Aging of Gold Nanoparticles: Ligand Exchange with Disulfides

ARTICLE pubs.acs.org/Langmuir

Aging of Gold Nanoparticles: Ligand Exchange with Disulfides Yun Ma and Victor Chechik* Department of Chemistry, University of York, Heslington,York YO10 5DD, United Kingdom ABSTRACT: Aging of thiolate protected gold nanoparticles (AuNPs) results in reduced reactivity in the disulfide exchange as monitored by electron paramagnetic resonance (EPR) spectroscopy with a bisnitroxide disulfide incoming ligand. Factors determining the reactivity of the aged particles were investigated. The presence of different binding sites on the surface of AuNPs and a surface reorganization process during aging can explain observed reactivity trends.

’ INTRODUCTION The studies of gold nanoparticles (AuNPs) have led to numerous applications in catalysis,1 5 imaging,6 9 sensing,10 15 and drug delivery.16 18 This field experienced rapid growth after the 1990s, when Brust, Schiffrin, and co-workers reported19 21 the biphasic synthetic method. Traditionally, AuNPs were synthesized by citrate reduction method, resulting in nanoparticles protected by electrostatic repulsion which cannot be isolated or redispersed. The new, facile two-phase synthesis of thiolate stabilized AuNPs made them much easier to handle. Another important development in this field was the ligand exchange reaction reported by Murray and coworkers.22 Many of the applications of AuNPs depend on their functionalization. Ligand exchange reaction is an extremely useful tool for introduction of functional groups into AuNPs. Polyhomo-23 and polyhetero-24 functionalized AuNPs could be readily obtained using ligand exchange. The mechanism of ligand exchange, however, proved complicated. Thiolate protected AuNPs undergo ligand exchange reaction with thiols via an associative (SN2-type) mechanism,22,24 26 yielding a new thiol. Disulfides were found to be much less reactive. The ligand exchange reaction of thiolate protected AuNPs with disulfides was found27,28 to follow a dissociative (SN1 type) mechanism, in which desorption of the outgoing ligand is the rate determining step. After dissociation of the thiolate ligand, the vacant site on the gold surface can attack the S S bond of the incoming ligand (disulfide), leading to cleavage of the disulfide bond (Scheme 1). This is consistent with the studies of disulfide exchange in planar self-assembled monolayers (2-D SAMs) which suggested that the S S bond cleaves during the slow exchange reaction.29 The extent of ligand exchange of AuNPs with disulfides was found to be much smaller than that with thiols: only a small number of ligands (5 7) on the nanoparticle surface can be replaced in this reaction. This implies the presence of different types of reactive sites on the AuNPs surface which have different reactivity in ligand exchange reactions. The nonuniform reactivity in similar processes has been earlier observed with planar 2-D SAMs and AuNPs.30,31 The different reactivity of different binding r 2011 American Chemical Society

sites was interpreted25 in terms of reactions starting from certain surface sites (e.g., classically defined vertex and edge sites in the case of AuNPs, or domain boundaries for 2-D SAMs). Other sites (e.g., terrace sites) react much slower. A later study26 also suggested that the rate of ligand exchange does not depend on the particle size, which supports the hypothesis that certain surface sites are primarily targeted in the initial ligand exchange reaction. However, the recently reported crystal structures of AuNPs showed complex geometries. Therefore, the different reactivity of the binding sites is unlikely to be related to simple geometric features. An earlier study by our group showed that aging of AuNPs in solution strongly affects the rate of the ligand exchange reaction of AuNPs with disulfides.32 The reactivity of AuNPs in place-exchange with disulfides was dramatically reduced by aging in solution at room temperature. Freshly synthesized AuNPs were found to react nearly 10 times faster than aged particles. No appreciable size change was observed during aging. The origin and scope of this effect however remained unclear. Here, we studied the mechanistic features of aging effect of AuNPs. Interpretation of kinetic parameters made it possible to propose the structural changes of AuNPs during aging, which are consistent with the observed reactivity in ligand exchange reaction. We used AuNPs prepared by the Brust method.19 21 Although this synthesis gives fairly polydisperse AuNPs, it is very commonly used and is highly amenable to studying aging. The Brust method makes it possible to synthesize AuNPs very rapidly, thus minimizing aging during the synthesis step. Rapid synthesis also increases the chances of kinetically trapping the defect sites on the surface which were suspected to play a major role in the aging process. Received: May 31, 2011 Revised: October 3, 2011 Published: October 10, 2011 14432

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Scheme 1. Ligand Exchange Reaction of Disulfides with Thiolate Protected AuNPs

Scheme 2. Ligand Exchange Reaction of AuNPs with a Bisnitroxide Disulfidea

a

The exchange peaks of the disulfide biradical (shown with arrows) diminish during the reaction.

’ EXPERIMENTAL SECTION Typical Synthesis of AuNPs. AuNPs were prepared by the Brust two-phase protocol.19 21 In a typical synthesis, hydrogen tetrachloroaurate trihydrate (HAuCl4 3 3H20, 1.0 g, 2.5 mmol) was dissolved in deionized water to make a 1% w/w solution. The HAuCl4 (aq) solution was then mixed with tetraoctylammonium bromide (TOAB, 280 mg) and methylbenzene (10 mL) and stirred for 3 min. The color of the aqueous phase turned from yellow to colorless, while the color of the organic phase became red-brown. A 10% w/w solution of alkanethiol (0.1 mmol) in methylbenzene was then added to the reaction mixture. Immediately afterward (e.g., in 20 s), an aqueous solution (3 mL) of NaBH4 (40 mg, 1.05 mmol) was added under vigorous stirring. Au(III) was reduced to Au(0) within seconds, which can be observed by the color change of the organic phase to black. In order to minimize aging, the reaction time was limited to 3 min, and the organic phase was separated thereafter. Solvent was evaporated at 35 °C under vacuum, and the crude particles were washed with methanol (3  50 mL aided with sonication) and dried under N2 flow. The entire preparation typically takes ca. 1 h and hence minimizes the aging effects. In our hands, the typical yield is 75%.33 Characterization of AuNPs. AuNPs were characterized by transmission electron microscopy (TEM), UV vis, thermogravimetric analysis (TGA), and elemental analysis. Characterization of n-butanethiol protected AuNPs (C4H9S-AuNPs) is given as an example (Figure 5). TEM revealed the average particle diameter 2.4 ( 0.7 nm. The UV vis spectrum showed a weak plasmon band at 520 nm consistent with the small particle size. Nanoparticle synthesis showed small batch-to-batch variability in the intensity of the plasmon band in the UV spectra. However, TEM measurements showed the same particle size within experimental error.

Figure 1. Kinetic profiles and first-order rate constants of ligand exchange reactions of C4S-AuNPs and disulfide 1 in 1:1 ratio, at 20 °C. TGA showed the thermal decomposition at 200 °C and gave a mass ratio of 14% organic content to 86% gold core. Elemental analysis (found: 7.119% C, 1.187% H) was consistent with the composition of the ligand shell (n-butanethiol, C4H9SH). AuNPs protected by other ligands showed similar composition. Aging of AuNPs. Freshly prepared particles were dried and dissolved in chlorobenzene to make a 10 4 M solution. AuNPs were then aged in solution at room temperature. Chlorobenzene was chosen as a low volatility common solvent for both the incoming ligand and the nanoparticles. Aging was carried out in ambient atmosphere. However, a control experiment carried out under nitrogen showed that the aging behavior does not depend on the presence of air. Ligand Exchange. The ligand exchange reactions were monitored with electron paramagnetic resonance (EPR) spectroscopy, by employing a functionalized ligand, bisnitroxide disulfide 1 (Scheme 2).27 This disulfide contains two spin labeled branches which gives a five-line EPR spectrum due to spin spin interactions. This disulfide biradical is stable at 90 °C in a chlorobenzene solution, as its EPR spectrum does not change over time. When reacting with gold nanoparticles, cleavage of the S S bridge leads to diminishing exchange peaks (Scheme 2) which makes it possible to monitor the kinetics of ligand exchange.27 The EPR signal of nitroxide attached to the AuNP surface shows broad peaks due to restricted tumbling. The lack of ligand leaching from the AuNP surface is shown by the absence of EPR signal of free ligand (which gives a sharp spectrum). Typically, ligand exchange reactions were carried out with chlorobenzene solutions of 10 4 M AuNPs and 5  10 5 M disulfide 1 at different ratios. The ratios quoted in this work refer to the nanoparticle/ thiolate ligand molar ratio. The nanoparticle concentration was calculated using an empirical formula Au204Ligand75.34 Since one molecule of disulfide 1 has two thiolate braches, the ratio quoted as 1:1 means AuNP/disulfide 1 molar ratio 2:1.

’ RESULTS AND DISCUSSION Aging Effect on C4S-AuNPs. In order to confirm the earlier observations,32 we carried out ligand exchange of C4S-AuNPs with disulfide 1 at 20 °C using a 1:1 AuNP/disulfide ratio. A series of EPR spectra were recorded, and the kinetic profiles for fresh and aged AuNPs were generated. The kinetic parameters were obtained from fitting the data to a first order kinetic model. Significant decay of reactivity of aged particles was clearly observed. The reaction rate of fresh C4S-AuNPs was almost 10 times as fast as the rate for particles aged for 79 h (Figure 1). This is consistent with the earlier report.32 Ligand Dependence of the Aging Effect. The effect of protecting ligand on ligand exchange reaction of AuNPs with thiols was investigated by Murray and co-workers.25 AuNPs protected by short chain thiolates were found to be more “exchangeable”, in terms of faster reaction rate with thiols and 14433

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Figure 2. Normalized kinetic profiles and rate constants of ligand exchange reactions of C8S-AuNPs and disulfide 1 in 1:1 ratio, at 20 °C.

Figure 5. TEM images of freshly prepared (right) and aged (left) AuNPs.

Figure 3. Normalized kinetic profiles and rate constants of ligand exchange reactions of C18S-AuNPs and disulfide 1 in 1:1 ratio, at 20 °C.

Figure 6. UV vis spectra of C4S-AuNPs at different aging times. Figure 4. Reduced reaction rate of aged C4S-, C8S-, and C18S-AuNPs in ligand exchange reactions with disulfide 1.

larger extent of exchange. This was interpreted in terms of higher thermodynamic stability of long chain thiolates on the gold surface (e.g., due to favorable chain chain interactions between adjacent ligands).25 In order to test if a similar effect can be observed for ligand exchange with disulfides, we varied the length of the outgoing ligand in the exchange reaction with disulfide 1. The ligand exchange reactions of n-octanethiol protected AuNPs (C8S-AuNPs) were found to be slower than those for C4SAuNPs, and a clear decay of reaction rate was also observed with increasing aging time (Figure 2). For instance, the reaction rate of fresh C8S-AuNPs with 1 in a 1:1 ratio at at 20 °C was found to be 6 times as fast as that for particles aged for 185 h. Further increase of the chain length of the protecting ligand led to a similar effect. The reaction of fresh n-octadecanethiol protected AuNPs (C18S-AuNPs) with disulfide 1 in a 1:1 AuNP/ ligand ratio at 20 °C was 3 times faster than that for particles aged for 174 h (Figure 3). By comparing the reaction rates of C4S-, C8S-, and C18S-AuNPs (Figure 4), a few interesting observations can be made. First, the reactivity of fresh AuNPs showed strong dependence on the chain length of the protecting thiolate ligand. However, for aged particles, the reaction rates of AuNPs with different protecting

ligands were very similar. The chain length of the outgoing ligand thus only affects the reaction rate of the fresh particles. Second, aging has the greatest effect on reaction kinetics in the first day or even the first few hours after the AuNP preparation. The rates then level off. This effect is independent of the chain length of the protecting ligand. Since dissociation of the outgoing ligand is the rate-determining step in the ligand exchange with disulfides, these observations suggest that desorption of thiolate ligand from the fresh AuNPs depends on its chain length. One can conclude therefore that the strength of bonds between ligands and most reactive sites on the AuNP surface increases with the ligand chain length. Presumably, aging leads to surface reorganization which in turn results in better coordination of Au thiolates. The effect of chain length on the reactivity of the aged particles thus becomes smaller. Effect of Aging on AuNPs Particle Size. The variation of AuNP size during aging was monitored by TEM. No change was observed for C4S-AuNPs aged in a chlorobenzene solution for 4 weeks (Figure 5). As TEM images cannot reveal very small changes in particle size, UV vis spectroscopy was used to monitor the particle size during aging. The surface plasmon band of AuNPs is very sensitive to small changes in particle size/ morphology. C4S-AuNPs were aged in a 10 4 M chlorobenzene solution. At different aging times, aliquots of the AuNPs solution 14434

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Langmuir Scheme 3. Etching of Gold by Molecular Oxygen in the Presence of Cyanide

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Table 1. First Order Rate Constants of Cyanide Induced Decomposition of C4S-AuNPs time of aging/h

first order rate constant/s

0

5.7  10

3

52 83

4.7  10 4.2  10

3

1

kaged/kfresh

0.82 0.73

3

Table 2. Aging Effect on the Extent of Ligand Exchange in a Reaction of 1:10 C4S-AuNPs/Disulfide 1 at 40 °C no. of ligand exchanged aging time/h

Figure 7. Kinetic profiles of CN -induced C4S-AuNP decomposition monitored by UV vis spectroscopy at 520 nm.

were diluted to 5  10 7 M to record UV spectra (Figure 6). Only random small variations to the surface plamon band of AuNPs were observed. This suggests that the size of AuNPs does not change with aging within experimental error. Reduced Reactivity of Aged AuNPs in Cyanide Induced Decomposition. Since nanoparticle size was unaffected by aging, it is likely that the effect of aging is related to the presence of different binding sites and surface coverage on AuNPs. In order to understand the scope of this effect, we tested the aging effect on other chemical processes. Cyanide induced AuNP decomposition might also depend on the presence of defect sites and hence might be modulated by aging. We thus explored the rate cyanide etching of AuNPs. Cyanide etches gold in the presence of O2. In this reaction, Au(0) is oxidized to Au(I) by oxygen and cyanide acts as a ligand for the released Au(I) ions (Scheme 3).35 Studies36 38 of alkanethiolate 2-D SAMs on flat Au surfaces confirmed that cyanide facilitates the dissociation of thiolate ligands by etching the underlyling gold layer. Murray et al. observed35 that the rate of cyanide induced etching of thiolate AuNPs decreased with increasing thiolate chain length (this was interpreted in terms of better steric protection of the Au surface by long chain thiolates). In order to quantify aging effect on cyanide etching, aliquots of 10 4 M C4S-AuNPs solution were taken at different aging times, dried under a flow of N2 gas, and redissolved in tetrahydrofuran to make a 2  10 6 M solution. The solution was then mixed with aqueous KCN (3.5  10 4 M) in a 1:1 (v/v) ratio (this corresponds to Au/CN ratio 10:1). Since the position of the surface plasmon band at 520 nm does not change with aging, cyanide induced decomposition of AuNPs was monitored by UV vis spectroscopy (Figure 7). Kinetic data clearly show reduced reactivity of aged AuNPs in cyanide induced decomposition. We speculate that the cyanide induced decomposition starts from the defect sites on AuNPs. In aged particles, surface reorganization leads to the stabilization of the defects sites which reduces the rate of etching. We note that,

per particle

0

6.0

7

6.1

25

5.8

68

5.3

102

5.5

164

6.0

in this reaction, the effect of aging is not as significant as observed in ligand exchange with disulfides. Aging for 83 h resulted in only 30% reduction in the reaction rate (Table 1), whereas the rate of ligand exchage was slowed down 10-fold under similar aging conditions (Figure 1). Extent of Ligand Exchange Reactions of AuNPs with Disulfides. In the reaction of AuNPs with disulfides, only a small proportion of ligands undergo ligand exchange. We were keen to test whether this number of exchangeable sites is affected by the aging process. In order to estimate the maximum extent of exchange, the reaction of C4S-AuNPs with disulfide 1 was carried out using 1:10 AuNP/disulfide ratio at 40 °C. The large excess of disulfide ensured that all exchangeable sites can undergo the exchange reaction. The time dependence of the concentration of disulfide 1 (determined by EPR) was fitted to the first order rate equation which included an extra term to account for the excess disulfide. The number of exchangeable sites per particle was then calculated using AuNP composition obtained from the TEM/ TGA/elemental analysis data (Table 2). The data in the table show that the aging process has no effect on the number of reactive sites within experimental error. On average, ca. 6 ligands were exchanged per particle. The absence of aging effect on the number of exchangeable sites was reproduced for several AuNP batches, although the absolute number of exchangeable ligands per particle was somewhat batch-dependent. This result is consistent with the batch-dependent number of defect sites on AuNPs. We also tested if the maximum extent of exchange depends on the AuNP:disulfide 1 ratio. C4S-AuNPs aged for 2 weeks were reacted with disulfide 1 in 1:3, 1:5, 1:10, 1:20 and 1:30 ratios at 50 °C. The maximum number of exchangeable ligands per particle was calculated in a similar way by fitting to a first order kinetic model (Table 3). In reactions with 1:3 and 1:5 AuNP:disulfide ratio, almost all disulfide was consumed. However, reactions with lower AuNP:disulfide ratio (1:10, 1:20 and 1:30) showed the presence of excess disulfide at the end of the reaction. The number of exchanged ligands did not depend on the AuNP:disulfide 1 ratio. Varying the reaction temperature, however, significantly affected the maximum extent of the ligand exchange reaction and 14435

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Table 3. Number of exchanged thiolate ligands per particle in ligand exchange reactions using different AuNP/disulfide ratio

Scheme 4. Aging of Thiolate Protected AuNPsa

Number of thiolate AuNP/disulfide ratio

exchanged per particle

1:3

2.8

1:5

4.6

1:10

6.7

1:20 1:30

7.4 6.4 a

Figure 8. Kinetic profiles of the ligand exchange reaction of C4S-AuNPs and disulfide 1 in a 1:20 ratio at 50, 70, and 90 °C.

the reaction kinetics. Figure 8 shows kinetic plots for the ligand exchange reaction of C4S-AuNPs with disulfide 1 using a 1:20 AuNP/disulfide ratio at different temperatures (e.g., 50, 70, and 90 °C). The maximum extent of ligand exchange reaction increased with temperature. Presumably, reactions performed at 70 and 90 °C engaged more reactive sites than reactions carried out at 50 °C. In addition, the reactions at high temperature did not follow first order but appeared to be zeroth order. This result is consistent with the presence of different surface sites on the AuNP surface. At 50 °C, only a small number of sites on AuNPs are reactive and the ligand exchange follows first order kinetics. At high temperature, other sites on the nanoparticle surface become activated. As the number of exchangable sites at high temperature becomes greater than the number of molecules of the incoming ligand, disulfide 1 is no longer in excess and the reaction appears to have a zeroth order. Different Surface Sites and Surface Reorganization of AuNPs. Taken together, the kinetic data on aging effect make it possible to propose the mechanism for this process. The recent crystal structures39,40 of thiolate protected AuNPs suggest that the Au core has a regular geometry which is appended by several different gold atoms in the outer shell networked via the thiolate ligands. We propose that freshly made AuNPs have defect sites on the Au surface and that only these defect sites show reactivity in ligand exchange reaction with disulfides. This suggestion is supported by the fact that the number of exchangeable sites varies significantly from batch to batch. Moreover, the number of exchangeable sites is quite small (ca. 5 7 per nanoparticle) and is not consistent with the number of regular geometrical features on the Au nanoparticle surface (such as the number of vertex or edge

Gold atoms in the outer shell are represented by black dots.

sites, or thiolate staples). Thus, ligand exchange with disulfides must be attributed to the defect sites. The reactivity of defect sites in exchange with disulfides is indeed expected to be higher than that of other sites. The defect sites are likely to be less coordinated and networked with the other gold atoms and thiolate ligands (Scheme 4). Hence, the thiolates attached to the Au atoms at defect sites are more labile. The rate-determining step in ligand exchange with disulfides is the dissociation of outgoing ligand, as these reactions show zeroth order with respect to the incoming ligand.27,28 The easier ligand dissociation from defect sites thus makes them reactive in ligand exchange with disulfide. As the nanoparticle diameter does not change during ligand exchange, the aging must involve a surface reorganization process: the defect sites probably become better coordinated with other gold atoms, which reduces the reactivity of these sites (Scheme 4). This is consistent with all observations made in this work. For instance, the number of exchangeable sites does not change during aging, as surface reorganization changes the reactivity of the defect sites but not their number. The lower reactivity of freshly made AuNPs protected by long chains thiols is presumably due to the stronger Au ligand bonds at defect sites in these materials. This is consistent with the chain length dependence on the rate of formation of 2-D SAMs. As AuNPs protected by different chain length thiolates are aged, all defect sites become bonded to the other gold atoms, thus leading to a similar reactivity of aged AuNPs in ligand exchange reaction. At low temperature (e.g., room temperature), only the defect sites are engaged in the ligand exchange reactions with disulfides. At higher temperature (above 70 °C), other surface sites (e.g., gold thiolate “staples”) become activated. This explains the significant increase in the number of exchangeable ligands at high temperature.

’ CONCLUSIONS Aging of AuNPs in solution at room tempearture results in reduced reactivity in defect site-related reactions, including ligand exchange with disulfides and cyanide induced AuNP decomposition. The effect of aging was found to be a general feature of AuNPs, which was attributed to surface reorganization. We propose that fresh AuNPs have defect sites (e.g., less coordinated gold thiolates in the outer layer not networked with the other outer shell gold “staples”). These sites show highest reactivity. During aging, the “defect” gold thiolates become better coordinated and connected with the other gold 14436

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Langmuir atoms. This process does not affect the number of defect sites but reduces their reactivity.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected].

’ ACKNOWLEDGMENT The authors thank the University of York (Wild Fund) for financial support. Dr. Marco Conte is thanked for TEM analysis. Dr. Philip Helliwell is thanked for TGA. ’ REFERENCES (1) Haruta, M.; Kobayashi, T.; Sano, H.; Yamada, N. Chem. Lett. 1987, 405. (2) Haruta, M.; Yamada, N.; Kobayashi, T.; Iijima, S. J. Catal. 1989, 115, 301. (3) Haruta, M.; Tsubota, S.; Kobayashi, T.; Kageyama, H.; Genet, M. J.; Delmon, B. J. Catal. 1993, 144, 175. (4) Sakurai, H.; Tsubota, S.; Haruta, M. Appl. Catal., A 1993, 102, 125. (5) Haruta, M. Catal. Today 1997, 36, 153. (6) Souza, G. R.; Christianson, D. R.; Staquicini, F. I.; Ozawa, M. G.; Snyder, E. Y.; Sidman, R. L.; Miller, J. H.; Arap, W.; Pasqualini, R. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 1215. (7) Alric, C.; Taleb, J.; Le Duc, G.; Mandon, C.; Billotey, C.; Le Meur-Herland, A.; Brochard, T.; Vocanson, F.; Janier, M.; Perriat, P.; Roux, S.; Tillement, O. J. Am. Chem. Soc. 2008, 130, 5908. (8) Hainfeld, J. F.; Slatkin, D. N.; Focella, T. M.; Smilowitz, H. M. Br. J. Radiol. 2006, 79, 248. (9) Warsi, M. F.; Adams, R. W.; Duckett, S. B.; Chechik, V. Chem. Commun. 2010, 46, 451. (10) Astruc, D.; Daniel, M. C.; Ruiz, J. Chem. Commun. 2004, 2637. (11) Castaneda, M. T.; Alegret, S.; Merkoci, A. Electroanalysis 2007, 19, 743. (12) Bunz, U. H. F.; Rotello, V. M. Angew. Chem., Int. Ed. 2010, 49, 3268. (13) Raschke, G.; Kowarik, S.; Franzl, T.; Sonnichsen, C.; Klar, T. A.; Feldmann, J.; Nichtl, A.; Kurzinger, K. Nano Lett. 2003, 3, 935. (14) Pasquato, L.; Pengo, P.; Scrimin, P. J. Mater. Chem. 2004, 14, 3481. (15) Labande, A.; Ruiz, J.; Astruc, D. J. Am. Chem. Soc. 2002, 124, 1782. (16) Ghosh, P.; Han, G.; De, M.; Kim, C. K.; Rotello, V. M. Adv. Drug Delivery Rev. 2008, 60, 1307. (17) Paciotti, G. F.; Kingston, D. G. I.; Tamarkin, L. Drug Dev. Res. 2006, 67, 47. (18) Paciotti, G. F.; Myer, L.; Weinreich, D.; Goia, D.; Pavel, N.; McLaughlin, R. E.; Tamarkin, L. Drug Delivery 2004, 11, 169. (19) Brust, M.; Fink, J.; Bethell, D.; Schiffrin, D. J.; Kiely, C. J. Chem. Soc., Chem. Commun. 1995, 1655. (20) Brust, M.; Bethell, D.; Schiffrin, D. J.; Kiely, C. J. Adv. Mater. 1995, 7, 795. (21) Brust, M.; Walker, M.; Bethell, D.; Schiffrin, D. J.; Whyman, R. J. Chem. Soc., Chem. Commun. 1994, 801. (22) Templeton, A. C.; Wuelfing, W. P.; Murray, R. W. Acc. Chem. Res. 2000, 33, 27. (23) Hostetler, M. J.; Green, S. J.; Stokes, J. J.; Murray, R. W. J. Am. Chem. Soc. 1996, 118, 4212. (24) Ingram, R. S.; Hostetler, M. J.; Murray, R. W. J. Am. Chem. Soc. 1997, 119, 9175. (25) Hostetler, M. J.; Templeton, A. C.; Murray, R. W. Langmuir 1999, 15, 3782.

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