Sensing Strategy for Lithium Ion Based on GoldNanoparticles

Sherine O. Obare, Rachel E. Hollowell, and Catherine J. Murphy*

University of South Carolina, Department of Chemistry and Biochemistry, Graduate ScienceResearch 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 herereport the functionalization of 4 nm Au particles with a 1,10-phenanthroline ligand that binds selectivelyto Li+. The ligand binds to Li+ by forming a 2:1 ligand-metal complex, causing Au nanoparticles toaggregate. Au nanoparticle aggregation causes a shift in the extinction spectrum with a concomitant colorchange, providing a useful optical method of detecting Li+ in aqueous solution.

Introduction

Metal nanoparticles are emerging as important colo-rimetric reporters due to their high extinction coefficients,which are several of orders of magnitude larger than thoseof organic dyes.1 Gold nanoparticles display plasmonabsorption bands that depend on their shape and size.2-4

Particle aggregation results in further color changes ofgold nanoparticle solutions due to mutually induceddipoles that depend on interparticle distance and ag-gregate size.5-8 Gold nanoparticle aggregation inducedby analytes has been demonstrated for DNA,8-12 severalmetal ions,13,14 and antibodies.15 In these experiments,recognition of the analyte is built into a receptor moleculethat is covalently linked to the gold nanoparticle surface;for example, EDTA has been used as the surface-boundreceptor for generic metal ions,13 and a crown ether hasbeen used as the surface-bound receptor for potassiumion.14

Li+ detection has long been of interest to both themedical and industrial communities because of its po-tential applications in science, medicine, and technology.Understanding lithium transport in complex biomedicalenvironments16,17 and in batteries18-20 is important, and

thus we have focused on developing optical sensors oflithium in solution.21-24 The development of Li+-selectivesensors has been neglected in comparison to that for metalions such as Na+, K+, Ca2+, and Mg2+, though a few organicchromophores have been reported.25-32

One of the limitations of developing organic chro-mophores for practical Li+ detection is their lack ofsolubility in aqueous media. To overcome this obstacle,we have turned to nanotechnology, which is opening newavenues in sensor design.33-35 Here, we have made use ofthe aggregation-induced color changes of Au nanoparticlesin aqueous solutions as an optical sensor for Li+. The goldnanoparticles have been coated with an organic liganddesigned to selectively bind to Li+ in a 2:1 fashion. As Li+

is introduced to a solution of ligand-coated Au nanopar-ticles, the Li+ should bind to the ligand and in turn causethe gold particles to aggregate (Figure 1). The degree ofaggregation depends on the Li+ concentration. Our workis similar in conception to that of Rosenzweig’s work withantibodies; in that case, optical changes were monitoredat 620 nm as the analyte increased the degree ofaggregation of functionalized gold nanoparticles.15 Incomparison to the generic metal ion work of Hupp, ourpaper reports titration data that are specific for aparticular metal ion. 13

* To whom correspondence should be addressed. Telephone:(803) 777-3628. Fax: (803) 777-9521. E-mail: murphy@mail.chem.sc.edu.

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10407Langmuir 2002, 18, 10407-10410

10.1021/la0260335 CCC: $22.00 © 2002 American Chemical SocietyPublished on Web 11/15/2002

Experimental Section

Materials and Instrumentation. Sodium citrate, sodiumborohydride, HAuCl4‚3H2O, lithium perchlorate, sodium per-chlorate, potassium perchlorate, 1,10-phenanthroline, n-butyl-lithium, potassium bromide, sodium bicarbonate, and 2-amino-ethanethiol were obtained from Aldrich Chemicals and used asreceived. Ultrapure deionized water (Continental Water Systems)was used to prepare all aqueous solutions.

Gold nanoparticles were viewed using a JEOL TEM-100CXIItransmission electron microscope operating at 80 kV. Sizing wasenabled using an AMT Kodak Megaplus digital camera andsoftware. Samples were prepared for electron microscopy byevaporating 1 mL of nanoparticle solution (at 25 °C) on formar-coated copper grids. Extinction spectra of nanoparticle solutionswere acquired using a Cary 500 Scan UV-vis-NIR spectro-photometer.

Synthesis of 4 nm Au Nanoparticles. Gold nanoparticlesless than 10 nm in diameter were synthesized following a methoddeveloped by us.36 In a clean Erlenmeyer flask were placed 18.5mL of deionized H2O, 0.5 mL of a 1.0 × 10-2 M aqueous HAuCl4trihydrate solution, and 0.5 mL of a 0.01 M aqueous sodiumcitrate solution. The resulting yellow solution was stirred for 5min, and 0.5 mL of a 0.1 M aqueous NaBH4 solution was addedto it. The solution color changed to orange. This reaction producedca. 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 showeda maximum at 512 nm.

Synthesis of 32 nm Au Nanoparticles. The ca. 4 nm Aunanoparticles produced from the reaction described above wereused 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 thesurfactant, cetyltrimethylammonium bromide (CTAB) in water,and 5 mL of a 1 × 10-2 M HAuCl4 solution was prepared. Four25 mL Erlenmeyer flasks were taken and labeled A, B, C, andD. In each flask, 9 mL of the growth solution was placed and 50mL of a 0.1 M ascorbic acid solution in water was added. Additionof ascorbic acid to the growth solution changed its color fromyellow to colorless. To flask A, 2.5 mL of the ca. 4 nm gold seedswas added, and the solution was stirred for 10 min, resulting in5.5 nm orange-pink-colored gold nanoparticles. To flask B, 2.5mL of the particles in flask A was added to the contents of theflask, and stirring took place for 10 min. The color of the resultingsolution was a light shade of pink. The nanoparticles preparedin this manner were 8.0 nm in diameter. To flask C, 1.0 mL ofthe solution from flask B was added, and the solution was stirredvigorously for 10 min, resulting in 18 nm particles. To flask D,1.0 mL of the solution from flask C was added while vigorouslystirring for 10 min. The color changed to deeper red (λmax for

absorption at 525 nm), and the reaction resulted in particles 32nm in diameter.

Synthesis of 2,9-Dibutyl-1,10-phenanthroline-5,6-ami-noethanethiol (2). 2,9-Dibutyl-1,10-phenanthroline-5,6-dionewas prepared from 2,9-dibutyl-1,10-phenanthroline following aliteratureprocedure.21 2,9-Dibutyl-1,10-phenanthroline-5,6-dionewas dissolved in ethanol and reacted with 2 equiv of 2-amino-ethanethiol in a condensation reaction (Scheme 1). The reactionwas heated at reflux for 12 h, after which time the product hadprecipitated. The reaction mixture was allowed to cool to roomtemperature, and the product was filtered and then recrystallizedfrom methanol. The crystals were filtered under a nitrogenatmosphere and then stored in a desiccator. The yield for thereaction was 69%. 1H NMR (CDCl3, 300 MHz) δ: 8.24-8.21 (d,

(36) Jana, N. R.; Gearheart, L.; Murphy, C. J. Langmuir 2001, 17,6782.

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

Figure 2. TEM image of ca. 4 nm Au nanoparticles and thecorresponding size distribution histogram.

Scheme 1. Synthesis of 2, a 1,10-PhenanthrolineDerivative that Binds Selectively to Li+

Functionalized with a Thiol Group at the 5 and 6Positions to Bind to Gold

10408 Langmuir, Vol. 18, No. 26, 2002 Obare et al.

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-phenanthrolineprecursor 1 has been found to be a selective Li+ sensor exhibitingfluorescence enhancement upon Li+ complexation.25-27 Forcomparison, the interaction of 2 with Li+ was investigated toconfirm that the Li+-binding front end of the molecule was notaltered by the chemistry at the back end (data not shown). Severalsolutions of the ligand were prepared in the solvents methanol,ethanol, tetrahydrofuran, and acetonitrile (because 2 is not watersoluble). The solutions were then each titrated with Li+, andlithium ion binding was monitored by ligand fluorescence, sincetheabsorbanceof the ligandalone is insensitive to Li+.An increasein Li+ concentration resulted in a decrease of 2’s fluorescenceintensity and was accompanied by a red-shift for all solventenvironments tested. Optical changes were observed up to 3 mMLi+ 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 ofa 2.5 × 10-4 M solution of the ca. 4 nm Au nanoparticles (basedon Au atoms) was placed in a clean Erlenmeyer flask, and 1 mLof the ligand 2 solution was added to the contents of the flask.The solution was allowed to stir for over 12 h to ensure completereaction at the gold surface. Similar procedures were used forthe 32 nm Au nanoparticles. Nanoparticles were minimallypurified by centrifugation and resuspension in water.

Results and Discussion

The strategy we have used makes use of a liganddesigned to bind specifically to Li+ at the “front end” witha stoichiometry of 2:1 ligand/metal. The “back end” of theligand is linked to the Au nanoparticles through a thiolgroup. As Li+ is introduced to a solution of ligand-coatedAu nanoparticles, it acts as a bridge to induce aggregationof the gold nanoparticles (Figure 1). Au nanoparticleaggregation results in visible color changes. These colorchanges arise from a combination of absorption andscattering of light by the nanoparticle solutions.6-12

Interaction of Nonfunctionalized 4 nm Gold Nano-particles with Li+. The effect of Li+ on Au nanoparticleswithout the coating of 2 was investigated as a controlexperiment. A spectroscopic titration of Li+ (1.0 M LiClO4)with the 4 nm Au particles (2.5 × 10-4 M in Au atoms) wasperformed; increasing the Li+ concentration resulted inprecipitation of the Au nanoparticles due to chargescreening effects. A representative UV-visible spectrumof this titration is shown in Figure 3. As Li+ is introducedinto the solution, the particles scatter light and precipitatefrom solution.

Interaction of Functionalized 4 nm Gold Nano-particles with Li+. Coating the 4 nm Au nanoparticleswith the Li+ binding ligand 2 resulted in a slight colorchange from orange to a darker shade of orange. Thesolution was then filtered and analyzed by UV-visibleabsorption spectroscopy and TEM. The plasmon absor-bance band of the ligand-coated Au particles in comparisonto that of the nonfunctionalized Au particles was slightlyred-shifted as expected for a thiolated Au surface.6,9 Theslight shift in wavelength may also be attributed tocentrifugation of the ligand-coated Au particles, whichaffects the size distribution. The transmission electronmicrograph shows particles that are not aggregated, withan average diameter of 4.7 nm, slightly larger than theoriginal nanoparticles (4.3 nm average).

The thiol of 2 binds to the Au surface forming an Au-Sbond, leaving the Li+ binding site exposed. Titration of

the ligand-coated Au nanoparticles with Li+ did not resultin particle precipitation as was observed with the non-coated particles. Increasing the Li+ concentration resultedin a smooth red-shift of the plasmon absorption bandmaximum, indicating particle aggregation (Figure 4)which was confirmed by TEM (Figure 5). At the end of thetitration, the color of the solution had changed from orangeto gray, and no precipitation or cloudiness was observedin the solution. A plot of the red-shift in the visibleextinction band maximum of the gold nanoparticle con-centration versus Li+ (Figure 6) reveals a linear relation-ship, indicating that the system can be used to quanti-tatively detect Li+ in an aqueous medium from ∼10-100mM.

A Comparison of 4 nm to 32 nm FunctionalizedAu Nanoparticles. Similar lithium ion titration experi-ments were conducted with 2-functionalized 32 nm Aunanoparticles. Similar red-shifts in the extinction spectrawere observed (data not shown), although the peaks werefar broader and it was harder to assign their wavelengthmaxima than for the 4 nm Au nanoparticles. At the endof the titration, the 32 nm particle solution color hadchanged from red to gray. After the titration, the particleswere measured by TEM and the results were compared

Figure 3. Representative UV-visible spectra of nonfunction-alized 4 nm Au nanoparticles exposed to various concentrationsof lithium perchlorate in water, showing nanoparticle precipi-tation. Bottom curve: nanoparticles in the absence of Li+. Thearrow indicates addition of lithium salt. Top curves: from topto bottom [Li+] ) 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mM.

Figure 4. UV-visible extinction spectra of 2-functionalized4 nm Au nanoparticles (2.5 × 10-4 M in Au atoms) in thepresence of increasing concentrations of Li+. From left to right,concentrations of Li+ are 0, 9, 19, 29, 38, 48, 57, 65, 74, 83, and90 mM.

Sensing Strategy for Lithium Ion Langmuir, Vol. 18, No. 26, 2002 10409

to those found for the coated 4 nm Au nanoparticles. These32 nm particles were less aggregated compared to the 4nm nanoparticles for the same Li+ concentration, and theyhad formed a network of slightly elongated Au particles.Total aggregation of the 32 nm nanoparticles requirednear molar amounts of Li+.

The observation that the 4 nm Au particles are moresensitive to Li+ and thus aggregate with a lower Li+

concentration in solution, in comparison to the 32 nm Auparticles, can be understood from simple surface areaarguments. The “footprint” of the Li+-2 complex on asurface is estimated to be ∼1 nm2; assuming full surfacecoverage of 2 on both large and small particles, fewer Li+

bridges are needed to aggregate the smaller 4 nmnanoparticles (surface area, ∼50 nm2) compared to thelarger 32 nm nanoparticles (surface area, ∼3200 nm2).The ratio of the surface areas of 32 nm nanoparticles to

those of 4 nm nanoparticles is ∼64, similar to the orderof magnitude difference in Li+ required to aggregate the32 nm nanoparticles in comparison to the 4 nm nano-particles.

Selectivity to Lithium Ion. We carried out experi-ments to investigate the selectivity of the 2-functionalized4 nm Au nanoparticles for Li+ compared to Na+ and K+.Figure 7 shows that the extinction band of the 2-coatedAu nanoparticles is affected only by Li+ at 50 mMconcentration and not by equal amounts of Na+ or K+.Thus, coated Au nanoparticles can be used to visuallydetect Li+ with little interference from Na+.

ConclusionWe have successfully developed a method to detect Li+

in an aqueous environment through surface engineeringof Au nanoparticles. The detection is optical, based onred-shifts in the extinction spectra; alternately, one couldmonitor increased optical density at a wavelength wellred-shifted from the original nanoparticle extinctionmaximum.15 Nanoparticles of a larger diameter requirea larger amount of Li+ to aggregate than smaller nano-particles; hence smaller nanoparticles are desirable forlower detection limits. The system can be effectively usedto detect concentrations of Li+ in the ∼10-100 mM range.Similar systems can be designed to detect other analytesof interest by developing selective ligands for a 2:1 ligand/analyte complex.

Acknowledgment. We thank DOE-EPSCoR and NSFfor funding and the anonymous reviewers for helpfulcomments.

LA0260335

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

Figure 6. Graph of the red-shift in the visible wavelengthmaximum for 2-coated 4 nm Au nanoparticles as a function of[Li+]; the raw data are shown in Figure 4.

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

10410 Langmuir, Vol. 18, No. 26, 2002 Obare et al.