Selective Fluorescence Detection of Cysteine over Homocysteine and Glutathione Based on a Cysteine-Triggered Dual Michael Addition/Retro-aza-aldol Cascade Reaction

In this work, a cysteine (Cys)-triggered dual Michael addition/retro-aza-aldol cascade reaction has been exploited and utilized to construct a fluorescent probe for Cys for the first time. The resulting fluorescent probe 8-alkynylBodipy <b>1</b> contains an activated alkynyl unit as Michael receptor and a Bodipy dye as fluorescence reporter and can highly selectively detect Cys over homocysteine (Hcy)/glutathione (GSH) as well as other amino acids with a significant fluorescence off–on response (∼4500-fold) and an ultralow detection limit (0.38 nM). The high selectivity of <b>1</b> for Cys could be attributed to a kinetically favored five-membered cyclic intermediate produced by the dual Michael addition of Cys with the activated alkynyl unit of <b>1</b>. The big fluorescence off–on response is due to the subsequent retro-aza-aldol reaction of the five-membered cyclic intermediate that results in the release of a highly fluorescent 8-methylBodipy dye <b>2</b>. The probe has been successfully used to detect and image Cys in serum and cells, respectively

Study selection diagram.

<p>Study selection diagram.</p

Funnel plot with 95% confidence intervals (CI) to assess for evidence of publication bias.

<p>Funnel plot with 95% confidence intervals (CI) to assess for evidence of publication bias.</p

Quality of included RCTs.

<p> <b>NS = not specified or available.</b></p

Characteristics of included studies-continued.

<p>Statin = statin-treated group (high-dose);Control = control group (low-dose or non-statin);CAG = coronary angiography;PCI = percutaneous coronary intervention;CrCl = creatinine clearance;Scr = serum creatinine;CRP = C-reactive protein;eGFR = estimated glomerular filtration rate;NAC = N-acetylcysteine;NS = 0.9% sodium chloride; NS = not specified or available.</p

Characteristics of included studies.

<p>Statin = statin-treated group(high-dose);Control = control group(low-dose or non-statin);CAG = coronary angiography;PCI = percutaneous coronary intervention;CrCl = creatinine clearance;Scr = serum creatinine;eGFR = estimated glomerular filtration rate;NAC = N-acetylcysteine;NS = 0.9% sodium chloride.</p

Forest plot of risk ratios and 95% confidence intervals (CI) for the incidence of CIN among patients assigned to short-term high-dose statin treatment versus low-dose or non-statin.

<p>Forest plot of risk ratios and 95% confidence intervals (CI) for the incidence of CIN among patients assigned to short-term high-dose statin treatment versus low-dose or non-statin.</p

Forest plot of risk ratios and 95% confidence intervals (CI) for the incidence of CIN among patients assigned to statin therapy versus control according to renal function.

<p>Forest plot of risk ratios and 95% confidence intervals (CI) for the incidence of CIN among patients assigned to statin therapy versus control according to renal function.</p

Forest plot of risk ratios and 95% confidence intervals (CI) for the incidence of CIN among patients assigned to statin therapy versus control according to Jadad score.

<p>Forest plot of risk ratios and 95% confidence intervals (CI) for the incidence of CIN among patients assigned to statin therapy versus control according to Jadad score.</p

Forest plot of risk ratios and 95% confidence intervals (CI) for the incidence of CIN among patients assigned to statin therapy versus control with NAC using or not.

<p>Forest plot of risk ratios and 95% confidence intervals (CI) for the incidence of CIN among patients assigned to statin therapy versus control with NAC using or not.</p