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Sensing Strategy for Lithium Ion Based on Gold Nanoparticles

Sherine O. Obare, Rachel E. Hollowell, and Catherine J. Murphy*
University of South Carolina, Department of Chemistry and Biochemistry, Graduate Science Research Center, Columbia, South Carolina 29208 Received June 4, 2002. In Final Form: October 21, 2002
The detection of Li+ is currently in demand for both biomedical and industrial applications. We here report the functionalization of 4 nm Au particles with a 1,10-phenanthroline ligand that binds selectively to Li+. The ligand binds to Li+ by forming a 2:1 ligand-metal complex, causing Au nanoparticles to aggregate. Au nanoparticle aggregation causes a shift in the extinction spectrum with a concomitant color change, providing a useful optical method of detecting Li+ in aqueous solution.

Introduction Metal nanoparticles are emerging as important colorimetric reporters due to their high extinction coefficients, which are several of orders of magnitude larger than those of organic dyes.1 Gold nanoparticles display plasmon absorption bands that depend on their shape and size.2-4 Particle aggregation results in further color changes of gold nanoparticle solutions due to mutually induced dipoles that depend on interparticle distance and aggregate size.5-8 Gold nanoparticle aggregation induced by analytes has been demonstrated for DNA,8-12 several metal ions,13,14 and antibodies.15 In these experiments, recognition of the analyte is built into a receptor molecule that is covalently linked to the gold nanoparticle surface; for example, EDTA has been used as the surface-bound receptor for generic metal ions,13 and a crown ether has been used as the surface-bound receptor for potassium ion.14 Li+ detection has long been of interest to both the medical and industrial communities because of its potential applications in science, medicine, and technology. Understanding lithium transport in complex biomedical environments16,17 and in batteries18-20 is important, and
* To whom correspondence should be addressed. Telephone: (803) 777-3628. Fax: (803) 777-9521. E-mail: murphy@ mail.chem.sc.edu.
(1) Labande, A.; Astruc, D. Chem. Commun. 2000, 1007. (2) Schmid, G. Clusters and Colloids: From Theory to Applications; VCH: New York, 1994. (3) Henglein, A. J. Phys. Chem. 1993, 97, 5457. (4) Belloni, J. Curr. Opin. Colloid Interface Sci. 1996, 1, 184. (5) Kreibig, U.; Vollmer, M. Optical Properties of Metal Clusters; Springer: Berlin, 1995. (6) Storhoff, J. J.; Lazarides, A. A.; Mucic, R. C.; Mirkin, C. A.; Letsinger, R. L.; Schatz, G. C. J. Am. Chem. Soc. 2000, 122, 4640. (7) Lazarides, A. A.; Schatz, G. C. J. Phys. Chem. B 2000, 104, 460. (8) Mirkin, C. A.; Storhoff, J. J. Chem. Rev. 1999, 99, 1849. (9) Storhoff, J. J.; Elghanian, R.; Mucic, R. C.; Mirkin, C. A.; Letsinger, R. L. J. Am. Chem. Soc. 1998, 120, 1959. (10) Elghanian, R.; Storhoff, J. J.; Mucic, R. C.; Letsinger, R. L.; Mirkin, C. A. Science 1997, 227, 1078. (11) Mirkin, C. A.; Letsinger, R. L.; Mucic, C. A.; Storhoff, J. J. Nature 1996, 382, 607. (12) Reynolds, R. A.; Mirkin, C. A.; Letsinger, R. L. J. Am. Chem. Soc. 2000, 122, 3795. (13) Kim, Y.; Johnson, R. C.; Hupp, J. T. Nano Lett. 2001, 1, 165. (14) Lin, S. Y.; Liu, S. W.; Lin, C. M.; Chen, C. H. Anal. Chem. 2002, 74, 330. (15) Thanh, N. T. K.; Rosenzweig, Z. Anal. Chem. 2002, 74, 1624. (16) Keck, P. E.; McElroy, S. L.; Strakowski, S. M.; Soutullo, C. A. J. Clin. Psychiatry 2000, 61, 33. (17) Lennkh, C.; Simhandl, C. Int. Clin. Psychopharm. 2000, 15, 1. (18) Aurbach, D. J. Power Sources 2000, 89, 206.

thus we have focused on developing optical sensors of lithium in solution.21-24 The development of Li+-selective sensors has been neglected in comparison to that for metal ions such as Na+, K+, Ca2+, and Mg2+, though a few organic chromophores have been reported.25-32 One of the limitations of developing organic chromophores for practical Li+ detection is their lack of solubility in aqueous media. To overcome this obstacle, we have turned to nanotechnology, which is opening new avenues in sensor design.33-35 Here, we have made use of the aggregation-induced color changes of Au nanoparticles in aqueous solutions as an optical sensor for Li+. The gold nanoparticles have been coated with an organic ligand designed to selectively bind to Li+ in a 2:1 fashion. As Li+ is introduced to a solution of ligand-coated Au nanoparticles, the Li+ should bind to the ligand and in turn cause the gold particles to aggregate (Figure 1). The degree of aggregation depends on the Li+ concentration. Our work is similar in conception to that of Rosenzweigs work with antibodies; in that case, optical changes were monitored at 620 nm as the analyte increased the degree of aggregation of functionalized gold nanoparticles.15 In comparison to the generic metal ion work of Hupp, our paper reports titration data that are specific for a particular metal ion. 13
(19) Lantelme, F.; Groult, H.; Kumagai, N. Electrochim. Acta 2000, 45, 3171. (20) Meyer, W. H. Adv. Mater. 1998, 10, 439. (21) Obare, S. O.; Murphy, C. J. Inorg. Chem. 2001, 40, 6080. (22) Obare, S. O.; Murphy, C. J. New. J. Chem. 2001, 25, 1600. (23) Qin, W.; Obare, S. O.; Murphy, C. J.; Angel, S. M. Analyst 2001, 126, 1499. (24) Qin, W.; Obare, S. O.; Murphy, C. J.; Angel, S. M. Anal. Chem. 2002, 74, 4757. (25) Sugihara, H.; Hirantani, K. J. Synth. Org. Chem. Jpn. 1994, 52, 530. (26) Sugihara, H.; Okada, T.; Hiratani, K. Anal. Sci. 1993, 9, 593. (27) Hiratani, K.; Nomoto, M.; Sugihara, H.; Okada, T. Analyst 1992, 117, 1491. (28) Nakashima, K.; Nakatsuji, S.; Akiyama, S. Talanta 1984, 31, 749. (29) Nishida, H.; Katayama, Y.; Katsuki, H.; Nakamuru, M.; Takagi, M.; Ueno, K. Chem. Lett. 1982, 1853. (30) Kimura, K.; Iketani, S.; Shono, T. Anal. Chim. Acta 1987, 203, 85. (31) Rodrguez, L. C.; Linares, C. J.; Ceba, M. R. Fresenius J. Anal. Chem. 1996, 356, 320. (32) Hiratani, K. Analyst 1988, 113, 1065. (33) Shipway, A. N.; Willner, I. Chem. Commun. 2001, 2035. (34) Panchapakesan, B.; DeVoe, D. L.; Widmaier, M. R.; Cavicchi, R.; Semancik, S. Nanotechnology 2001, 12, 336. (35) Shipway, A. N.; Katz, E.; Willner, I. ChemPhysChem 2000, 1, 18.

10.1021/la0260335 CCC: $22.00 2002 American Chemical Society Published on Web 11/15/2002

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Figure 1. Detection scheme for Li+ with functionalized gold nanoparticles. Au nanoparticles are surface derivatized with a ligand Y that binds to lithium ions in a bidentate fashion. Upon introduction of lithium ion (small dark circles) into the solution, nanoparticle aggregation is induced, which is manifested as a visible color change in the solution.

Experimental Section
Materials and Instrumentation. Sodium citrate, sodium borohydride, HAuCl43H2O, lithium perchlorate, sodium perchlorate, potassium perchlorate, 1,10-phenanthroline, n-butyllithium, potassium bromide, sodium bicarbonate, and 2-aminoethanethiol were obtained from Aldrich Chemicals and used as received. Ultrapure deionized water (Continental Water Systems) was used to prepare all aqueous solutions. Gold nanoparticles were viewed using a JEOL TEM-100CXII transmission electron microscope operating at 80 kV. Sizing was enabled using an AMT Kodak Megaplus digital camera and software. Samples were prepared for electron microscopy by evaporating 1 mL of nanoparticle solution (at 25 C) on formarcoated copper grids. Extinction spectra of nanoparticle solutions were acquired using a Cary 500 Scan UV-vis-NIR spectrophotometer. Synthesis of 4 nm Au Nanoparticles. Gold nanoparticles less than 10 nm in diameter were synthesized following a method developed by us.36 In a clean Erlenmeyer flask were placed 18.5 mL of deionized H2O, 0.5 mL of a 1.0 10-2 M aqueous HAuCl4 trihydrate solution, and 0.5 mL of a 0.01 M aqueous sodium citrate solution. The resulting yellow solution was stirred for 5 min, and 0.5 mL of a 0.1 M aqueous NaBH4 solution was added to it. The solution color changed to orange. This reaction produced ca. 4 nm Au particles. Transmission electron microscopy (TEM) confirmed that the average nanoparticle diameter was 4.3 nm (Figure 2). The extinction spectrum of the nanoparticles showed a maximum at 512 nm. Synthesis of 32 nm Au Nanoparticles. The ca. 4 nm Au nanoparticles produced from the reaction described above were used as seeds for the preparation of 32 nm Au nanoparticles.36 A growth solution consisting of 200 mL of a 0.1 M solution of the surfactant, cetyltrimethylammonium bromide (CTAB) in water, and 5 mL of a 1 10-2 M HAuCl4 solution was prepared. Four 25 mL Erlenmeyer flasks were taken and labeled A, B, C, and D. In each flask, 9 mL of the growth solution was placed and 50 mL of a 0.1 M ascorbic acid solution in water was added. Addition of ascorbic acid to the growth solution changed its color from yellow to colorless. To flask A, 2.5 mL of the ca. 4 nm gold seeds was added, and the solution was stirred for 10 min, resulting in 5.5 nm orange-pink-colored gold nanoparticles. To flask B, 2.5 mL of the particles in flask A was added to the contents of the flask, and stirring took place for 10 min. The color of the resulting solution was a light shade of pink. The nanoparticles prepared in this manner were 8.0 nm in diameter. To flask C, 1.0 mL of the solution from flask B was added, and the solution was stirred vigorously for 10 min, resulting in 18 nm particles. To flask D, 1.0 mL of the solution from flask C was added while vigorously stirring for 10 min. The color changed to deeper red (max for
(36) Jana, N. R.; Gearheart, L.; Murphy, C. J. Langmuir 2001, 17, 6782.

Figure 2. TEM image of ca. 4 nm Au nanoparticles and the corresponding size distribution histogram. Scheme 1. Synthesis of 2, a 1,10-Phenanthroline Derivative that Binds Selectively to Li+ Functionalized with a Thiol Group at the 5 and 6 Positions to Bind to Gold

absorption at 525 nm), and the reaction resulted in particles 32 nm in diameter. Synthesis of 2,9-Dibutyl-1,10-phenanthroline-5,6-aminoethanethiol (2). 2,9-Dibutyl-1,10-phenanthroline-5,6-dione was prepared from 2,9-dibutyl-1,10-phenanthroline following a literature procedure.21 2,9-Dibutyl-1,10-phenanthroline-5,6-dione was dissolved in ethanol and reacted with 2 equiv of 2-aminoethanethiol in a condensation reaction (Scheme 1). The reaction was heated at reflux for 12 h, after which time the product had precipitated. The reaction mixture was allowed to cool to room temperature, and the product was filtered and then recrystallized from methanol. The crystals were filtered under a nitrogen atmosphere and then stored in a desiccator. The yield for the reaction was 69%. 1H NMR (CDCl3, 300 MHz) : 8.24-8.21 (d,

Sensing Strategy for Lithium Ion

2H, J ) 6 Hz), 7.36-7.33 (d, 2H, J ) 6 Hz), 3.85-3.80 (q, 4H, J ) 4 Hz), 3.61-3.57 (q, 4H, J ) 4 Hz), 3.10-3.04 (t, 4H, J ) 8.04 Hz), 1.90-1.81 (m, 4H, J ) 7.66 Hz), 1.50-1.39 (m, 4H, J ) 7.20 Hz), 1.12-1.08 (t, 2H, J ) 5.33 Hz), 1.00-0.96 (t, 6H, J ) 7.26 Hz). Elemental analysis (Robertson Microlit Laboratories, Inc., Madison, NJ) calculated: C, 65.13; H, 7.74; N, 12.66. Found: C, 64.21; H, 7.32; N, 11.93. Interaction of 2 with Li+. The dibutyl-1,10-phenanthroline precursor 1 has been found to be a selective Li+ sensor exhibiting fluorescence enhancement upon Li+ complexation.25-27 For comparison, the interaction of 2 with Li+ was investigated to confirm that the Li+-binding front end of the molecule was not altered by the chemistry at the back end (data not shown). Several solutions of the ligand were prepared in the solvents methanol, ethanol, tetrahydrofuran, and acetonitrile (because 2 is not water soluble). The solutions were then each titrated with Li+, and lithium ion binding was monitored by ligand fluorescence, since the absorbance of the ligand alone is insensitive to Li+. An increase in Li+ concentration resulted in a decrease of 2s fluorescence intensity and was accompanied by a red-shift for all solvent environments tested. Optical changes were observed up to 3 mM Li+ for 10-5 M of 2 in organic solvents. Functionalization of Au Nanoparticles with 2. A 2.5 10-4 M solution of 2 in ethanol was prepared. Ten milliliters of a 2.5 10-4 M solution of the ca. 4 nm Au nanoparticles (based on Au atoms) was placed in a clean Erlenmeyer flask, and 1 mL of the ligand 2 solution was added to the contents of the flask. The solution was allowed to stir for over 12 h to ensure complete reaction at the gold surface. Similar procedures were used for the 32 nm Au nanoparticles. Nanoparticles were minimally purified by centrifugation and resuspension in water.

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Figure 3. Representative UV-visible spectra of nonfunctionalized 4 nm Au nanoparticles exposed to various concentrations of lithium perchlorate in water, showing nanoparticle precipitation. Bottom curve: nanoparticles in the absence of Li+. The arrow indicates addition of lithium salt. Top curves: from top to bottom [Li+] ) 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mM.

Results and Discussion The strategy we have used makes use of a ligand designed to bind specifically to Li+ at the front end with a stoichiometry of 2:1 ligand/metal. The back end of the ligand is linked to the Au nanoparticles through a thiol group. As Li+ is introduced to a solution of ligand-coated Au nanoparticles, it acts as a bridge to induce aggregation of the gold nanoparticles (Figure 1). Au nanoparticle aggregation results in visible color changes. These color changes arise from a combination of absorption and scattering of light by the nanoparticle solutions.6-12 Interaction of Nonfunctionalized 4 nm Gold Nanoparticles with Li+. The effect of Li+ on Au nanoparticles without the coating of 2 was investigated as a control experiment. A spectroscopic titration of Li+ (1.0 M LiClO4) with the 4 nm Au particles (2.5 10-4 M in Au atoms) was performed; increasing the Li+ concentration resulted in precipitation of the Au nanoparticles due to charge screening effects. A representative UV-visible spectrum of this titration is shown in Figure 3. As Li+ is introduced into the solution, the particles scatter light and precipitate from solution. Interaction of Functionalized 4 nm Gold Nanoparticles with Li+. Coating the 4 nm Au nanoparticles with the Li+ binding ligand 2 resulted in a slight color change from orange to a darker shade of orange. The solution was then filtered and analyzed by UV-visible absorption spectroscopy and TEM. The plasmon absorbance band of the ligand-coated Au particles in comparison to that of the nonfunctionalized Au particles was slightly red-shifted as expected for a thiolated Au surface.6,9 The slight shift in wavelength may also be attributed to centrifugation of the ligand-coated Au particles, which affects the size distribution. The transmission electron micrograph shows particles that are not aggregated, with an average diameter of 4.7 nm, slightly larger than the original nanoparticles (4.3 nm average). The thiol of 2 binds to the Au surface forming an Au-S bond, leaving the Li+ binding site exposed. Titration of

Figure 4. UV-visible extinction spectra of 2-functionalized 4 nm Au nanoparticles (2.5 10-4 M in Au atoms) in the presence of increasing concentrations of Li+. From left to right, concentrations of Li+ are 0, 9, 19, 29, 38, 48, 57, 65, 74, 83, and 90 mM.

the ligand-coated Au nanoparticles with Li+ did not result in particle precipitation as was observed with the noncoated particles. Increasing the Li+ concentration resulted in a smooth red-shift of the plasmon absorption band maximum, indicating particle aggregation (Figure 4) which was confirmed by TEM (Figure 5). At the end of the titration, the color of the solution had changed from orange to gray, and no precipitation or cloudiness was observed in the solution. A plot of the red-shift in the visible extinction band maximum of the gold nanoparticle concentration versus Li+ (Figure 6) reveals a linear relationship, indicating that the system can be used to quantitatively detect Li+ in an aqueous medium from 10-100 mM. A Comparison of 4 nm to 32 nm Functionalized Au Nanoparticles. Similar lithium ion titration experiments were conducted with 2-functionalized 32 nm Au nanoparticles. Similar red-shifts in the extinction spectra were observed (data not shown), although the peaks were far broader and it was harder to assign their wavelength maxima than for the 4 nm Au nanoparticles. At the end of the titration, the 32 nm particle solution color had changed from red to gray. After the titration, the particles were measured by TEM and the results were compared

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Figure 5. TEM image of 4 nm 2-coated Au nanoparticles after titration with Li+; the particles are aggregated.

Figure 7. Optical spectra showing the selectivity of the ligandcoated 4 nm Au nanoparticles (2.5 10-4 M in Au atoms) to Li+ in comparison to Na+ and K+ at metal ion concentrations of 50 mM. Dashed line, Au nanoparticles alone; dotted line, Au nanoparticles in the presence of K+; dotted-dashed line, Au nanoparticles in the presence of Na+; solid line, Au nanoparticles in the presence of Li+.

those of 4 nm nanoparticles is 64, similar to the order of magnitude difference in Li+ required to aggregate the 32 nm nanoparticles in comparison to the 4 nm nanoparticles. Selectivity to Lithium Ion. We carried out experiments to investigate the selectivity of the 2-functionalized 4 nm Au nanoparticles for Li+ compared to Na+ and K+. Figure 7 shows that the extinction band of the 2-coated Au nanoparticles is affected only by Li+ at 50 mM concentration and not by equal amounts of Na+ or K+. Thus, coated Au nanoparticles can be used to visually detect Li+ with little interference from Na+.
Figure 6. Graph of the red-shift in the visible wavelength maximum for 2-coated 4 nm Au nanoparticles as a function of [Li+]; the raw data are shown in Figure 4.

to those found for the coated 4 nm Au nanoparticles. These 32 nm particles were less aggregated compared to the 4 nm nanoparticles for the same Li+ concentration, and they had formed a network of slightly elongated Au particles. Total aggregation of the 32 nm nanoparticles required near molar amounts of Li+. The observation that the 4 nm Au particles are more sensitive to Li+ and thus aggregate with a lower Li+ concentration in solution, in comparison to the 32 nm Au particles, can be understood from simple surface area arguments. The footprint of the Li+-2 complex on a surface is estimated to be 1 nm2; assuming full surface coverage of 2 on both large and small particles, fewer Li+ bridges are needed to aggregate the smaller 4 nm nanoparticles (surface area, 50 nm2) compared to the larger 32 nm nanoparticles (surface area, 3200 nm2). The ratio of the surface areas of 32 nm nanoparticles to

Conclusion We have successfully developed a method to detect Li+ in an aqueous environment through surface engineering of Au nanoparticles. The detection is optical, based on red-shifts in the extinction spectra; alternately, one could monitor increased optical density at a wavelength well red-shifted from the original nanoparticle extinction maximum.15 Nanoparticles of a larger diameter require a larger amount of Li+ to aggregate than smaller nanoparticles; hence smaller nanoparticles are desirable for lower detection limits. The system can be effectively used to detect concentrations of Li+ in the 10-100 mM range. Similar systems can be designed to detect other analytes of interest by developing selective ligands for a 2:1 ligand/ analyte complex. Acknowledgment. We thank DOE-EPSCoR and NSF for funding and the anonymous reviewers for helpful comments.
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