Palladacycle Based Fluorescence Turn-On Probe for Sensitive

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A Palladacycle based Fluorescence Turn-On Probe for Sensitive Detection of Carbon Monoxide Mingtai Sun, Huan Yu, Kui Zhang, Suhua Wang, Tasawar Hayat, Ahmed Alsaedi, and Dejian Huang ACS Sens., Just Accepted Manuscript • DOI: 10.1021/acssensors.7b00835 • Publication Date (Web): 02 Feb 2018 Downloaded from http://pubs.acs.org on February 4, 2018

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ACS Sensors

A Palladacycle based Fluorescence Turn-On Probe for Sensitive Detection of Carbon Monoxide Mingtai Sun†,‡,§, Huan Yu‡,§, Kui Zhang‡, Suhua Wang*,†,‡,#, Tasawar Hayat#,±, Ahmed Alsaedi#, Dejian Huang*ǁ † ‡

School of Environment and Chemical Engineering, North China Electric Power University, Beijing 102206, China. Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei, Anhui 230031, China.

‖

Food Science and Technology Programme, Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543. # NAAM Research Group, King Abdulaziz University, Jeddah 21589, Saudi Arabia. ± Department of Mathematics, Quaid-I-Azam University, Islamabad 44000, Pakistan.

Supporting Information Placeholder ABSTRACT: New selective and sensitive fluorescence probes have always being much in demand for carbon monoxide, an important gasotransmitter molecule, which involves in critical physiological and pathophysiological process in mammal cardiovascular system. In this work, we synthesized a new palladacycle compound as a fluorescence turn-on probe for selective and quantitative detection of carbon monoxide. The weakly fluorescent probe quickly and selectively reacts with carbon monoxide and releases a highly fluorescent benzimidazole moiety, due to protonolysis of the palladacycle, which greatly enhances the fluorescence intensity. The selective reaction was against interfering from other possible co-existing reactive oxygen species, and achieved a detection limit of ~ 0.06 µM. Furthermore, the fluorescence turn-on probe was demonstrated with high cellular uptake rate and successfully applied for cell imaging of carbon monoxide in living cells.

KEYWORDS: carbon monoxide, palladacycle, fluorescent probe, benzimidazole, endogenous CO, cell imaging Carbon monoxide (CO) is an important intracellular signaling molecule and belongs to the family of gasotransmitter molecules (NO, H2S and CO), which involve in the regulation of a wide range of biological functions in vasodilation, antiapoptotic, antiinflammatory, antiproliferative activities, and neurotransmission.1, 2 Recently, carbon monoxide-releasing molecules (CORMs) capable of delivering controlled quantities of CO gas to cells and tissues have been developed for the treatment of several pathological conditions.3 However, the further investigation of physiological and pathophysiological roles of CO needs highly selective and sensitive fluorescent probes. Although a variety of quantification techniques for gasotransmitters have been developed,4, 5 fluorescence-based methods are more favorable because of their spatiotemporal resolution and high selectivity6, 7 when combined with other analytical methods including the colorimetric method,8-11 and electrochemical analysis.12 In 2012, He’s group and Chang’s group independently reported two fluorescent probes for the detection of CO using a biosensor13 and organometallic palladium

(Pd) complex,14 respectively. The two probes demonstrate the advantages of fluorescence method for the detection and imaging application of endogenous CO which have been shortly reviewed or highlighted.15, 16 Afterwards, several fluorescent probes have emerged based on organometallic complexes due to the strong binding affinity of CO to the central metals.17-19 Lin’s group reported two-photon fluorescent probes based on palladacycles for CO detection.20 Yan et al. reported a fluorescent chemsensor based on the transformation of a weakly fluorescent iodide to a strongly fluorescent amino product.21 These reported methods need multiple substrates and exhibit relatively high detection limit, which hinder their direct practicability in biological application. After that, the use of allyl ether as a reaction site in the presence of PdCl2 for construction of fluorescent CO probes has been reported with good water-solubility and fluorescence turn on signal.22-25 The chemosensor exhibits low background and remarkable fluorescence turn-on response. Recently, Moragues et al. reported a ruthenium(II) complex capable of both chromogenic and fluorogenic sensing of CO in air with exceptional sensitivity and selectivity in the solid state.26 However, the organometallic rhodium complex is only soluble in organic solvents and is difficult for the real-time detection of physiological levels of CO in living cells.27 Hence, new robust and sensitive CO probes based on Pd complexes are still highly demanded for the investigation of COmediated cellular signaling mechanisms. In fact, the Pd-mediated complexes have been widely used in organic synthesis, anticancer, antiproliferative, and catalyst for CO mediated carboxylation,28, 29 in which the palladacycle is considered to be the key intermediate. A few of issues need to be considered on the design of palladacycles based probes, such as good water solubility and stability, specific reactivity, and fast fluorescence response. In addition, the reaction of CO with palladacycles depends on the nature of the ligand and the size of the ring. Thus the structure-activity relationship of palladacycle, the space effect of ligand substitution groups, and electronic properties should be optimized to improve the analytical performance for CO detection. Herein, we report a new palladacycle combined with benzimidazole moiety for selective and quantitative detection of CO. As far as we know, a series of benzimidazole like compounds have been

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reported for the carbonylation of palladacycles involved in CO insertion mechanism.28 Inspired by these findings, we designed a fluorescent benzimidazole functionalized palladacycle for CO due to its binding ability to the palladium, subsequently releasing the fluorescence compound. To improve the water solubility, the carboxyl groups were functionalized on the benzimidazole moiety. The synthesized palladacycle was non-fluorescent due to the heavy-atom electronic effects of palladium. We nickname the palladacycle compound as “HFCO-1” from here on for easy communication. Upon addition of CO, the fluorescence of HFCO1 was switched on immediately with high contrast of fluorescence intensity. Comparing with those analytical methods for CO based on colorimetry, the probe exhibits higher sensitivity, selectivity, and fast response. Taking advantage of the easy preparation and hydrophilic property, the as-prepared HFCO-1 was demonstrated remarkable for sensing CO in buffer solutions and in living cells.

Scheme 1. The synthesis of the CO probe Pd2(BBA)Cl2 (HFCO-1). NH2

CHO

N H

DMF

NH2

HOOC

N

NaHSO3

HOOC BBA

HN N 1. Pd(OAc)2, HOAc 2. LiCl, EtOH

HOOC

Pd Cl

Cl Pd

COOH

N NH

HFCO-1

Benzimidazole ligand (BBA) was prepared by the condensation30 of o-diaminobenzene with 4-formylbenzoic acid31 in high yield (Scheme 1), and characterized by 1H and 13C NMR spectra (Figure S1-S2 in the supporting information). The ligand containing a carboxyl group was chosen for the hydrophilic properties. The palladacycles were then readily prepared by stirring a mixture of the ligand and Pd(OAc)2 in HOAc, followed by the treatment with saturated LiCl solution in acetone to produce the chloride bridged palladacycle dimers as brown solid (HFCO-1). The chemical structure is confirmed by ESI-MS, IR, 1H NMR and 13 C NMR spectra (Figure S3-S5 in the supporting information). The neutral form of the palladacycle was slight soluble in water, and soluble in basic water, acetone, DMF, and DMSO. The spectral properties of HFCO-1 was first investigated in aqueous solution buffered at physiological pH (20 mM HEPES, pH 7.4, 50% EtOH). HFCO-1 dissolved in HEPES buffer solution showed weak fluorescence with maximum emission at 415 nm (ɸf = 0.009). The low fluorescence quantum yield could be attributed to the heavy atom electronic effects of palladium.14 The reaction of HFCO-1 with CO was then examined by bubbling gaseous CO to the solution of HFCO-1. The exposure of HFCO-1 (1 µM in 20 mM HEPES buffer, pH 7.4) to CO resulted in a rapid and dramatic fluorescence turn-on at 415 nm (Figure S6 in the supporting information). Meanwhile, the solution changed from no fluorescence to bright blue fluorescence under a UV lamp, which could be clearly visualized with the naked eyes. Within 20 min after exposure to excess amounts of CO, a 20-fold fluorescence increment was achieved. The fluorescence quantum yield of the probe increased more than 20 times (QY = 0.28) as measured at 20 min after exposure to CO. Here the concentration of free ligand of BBA was determined to be 1.9 µM.

Figure 1. Kinetic responses of HFCO-1 to CORM-2 at different concentrations under physiological conditions. Increments of fluorescent intensity of the probe HFCO-1 (1 µM) against time after the addition of different amounts of carbon monoxide (CORM-2, 0-8.0 µM). For confirmation, the addition of carbon monoxide aqueous solution to the probe solution also quickly increased the fluorescence intensity. For accurate quantification, carbon monoxide releasing molecules (CORM-2) were selected as a CO source for the remaining experiments because its concentration could be easily controlled. It has been documented that approximately 0.7 moles of CO could be liberated for each mole of CORM-2.32 The reaction kinetics of the HFCO-1 probe in HEPES buffer solution to various concentrations of CORM-2 was first investigated. As shown in Figure 1, the fluorescence intensities gradually increased after the addition of CORM-2 and reached the maxima in 20 min. The fluorescence intensities of the HFCO-1 probe kept almost constant after 20 min irradiation at 320 nm, showing a good photostability under the assay conditions, which is important for a potentially applicable probe. For consistent, the experimental data were all obtained at 20 min after the addition of CORM-2 for quantitative analysis (Figure 2). It was demonstrated that the HFCO-1 showed a good dose−response to CORM-2 in a linear relationship (R2 = 0.996). The limit of detection (LOD) and limit of quantification (LOQ) for CO were calculated using the equations: LOD = 3 σ/k and LOQ = 10 σ/k, respectively, where σ is the standard deviation of a blank, and k is the slope of the calibration line. A good limit of detection (LOD) for CO at ∼ 0.06 µM was obtained, and the limit of quantification was estimated to be ∼ 0.18 µM, which is comparable to that of the ruthenium(II) complex (1 ppb) for gaseous CO26 and much lower than most of those reported CO probes.13, 14, 20-22

Figure 2. The fluorescence spectra of the probe HFCO-1 after the addition of CORM-2 (0-8 µM) in 20 mM HEPES buffer solution (pH 7.4, EtOH 50% v/v) (λem = 415 nm, λex = 320 nm). Inset

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ACS Sensors shows the dose−response curve for the fluorescence intensity of HFCO-1 (1 µM) with the added amount of CORM-2 (I/I0 = 1.743 + 3.019x, R2 = 0.994). x represents the concentration of added CORM-2. I and I0 are the fluorescence intensity of the probe after and before the addition of CORM-2. The selectivity of HFCO-1 toward other biologically relevant reactive oxygen or nitrogen species including hydrogen peroxide (H2O2), superoxide anions (·O2-), tert-butyl peroxyl radical (TBO·), tert-butylhydroperoxide (TBHP), nitric oxide (NO), peroxynitrite (ONOO-), hydrogen sulfide (H2S), and hydroxyl radical (·OH) were examined at the same conditions as CO (Figure 3). In addition, other species such as nitrogen bases tryptophan (Trp), serine (Ser), sulfur species (GSH, Cys, Hcy) and ions (F-, NO2-, I-) were also evaluated for the reactive performance to probe HFCO-1. Clearly, only CO turns on the fluorescence intensity of HFCO-1 within 20 minutes, and other species failed to turn on the fluorescence or showed negligible fluorescence enhancement. The results indicate that HFCO-1 does not react with other species or the reaction rate is very slow in buffer solution. The high selectivity of HFCO-1 could be used for the determination of CO in physiological conditions. The good selectivity can be attributed to the strong coordination-insertion ability of CO to the Pd-C bond in the structure of palladacycles.20

Figure 3. Time-dependent fluorescence responses of 1 µM HFCO-1 to CO and other biologically relevant reactive oxygen, nitrogen, and sulfur species. The bars represent increased fluorescence intensity at 415 nm at 1, 3, 5, 10, and 20 min after addition of various species. 1, Control (HFCO-1, 1 µM); 2, CO (CORM-2, 8 µM); 3, HClO (NaClO, 20 µM); 4, H2O2 (200 µM); 5, TBHP (tBuOOH, 20 µM); 6, H2S (Na2S, 20 µM ); 7, ·OH (20 µM); 8, ·O2(20 µM); 9, NO (DEA/NO, 20 µM); 10, ONOO− (20 µM); 11, Trp (20 µM); 12, Ser (20 µM); 13, Cys (100 µM); 14, Hcy (100 µM); 15, GSH (100 µM); 16, I- (20 µM);17, F- (20 µM); 18, NO2- (20 µM);. All data were acquired in 20 mM HEPES (EtOH 50% v/v) at pH 7.4 (λex = 320 nm, λem = 415 nm). The reaction mechanism between HFCO-1 and CO was investigated by using absorption spectral and MS spectral measurements. The HFCO-1 dissolved in HEPES buffer solution initially shows a clear absorption band at 304 nm (Figure S7 in supporting information). After addition of CO, the absorption band increased with time, accompanied by a new absorption band at 317 nm emerging. Meanwhile, the original absorption shoulder at about 400 nm gradually decreased, leading to the formation of an isosbestic point at 376 nm. The results suggested that the coordination state has been altered upon addition of CO and the BBA ligand may be liberated from the complex. This is further confirmed by the identical absorption spectra between BBA and the reaction products HFCO-1 with CO (Figure S7b).

To verify the above assumption, the chemical structure of ligand BBA, complex HFCO-1, and the reaction product with CO were further investigated by ESI-MS spectroscopy. The ligand BBA shows a deprotonated peak at m/z = 236.98 (Figure S8a), while HFCO-1 shows a single molecule state at m/z = 376.82 and its chloride dimer at m/z = 756.71 in negative mode (Figure S8b), respectively. The high resolution mass spectra confirm the chemical structure of HFCO-1. CO reacted with HFCO-1 and clearly gave the release of BBA with m/z = 236.98 from the complex (Figure S8c). These results showed that the Pd complex functions protonolysis upon addition of CO20. The mechanism was similar with that reported by Lin’s group18, 20 but different with that of Chang’s probe11.

Figure 4. Fluorescence microscopy images of CO in living A549 cells using HFCO-1 under UV light excitation. (a) bright-field image of A549 cells incubated with HFCO-1 (1 µM) for 20 min at 37 °C. (b) fluorescence image of (a); (c) bright-field image of A549 cells incubated with 2 µM CORM-2 for 30 min at 37 °C and 1 µM HFCO-1 for the final 20 min; (d) fluorescence image of (c); (e) bright-field image of A549 cells incubated with 10 µM CORM-2 for 30 min at 37 °C and 1 µM HFCO-1 for the final 20 min; (f) fluorescence image of (e). Finally, the probe HFCO-1 has been applied to visualize CO in live human lung adenocarcinoma A549 cells using fluorescence microscopy. For potential bio-imaging and bio-sensing application in living cells, the cytotoxicity of the probe was firstly evaluated with MTT viability assay which was performed on A549 cells incubated with the probe at various concentrations from 0.5 to 10 µM for 12 hours and 24 hours, respectively (Figure S9). The MTT results clearly show that the cell viability is higher than 92% even incubated with 10 µM of HFCO-1 for 24 hours, suggesting the low cytotoxicity of the probe HFCO-1 to A549 cells. The fluorescence imaging was then performed in the A549 cells (Figure 4). The living cells were incubated with either CORM-2 (2 µM and 10 µM, respectively) or a vehicle control for 30 min, and then the cells were treated with 1 µM HFCO-1 for another 20 min. As a control, the A549 cells incubated with only the probe HFCO1 showed almost no fluorescence (Figure 4a-b). However, the cells treated with CORM-2 (2 µM and 10 µM, respectively) and further treated with the probe exhibit brighter fluorescence (Figure 4c-d and Figure 4e-f). Further experiment on the fluorescence imaging for CO with less incubation time (5 and 10 min) showed

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that 10 min incubation of the probe could light on the fluorescence of the cells pretreated with CORM-2, which means that the probe also exhibited fast response to CO in vivo (Figure S10). Encouraged by the above result, we further investigated the performance of the probe HFCO-1 for imaging endogenous CO, which would be naturally produced by the action of heme oxygenase (HO) on the heme from the rupture of hemoglobin.2 It is reported that heme can increase HO-1 expression which lead to subsequent CO generation. So the cells were treated with hemin chloride to increase the intracellular CO levels (Figure S11). When the cells incubated with hemin for 4h followed by probe HFCO-1 for 20 min, a clear blue fluorescence image was observed. In comparison, no fluorescence enhancement was obtained for the control cells pretreated with probe HFCO-1 only. In addition, a more remarkable response was presented when the cells were treated with hemin for 8h, where more CO was generated. The results indicate that the probe HFCO-1 is cell permeable, low-toxic, and capable for cell imaging and detection of CO in vivo. In summary, we have synthesized a highly sensitive and selective turn-on fluorescence probe for CO in buffer solutions and living cells. The reaction was based on the carbonylation of palladacycle involved in CO insertion mechanism by building a functionalized palladacycle with low background fluorescence. The palladacycle probe was no fluorescent and could release the highly fluorescent ligand in the presence of CO or CO donor. The probe has then been demonstrated for CO detection with sensitive and fast response in buffer solutions. Quantitative analysis showed a good limit of detection (LOD) for CO at ∼ 0.06 µM, and the limit of quantification was ∼ 0.18 µM, respectively. Intracellular imaging results indicate that the probe is cell permeable, low-toxic, and capable for cell imaging and detection of CO in vivo. The probe displays advantages such as being easy-to-make, fast and selective fluorescence turn-on response. Next efforts will be focused on the construction of new probes giving visible or near infra-red fluorescence with good biocompatibility and realtime properties.

ASSOCIATED CONTENT Supporting Information Details about the characterization of the probe, spectra and mechanism data as shown in Figures S1−S11. The Supporting Information is available free of charge on the ACS Publications website.

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]; [email protected].

Author Contributions §

M. S and H. Y contributed equally to this work.

ACKNOWLEDGMENT We acknowledge the financial support from the National Key Research and Development Program of China (2017YFA0207000), the National Natural Science Foundation of China (Grant Nos. 21475134, 21507135, 21775042, 21302187 and 91439101), the Fundamental Research Funds for the Central Universities (2016ZZD06). DH thanks Singapore Ministry of Education for financial support (grant no: MOE2014-T2-1-134).

REFERENCES (1) Motterlini, R.; Otterbein, L. E., The therapeutic potential of carbon monoxide. Nat. rev. Drug discov. 2010, 9, 728-743.

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(2) Wu, L.; Wang, R., Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmaco. Rev. 2005, 57, 585-630. (3) Motterlini, R.; Haas, B.; Foresti, R., Emerging concepts on the antiinflammatory actions of carbon monoxide-releasing molecules (CO-RMs). Medical Gas Research 2012, 2, 28. (4) Konopacky, Q. M.; Barman, T. S.; Macintosh, B. A.; Marois, C., Detection of carbon monoxide and water absorption lines in an exoplanet atmosphere. Science 2013, 339, 1398-1401. (5) Cao, Y.; Li, D. W.; Zhao, L. J.; Liu, X. Y.; Cao, X. M.; Long, Y. T., Highly selective detection of carbon monoxide in living cells by palladacycle carbonylation-based surface enhanced Raman spectroscopy nanosensors. Anal. Chem. 2015, 87, 9696-9701. (6) Zhang, Y.; Guan, L.; Yu, H.; Yan, Y.; Du, L.; Liu, Y.; Sun, M.; Huang, D.; Wang, S., Reversible Fluorescent Probe for Selective Detection and Cell Imaging of Oxidative Stress Indicator Bisulfite. Anal. Chem. 2016, 88, 4426-31. (7) Yu, H.; Du, L.; Guan, L.; Zhang, K.; Li, Y.; Zhu, H.; Sun, M.; Wang, S., A ratiometric fluorescent probe based on the pi-stacked graphene oxide and cyanine dye for sensitive detection of bisulfite. Sens. Actuators, B 2017, 247, 823-829. (8) Benito-Garagorri, D.; Puchberger, M.; Mereiter, K.; Kirchner, K., Stereospecific and reversible CO binding at iron pincer complexes. Angew. Chem. Int. Ed. 2008, 47, 9142-9145. (9) Heylen, S.; Martens, J. A., Progress in the chromogenic detection of carbon monoxide. Angew. Chem. Int. Ed. 2010, 49, 7629-7630. (10) Moragues, M. E.; Esteban, J.; Ros-Lis, J. V.; Martinez-Manez, R.; Marcos, M. D.; Martinez, M.; Soto, J.; Sancenon, F., Sensitive and selective chromogenic sensing of carbon monoxide via reversible axial CO coordination in binuclear rhodium complexes. J. Am. Chem. Soc. 2011, 133, 15762-15772. (11) Marin-Hernandez, C.; Toscani, A.; Sancenon, F.; Wilton-Ely, J. D.; Martinez-Manez, R., Chromo-fluorogenic probes for carbon monoxide detection. Chem. Commun. 2016, 52, 5902-5911. (12) Zhang, Y.; Cui, S.; Chang, J.; Ocola, L. E.; Chen, J., Highly sensitive room temperature carbon monoxide detection using SnO2 nanoparticle-decorated semiconducting single-walled carbon nanotubes. Nanotechnology 2013, 24, 025503. (13) Wang, J.; Karpus, J.; Zhao, B. S.; Luo, Z.; Chen, P. R.; He, C., A selective fluorescent probe for carbon monoxide imaging in living cells. Angew. Chem. Int. Ed. 2012, 51, 9652-9656. (14) Michel, B. W.; Lippert, A. R.; Chang, C. J., A reaction-based fluorescent probe for selective imaging of carbon monoxide in living cells using a palladium-mediated carbonylation. J. Am. Chem. Soc. 2012, 134, 15668-15671. (15) Heinemann, S. H.; Hoshi, T.; Westerhausen, M.; Schiller, A., Carbon monoxide--physiology, detection and controlled release. Chem. Commun. 2014, 50, 3644-3660. (16) Yuan, L.; Lin, W.; Tan, L.; Zheng, K.; Huang, W., Lighting up carbon monoxide: fluorescent probes for monitoring CO in living cells. Angew. Chem. Int. Ed. 2013, 52, 1628-1630. (17) Li, Y.; Wang, X.; Yang, J.; Xie, X.; Li, M.; Niu, J.; Tong, L.; Tang, B., Fluorescent Probe Based on Azobenzene-Cyclopalladium for the Selective Imaging of Endogenous Carbon Monoxide under Hypoxia Conditions. Anal. Chem. 2016, 88, 11154-11159. (18) Liu, K.; Kong, X.; Ma, Y.; Lin, W., Rational Design of a Robust Fluorescent Probe for the Detection of Endogenous Carbon Monoxide in Living Zebrafish Embryos and Mouse Tissue. Angew. Chem. Int. Ed. 2017, 56, 13489-13492. (19) Torre, C.; Toscani, A.; Marin-Hernandez, C.; Robson, J. A.; Terencio, M. C.; White, A. J. P.; Alcaraz, M. J.; Wilton-Ely, J.; MartinezManez, R.; Sancenon, F., Ex Vivo Tracking of Endogenous CO with a Ruthenium(II) Complex. J. Am. Chem. Soc. 2017, 139, 18484-18487. (20) Zheng, K.; Lin, W.; Tan, L.; Chen, H.; Cui, H., A unique carbazole–coumarin fused two-photon platform: development of a robust two-photon fluorescent probe for imaging carbon monoxide in living tissues. Chem. Sci. 2014, 5, 3439. (21) Yan, T.; Chen, J.; Wu, S.; Mao, Z.; Liu, Z., A rationally designed fluorescence chemosensor for on-site monitoring of carbon monoxide in air. Org. Lett. 2014, 16, 3296-3299. (22) Pal, S.; Mukherjee, M.; Sen, B.; Mandal, S. K.; Lohar, S.; Chattopadhyay, P.; Dhara, K., A new fluorogenic probe for the selective detection of carbon monoxide in aqueous medium based on Pd(0) mediated reaction. Chem. Commun. 2015, 51, 4410-4413.

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ACS Sensors (23) Feng, W.; Liu, D.; Feng, S.; Feng, G., Readily Available Fluorescent Probe for Carbon Monoxide Imaging in Living Cells. Anal. Chem. 2016, 88, 10648-10653. (24) Yan, J.-w.; Zhu, J.-y.; Tan, Q.-f.; Zhou, L.-f.; Yao, P.-f.; Lu, Y.-t.; Tan, J.-h.; Zhang, L., Development of a colorimetric and NIR fluorescent dual probe for carbon monoxide. RSC Adv. 2016, 6, 65373-65376. (25) Feng, W.; Hong, J.; Feng, G., Colorimetric and ratiometric fluorescent detection of carbon monoxide in air, aqueous solution, and living cells by a naphthalimide-based probe. Sens. Actuators, B 2017, 251, 389-395. (26) Moragues, M. E.; Toscani, A.; Sancenon, F.; Martinez-Manez, R.; White, A. J.; Wilton-Ely, J. D., A chromo-fluorogenic synthetic "canary" for CO detection based on a pyrenylvinyl ruthenium(II) complex. J. Am. Chem. Soc. 2014, 136, 11930-11933. (27) Toscani, A.; Marin-Hernandez, C.; Moragues, M. E.; Sancenon, F.; Dingwall, P.; Brown, N. J.; Martinez-Manez, R.; White, A. J.; WiltonEly, J. D., Ruthenium(II) and osmium(II) vinyl complexes as highly sensitive and selective chromogenic and fluorogenic probes for the sensing of carbon monoxide in air. Chem. Eur. J. 2015, 21, 14529-14538. (28) Dupont, J.; Consorti, C. S.; John, S., The Potential of Palladacycles: More Than Just Precatalysts. Chem. Rev. 2005, 105, 25272571. (29) García-López, J.-A.; Oliva-Madrid, M.-J.; Saura-Llamas, I.; Bautista, D.; Vicente, J., Reactivity toward CO of Eight-Membered Palladacycles Derived from the Insertion of Alkenes into the Pd–C Bond of Cyclopalladated Primary Arylalkylamines of Pharmaceutical Interest. Synthesis of Tetrahydrobenzazocinones, Ortho-Functionalized Phenethylamines, Ureas, and an Isocyanate. Organometallics 2012, 31, 6351-6364. (30) Sun, M.; Du, L.; Yu, H.; Zhang, K.; Liu, Y.; Wang, S., An intramolecular charge transfer process based fluorescent probe for monitoring subtle pH fluctuation in living cells. Talanta 2017, 162, 180-186. (31) Kus, C.; Sozudonmez, F.; Altanlar, N., Synthesis and antimicrobial activity of some novel 2-[4-(substituted piperazin-/piperidin1-ylcarbonyl)phenyl]-1H-benzimidazole derivatives. Arch. Pharm. 2009, 342, 54-60. (32) Motterlini, R., Carbon Monoxide-Releasing Molecules: Characterization of Biochemical and Vascular Activities. Circ. Res. 2002, 90, e17-e24.

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Table of Contents (TOC)

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