Rapid Turn-On Fluorescence Detection of Copper(II): Aromatic

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Rapid Turn-On Fluorescence Detection of Copper (II): Aromatic Substituent Effects on Response Rate Jiyoung Jung, Junyong Jo, and Adriana Dinescu Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.7b00269 • Publication Date (Web): 13 Sep 2017 Downloaded from http://pubs.acs.org on September 14, 2017

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Organic Process Research & Development

Rapid Turn-On Fluorescence Detection of Copper (II): Aromatic Substituent Effects on Response Rate AUTHOR NAMES. Jiyoung Jung 1*, Junyong Jo2* and Adriana Dinescu3

AUTHOR ADDRESS. 1

Penn State University, Dunmore, PA 18512, United States; [email protected]

2

Merck Research Laboratories, Rahway, NJ 07065, United States; [email protected]

3

Centenary University, Hackettstown, NJ 07840, United States; [email protected]

KEYWORDS. Copper; Fluorescence; Turn-on response; Reaction-based probe, Benzotriazole, Azo dye

ABSTRACT. Oxidative cyclization of o-phenylazo aniline was utilized as a turn-on fluorescent probe of copper (II) ion. The number and the position of electron donating groups on the probes were systematically varied to investigate the effect of aryl substituent on reactivity toward

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copper ion. Among the series of analogous probes, the 2,4,6-trimethoxy substituted probe exhibits not only faster (40-times faster) reaction but also lower detection limit (20-times lower) than previously reported probe under the identical conditions. The comparative kinetic studies reveal that both the number and position of substitution have a significant impact on the reactivity toward copper, which will be discussed in the manuscript.

Introduction Copper-mediated catalytic reactions have received extensive attention due to their versatile roles in catalytic cycles. More than ever, recent industrial trends emphasize process development with more earth-abundant metal catalysts1,2 such as copper3, iron4, cobalt5, manganese6 and nickel7. For large scale manufacturing, however, the contamination with those metal ions is one of the biggest quality concerns, so there are enormous efforts to remove elemental impurities from the products8-11. The quality control of such metal ions becomes more pronounced in pharmaceutical compounds because the residual amount of metal impurities can cause various deleterious effects on patients12-17. The specifications of the final drug substance or process intermediates are very tightly regulated by governmental agencies such as FDA, EPA and EMA18-20. Currently, the most common analytical method for residual metal contents is inductively coupled plasma with mass spectrometry (ICP-MS) or optical emission spectrometry (ICP-OES), which provides high accuracy and sensitivity (typically down to ppb level). The major drawback of ICP methods, however, is limited accessibility (presumably due to expensive instrumentation) and limited high-throughput capability21,22. Therefore, there has been a need for alternative methods which are more user-friendly, portable, inexpensive and high-throughput amendable


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making them more suitable for ‘point-of-use’. One appealing approach is the fluorimetric and colorimetric method where a probe molecule shows dramatic changes in emission and/or absorption upon exposure to the target analyte23-29. To date, copper-responding probes had been developed with various approaches30 including chromophore-embeded polymer31 and complex formation32. Herein we disclose our recent development of reaction-based copper detectors and comparative kinetic studies to identify the most practical probe for potential applications. Background: Design considerations The fundamental requirements for a “good” probe molecule would be high sensitivity and selectivity toward the target analyte, such as a metal ion or other toxic anions of interest. More detailed criteria, however, can be differently defined depending on where those probes are applied to. For example, in a biological application such as nitric oxide (NO) detection in kidney33 and mitochondrial hydrogen sulfide (H2S) detection in mammalian cells34, solubility in water and cell permeability would be additional critical components to evaluate the probe molecules. Similarly, as demonstrated in other reported examples with palladium detector molecules, a screening method of residual metal impurities in pharmaceutical compounds requires fast reaction completion to enable high-throughput analysis35. Recently we found a copper-mediated cyclization of ortho-phenylazo aniline where the adjacent azo-aniline moiety undergoes oxidative cyclization by net removal of 2H+/2e–, which is in good agreement with previous reports that describe mechanistic aspect of the reaction36,37. The typical reaction conditions, however, require high temperature and elongated time to complete the chemical transformation38. Based on the mechanistic understanding, we envisioned that implementation of more electron donating groups (EDG) on the probe would accelerate the


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reaction39, and one N,N-diethylamino group indeed renders the reaction to occur at room temperature. Although the reaction rate was also remarkably shortened to approximately 5–10 minutes, such slow reaction limits the capability of high-throughput analysis such as flow injection mode which is normally completed in less than 1 minute35. Thus, a series of probe molecules which have a common skeleton of o-phenylazo aniline as the copper binding site were prepared through a straightforward and modular synthetic route (Scheme 1).

Scheme 1. Synthetic route and methoxy group substituted o-phenylazo aniline.

As shown in the Scheme 1, m-phenylenediamine was chosen as the azo-coupling partner because two amino groups will dictate the coupling position (ortho- and para-position of each amino group, respectively) so that the reaction will exclusively afford the single corresponding


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azo-product. Each substituted aniline was first subjected to acidification followed by diazonium formation with sodium nitrite at low temperature (2–8oC) using an ice bath. The formed diazonium salt was then transferred to the solution of m-phenylenediamine in the basic aqueous methanol to afford the corresponding o-phenylazo anilines in moderate to high yield (70–95%). The position and/or the number of methoxy groups on aniline were systematically differed to facilitate the comparative kinetic studies. Materials and Methods General considerations All reagents were obtained from commercial suppliers and used as received unless otherwise noted. Synthesis Synthesis of other probes 2–5 can be found in Supporting Information. ((2,4,6-trimethoxyphenyl)diazenyl)benzene-1,3-diamine (Probe 1). To a stirred MeOH solution (10 mL) of 2,4,6-trimethoxyaniline (332.48 mg, 1.81 mmol) was added slowly conc. HCl (2.3 mL). At 2−5 °C using an ice bath, an aqueous solution (2 mL) of NaNO2 (161.58 mg, 2.41 mmol) was added dropwise to generate the azonium intermediate, and the reaction mixture was stirred for 5 min. In a separate flask, a solution of m-phenylenediamine (254.42 mg, 2.35 mmol) and sodium hydroxide (751 mg) in MeOH−H2O (1:1, v/v; 5 mL) was kept at 2−5 °C. With stirring, the azonium intermediate was added dropwise to the m-phenylenediamine solution while maintaining the temperature of the reaction at 2−5 oC. After stirring for 30 min, water (200 mL) was added to induce precipitation of a deep purple solid, which was isolated by filtration and washed thoroughly with water to furnish probe 1 (383.57mg, yield = 70%). 1H NMR (400 MHz, CD3CN, 298 K): δ 7.37 (d, J = 8.0 Hz, 1H), 6.58 (dd, J = 8.0, 4.0 Hz, 1H), 6.38 (s, 2H), 5.99 (d, J = 2.0 Hz, 1H), 3.94 (s, 6H), 3.91 (s, 3H); 13C NMR (100 MHz, with TFA in Acetone-d, 298


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K): δ 163.55, 154.69, 134.71, 130.52, 130.34, 127.56, 125.59, 116.31, 115.09, 90.54, 55.21, 54.61. HRMS (ESI) calcd for C15H19N4O3 [M + H]+ 303.1452; found 303.1454. Measurements 1H NMR and 13C NMR spectra were recorded on a 400 MHz Bruker NMR spectrometer. Chemical shifts were reported versus tetramethylsilane and referenced to the residual solvent peaks. High-resolution electrospray ionization (ESI) mass spectra were obtained on a Thermo LTQ Orbitrap. UV-Vis profile of probe molecules solutions were obtained by using a diode array spectrophotometer (Agilent 8453 UV-vis spectrophotometer, Agilent Technologies, Santa Clara, CA) in a quartz cuvette. Fluorescence measurements were conducted on a Modulus II Microplate Multimode Reader with SpectraMax (Molecular Device, Sunnyvale, CA). Fluorescence quantum yields were determined by standard methods,40 using the corresponding benzotriazole of Probe 6 (ΦF = 0.39 in acetonitrile solution; λexc = 320 nm)39 as a standard. The sample absorbance was maintained < 0.1 to minimize internal absorption. Comparative kinetic studies on probes were conducted in MeCN solution by addition of aliquot amount (20 µL – 50 µL) of aqueous stock solution of copper (II) acetate (240 mM) into the solution sample ([probe] = 40 µM, 3 mL) under pseudo-first order kinetic conditions. With constant stirring at T = 298 K, the time-dependent changes in the absorbance were monitored at the absorption maxima of each probe molecule. The ∆A vs time were fitted by a nonlinear regression method (OriginPro 2017) using eq 1, in which the parameters k′ (= k[Cu2+]0) and A (= absorbance at t → ∞) were allowed to vary.


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Results and Discussion Photophysical properties of o-phenylazo anilines and benzotriazoles With a series of ophenylazo anilines in hand, photophysical properties upon exposure to copper (II) ion were investigated. Similar to general azo compounds, the probe molecules 1–5 show a very intense yellow-red color with the range of λabs = 450–600 nm in absorption spectra (Figure 1a). Upon addition of copper (II) ion, however, this feature of the azo compounds disappears and concomitantly a new band at lower wavelength (λabs = 350 nm) appears. While the UV-vis shows ratiometric changes, the o-phenylazo anilines commonly remain almost non-fluorescent in acetonitrile solution as typical azo compounds. Upon addition of copper, molecular probes immediately elicit a strong emission band at λem = 420 nm with high quantum yield (ФF = 16% for probe 1 in MeCN, λex = 335 nm, Figure 1b). Since our series of probe molecules share a common skeleton, the absorption and emission maxima only show a negligible difference regardless of the substitutions (Figure S1–S4 and Table S1).


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Figure 1. (a) UV-vis and (b) fluorescence spectra (λex = 335 nm) of probe 1 prior to (solid line) and after (dotted line) addition of copper (II) ion. [1] = 40 µM in MeCN, T = 298 K. 40 equiv. of Cu2+(aq) added to the solution of 1. Arrows indicate the changes upon addition of copper. Insert: photograph of probe 1 prior to (left) and after (right) copper addition.

Chemical transformation: o-phenylazo anilines to benzotriazoles Chemical transformation from probe 1 to the corresponding benzotriazole has been captured by HPLC, and confirmed by HRMS and NMR. As shown in Figure 2, the starting probe molecule 1 and the cyclized product are readily separated by HPLC with baseline resolution. Chromatograms prior to and after treatment of probe 1 with copper exhibit no significant formation of other peaks which indicates a clean oxidative cyclization of o-phenylazo aniline to benzotriazole. The time-dependent absorption spectra also shows the isosbestic point at λabs = 415 nm which strongly supports the clean chemical conversion between two species (Figure S5). In addition, chemical shifts in 1H NMR prior to and after Cu2+ addition also supports one-to-one stoichiometric conversion (Figure S6). Clean chemical conversion from the original probe molecule to the corresponding cyclized product is a very important requirement for kinetic consideration. It is primarily because the


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signal readout for time-dependent changes should be interference-free from absorption or emission of other potential species.

Figure 2. A partial HPLC chromatogram of probe 1 prior to and after copper (II) addition. (HPLC conditions: mobile phase A and B: 10 mM ammonium formate (pH = 8.5) in water and in MeCN, respectively. Acquity BEH C18 column (2.1 × 500mm, 1.7µm), T = 298K. UV detector at λabs = 254 nm).

Kinetic comparison: Structure–Reactivity relationships A comparative kinetic study was carried out to explore the structure-reactivity relationship of the series of o-phenylazo anilines. In order to establish the pseudo-first order reaction condition, excess copper (> 40 equiv.) was added to the solution of each probe (40 µM in acetonitrile). The time-dependent responses toward copper (II) ion were monitored by UV-vis spectroscopy at absorption maximum of each probe molecule. The exponential change of absorbance as a function of time was fitted using equation 1 to determine the pseudo-first-order rate constant k’ (Figure 3).


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(1)

Figure 3. Time-dependent changes in relative absorbance at λabs = 560 nm (for probe 1), λabs = 470 nm (for the benchmark 6) and λabs = 470 nm (for probe 2), respectively. [probe] = 40 µM in MeCN, [Cu2+] = 2.4 mM in water. T= 298 K.

As anticipated, molecular probes 3–5 which have either one methoxy substitution or three methoxy substitutions at meta-position of azo moiety undergo much slower reaction than the benchmark compound 6 (Figure S7). With two methoxy substitution at the ortho- and paraposition, however, comparable rate constants (2: 5.0 M–1 s–1 vs 6: 9.4 M–1 s–1) are obtained under identical conditions. When all methoxy substitution are positioned at ortho- and para-, probe 1 undergoes an approximately 40-times faster reaction (354.8 M–1 s–1) than the benchmark compound 6. As shown in Figure 3, in the presence of the same amount of copper, benchmark compound 6 and probe 2 can only achieve 50% and 30% of reaction completion, respectively.


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The probe molecule 1 , however, almost reaches a plateau within 20–30 seconds under identical conditions. Therefore the remarkable reactivity of probe 1 can be further applied toward highthroughput analysis. It should be noted that in spite of the same number of methoxy groups, probe 1 and probe 4 show completely different reactivities. Computational results To augment the experimental results, DFT calculations were carried out in the gas phase using Gaussian 09 software package (Supporting Information). From a theoretical point of view, nucleophilic behavior of organic compounds can be estimated by reactivity indices and electronic structure calculations. Consistent with kinetic results, calculated global nucleophilicity index shows that probe 1 is most reactive, while probes 4 and 5 are least reactive (Table S2). As expected, natural charges indicated that nitrogen atom of amine group is the reactive site for Cu2+ binding. Therefore, interaction energies between Cu2+ and each probe should provide a better quantitative measure of chemical reactivity (Table S3). Based on previous findings35, the electron transfer from amine to copper ion is rate-limiting step of cyclization reaction. Hence, best nucleophiles are those having a stronger interaction with Cu(II) ion. The comparative analysis of interaction energies (1 > 2 > 6 > 4 > 3 > 5) correlates fairly well with experimentally determined rate constants (1 >> 6 > 2 > 3 > 4 > 5). Minor differences between experiment and theory (6 vs. 2 and 3 vs. 4) occurred only for compounds with similar rate constants and were probably caused by solvent effects. Practical considerations Since probe 1 shows dramatic changes in both color and fluorescence, either photophysical properties can be used to assay the copper contents in the sample. As shown in Figure 4a, when excited at λem = 335 nm, the fluorescence intensity at λem = 420 nm shows a nice linearity with as low as 2.4 µM of copper ion. Additionally HPLC method can provide unambiguous assay of the benzotriazole product by clear separation from the starting


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material. With further diluted standard solution of copper, the peak area of the benzotriazole also displays a linear relationship with the concentration of copper down to the 0.57 µM level. The lowest concentration of copper (0.57 µM) would approximately corresponds to 35 ppm level of copper in 10 mg unknown solid sample such as drug substances and process intermediates from pharmaceutical process (Figure 4b). Both detection limits by fluorescence and HPLC methods are much lower than the analogous benchmark compound (10 µM)36. Such a low detection limit and the linearity over a wide range of copper indicate that the probe 1 can be readily applied to detect residual levels of copper in the samples.

Figure 4. (a) A plot of fluorescence intensity at λem = 420 nm of probe 1 after addition of Cu2+ (2.3 µM–47 µM); Insert: photograph of probe 1 with 0, 7.9, 15.8 and 23.8 µM of Cu2+(aq) from the left to the right and (b) plot of peak area of product by HPLC vs concentration of Cu2+ (0.57 µM–0.57 mM); Insert: photograph of probe 1 with 5.7, 57, 114 and 570 µM of Cu2+(aq) from the left to the right.

Conclusion


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A series of colorimetric/fluorimetric copper probe molecules have been developed. Such molecular probes share a common scaffold, ortho-(phenylazo)aniline, which undergoes oxidative cyclization in the presence of copper (II). The reactivity toward copper ions is studied by systematically adjusting both the number and the substitution position of the electron-donating groups (EDG) in the molecular probes. Our study clearly provides a significant insight into the structure-reactivity relationships of copper probe molecules. Not only the number of EDGs but also the position of EDGs shows markedly different kinetic rates upon exposure to copper ions. The probe 1 which has three methoxy groups on ortho- and paraposition is exceedingly reactive and shows linear response toward copper ion with both dramatic color changes (red to pale yellow) and fluorescence (blue emission turn-on). The rapidly responding copper probe can be implemented in various fields including environmental (e.g., drinking water) and biological applications (e.g., diagnostic imaging). Practical application such as pharmaceutical compounds contaminated with copper is under way in our research group.

ASSOCIATED CONTENT The following files are available free of charge. Synthesis and Photophysical properties of Probe 2–5.

AUTHOR INFORMATION Corresponding Author Jiyoung Jung


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Penn State University, Dunmore, PA 18512, United States; [email protected], Tel.: +1-570-9632559 Junyong Jo Merck Research Laboratories, Rahway, NJ 07065, United States; [email protected], Tel. +1-732-594-7744

ACKNOWLEDGMENT We gratefully acknowledge the financial support from Penn State University. and computational resources provided by NSF, XSEDE and San Diego Supercomputing Center, under grant number TG-CHE160074.

REFERENCES 1.

Su, B.; Cao, Z.-C.; Shi, Z.-J., Acc. Chem. Res. 2015, 48, 886–896.

2.

Holland, P. L., Acc. Chem. Res. 2015, 48, 1696–1702.

3.

McCann, S. D.; Stahl, S. S., Acc. Chem. Res. 2015, 48, 1756–1766.

4.

Morris, R. H., Acc. Chem. Res. 2015, 48, 1494–1502.

5.

Gandeepan, P.; Cheng, C.-H., Acc. Chem. Res. 2015, 48, 1194–1206.

6.

Liu, W.; Groves, J. T., Acc. Chem. Res. 2015, 48, 1727–1735.

7.

Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.; Garg, N. K.; Percec, V., Chem. Rev. 2011, 111, 1346–1416.

8.

Welch, C. J.; Shaimi, M.; Biba, M.; Chilenski, J. R.; Szumigala, R. H.; Dolling, U.; Mathre, D. J.; Reider, P. J., J. Sep. Sci. 2002, 25, 847–850.


14

Page 15 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


9.

Welch, C. J.; Albaneze-Walker, J.; Leonard, W. R.; Biba, M.; DaSilva, J.; Henderson, D.; Laing, B.; Mathre, D. J.; Spencer, S.; Bu, X., Org. Process Res. Dev. 2005, 9, 198– 205.

10. Reginato, G.; Sadler, P.; Wilkes, R. D., Org. Process Res. Dev. 2011, 15, 1396–1405. 11. Miyamoto, H.; Sakumoto, C.; Takekoshi, E.; Maeda, Y.; Hiramoto, N.; Itoh, T.; Kato, Y., Org. Process Res. Dev. 2015, 19, 1054–1061. 12. Bush, A. I., Curr. Opin. Chem. Biol. 2000, 4, 184–191. 13. Gaggelli, E.; Kozlowski, H.; Valensin, D.; Valensin, G., Chem. Rev. 2006, 106, 1995– 2044. 14. Donnelly, P. S.; Xiao, Z.; Wedd, A.G., Curr. Opin. Chem. Biol. 2007, 11, 128–133. 15. Madsen, E.; Gitlin, J. D., Annu. Rev. Neurosci. 2007, 30, 317–337. 16. Gh Popescu, B. F.; Nichol, H., CNS Neurosci. Ther. 2010, 17, 256–268. 17. Millhauser, G. L., Acc. Chem. Res. 2004, 37, 79–85. 18. EMA guidelines: Specification limits for residues of metal catalysts or metal reagents. (accessed Aug 08, 2017). 19. ICH quality guidelines: Q3d guideline for elemental impurities. (accessed Aug 08, 2017). 20. Edition of the drinking water standards and health advisories (EPA 822-s-12–001); U.S. EPA office of science and technology, Washington, D.C., Ed. 2012. 21. Bu, X.; Koide, K.; Carder, E. J.; Welch, C. J., Org. Process Res. Dev. 2013, 17, 108– 113. 22. Koide, K.; Tracey, M. P.; Bu, X.; Jo, J.; Williams, M. J.; Welch, C. J., Nat. Commun. 2016, 7, 10691–10698.


15


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 17

23. Martínez-Máñez, R.; Sancenón, F., Chem. Rev. 2003, 103, 4419–4476. 24. Rurack, K.; Resch-Genger, U., Chem. Soc. Rev. 2002, 31, 116–127. 25. Anslyn, E. V., J. Org. Chem. 2007, 72, 687–699. 26. Thomas, S. W.; Joly, G. D.; Swager, T. M., Chem. Rev. 2007, 107, 1339–1386. 27. Domaille, D. W.; Que, E. L.; Chang, C. J., Nat. Chem. Biol. 2008, 4, 168–175. 28. Chan, J.; Dodani, S. C.; Chang, C. J., Nat. Chem. 2012, 4, 973–984. 29. Jung, J.; Dinescu, A., Tetrahedron Lett. 2017, 58, 358–361. 30. Li, X.; Gao, X.; Shi, W.; Ma, H., Chem. Rev. 2014, 114, 590–659. 31. Ma, H.; Huang, Y.-X.; Liang, S.-C., Anal. Chim. Acta 1996, 334, 213–219. 32. Sun, C.; Chen, J.; Ma, H.; Liu, Y.; Zhang, J.; Liu, Q., Sci. China Chem. 2011, 54, 1101– 1108. 33. Sasaki, E.; Kojima, H.; Nishimatsu, H.; Urano, Y.; Kikuchi, K.; Hirata, Y.; Nagano, T., J. Am. Chem. Soc. 2005, 127, 3684–3685. 34. Qian, Y.; Karpus, J.; Kabil, O.; Zhang, S.-Y.; Zhu, H.-L.; Banerjee, R.; Zhao, J.; He, C., Nat. Commun. 2011, 2, 495. 35. Bu, X.; Williams, M.; Jo, J.; Koide, K.; Welch, C. J., Chem. Commun. 2017, 53, 720– 723. 36. Schmidt, M. P.; Hagenböcker, A., Ber. Dtsch. Chem. Ges. 1921, 54, 2201–2207. 37. Schmidt, M. P.; Hagenböcker, A., Ber. Dtsch. Chem. Ges. 1921, 54, 2191–2200. 38. Nigh, W. G., Org. Chem. 1973, 5, 1–96. 39. Jo, J.; Lee, H. Y.; Liu, W.; Olasz, A.; Chen, C.-H.; Lee, D., J. Am. Chem. Soc. 2012, 134, 16000–16007. 40. Williams, A. T. R.; Winfield, S. A.; Miller, J. N., Analyst 1983, 108, 1067–1071.


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Table of Contents Graphic 254x105mm (150 x 150 DPI)


Rapid Turn-On Fluorescence Detection of Copper(II): Aromatic

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