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The mechanism of a place-exchange reaction of ligand-protected Au nanoparticles was investigated using diradical disulfide spin labels. Analysis of re...
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Mechanistic Study of a Place-Exchange Reaction of Au Nanoparticles with Spin-Labeled Disulfides Petre Ionita,† Agneta Caragheorgheopol,† Bruce C. Gilbert,‡ and Victor Chechik*,‡ Department of Chemistry, University of York, Heslington, York YO10 5DD, U.K, Romanian Academy, Institute of Physical Chemistry “I. G. Murgulescu”, Spl. Independentei 202, 77208 Bucharest, Romania Received July 26, 2004. In Final Form: September 25, 2004 The mechanism of a place-exchange reaction of ligand-protected Au nanoparticles was investigated using diradical disulfide spin labels. Analysis of reaction mixtures using a combination of GPC and EPR allowed us to determine concentration profile and propose a kinetic model for the reaction. In this model, only one branch of the disulfide ligand is adsorbed on the Au surface during exchange; the other branch forms mixed disulfide with the outgoing ligand. The two branches of the disulfide ligand therefore do not adsorb in adjacent positions on the surface of Au nanoparticles; this was ultimately proven by the powder EPR spectra of frozen exchange reaction mixtures. Our data also suggest the presence of different binding sites with different reactivity in the exchange reaction. The most-active sites are likely to be nanoparticle surface defects.

Introduction Place-exchange reaction is an extremely versatile and important method for preparation of functionalized metal nanoparticles.1 In this reaction, addition of presynthesized ligand-protected nanoparticles to a solution of another ligand effects partial replacement of the protecting shell on the nanoparticle surface (Scheme 1). The reaction is most studied for thiol-protected Au nanoparticles; its simplicity and applicability to a wide range of different ligands made it a popular synthetic tool. The mechanism of the exchange reaction of Au nanoparticles with thiols was extensively studied by R. W. Murray’s group. They showed that the initial phase of the reaction is first order with respect to each reagent (e.g., Au nanoparticles and incoming ligands), consistent with an associative reaction pathway.2 This was further supported by a recent observation of the sensitivity of the place-exchange reaction to the electronic effects of the incoming ligand.3 On the other hand, molecular oxygen4 and positive electrical charge5 were shown to substantially accelerate the rate of exchange, possibly inducing formation of the intermediate Au(I) species. The latter results suggest a dissociative pathway, perhaps competing with the main associative mechanism. A small number of ligands were found to exchange rapidly; this initial fast reaction is then followed by a much slower process. Not all ligands can however be exchanged on the nanoparticle surface even at long reaction times. These observations point to the presence of different types of binding sites on the nanoparticle surface.2 Au nano-

Scheme 1. Place-Exchange Reaction at the Surface of Thiol-Protected Au Nanoparticles

particles are faceted, and it was postulated that vertex and edge sites are more reactive in exchange reaction than terrace sites. Recently, we communicated preliminary results of a place-exchange reaction with disulfides studied using spinlabeling techniques.6 Disulfides are generally considered inactive in the exchange reaction, but we found that they undergo partial exchange with short-chain thiol-protected Au particles. The exchange reaction was found to be zeroth order with respect to the incoming ligand concentration, which was interpreted in terms of a dissociative pathway.6 Interestingly, the rate of exchange slowed substantially upon aging of the nanoparticles in solution.7 Here, we report further mechanistic details of exchange reaction of Au nanoparticles with disulfides. The reaction kinetics were conveniently studied by EPR; to establish a full kinetic profile of the reaction, we coupled EPR analysis with GPC separation of reaction mixtures. The study was also extended to phosphine-protected nanoparticles which are more active in exchange reaction and allow rapid replacement of most ligands.8,9 The spinlabeled ligands, 1 and 2, and nanoparticles, 3 and 4, used in this work are shown in Figure 1. Results and Discussion

* Author to whom correspondence should be addressed. E-mail: [email protected]. † Institute of Physical Chemistry. ‡ University of York.

Preparation of Au Nanoparticles 3 and 4. Au nanoparticles were synthesized following published procedures.10,11 TEM images of nanoparticles are shown in Figure 2. The average particle size was 2.4 ( 0.6 and 1.4

(1) Templeton, A. C.; Wuelfing, W. P.; Murray, R. W. Acc. Chem. Res. 2000, 33, 27. (2) Hostetler, M. J.; Templeton, A. C.; Murray, R. W. Langmuir 1999, 15, 3782. (3) Donkers, R. L.; Song, Y.; Murray, R. W. Langmuir 2004, 20, 4703. (4) Song, Y.; Huang, T.; Murray, R. W. J. Am. Chem. Soc. 2003, 125, 11694. (5) Song, Y.; Murray, R. W. J. Am. Chem. Soc. 2002, 124, 7096.

(6) Ionita, P.; Caragheorgheopol, A.; Gilbert, B. C.; Chechik, V. J. Am. Chem. Soc. 2002, 124, 9048. (7) Chechik, V. J. Am. Chem. Soc. 2004, 126, 7780. (8) Chechik, V.; Wellsted, H. J.; Korte, A.; Gilbert, B. C.; Caldararu, H.; Ionita, P.; Caragheorgheopol, A. Faraday Discuss. 2004, 125, 279; (9) Wellsted, H.; Sitsen, E.; Caragheorgheopol, A.; Chechik, V. Anal. Chem. 2004, 76, 2010.

10.1021/la048121q CCC: $27.50 © 2004 American Chemical Society Published on Web 11/11/2004

Mechanistic Study of Place-Exchange Reaction

Figure 1. Nanoparticles and ligands used in this study.

( 0.3 nm for nanoparticles 4 and 3, respectively. Particle size depends on a number of factors, including the reaction stoichiometry and the nature of the ligand headgroup. As we used identical reaction conditions for the synthesis of nanoparticles 3 and 4 (1:1 ligand-to-metal ratio), the difference in particle size is due to the different affinity of thiol and phosphine-based ligands for the growing Au particles. The particle size was consistent with the literature reports. The distribution of particle size was fairly broad but quite symmetrical, with a nearly Gaussian shape. The average number of Au atoms in a nanoparticle was estimated from the particle diameter as measured by TEM. The number of ligands per nanoparticle was then calculated from the elemental analysis data. These data showed excellent agreement with molecular formulas reported in the literature (Au101(PPh3)21Cl5 and Au500(C4H9S)150 for nanoparticles 3 and 4, respectively). These formulas were used to calculate the stoichiometry of nanoparticle reactions throughout this study. Product Analysis of the Exchange Reaction of Au Nanoparticles with Disulfides. The exchange reaction effects replacement of ligands on the nanoparticle surface (Scheme 1). If the incoming ligand is a disulfide, the two branches of the molecule can either adsorb together on the nanoparticle surface or become separated during exchange reaction. The use of spin labels can help differentiate between these two possibilities due to the sensitivity of EPR spectra to the interspin distances. For instance, solution EPR spectra of strongly coupled bisnitroxides show a characteristic five-line pattern due to the hyperfine interaction with the nitrogen atom and the spin exchange interaction between the two unpaired electrons.12 Solution EPR spectra of mononitroxides show simpler three-line spectra due to the hyperfine interaction (but no spin exchange). The line shape of the EPR spectra can thus be used to determine the presence of one spin label in the vicinity of the other. In our earlier work, we investigated the exchange reaction between Au nanoparticles 4 and disulfide 1. We observed that the five-line spectra of disulfide 1 were transformed into three lines during reaction (Figure 3).6 The disappearance of the second and fourth peaks in the spectra (arrowed in Figure 3) suggested that, following (10) Weare, W. W.; Reed, S. M.; Warner, M. G.; Hutchinson, J. E. J. Am. Chem. Soc. 2000, 122, 12890. (11) Brust, M.; Walker, M.; Bethell, D.; Schiffrin, D. J.; Whyman, R. J. Chem. Soc., Chem. Commun. 1994, 801. (12) Parmon, V. N.; Kokorin, A. I.; Zhidomirov, G. M.; Zamaraev, K. I. Mol. Phys. 1975, 30, 695.

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adsorption on the Au surface, the nitroxides of disulfide 1 are no longer in the vicinity of each other. We speculated therefore that the two branches of the disulfide molecule are separated during exchange reaction. The disappearance of the spin exchange peaks (as arrowed in Figure 3), however, could be due to other factors. Exchange interaction in flexible diradicals critically depends on the frequency of collisions of the spinbearing functional groups.13 The EPR spectral changes observed during ligand exchange could therefore be due to the reduced frequency of collisions of the nitroxides in a viscous environment of the ligand-protected Au nanoparticle and do not necessarily imply that the two branches of the disulfide are adsorbed far apart from each other. To test reliably if the disulfide branches are separated during ligand exchange, we studied EPR spectra of the frozen exchange-reaction mixtures. Such spectra are usually not affected by the spin exchange interaction (as nitroxides are immobilized in frozen solutions and hence have very low frequency of collisions), but are sensitive to the dipole-dipole interaction between neighboring nitroxides. The unpaired electron has a strong magnetic dipole which perturbs the magnetic field at nitroxide functionalities in its vicinity, thus effectively shifting their EPR spectra.14 This dipole-dipole interaction does not affect fast-tumbling solution samples (as it is averaged out to zero). In frozen samples, however, the dipole-dipole interaction substantially alters the shape of the spectrum. This effect is noticeable for distances up to 2-3 nm.14 Quantitatively, the effect of dipole-dipole interaction could be estimated by the empirical parameter d1/d, which measures the ratio of the peak heights (Figure 4). This parameter was shown to be sensitive to the distance between adjacent nitroxides and hence a convenient measure of the strength of the dipole-dipole interactions.14,15 To a good approximation, it is inversely proportional to the distance between interacting nitroxides. Figure 4 shows EPR spectra of frozen solutions of diradical 1 and the products of exchange reaction of nanoparticles 4 with ligands 1 and 2. The spectrum of free diradical 1 shows characteristic broadening due to the dipole-dipole interaction between the two nitroxides. This is confirmed by the high value of the d1/d parameter (0.69). The product of exchange reaction of nanoparticles 4 (in large excess) with monoradical 2, however, shows a different pattern (Figure 4). This reaction produces Au nanoparticles labeled with isolated nitroxides; no line broadening is observed in the EPR spectrum, and the value of d1/d is small (0.52). Importantly, exchange reaction of nanoparticles 4 with diradical 1 also gives an EPR spectrum with no detectable line broadening (Figure 4). The value of the d1/d parameter for this sample is indistinguishable from that of the isolated monoradical (0.52). This implies that the spin labels on the Au surfaces are well separated from each other (e.g., by more than 2 nm). We conclude therefore that the two branches of the disulfide ligand do not adsorb together on the Au surface. This is consistent with our earlier suggestion; the new evidence however is much more rigorous. (13) Molin, Ju. N.; Salikhov, K. M.; Zamaraev, K. I. Spin Exchange; Springer: Berlin, 1980. (14) Likhtenshtein, G. I. Spin Labeling Methods in Molecular Biology; Wiley: New York, 1976. (15) Kokorin, A. I.; Zamaraev, K. I.; Grigoryan, G. L.; Ivanov, V. P.; Rozantsev, E. G. Biofizika 1972, 17, 34 (in Russian). Likhtenshtein, G. I. Biophysical Labeling Methods in Molecular Biology; Cambridge University Press: New York, 1993. Kulikov, A. V.; Likhtenstein, Adv. Mol. Relax. Interact. Processes 1997, 10, 47; Kokorin, A. I. Dr. Thesis, Moscow, 1973 (in Russian).

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Figure 2. TEM images of triphenylphosphine (a) and butanethiol-protected Au nanoparticles (b) and the corresponding size distribution histograms. The average particle size was 1.4 ( 0.3 and 2.4 ( 0.6 nm, respectively.

Figure 3. Room-temperature EPR spectra of ligand 1 and the product of exchange reaction of ligand 1 and butanethiolprotected Au nanoparticles 4 (reaction stoichiometry one ligand per nanoparticle). Spectra were run in 1% DCM/toluene. The peaks due to the exchange interaction between adjacent nitroxides are shown with the arrows.

A Study of the Reaction Intermediate. The separation of the two branches of the incoming disulfide ligand

implies that only one branch adsorbs on the Au surface in a single reaction act. At the end of the reaction, however, all incoming ligand is adsorbed on the nanoparticles. This suggests that the other branch forms an intermediate which can also participate in the exchange reaction. To investigate the possible structure of such an intermediate, we have separated the reaction mixture of ligand 1 and nanoparticles 4 using gel permeation chromatography (GPC).9 The GPC fractions were analyzed by EPR. We found that, apart from the starting disulfide 1 and the reaction product (spin-labeled nanoparticles), another isolated material is EPR-active. The EPR spectra of this material showed a typical nitroxide triplet with no spinspin interactions, implying the presence of one nitroxide group in the molecule. Interestingly, it eluted after ligand 1 during GPC, suggesting that it is a very small molecule. The amount of this mononitroxide intermediate increased in the beginning of the reaction reaching ca. 30% of the total spin label concentration, and then slowly decayed to zero. A possible structure of the intermediate is a mixed disulfide of spin label 1 with the outgoing ligand (Scheme 2). Alternatively, it could be a nitroxide-containing thiolate ion or an Au thiolate. Au thiolates have been earlier proposed as intermediates in the exchange process between Au nanoparticles and alkanethiols.16 The latter reaction is facilitated in the presence of oxygen, which is probably needed to generate an Au thiolate. However, we earlier reported that disulfide exchange is not influenced by oxygen.7 It is therefore unlikely that Au thiolates play a (16) Schaaff, T. G.; Whetten, R. L. J. Phys. Chem. B 1999, 103, 9394; Hicks, J. F.; Miles, D. T.; Murray, R. W. J. Am. Chem. Soc. 2002, 124, 13322.

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Figure 4. EPR spectra of frozen solutions of diradical 1 and the products of exchange reaction of nanoparticles 4 with ligands 1 and 2. Spectra were run in 1% DCM/toluene at 110 K. The ratios of peak heights d1/d are shown under the spectra. Scheme 2. Formation of a Mixed Disulfide during Exchange Reaction

major role in disulfide exchange. We have also analyzed a sample of intermediate using ICP-OES spectroscopy, which showed absence of Au within experimental error (ca. 5% of the concentration of the intermediate). This supports our hypothesis that the mononitroxide intermediate is not an Au thiolate. We believe the intermediate is most likely to be a mixed disulfide of the spin label with the outgoing ligand. The fact that it has a longer GPC retention time than diradical 1 implies that the intermediate has a smaller molecular size than diradical 1. This agrees well with the structure of mixed disulfide with a small outgoing ligand (butanethiol). Accumulation of fairly large amount of the intermediate suggests that it has low reactivity in the exchange reaction. It is therefore unlikely to be a thiolate ion. The mixed disulfide structure of the intermediate is further supported by good fit with the kinetic model and results from exchange reaction using phosphine-protected Au nanoparticles (vide infra). Unfortunately, analysis by ESI mass spectroscopy gave inconclusive results, and we were unable to obtain further evidence for the structure of the intermediate. Kinetics of the Exchange Reaction. To get a better mechanistic understanding of the ligand exchange, we studied kinetics of the reaction of Au nanoparticles 3 with disulfide 1. The kinetic runs were carried out in chlorobenzene, as it is a common solvent for both reagents (within the concentration range studied) and is nonvolatile, which prevents solvent losses during sample preparation and reaction. Some reactions were also monitored in dichloromethane (DCM)/toluene mixtures. As the EPR spectra of disulfide 1 change from a five-line to a threeline pattern during exchange (vide supra), it was convenient to monitor the reaction by EPR. The height of the second peak in the spectrum (the spin-exchange peak, arrowed in Figure 3) was assumed to be linearly proportional to the concentration of unreacted disulfide 1 in the reaction mixture. The time dependences of the disulfide 1 concentration were then fitted with an exponential decay function, which in all cases gave good fit (Figure 5). Not all ligands at the surface of Au nanoparticles can be replaced using disulfides as incoming ligands; the maximum number of “exchangeable” sites on an Au particle surface is ca. 4-6. Therefore, in our study, we used ex-

Figure 5. Decay of disulfide ligand 1 in an exchange reaction with nanoparticles 4 in chlorobenzene. The solid line shows experimental data, the dashed line represents the best fit with an exponential decay function. Initial concentrations of spin label and nanoparticles were 10-4 and 5 × 10-5 M, respectively.

change reaction stoichiometry which did not exceed three thiolate ligands per nanoparticle (e.g., taking into account that one molecule of disulfide 1 produces two thiolate ligands). Under these conditions, all disulfide 1 was adsorbed on the nanoparticles at the end of reaction, and the kinetics up to 50% conversion could be assumed to be pseudo-first order. We found that minute differences in nanoparticle synthesis procedure have substantial effect on their reactivity and the data obtained using different nanoparticle preparations cannot be compared within the same series. We also recently reported that solutions of nanoparticles 4 undergo an aging process which dramatically slows the exchange reaction.7 To obtain reproducible results, the kinetic study was thus performed with a freshly prepared batch of nanoparticles, which was stored in the dry form at -20 °C prior to use. To further reduce the effect of aging, the preparation and workup times were minimized during nanoparticle synthesis. The kinetics of ligand exchange were monitored for different concentrations of disulfide 1 and nanoparticles 4. The half-reaction times obtained are in Table 1. As there are two nitroxide moieties in the molecule of disulfide 1, the concentrations of spin label referred to in this paper equal twice the concentration of the disulfide 1. To determine the kinetic order of the reaction, we plotted the half-reaction times vs concentration of starting materials in double-logarithm coordinates. The plots are

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Table 1. Half-Reaction Times for Exchange of Nanoparticles 4 with Diradical 1 in Chlorobenzene spin label concentration, M

concentration of Au nanoparticles, M

half-reaction time, min

1.25 × 10-5 2.5 × 10-5 5 × 10-5 5 × 10-5 7.5 × 10-5 10-4 10-4

2.5 × 10-5 2.5 × 10-5 5 × 10-5 2.5 × 10-5 2.5 × 10-5 5 × 10-5 10-4

1.98 3.30, 3.65a 2.24 9.76 10.8 5.33 1.56, 1.73a

a

Results of duplicate runs.

in Figure 6. The slopes of the best-fit lines can be used to calculate the reaction order (see Appendix 1). The kinetic order with respect to the concentration of Au was found to be 1.6 in chlorobenzene (Figure 6) and 1.2 in DCM. These noninteger values could be due to experimental error; they also might indicate the complexity of processes taking place in the exchange reaction mixture. It is likely that the ligand exchange is first order with respect to the nanoparticle concentration; the deviation of the experimentally determined order from unity is probably due to competing side reactions, e.g., aging of Au nanoparticles.7 The reaction order with respect to the concentration of diradical was found to be 0.02 in chlorobenzene and -0.1 in DCM. This confirmed our earlier data on the same reaction in a 1% DCM/toluene mixture.6 Thus, the reaction order with respect to the concentration of diradical is zero within experimental error. This may appear inconsistent with the aforementioned exponential decay of the diradical concentration in kinetic runs which is normally typical of the first order processes (Figure 5); the apparent contradiction however can be explained by the kinetic model proposed for the reaction (vide infra). A zeroth order can be observed in two cases: (i) diradical 1 undergoes preassociation to form a complex which then slowly undergoes ligand exchange or (ii) the first step is rate-determining, but the diradical does not take part in this step. Preassociation can be ruled out, as any adsorption of diradical on the Au nanoparticle would dramatically change its dynamics; no sign of this was, however, observed in EPR spectra. We conclude therefore that the diradical is not involved in the rate-determining step. The mechanism of the exchange reaction of Au nanoparticles with disulfides is hence likely to be dissociative, with the bond between the Au nanoparticle and the outgoing ligand breaking in the rate-determining step. It is interesting to mention that a small fractional order with respect to the concentration to the incoming ligand has been reported in a recent publication.17 To account for the experimentally determined order (0.33-0.38), the authors suggest that replacement of one ligand on a nanoparticle makes a number of other ligands more prone to exchange. In our case, however, this scheme is unlikely to operate, as the extent of the exchange reaction is rather small (e.g., even in the presence of large excess of incoming ligand only 4-6 ligands per nanoparticle can be exchanged). Nonetheless, this example illustrates that there might be other mechanistic schemes consistent with our kinetic data. In summary, a possible model to fit our kinetic data (in particular, the apparent zeroth order with respect to the disulfide concentration) is a dissociative, “SN1”-like mechanism. In the first step of this mechanism, Au nanoparticles undergo a slow monomolecular reaction (e.g., dissociation of an outgoing ligand from the nanoparticle

Figure 6. Plot of the half-reaction time vs reagent concentrations in double-logarithm coordinates. Chlorobenzene was used as solvent. The concentration of diradical 1 was kept constant at 10-4 M while the concentration of Au nanoparticles 4 was varied (filled circles); the concentration of Au nanoparticles 4 was kept constant at 2.5 × 10-5 M while the concentration of diradical 1 was varied (open circles).

surface to form a physisorbed thiolate ion or thiolate radical), followed by a faster reaction with the incoming ligand. Kinetic Model of the Exchange Reaction. To test the validity of proposed mechanistic details, we determined time-dependent concentration profiles of all components of the exchange reaction, e.g., starting material, intermediate, and product. The samples of the reaction mixture of nanoparticles 4 and ligand 1 were separated by GPC at different reaction times. The amount of nitroxides in different GPC fractions was quantified by double integration of EPR spectra and comparison of the data with a calibration curve obtained using TEMPO solutions of different concentrations. Good separation of all components was observed in most cases, but some GPC fractions showed incomplete separation of ligand 1 and the intermediate. In these fractions, the amount of each compound was quantified by line-shape deconvolution. The results of two such experiments are graphically shown in Figure 7. To simulate these concentration profiles, we constructed a tentative kinetic model based on mechanistic details discussed in previous sections. The exchange reaction starts with a slow dissociative rate-determining step (Scheme 3, reaction 1), which involves dissociation of a ligand from Au (probably producing a nanoparticlephysisorbed thiolate ion). The activated nanoparticle then reacts with the incoming disulfide ligand. One branch of the disulfide gets adsorbed on Au, while the other forms a mixed disulfide with the outgoing ligand (reaction 2). The mixed disulfide intermediate can also participate in further exchange reaction with the Au nanoparticles (reactions 3-5). To help visualize the reaction with asymmetrical disulfides, which give different products depending on which branch of the incoming ligand is adsorbed on Au, we highlighted different branches in the asymmetrical disulfides with an italic or an underlined typeface. Outgoing ligands are shown in bold. For simplicity, we assumed that all disulfides react with the activated Au particles with equal rates; symmetrical disulfides react twice as fast as asymmetrical ones for statistical reasons. The proposed reaction scheme explains the apparent discrepancy between the zeroth order of the reaction with respect to the concentration of diradical and exponential line shape for the decay of diradical during reaction (which (17) Montalti, M.; Prodi, L.; Zaccheroni, N.; Baxter, R.; Teobaldi, G.; Zerbetto. F. Langmuir 2003, 19, 5172. The authors would like to thank the reviewer for bringing this paper to their attention.

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Figure 7. Kinetic data for the exchange reaction of disulfide 1 with Au nanoparticles 4. Open circles, filled triangles, and open triangle show the concentrations of spin-labeled Au nanoparticles, disulfide 1, and mixed disulfide intermediate, respectively. The reaction was carried out at room temperature in 50% DCM/toluene (a) and DCM (b). Initial concentration of Au nanoparticles 4 was 5 × 10-4 M. The initial concentration of disulfide 1 was 10-3 M (a), 5 × 10-4 M (b). Scheme 3. Proposed Mechanism for the Exchange Reaction of Au Nanoparticles with Disulfide Ligands

is normally typical of first order reactions, vide supra). The equations in Scheme 3 could be used to obtain the rate law for the diradical L′-S-S-L′ (eq 1, see Appendix B for full details).

d[L′-S-S-L′] [L′-S-S-L′] ) - k1 × [Au-S-L] × dt [L′-S-S-L′]0 (1) Here, [Au-S-L] and [L′-S-S-L′] are the current concentrations of the Au nanoparticles 4 and diradical 1, respectively; [L′-S-S-L′]0 is the initial concentration of diradical 1. One can see that integration of this kinetic equation assuming excess of Au nanoparticles 4 gives an exponential decay function (see Appendix B for details). This justifies the use of exponential function to fit kinetic data. On the other hand, the initial rate does not depend on the concentration of the diradical (as [L′-S-S-L′] ) [L′S-S-L′]0 at t ) 0 and hence (d[L′-S-S-L′])/(dt) ) - k1[Au-S-L]). The reaction is therefore zeroth order with respect to the initial concentration of disulfide ligand. The concentration profiles in Figure 7 were fitted with a model based on Scheme 3. The simulated data are shown as solid lines. Full details of the kinetic equations are given in Appendix B. Unfortunately, in this particular case, the Au nanoparticles were not in sufficient excess with respect to the incoming ligand, and the reactions

never went to completion. Nevertheless, the model expression (which contained only two variable parameters) fitted experimental data reasonably well. The exchange reaction system is very complex; it is probably affected by the nonequivalence of the binding sites on the Au surface, the polydispersity of the Au nanoparticle size, uneven distribution of the ligands on nanoparticles, aging effects, and possibly some side reactions. Our simple kinetic model was not intended to adequately describe this complexity. Instead, we attempted to unravel some basic details of the main reactions taking place in this system. It is possible to obtain a much better fit if one introduces more variable parameters (e.g., by lifting the fixed relationship between the rates of reactions 3-5 in Scheme 3). Such models, however, are harder to justify. We believe that the good agreement between the experimental data and our very simple kinetic model (with the minimum number of variable parameters) supports our interpretation of the basic mechanistic details and the proposed mixed disulfide structure of the reaction intermediate. Exchange Reaction with Phosphine-Protected Au Nanoparticles 3. As the exchange reaction with disulfides only allows one to replace a few ligands on the nanoparticle surface, we were interested in exploring weaker outgoing ligands to improve the efficiency of the exchange reaction. A number of weaker protecting ligands for Au nanoparticles have been reported, including amines,18 tetraalkylammonium salts,19 thioethers,20 phosphines,21 etc. Unfortunately, weak ligands do not offer sufficient protection from aggregation, and Au nanoparticles protected by most of these materials would only be stable in the presence of excess ligand. We found that triphenylphosphine-protected Au nanoparticles are best suited for our purposes due to high reactivity in the exchange reactions. Although they also show limited stability and precipitate from solution upon prolonged storage (e.g., several days to several weeks), they are stable within the time scale of our experiments. They are also stable enough to survive purification by preparative GPC. For kinetic studies, we used freshly prepared batches of these nanoparticles. The kinetic behavior of the exchange reaction of (18) Leff, D. V.; Brandt, L.; Heath, J. R. Langmuir 1996, 12, 4723. Selvakannan, PR.; Mandal, S.; Pasricha, R.; Adyanthaya, S. D.; Sastry, M. Chem. Commun. 2002, 1334. (19) Lin, X. M.; Sorensen, C. M. Chem. Mater. 1999, 11, 198. (20) Li, X. M.; de Jong, M. R.; Inoue, K.; Shinkai, S.; Huskens, J.; Reinhoudt, D. N. J. Mater. Chem. 2001, 11, 1919. (21) Warner, M. G.; Reed, S. M.; Hutchinson, J. E. Chem. Mater. 2000, 12, 3316.

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nanoparticles 3 with disulfide 1 is quite similar to that of thiol-protected nanoparticles 4. The reaction shows approximately first order with respect to the nanoparticle concentration. The absolute values of rate constants are, however, much higher. For instance, in 1% DCM/toluene, the rate constant was 0.08 min-1 at room temperature (initial concentrations of nanoparticles 3 and disulfide 1 were 2 × 10-5 M and 2 × 10-4 M, respectively). This is ca. 20-50 times faster than the corresponding reaction of nanoparticles 4 (the more-accurate comparison is not possible due to a strong batch dependence of the nanoparticle reactivity). The faster reaction of nanoparticles protected by poorer ligand 3 is consistent with the dissociative reaction mechanism. We were particularly interested in investigating the reaction intermediates for the reaction with nanoparticles 3. To detect a possible intermediate, the reaction mixtures of nanoparticles 3 and disulfide 1 were separated by GPC at different reaction times. EPR analysis of individual fractions revealed the presence of a small amount of a monoradical eluting at a similar retention time as the mixed disulfide intermediate for the reaction of nanoparticles 4. This monoradical however can only be detected near the end of the reaction and the maximum amount we were able to observe is ca. 4% of the spin label. For comparison, the mixed disulfide intermediate in reaction with nanoparticles 4 accounts for up to 30% of the spin label. We believe that these data support our assumption that the intermediate in reaction of nanoparticles 4 is a mixed disulfide with the outgoing ligand. Phosphineprotected particles 3 have triphenylphosphine as an outgoing ligand. It obviously cannot form a mixed disulfide with the spin label, which is consistent with the detection of only very small amount of the intermediate in this case. The nature of this latter intermediate is not clear. It could be a thiolate anion or an Au thiolate. Unfortunately, the small quantity of the intermediate made further structural analysis impractical. Exchange reaction with nanoparticles 3 proceeds much further than with particles 4. Substantially more than 50% of the ligands could be replaced using disulfides as incoming ligands with nanoparticles 3. This could be compared with only 3-5% of exchangeable ligands on the surface of nanoparticles 4. The strong dependence of the extent of reaction on the nature of the outgoing ligand clearly points to the inequivalence of binding sites on the surface of Au nanoparticles The nature of the difference between binding sites is, however, not clear. One possible explanation suggests that as the nanoparticles are faceted, the vertex, edge, and terrace sites have different properties. This, however, contradicts our results, as there are certainly more than 5% of the vertex binding sites in small particles studied here. It is more likely in our view that there is a small number of defect sites on the particles which are most active in exchange reaction. Interestingly, the kinetics of exchange reaction with phosphine-protected nanoparticles at high conversion no longer obeys a single exponential decay law. At least two exponents are required to fit the data adequately (Figure 8). Such behavior could in principle be explained by the different reactivities of nanoparticles of different sizes. In our case, however, the particle size distribution is clearly monomodal (Figure 2); it is therefore unlikely that the polydispersity is the sole cause of the double exponential kinetics. We believe that the complex kinetics are due to the inequivalence of the binding sites on the nanoparticle surface, with some sites undergoing faster exchange (first exponential) than the others (second exponential).

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Figure 8. Kinetic curve for the reaction of nanoparticles 3 (10-5 M) and disulfide 1 (10-4 M). The reaction was monitored in 1% DCM/toluene at 50 °C. The dashed line shows the best fit with a single-exponential decay function; the solid line shows best fit with a mixture of two exponentials.

Conclusions Our mechanistic study of the exchange reaction of Au nanoparticles with disulfides revealed that only a small proportion of binding sites at the Au surface (3-5%) are active in exchange. Triphenylphosphine-protected particles were more reactive; however, the kinetics of exchange at high conversions required at least two exponential functions for adequate fit. These experiments suggest the presence of several different types of binding sites on the Au surface with different reactivity toward exchange. We believe that the most-active sites are likely to be defects rather than geometrical features (e.g., vertexes or edges) of the particles. The two branches of the disulfide molecule get separated during exchange, and reaction with thiol-protected particles leads to the formation of an intermediate. On the basis of the EPR, GPC, and kinetic analysis of this intermediate, we believe that it is a mixed disulfide of an outgoing ligand with an incoming one. An intermediate (containing an incoming ligand) is also formed during exchange reaction with phosphine-protected particles, albeit in a much smaller quantity. The structure of the latter intermediate is unclear; it could be an Au thiolate or a thiolate ion. Kinetic analysis revealed that the reaction is zeroth order with respect to the concentration of an incoming disulfide; the reaction order with respect to the concentration of Au nanoparticles is noninteger but close to one. This suggests a dissociative rate-determining step of the exchange reaction. On the basis of all available data, we suggested a mechanism for the exchange reaction (Scheme 3). This mechanism is, however, likely to be complicated by competing side reactions. Experimental Section Materials and Methods. All solvents (Fisher) were used as received. Spin labels were synthesized as described in an earlier publication.8 Triphenylphosphine- and n-butanethiol-protected Au nanoparticles were prepared using published procedures (1:1 stoichiometry of ligand to Au was used in the synthesis of butanethiol-protected particles).10,11 During the synthesis of butanethiol-protected particles, the reaction and workup times were minimized to reduce aging effects. Triphenylphosphineprotected particles were purified by gel permeation chromatography (GPC) to remove small-molecule impurities. GPC was performed using Biobeads S-X1 gel (200-400 mesh) and DCM as the mobile phase. EPR spectra were recorded on a JEOL JES-RE1X spectrometer (X-band) with a 100 kHz modulation frequency. The fitting of experimental data with kinetic models was carried out using DynaFit software.22 (22) Kuzmic P. Anal. Biochem. 1996, 237, 260. The free software can be downloaded from http://www.biokin.com/dynafit.

Mechanistic Study of Place-Exchange Reaction

Langmuir, Vol. 20, No. 26, 2004 11543

Exchange Reaction. Stock solutions of the desired Au nanoparticles and ligand in the appropriate solvent were mixed at room temperature and monitored by EPR. The kinetics of the reaction was monitored by the disappearance of the second peak in the EPR spectra. A control experiment was carried out in inert atmosphere. The absence of air was confirmed by the narrow line width of the EPR peaks throughout the reaction (the presence of the paramagnetic oxygen molecule in solution leads to the line broadening due to dipole-dipole interactions). Some reaction mixtures were separated by GPC. To prove the absence of Au in the reaction intermediate, the appropriate GPC fraction was evaporated to dryness and dissolved with aqua regia. The resultant solution was evaporated, redissolved in water, and subjected to ICP-OES analysis.

AuS f AuS* k1

(1)

AuS* + MM f AuM + MS k2

(2)

AuS* + MS f AuM + SS k2/2

(3)

AuS* + MS f AuS + MS k2/2

(4)

AuS* + SS f AuS + SS k2

(5)

AuM f AuM* k3

(6)

MM + AuM* f MM + AuM k2

(7)

MS + AuM* f AuM + MS k2/2

(8)

Appendix A

MS + AuM* f AuS + MM k2/2

(9)

Determination of Reaction Order. Let A ) concentration of Au nanoparticles and B ) concentration of incoming ligand. Au nanoparticles are in excess. The general kinetic equation for the concentration of incoming ligand can be written as dB/dt ) -kAnBm, where k is a rate constant and n and m are reaction orders with respect to the concentration of nanoparticles and incoming ligand, respectively. Rearrangement of this equation followed by integration until half-reaction time gives the following equation.

SS + AuM* f AuS + MS k2

(10)

τ ) - ∫0 ∫BB /2 dB m B 0

1/2

0

kAndt

As Au nanoparticles are in excess, A is constant (A ) A0), and the above equation can be further rearranged as shown below.

( )

( () )

B0 1-m 1 1-m B01-m 1 B0 2 2 ) 1-m 1-m 1-m

τ1/2 )

1-m

) kA0nτ1/2

Here, AuS, MM, SS, AuM, and MS are nanoparticles 4, disuflide 1, butane disulfide (outgoing ligand), spinlabeled Au nanoparticles, and mixed disulfide intermediate, respectively. AuS* and AuM* are Au nanoparticles which have been activated through dissociation and physisorption of the butanethiolate and spin-labeled ligand, respectively. Equations 1-5 could be used to determine the rate law for the exchange reaction. Using steady-state approximation (as the first step is rate-determining), d[AuS*]/dt ) 0. Applying this to equations 1-5,

d[AuS*]/dt ) k1[AuS] - k2[AuS*][MM] k2[AuS*][MS] - k2[AuS*][SS] ) 0 (11) Mass balance for the reaction could be written as [MM] + [MS] + [SS] ) [MM]0, where [MM]0 is initial concentration of the disulfide. Applying this to eq 12 gives k1[AuS] ) k2[AuS*][MM]0 or

( (21) )

B01-m 1 -

1-m

[AuS*] )

(1 - m)kA0n

1 1-m 12 log τ1/2 ) (1 - m) log B0 - n log A0 + log k(1 - m)

()

One can see that if B0 is kept constant, plotting log τ1/2 vs log A0 gives a straight line with the slope -n; if A0 is kept constant, plotting log τ1/2 vs log B0 gives a straight line with the slope 1 - m. The reaction order can thus be calculated from the slopes of the τ1/2 vs concentration in double logarithm coordinates. Appendix B Kinetic Model. The following kinetic model was used to fit the experimental data in Figure 7. This model is an expansion of the one in Scheme 3; equations (6-10) were added to make the exchange reversible; they are only necessary if insufficient excess of Au nanoparticles is used. Only two parameters describing the rate-determining steps (k1 and k3) were optimized during the fitting procedure; the rate of the fast steps (k2) does not influence the kinetics; it was assigned an arbitrary large number.

k1[AuS]

(12)

k2[MM]0

The kinetic equation for the diradical is (d[MM])/(dt) ) -k2 × [AuS*] × [MM]. Combining this with eq 12 gives

[MM] d[MM] ) -k1 × [AuS] × dt [MM]0

(13)

The kinetic eq 13 describes the concentration profile of disulfide 1 in the exchange reaction (rate law). This is the same equation as eq 1 in the main text of the manuscript. Integration of this kinetic equation assuming excess of [AuS] and constant [MM]0 gives eqs 14 and 15.

d[MM] ) 0 [MM]

[MM] ∫[MM]

dt ∫0t -k1 × [AuS] × [MM]

)

0

-k1 ×

[AuS] × [MM]0

[MM] ) [MM]0 e-k1[AuS]t/[MM]0

∫0t dt

(14) (15)

One can see that eq 15 is an exponential decay function. This justifies the use of exponential function to fit kinetic data.

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On the other hand, the initial rate does not depend on the concentration of the diradical (as [MM] ) [MM]0 at t ) 0 and hence eq 13 can be rewritten as d[MM]/dt ) -k1[AuS]). The reaction is therefore zeroth order with respect to the initial concentration of disulfide ligand.

Ionita et al.

Acknowledgment. The authors acknowledge EPSRC (GR/S45300/01), NATO (PST.EV.980030), and ESF “Reactor” program for funding. We thank Dr. A. C. Whitwood for help with instrumentation and discussions. LA048121Q