in demand and carried out by introducing low level of CO. [1] But understanding the mechanism is still in its infancy due to detection of low level endogenous CO in subcellular organelles is very tough and promising results are shown mostly by fluorescent detection of the small molecules among various other techniques like piezoelectric sensors, semiconductor sensors, colorimetric probes, quartz crystal microbalance, Raman spectroscopy, transmission electron microscopy, gas chromatography, liquid chromatography and Xray diffraction. [2,[14][15][16][17][18][19][20][21][22][23][24] Although, various methods are available for detection of CO, the fluorescence light-up detection is considered the best method due to its easy and accurate sensing capability.…”

“…Incomplete combustion of fuels is the main source for CO and considered as one of the most toxic (colourless and odourless) gas due to its higher affinity towards the hemoglobin than oxygen molecules. CO poisoning renders reduction of O 2 concentration in cells of living organism as it binds readily with hemoglobin to produce carboxy‐hemoglobin and makes it unavailable for carrying O 2 , causing even death by affecting the central nervous system (permissible limit 10–300 ppm) . But the twist in the story lies on the fact that at very low concentration CO acts as a cell‐signalling agents thus carry positive influence in biological systems as well .…”

“…Thus, the act of CO has become inevitably significant to biological systems when its amount is optimum and even can has the potential to act as therapeutic agent . Recently it has been observed that CO act as (i) gasotransmitter, (ii) repair and control cardiovascular system by inhibiting platelet aggregation, (iii) through the stimulation of soluble guanylate cyclase reduces derogatory effect of chronic hypertension, (iv) protect against hypoxia and ischemic lung injury by inhibiting growth of human airway smooth muscle cell which prevent endothelial cell apoptosis . Research, clinical trials and also treatment for the prevention and cure of these diseases are highly in demand and carried out by introducing low level of CO .…”