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Instantaneous Colorimetric and Fluorogenic Detection of Phosgene with a Meso-Oxime-BODIPY Tae-Il Kim, Byunghee Hwang, Jean Bouffard, and Youngmi Kim Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.7b03316 • Publication Date (Web): 15 Nov 2017 Downloaded from http://pubs.acs.org on November 15, 2017

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Analytical Chemistry

Instantaneous Colorimetric and Fluorogenic Detection of Phosgene with a Meso-Oxime-BODIPY Tae-Il Kim,† Byunghee Hwang,† Jean Bouffard ‡ and Youngmi Kim*,† †

Department of Chemistry and Research Institute of Basic Sciences, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea, E-mail: [email protected], Fax: +82-2-961-0443 ‡ Department of Chemistry and Nano Science (BK 21 Plus), Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Korea ABSTRACT: The meso-oxime-substituted-1,3,5,7-tetramethyl BODIPY (1-oxime) was developed into a colorimetric and fluorogenic probe to selectively detect and quantify phosgene. The fast (< 10 s) and sensitive (LOD = 0.09 ppb) phosgene detection is achieved by the conversion of the meso-oxime to the meso-nitrile, resulting in a large fluorescence turn-on response. The utility of 1-oxime was established for the visual detection of phosgene in solution and in a practical solid-state platform, making it a suitable candidate for on-site monitoring of phosgene gas exposure in the workplace.

Phosgene (COCl2) is an important industrial chemical used in the manufacture of isocyanates as precursors to polyurethanes and polycarbonates, pesticides, dyes, and pharmaceuticals.1,2 It is a highly toxic gas even at low concentrations, for which it gained notoriety as the most deadly chemical warfare agent used during World War I.3 Although less lethal than other chemical weapons such as nerve gases, it is still considered as a viable chemical weapon for terrorist attacks because it can be easily made. Shortterm exposure to phosgene (> 3 ppm) causes irritation to the eyes, nose, throat, skin, and respiratory tract.4−9 Exposure to concentrations greater than 600 mg⋅min⋅m-3 may cause severe breathing difficulty and pulmonary edema.4−9 The U.S. National Institute for Occupational Safety and Health (NIOSH) recommends a permissible exposure limit (PEL) of 0.1 ppmv and specifies a concentration immediately dangerous to life and health (IDLH) of 2 ppmv. 10 In addition to industrial accidents and nefarious releases, phosgene can be also inadvertently generated from the thermal decomposition of chlorinated hydrocarbons and the photooxidation of chloroethylenes. Consequently, efficient and reliable methods to monitor occupational exposure to phosgene are essential for the health and safety of workers at risk in the workplace, and to survey contamination in the environment following industrial accidents. Detection technologies for monitoring phosgene have been developed, including chromatographic techniques coupled with mass spectrometry (GC/MS,11−13 HPLC/MS14,15), electrical methods,16−18 colorimetric procedures,19−21 and fluorogenic methods.22−31 Among them, fluorescence-based sensing systems are advantageous because of their operational simplicity, high sensitivity, low cost, and convenience for field use. Most fluorescent probes for phosgene reported so far share a common sensing scheme employing the acylation reaction of amine-containing coumarin,22,23 naphthalimide,24,25 BODIPY,26,27 rhodamine,28 pyronin,29 or benzothiadiazole30 fluorophores. In these designs, the fluorescence “off-on” switching mechanisms are based on the suppression of a photoinduced electron transfer (PeT)23,26,29 or intramolecular charge transfer (ICT)24,25,27,30 that results from the transformation of the electron-donating amine group to the electron-withdrawing urea derivative (Scheme 1a). Other approaches

rely on the modulation of fluorescence resonance energy transfer (FRET) via phosgene-induced covalent cross-linking (Scheme 1a),22 the ring opening of rhodamine derivatives,28 or the cyclization of a flexible chromophore precursor.31 Scheme 1. (a) Schematic illustration of previously developed fluorescent probes for phosgene detection based on PeT, ICT, or FRET mechanisms using amine-containing fluorophores. (b) Design of the colorimetric and fluorimetric phosgene probe 1-oxime that relies on the conversion of the meso-oxime to the meso-nitrile.

The output signal of amine-based fluorescent probes relying on PeT or ICT mechanisms is subject to the interference of acids, oxidizing agents, and acylating/phosphorylating chemicals, leading to false responses.32−35 In this paper, we report on a new design for a phosgene-selective fluorescent probe that was stimulat-

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ed by our earlier observation that the absorption/emission profiles, and the fluorescence quantum yields of meso-substituted-1,3,5,7tertramethyl BODIPY dyes are highly dependent on the sterics and electronics of their meso-substituents.36 In particular, 1,3,5,7tetramethyl BODIPY derivatives bearing sterically demanding substituents at the meso-position are associated with non-radiative relaxation pathways, resulting in markedly low fluorescence quantum yields (ΦF < 0.1). Moreover, the electronic transition energies are correlated with the Hammett substituent constants (σp) values for the meso substituents. Taking advantage of these features, we designed the meso-oxime-1,3,5,7-tetramethyl BODIPY (1-oxime, Scheme 1b) for the detection of phosgene, relying on its fast and selective dehydration to the corresponding nitrile (1-nitrile).

EXPERIMENTAL SECTION Materials and Instrumentation. All reagents were of the highest commercial quality and used as received without further purification. All solvents were spectroscopic grade unless otherwise noted. Anhydrous ethanol, pyridine, triphosgene, acetyl chloride, oxalyl chloride, p-toluenesulfonyl chloride (p-TsCl), diethyl chlorophosphate (DCP), and diethyl cyanophosphonate (DCNP) were obtained from Alfa Aesar. Polyethylene oxide (PEO, MW = 200,000) and phosphorus oxychloride (POCl3) were obtained from Sigma-Aldrich (Saint Louis, MO). Thionyl chloride (SOCl2), HCl, trifluoroacetic acid (TFA) and triethylamine (TEA) were obtained from Samchun Chemicals (Korea). Silica gel (40 µm) was obtained from Merck. Compounds meso-formyl-1,3,5,7tetramethyl-BODIPY (2) and 1-nitrile were prepared as described in the literature.36,37 Synthetic manipulations that required an inert atmosphere (where noted) were carried out under argon using standard Schlenk techniques. NMR (1H and 13C) spectra were recorded on Bruker 400 MHz spectrometer or JEOL 400 MHz spectrometer. The 1H and 13C chemical shifts were reported as δ in units of parts per million (ppm), referenced to the residual solvent. Splitting patterns are denoted as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br (broad). High-resolution electrospray ionization (HR-ESI) mass spectrum was obtained at the Korean National Center for Inter-University Research. Absorption spectra were obtained on a Scinco UV LAMBDA-465 spectrophotometer. Fluorescence measurements were recorded on a Hitachi F-7000 fluorescence spectrophotometer using quartz cuvettes with a path length of 1 cm. Fluorescence quantum yields were determined using fluorescein (ΦF = 0.95 in 0.1 N NaOH) or rhodamine-6G (ΦF = 0.94 in EtOH) as standards. Lifetime measurements were performed using a MicroTime-200 instrument at the Korea Basic Science Institute (KBSI), Daegu Center, South Korea. Synthesis of Probe 1-Oxime. To a stirred solution of compound 236,37 (60 mg, 0.22 mmol) in dry EtOH:pyridine (5 mL, 1:1, v:v) at room temperature was added hydroxylamine hydrochloride (150 mg, 2.2 mmol). After stirring at 60 °C for 10 minutes, the resulting mixture was cooled to room temperature. The reaction solvent was removed under reduced pressure, and the crude product was purified by column chromatography on silica gel using 10:1 hexanes:ethyl acetate as the mobile phase to afford 1-oxime as a red solid (57 mg, 90%).; 1H NMR (CDCl3, 400 MHz): δ = 8.23 (s, 1H), 7.76 (s, 1H), 6.06 (s, 2H), 2.54 (s, 6H), 2.19 (s, 6H); 13 C NMR (CDCl3, 100 MHz): δ = 157.0, 145.3, 142.3, 131.4, 129.7, 121.4, 16.1, 14.7; HR-MS (ESI): calcd. for C14H17N3OF2B [M+H]+ 292.1433, found 292.1433. Colorimetric and Fluorimetric Assays in Solution. Assays were carried out by titrating aliquots of triphosgene in CH3CN into a solution of 1-oxime (10 µM) in CH3CN containing triethyl-

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amine (TEA, 100 µM) at room temperature. Changes in the absorption and fluorescence spectra (λexc = 530 nm) of 1-oxime were then monitored. We also studied the colorimetric and fluorescence responses of 1-oxime upon exposure to two nerve gas simulants (diethyl chlorophosphate (DCP), diethyl cyanophosphonate (DCNP)), five acylating/phosphorylating agents (thionyl chloride (SOCl2), phosphorus oxychloride (POCl3), ptoluenesulfonyl chloride (p-TsCl), oxalyl chloride ((COCl)2), acetyl chloride (CH3COCl)), and two acids (trifluoroacetic acid (TFA), HCl), in solution and in the solid state. Solid-State Phosgene Sensing. The 1-oxime/PEOimpregnated TLC plate was prepared by dropping 5 µL of premixed solution of 1-oxime (1 mM) and polyethylene oxide (PEO, 0.3 mM) in CH2Cl2, on a piece of TLC plate (15 mm x 15 mm) and drying under air. Phosgene vapors at various concentrations were prepared, according to the literature procedure.26 Five concentrations of triphosgene solutions (0.675, 6.75, 33.75, 67.5, and 135 mM) were prepared in CHCl3, and 10 µL aliquots of each solution were deposited into 5 mL cylindrical vial, respectively, followed by the addition of 10 µL of CHCl3 containing 0.1% TEA to each vial. The 1-oxime/PEO-impregnated TLC plate was exposed to phosgene gas for 30 seconds, and all photos were taken under daylight and UV irradiation (365 nm).

RESULTS AND DISCUSSION Synthesis. The meso-oxime-1,3,5,7-tetramethyl-BODIPY dye 1-oxime was conveniently synthesized by reacting the corresponding meso-formyl-substituted dye 236,37 with hydroxylamine hydrochloride and pyridine (Scheme 2). The expected product of the sensing scheme 1-nitrile was also synthesized independently, according to previously reported procedures.36 Scheme 2. Synthetic scheme for 1-oxime.

Table 1. Photophysical properties of compounds in CH3CN. Compound

λabs,max [nm]

ΦFc

[M cm ]

λem,maxb [nm]

τavd [ns]

εa -1

-1

1-oxime

508

82000

533

0.0001

0.38

1-nitrile

554

105000

572

0.67

5.41

a Measured at each absorption maximum. bExcited at 480 nm for 1oxime and at 530 nm for 1-nitrile. cQuantum yields vs. Fluoroscein in 0.1 N NaOH (ΦFL = 0.95) for 1-oxime. Quantum yields vs. Rhodamine-6G in EtOH (ΦFL = 0.94) for 1-nitrile. dWeighted mean lifetime.

Photophysical Properties. The photophysical properties of 1oxime and 1-nitrile were first investigated (Table 1 and Figures S1− S3). Their absorption and emission profiles are negligibly affected by solvent polarity (Table S1). In CH3CN, probe 1-oxime displays absorption and emission maxima at 508 nm and 533 nm, respectively. As previously reported,36 1-nitrile exhibits red-shifted absorption and emission maxima (λmax,abs = 554 nm, λ max,em = 572 nm) as a consequence of the increased electron-withdrawing character of the CN group. Trends in the electronic transition energies for 1-oxime vs. 1-nitrile are in qualitative agreement with the calculated HOMO-


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LUMO gap (Figure 1a). These calculations also highlight the role of electron-withdrawing meso-substituents to preferentially stabilization the LUMO, and the lack of effective π-conjugation because the oxime group is nearly orthogonal to the plane of the chromophore in 1oxime, as a result of hindrance from the flanking methyl groups at the 1- and 7-positions. Unlike the typical BODIPY dyes that are strongly emissive in solution, 1-oxime is poorly luminescent with low fluorescence quantum yield (ΦF ~ 0.0001 in CH3CN), which is in sharp contrast with highly fluorescent 1-nitrile (ΦF = 0.67). The low fluorescence quantum yield and short excited-state lifetime for 1-oxime reflect a 43fold increase in its non-radiative deactivation rate constant (knr) by comparison to that of 1-nitrile (1-oxime: knr =2.6 x 109 s-1 τav = 0.38 ns; 1-nitrile: knr =6.1 x 107 s-1 τav = 5.41 ns, Table S2 and Figure S4), as expected for sterically congested 1,3,5,7-tetramethyl BODIPYs.36,38,39 This is consistent with the deviation from planarity of the boradiazaindacene ring system in the calculated optimized groundstate geometry of 1-oxime (Figure 1a). The importance of nonradiative deactivation pathways in 1-oxime is also supported by the marked dependence of its emission efficiency on medium viscosity, as observed in a frozen MeTHF glass (Figure 1b) or in a viscous glycerol solution (Figure 1c and Figure S5). Accordingly, the large differences between the photophysical properties of 1-oxime and 1nitrile (∆λabs = 46 nm; ∆λem = 39 nm; ΦF,1-nitrile/ΦF,1-oxime = 6700) make the oxime-to-nitrile conversion a suitable optical transducer to signal the detection of phosgene.

Figure 1. (a) Calculated frontier molecular orbitals for 1-oxime (left) and 1-nitrile (right) and their orbital energies (Hartrees). (b) Fluorescence emission spectra of 1-oxime in MeTHF at different temperatures (black: 298 K; red: 77K). Emission spectrum of 1-oxime at 298 K (black) is magnified 20-fold. (c) Fluorescence emission spectra of 1-oxime in ethanol-glycerol mixtures with different glycerol fractions (fglycerol (vol%), bottom to top; 0, 10, 25, 50, 75, 90, 99%) at 25 °C. Excited at 480 nm. [1-oxime] =10 µM. Phosgene Sensing in Solution. Due to the high toxicity of phosgene, triphosgene was used as a safer phosgene source. Phosgene was generated in-situ by the breakdown of triphosgene (bis(trichloromethyl) carbonate) in the presence of triethylamine (TEA).1 Assays were carried out by titrating in aliquots of triphosgene (0−50 µM) into a solution of 1-oxime (10 µM) in CH3CN containing TEA (100 µM, Figures S6−S8) at 25 oC. Changes in absorption and fluorescence emission (λex 530 nm) spectra were then monitored (Figure 2, and Figures S9−S13). The addition of triphosgene to 1-oxime immediately triggered red-shifts in the absorption and emission spectra consistent with the anticipated oxime-to-nitrile conver-

sion. Upon addition of triphosgene, the solution changes from light salmon to pink, as the absorption band at 508 nm decreases markedly, and the absorption band of 1-nitrile emerges and increases at 554 nm (Figure 2a). The single isosbestic point at 525 nm indicates the presence of only one spectroscopically distinct product, 1-nitrile. More noticeably, the reaction of 1-oxime with triphosgene in CH3CN-TEA resulted in an instant growth of a red-shifted emission band at 570 nm, and a dramatic enhancement of the emission intensity was observed depending on the concentration of triphosgene (Figures 2b and 2d). Time course studies revealed that the fluorescence turn-on process was complete within 10 seconds (Figure 3a and Figure S14). When 1 equivalent of triphosgene (≈ 3 equivalents of phosgene) was added, the solution of 1-oxime exhibited a ca. 11,000-fold increase in fluorescence intensity at 570 nm. A distinct change from a non-emissive solution to an intense yellow emission is easily discerned under a hand-held UV lamp (365 nm) (Figure 2b inset). Instant spectral responses of 1-oxime toward triphosgene/TEA were similarly observed in different solvents such as toluene and CH2Cl2 at 25 oC (Figures S15−S17).

Figure 2. (a) Absorption and (b) fluorescence emission spectra of 1oxime (10 µM) in CH3CN containing TEA (100 µM) immediately after the addition of different amounts of triphosgene (0–50 µM) at 25 °C. λexc=530 nm. Insets: Photographs of 1-oxime in CH3CN-TEA before (left) and after (right) the addition of triphosgene (20 µM), under ambient light (a) and 365 nm UV light (b). (c) Plot of the absorbance at 554 nm (A554) as a function of [triphosgene] (0−50 µM). Inset: Linear correlation between A554 and [triphosgene] (0−10 µM). (d) Plot of the relative fluorescence intensity (F/F0) at 570 nm as a function of [triphosgene] (0−50 µM). Inset: Linear correlation between F/F0 at 570 nm and [triphosgene] (0−10 µM). F0 and F correspond to the fluorescence intensity at 570 nm before and after the addition of triphosgene, respectively. A good linear correlation (R2 = 0.991) between the fluorescence intensity at 570 nm (F/F0) and the concentration of triphosgene in the range of 0–10 µM was also found (Figure 2d, inset). The detection limit was determined to be 0.31 nM for triphosgene, corresponding to 0.09 ppb phosgene, on the basis of 3σ/k (Figure S18), where σ is the standard deviation of a set of blank measurements (n = 25) and k is the slope of the calibration curve. Detection of phosgene by 1oxime is faster than for previously reported fluorescent probes, and its analytical sensitivity is also superior.40 Moreover, both 1-oxime and 1-nitrile in CH3CN displayed excellent photostability under continuous irradiation at a wavelength of 500 nm for 1 hour (Figure 3b). To confirm that the spectral responses could be attributed to the



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conversion of 1-oxime to 1-nitrile, as described in Scheme 1b, 1H NMR titration experiments and LC-MS analyses were carried out. 1H NMR spectra recorded after adding triphosgene−TEA to a solution of 1-oxime in CD3CN (Figure 4), showed that the hydroxyl proton (Ha) signal at 9.5 ppm and the formyl proton (Hb) signal at 8.2 ppm of 1oxime disappeared, and that pyrrolic proton signals were slightly shifted to downfield (Hc to Hc’), indicating the conversion of 1-oxime to 1-nitrile. LC-MS analysis of the assay solutions also corroborated the exclusive formation of 1-nitrile (Figure S19).

Figure 3. (a) Time-dependent increase in fluorescence intensity (λem = 570 nm) of 1-oxime (10 µM) in CH3CN-TEA at 25 °C upon addition of triphosgene (bottom to top: 0−50 µM). λex = 530 nm. (b) Photostability of 1-oxime (10 µM) and 1-nitrile (10 µM) in CH3CN at 25 °C. The remaining relative fluorescence intensities of 1-oxime (black) and 1-nitrile (red) as a function of irradiation time (0–3600 sec). Fluorescence intensities were measured at 533 nm for 1-oxime and at 572 nm for 1-nitrile. Irradiated at 500 nm.

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turn-on response of 1-oxime for phosgene (either triphosgene/TBACl or triphosgene/TBABr) over other electrophilic compounds was maintained (Figures S21−S23). However, assays with triphosgene/TBAX (X= Cl, Br) provided lower fluorescence turn-on responses (F/F0 at 570 nm) compared with those carried with triphosgene/TEA. Importantly, no fluorescence change occurs with triphosgene alone before the addition of either nucleophilic catalyst (Figure 5b). These results confirm the superior selectivity of 1-oxime towards phosgene by comparison to amine-based fluorescence probes that are cross-reactive with nerve agent simulants, acylating/phosphorylating chemicals, and simple acids, and would result in false positive responses.

Figure 5. Fluorescence turn-on responses of 1-oxime to various analytes. (a) Emission spectra of 1-oxime in CH3CN immediately (≤ 5 s) after the addition of the analytes at 25 °C. Inset shows relative fluorescence intensity (F/F0) at 570 nm upon addition of various analytes. 1: 1-oxime only as a control, 2: phosgene (triphosgene/TEA), 3: triphosgene, 4: CH3COCl, 5: (COCl)2, 6: POCl3, 7: SOCl2, 8: p-TsCl, 9: HCl, 10: TFA, 11: DCP, 12: DCNP. [1-oxime] = 10 µM. [TEA] = 100 µM. λex = 530 nm. [analyte] = 20 µM for triphosgene in (2) and 100 µM for others. (b) Time-dependent fluorescence responses of 1-oxime (10 µM) in CH3CN upon addition of triphosgene (20 µM), and subsequently addition of TEA (100 µM, blue) and TBABr (100 µM, red), respectively. Photographs of 1oxime immediately (≤ 5 s) after the addition of each analyte under (c) ambient light and (d) UV irradiation (365 nm).

Figure 4. Partial 1H NMR spectra of 1-oxime (1 mM) in CD3CN before (1) and after the addition of TEA (5 mM) and triphosgene (0.5 equiv (2); 1.5 equiv (3)) in CD3CN, and reference NMR spectrum of 1-nitrile (4) in CD3CN. Selectivity. The selectivity of 1-oxime toward phosgene over interfering compounds was assayed against triphosgene itself, five acylating/phosphorylating agents (CH3COCl, (COCl)2, POCl3, SOCl2, p-TsCl), two acids (HCl, TFA), and two nerve gas simulants (DCP, DCNP) (Figure 5). As shown in Figure 5a, a solution of 1oxime in CH3CN displayed a large increase in fluorescence at 570 nm only for phosgene (triphosgene/TEA), and no significant changes occurred with the other generic electrophiles, even at comparatively high concentrations and over extended reaction times (Figure S20). The presence of the TEA base is not required for the conversion of 1oxime to 1-nitrile; it merely acts as a nucleophilic catalyst for the conversion of triphosgene to phosgene in situ. Hence, when TEA was replaced with the nucleophillic though less basic anions Cl- or Br- as their tetrabutylammonium salts,41 the selective fluorescence

Figure 6. Photographs of color (a) and fluorescence (b) responses of TLC plate impregnated with 1-oxime/PEO upon exposure to various amounts of phosgene vapor (left to right: 0, 0.1, 1, 5, 10, 20 ppm) for 30 seconds. The fluorescence response images were taken under UV irradiation (365 nm). The phosgene vapor was generated in-situ by triphosgene in 10 µL chloroform solutions with 0.1% v/v TEA. Each TLC plate was placed in sealed vials containing triphosgene and TEA. Solid-State Phosgene Sensing. Given the promising results from the solution-based assays, we further probed the feasibility of a portable solid-state platform for the detection of phosgene gas based on 1-oxime. The latter would prove more useful to locate phosgene leaks within and around phosgene-processing facilities. For this pur-


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pose, an admixture of 1-oxime (1 mM) and polyethylene oxide (PEO, 0.3 mM) in CH2Cl2 was deposited onto a silica TLC plate (15 mm x 15 mm) and subsequently air-dried to provide a simple solidstate indicator. The TLC plate embedded with 1-oxime/PEO is initially light salmon color, and is non-emissive under a hand-held UV lamp (365 nm). For qualitative phosgene analysis, the TLC plate was placed in sealed chambers where gaseous phosgene was generated in-situ from triphosgene-TEA. As for solution-phase detection, colorimetric and fluorimetric sensory responses were observed within 30 sec exposure of the TLC plates to various amounts of phosgene (0.1−20 ppm, Figure 6). The emission change of the TLC plate was clearly visible even in the presence of only 1 ppm of phosgene. Importantly, whereas target phosgene gas caused noticeable colorimetric and fluorimetric transitions on the 1-oxime/PEO-embedded TLC plate, other interfering compounds did not give rise to false responses (Figure 7).

Figure 7. Photographs of color (a) and fluorescence (b) responses of TLC plate impregnated with 1-oxime/PEO upon exposure to vapor of various analytes for 30 seconds. 1: 1-oxime only as a control, 2: phosgene (triphosgene/TEA), 3: triphosgene, 4: CH3COCl, 5: (COCl)2, 6: POCl3, 7: SOCl2, 8: p-TsCl, 9: HCl, 10: TFA, 11: DCP, 12: DCNP.

CONCLUSION In summary, the phosgene-mediated dehydration of non-emissive probe 1-oxime to the highly fluorescent product 1-nitrile was exploited in the detection and quantification of phosgene in solution, and in the vapor phase following immobilization on a solid substrate. This chemodosimeter features an instant response (< 10 s), large fluorescence turn-on signal (F/F0 up to ca. 11,000-fold for 1 equiv. triphosgene), high sensitivity (LOD = 0.09 ppb), obvious color changes, and excellent selectivity for phosgene over other false positives such as acids, nerve agent simulants, and acylating/phosphorylating chemicals. Potential applications of this probe include the qualitative and quantitative monitoring of phosgene in the chemical industry.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Synthetic scheme, NMR data, and additional experimental details including spectroscopic data, colorimetric and fluorimetric assays in solution and solid state platform, and DFT calculations.

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] (Y.K.). Fax: +82-2-961-0443.

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT This research was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIP)

(NRF-2015R1A2A2A01004632 and NRF-2015R1A5A1008958). The authors thank Dr. Weon-Sik Chae of the KBSI Daegu Center for fluorescence lifetime measurements.

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