Langmuir 2003, 19, 9511-9517
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Reactivity of Acrylate-Terminated Au Nanoparticles: Suppressed Intramolecular Catalysis and Lack of Cooperative Effect Ste´phanie Koenig and Victor Chechik* Department of Chemistry, University of York, Heslington, York YO10 5DD, United Kingdom Received June 26, 2003. In Final Form: August 19, 2003 The cooperative effect in reactions of multifunctional compounds has been probed by monitoring the kinetics of the Michael addition of a dendritic polyamine to acrylate-terminated Au nanoparticles. Comparison of the kinetic data for this reaction with those for model monofunctional compounds showed the absence of any cooperativity. This was tentatively attributed to the high flexibility of the dendrimer and the inability of the system to bring mutually reactive functional groups sufficiently close to each other to achieve the rate enhancement effect. The subsequent reaction, methanolysis of the Michael adduct, was found to follow different mechanistic pathways in model monofunctional compounds and Au nanoparticles: while the model reaction undergoes intramolecular general base catalysis, no anchimeric assistance was observed for the reaction of Au nanoparticles. This difference in reactivity, which was attributed to steric effects, resulted in substantially different product distribution patterns for reactions of Au nanoparticles and model monofunctional compounds.
Introduction Metal nanoparticles coated by organic ligands are a very versatile and flexible type of supramolecular assemblies. The surface of these materials can be modified with a variety of functional groups, and coating the particles with a mixture of inert and functional ligands makes it possible to create controlled density of functional groups on the surface.1 This flexibility makes metal nanoparticles an ideal system to study chemical reactivity in organized and ordered assemblies. A systematic study by R. W. Murray’s group revealed that the general reactivity of nanoparticle-immobilized functional groups parallels that of free ligands.2 Reactions with bulky reagents, however, were retarded on the nanoparticle surface due to steric effects.3 Similar trends have been reported for organic reactions in self-assembled monolayers (SAMs) on planar surfaces.4 Interestingly, some recent studies showed more subtle mechanistic differences between reactivity patterns in free and immobilized ligands. In some cases, unusual intermolecular reactions were observed between adjacent chains of the surface-bound ligands in monolayers5 and nanoparticles.6 Because of the high surface curvature, however, nanoparticle-attached ligands are packed more loosely than those in planar monolayers, and this often leads to different mechanistic behavior in competing reactions.7 The presence of different types of binding sites * To whom correspondence should be addressed. E-mail: vc4@ york.ac.uk. (1) Templeton, A. C.; Wuelfing, W. P.; Murray, R. W. Acc. Chem. Res. 2000, 33, 27. Bo¨nnemann, H.; Richards, R. M. Eur. J. Inorg. Chem. 2001, 2455. (2) Templeton, A. C.; Hostetler, M. J.; Warmoth, E. K.; Chen, S.; Hartshorn, C. M.; Krishnamurthy, V. M.; Forbes, M. D. E.; Murray, R. W. J. Am. Chem. Soc. 1998, 120, 4845. (3) Templeton, A. C.; Hostetler, M. J.; Kraft, C. T.; Murray, R. W. J. Am. Chem. Soc. 1998, 120, 1906. (4) Chechik, V.; Crooks, R. M.; Stirling, C. J. M. Adv. Mater. 2000, 12, 1161. (5) Yan, L.; Marzolin, C.; Terfort, A.; Whitesides, G. M. Langmuir 1997, 13, 6704. (6) Akamatsu, K.; Hasegawa, J.; Nawafune, H.; Katayama, H.; Ozawa, F. J. Mater. Chem. 2002, 12, 2862.
on the surface of nanoparticles (e.g., terrace, vertex, edge, and defect sites) also has a strong impact on the reactivity of adsorbed ligands.8 For instance, Workentin et al. studied photochemical fragmentation of aryl ketones immobilized on the surface of Au nanoparticles.9 To account for the incomplete surface reaction (the maximum yield was ca. 80-90%), it was suggested that only the ligands positioned at or near the vertex or defect sites are reactive, whereas ligands embedded into flat terraces at the Au surface experience too much steric hindrance to undergo photofragmentation. Importantly, free ligands undergo two competing reactions, but only one type of reactivity was observed for surface-immobilized species. This was also attributed to the steric hindrance of surface-bound ketones. We were interested in studying the effect of cooperativity on the reactions at the surface of functionalized particles. A reaction between two multifunctional compounds (e.g., functionalized nanoparticles) could be expected to proceed faster than the same reaction between parent monofunctional ligands. This is because a reaction between the first pair of mutually reactive groups in multifunctional molecules will bring all the other pairs of reactive groups close to each other, thus creating a high effective concentration which could lead to an enhanced reaction rate (Scheme 1). The effect of bringing functional groups together on their reactivity has been studied by physical organic chemists for decades because of its relevance to enzymatic catalysis; the effective local concentration of mutually reactive groups in each other’s vicinity has been termed effective molarity (EM).10 We aimed to expand such studies to the supramolecular chemistry area, which provides a better model for biological reactions. Supramolecular assemblies offer superior control of the density of functional groups and flexibility. (7) Hu, J.; Zhang, J.; Liu, F.; Kittredge, K.; Whitesell, J. K.; Fox, M. A. J. Am. Chem. Soc. 2001, 123, 1464. (8) Hostetler, M. J.; Templeton, A. C.; Murray, R. W. Langmuir 1999, 15, 3782. (9) Kell, A. J.; Workentin, M. S. Langmuir 2001, 17, 7355. (10) Kirby, A. J. Adv. Phys. Org. Chem. 1980, 17, 187.
10.1021/la035132v CCC: $25.00 © 2003 American Chemical Society Published on Web 10/03/2003
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Scheme 1. Michael Addition of a Dendrimer to a Functionalized Au Particle
Chart 1. Mono- and Multifunctional Reagents Used in This Work
To ensure a complete reaction between multifunctional compounds, at least one reagent should be fairly flexible to be able to adopt a conformation fitting the shape of the other reagent (Scheme 1). These considerations led us to design a Michael addition reaction between acrylatefunctionalized Au nanoparticles and low-generation amineterminated dendrimers (see Chart 1). The nanoparticle environment is ideally suited to provide a high-density coverage of acrylate groups; the surface of the nanoparticles however is curved and rigid. Small dendrimers, on the other hand, offer the flexibility required to match the shape of the Au nanoparticles (Scheme 1). Our studies showed that the reaction between acrylatemodified nanoparticles 1b and an amine-terminated dendrimer 2b indeed afforded the Michael addition product. This compound however underwent a further reaction which was identified as ester solvolysis. Comparison of kinetic data for the reactions involving multifunctional and model monofunctional reagents (nbutylamine 2a and free acrylate ligand 1a) showed different kinetic behavior. Here, we discuss the kinetic and mechanistic features of these reactions. Results and Discussion Preparation of Acrylate-Terminated Au Nanoparticles. Conventionally, thiols are used as stabilizing
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ligands in Au nanoparticle synthesis. We however chose disulfide 1a as a reactive ligand (Scheme 2). This was due to synthetic convenience: preparation of the corresponding thiol was hampered by low yields caused by the side reactions and difficult purification, while the synthesis of the disulfide was straightforward. Au nanoparticles prepared using disulfide ligands were reported to be indistinguishable from those prepared using the parent thiols.11 Nanoparticles 1b were synthesized by reduction of HAuCl4 in the presence of ligand 1a and tetraoctylammonium bromide (TOAB) as a transfer agent, following Schiffrin’s biphasic procedure (Scheme 2).12 We noted however that prolonged exposure of ligand 1a or acrylate-modified nanoparticles 1b to the excess NaBH4 led to complete reduction of the double bond in the acrylate functionality [eq 1]. The structure of the reduction product (propionate ester) was confirmed by the assignment of peaks at 4.03 t (CH2OCOCH2CH3), 2.31 q (COCH2CH3), and 1.11 t (COCH2CH3) in the 1H NMR spectra of the reaction mixture.
Replacement of NaBH4 with a milder reducing agent, NaBH3CN [which does not react with ligand 1a but is still capable of reducing Au(III) to Au(0)], failed to produce stable nanoparticles. The Au(III) salt was reduced slowly to form bulk gold metal powder which precipitated even in the presence of a large excess of the stabilizing ligand. This can tentatively be explained by the competitive adsorption of cyanide onto the growing Au nanoparticles. An alternative route to gold nanoparticles 1b was also investigated. 11-Mercaptoundecanol-capped gold nanoparticles were synthesized from ligand 5 using Schiffrin’s procedure.12 They were then reacted with acryloyl chloride and triethylamine to form the acrylic functions on the surface of the particles. This reaction was reported to be delicate but feasible on a SAM of mercaptoundecanol on a planar gold surface.13 We found however that Au nanoparticles were completely destroyed under these conditions. Fortunately, optimization of the reaction conditions for the synthesis of nanoparticles 1b using NaBH4 made it possible to minimize the reduction of the acrylate functionality. The reaction time was shortened to just 20 s. At the end of this period, the reaction was quenched by separating the organic and aqueous layers. This strategy was only partially successful, as some borohydride was transferred to the organic phase by the phase-transfer agent required by Schiffrin’s procedure. However, washing the nanoparticle-containing organic phase with an aqueous HCl solution straight after phase separation was sufficient to destroy the excess NaBH4 and this procedure was successfully used for the preparation of nanoparticles 1b. The nanoparticles were characterized by 1H NMR. A typical NMR spectrum is in Figure 1. All signals of the surface-immobilized ligands were broad; the signals for the terminal functionalities (viz., CH2O at 4.13 ppm and double bond protons at 5.82, 6.11, and 6.36 ppm) were however well resolved from the other peaks, which allowed the values of their integrals to be reliably used to monitor the reactions at the nanoparticle (11) Porter, L. A.; Ji, D.; Westcott, S. L.; Graupe, M.; Czernuszewicz, R. S.; Halas, N. J.; Lee, T. R. Langmuir 1998, 14, 7378. (12) Brust, M.; Walker, M.; Bethell, D.; Schiffrin, D. J.; Whyman, R. J. Chem. Soc., Chem. Commun. 1994, 801. (13) Kim, J.-B.; Bruening, M. L.; Baker, G. L. J. Am. Chem. Soc. 2000, 122, 7616.
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Figure 1. 1H NMR spectrum of nanoparticles 1b. Assignment of the double bond protons is in Scheme 2.
Figure 3. 1H NMR of a reaction mixture containing 1a and 2a (a) and 1b and 2b (b) in CD3OD.
Figure 2. TEM image and size distribution histogram of nanoparticles 1b.
surface. Nanoparticles 1b were also characterized by transmission electron microscopy (TEM). The TEM image showed spherical particles with a uniform size distribution; the average diameter was 3.7 ( 0.8 nm (Figure 2). Michael Addition to Acrylates 1a and 1b. The addition of an amine (n-butylamine 2a or second-generation polypropylenimine dendrimer 2b) to the acrylate ligand 1a led to the gradual disappearance of the acrylic
protons at 5.7-6.4 ppm and the growth of new peaks at 4.01 and 2.75 ppm (Figure 3a). This was attributed to the formation of Michael addition product 7a (Scheme 3). As the reaction was performed in deuterated methanol, Michael addition gave rise to a β-deuterated amine (7a), which showed a characteristic doublet of the COCHDCH2N group at 2.75 ppm in the 1H NMR spectra (Figure 3a). The splitting is due to the spin-spin interactions of the CH2N group with the adjacent CHD group. If the reaction is performed in non-deuterated solvents (CH3OH/CHCl3), this peak appears as a triplet due to the CH2N group in COCH2CH2N. Formation of the Michael product was further confirmed by the 13C NMR and MS data (see the Experimental Section).
Scheme 2. Synthesis of Ligand 1a and Nanoparticles 1b
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Scheme 3. Addition of Amines 2a and 2b to Acrylates 1a or 1b
Longer reaction times however led to further changes in the 1H NMR spectra. The CH2O peak of the Michael addition product 7a was replaced by a new peak at 3.47 ppm which was assigned to the formation of the CH2OD group (alcohol 8a) (Figure 3a). Formation of alcohol 8a was further proved by 13C NMR and MS spectroscopy (see the Experimental Section). This slow reaction was originally thought to be ester aminolysis, as both butylamine and dendrimer 2b were in excess in the reaction mixture. We noted however that if the reaction was performed in CH3OH, a singlet peak appeared in 1H NMR spectra at 3.78 ppm which was absent when the reaction was carried out in CD3OD. 13C distortionless enhancement by polarization transfer (DEPT) NMR showed that this peak is due to a methyl ester, thus proving incorporation of the solvent molecule in the structure of the product. This reaction was therefore identified as methanolysis of the Michael adduct 7a. Kinetic data (vide infra) and mass spectrometry (MS) (see the Experimental Section) further confirmed this conclusion. Methyl ester 9a was characterized by MS and 13C NMR. When the reaction was performed with the acrylateterminated Au nanoparticles 1b, similar changes in the 1H NMR spectra were observed (Figure 3b). The disappearance of the acrylic signals at 5.6-6.4 ppm and formation of a broad peak at 2.76 ppm were consistent with the formation of the Michael addition product. The broadness of the CH2O peak at 4.07 ppm however did not allow observation of any changes in this area of the spectrum. Longer reaction times showed formation of the broad CH2OD peak at 3.51 ppm assigned to the nanoparticle-immobilized hydroxyundecanethiolate 8b and sharp peaks at 2.72 ppm (overlapping the broad peak of the Michael addition product) of methyl ester 9b. This was consistent with the methanolysis of the Michael adduct. Methyl ester 9b was characterized by 13C NMR. Kinetic Study. We used the intensities of the 1H NMR peaks to determine the concentration of all reagents and products in the reaction mixture. The concentrations were calculated as Macr/V rather than Mnano/V, where Macr and Mnano are the total number of moles of the acrylate groups and the numbers of moles of nanoparticles, respectively; V is the volume of the solution. This is because the reaction rate should be proportional to the concentration of nanoparticles Cnano times the number of acrylate groups in each particle Nacr (Nacr is the statistical coefficient for the reaction of a multifunctional compound). As Cnano ) Mnano/V, the reaction rate is proportional to CnanoNacr ) (MnanoNacr)/V ) Macr/V. The data were then fitted with a series of kinetic models using DynaFit software.14 Typical curves are shown in Figure 4. The relatively large deviation of theoretical curves from the experimental data at high conversion is largely due to the errors in the integration of broad NMR peaks (i.e., the sum of integrals for the signals of starting material and the products is somewhat different from the integral of the starting material signal at the beginning of the reaction). (14) Kuzmic, P. Anal. Biochem. 1996, 237, 260. The free software can be downloaded from http://www.biokin.com/dynafit.
Figure 4. Simulated curves and experimental concentrations of acrylates (9), Michael addition products (b), and methyl esters (4) in the reaction of 1a with 2a (ratio of 1/1.9) (a) and in the reaction of 1b with 2b (ratio of 1/15.5) (b).
We found that our data can be described in terms of just two reactions shown in Scheme 3. A more complex kinetic model including methanolysis of the starting material (acrylate 1b) did not improve the quality of data fitting. This is consistent with our prediction that methanolysis of acrylate 1b should be far slower than methanolysis of Michael adduct 7a due to the intramolecular general base catalysis in the latter case (vide infra). Even in the absence of intramolecular catalysis, the electron-withdrawing amine group in Michael adduct 7a should make it much more susceptible to methanolysis than conjugated acrylate 1b.15 The best fit in all cases (e.g., Figure 4) gave the expected overall second order for the Michael addition reaction. The rate constants kA are in Table 1. These values are constant at different concentrations of the starting materials, which further confirms the second order of the reaction. One can observe that the rate constants are virtually the same regardless of whether the amine or acrylate was mono- (e.g., butylamine 2a, ligand 1a) or multifunctional (e.g., dendrimer 2b, Au nanoparticles 1b). Steric crowding at the surface of the acrylate-terminated Au nanoparticles had therefore little effect on the rate of Michael addition. Such insensitivity of the reaction rate to the environment is probably due to the fact that Michael addition to the terminal acrylate functionality does not require the nucleophile to penetrate deeply into the organic layer on the nanoparticle surface. This behavior is consistent with (15) Halonen, E. A. Acta Chem. Scand. 1995, 9, 1492.
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Langmuir, Vol. 19, No. 22, 2003 9515 Table 1. Kinetic Data
acrylate
amine
acrylate/amine ratio
1a 1a 1b 1b 1a 1a 1b 1b
2a 2a 2a 2a 2b 2b 2b 2b
1/1.9 1/10.5 1/1.6 1/8.9 1/3.3 1/19.3 1/1.4 1/15.5
a
kA × 102 (L mol-1 min-1)a
kB × 104 (min-1)a
3.6 ( 0.2 3.2 ( 0.2 2.0 ( 0.1 1.7 ( 0.1 3.0 ( 0.1 2.7 ( 0.2 3.0 ( 0.1 3.1 ( 0.3
2.9 ( 0.1 3.8 ( 0.3
kB × 103 (L mol-1 min-1)a
1.0 ( 0.1 1.4 ( 0.4
3.2 ( 0.4 5.3 ( 1.0 2.0 ( 0.4 1.3 ( 0.4
ratio of Michael adduct to the methanolysis product at 90% conversion 0.10 2.83 2.90 1.63 1.34 8.74 6.74 10.53
The errors shown are standard errors as reported by the curve fitting software.
a number of previous studies on reactions in SAMs, which showed that the kinetics of surface reactions parallel those of bulk systems as long as the reagent does not need to penetrate a well-packed organic layer to reach a functional group buried under the surface.16 On the other hand, the reaction between two multifunctional reagents (e.g., dendrimer 2b and nanoparticles 1b) also occurred at the same rate as the corresponding reaction between monofunctional compounds (Table 1). This result implies the lack of cooperativity in the reaction of dendrimer with Au nanoparticles. One could expect that once the nanoparticle and the dendrimer get linked together by the first amide bond, all seven remaining dendrimer primary amino groups will be held in a close proximity of the acrylate functions (Scheme 1); this would lead to a substantial increase (up to 8-fold) of the observed reaction rate. Our data however show that this effect is in fact negligible. The accelerating effect of bringing two mutually reactive groups together is well documented for simple bifunctional molecules (e.g., intramolecular cyclizations).10 The origin of this effect has been a subject of debate in the literature for some 70 years.17 The most likely prerequisite for the dramatic rate increases observed in enzymatic reactions and some intramolecular reactions is holding mutually reactive groups very close to each other (perhaps as close as 2.5 Å).18 The direction of attack is also important.19 The reaction between the acrylate-terminated Au nanoparticles and the polyamine dendrimer is a rare example of an “intramolecular” cyclization in a supramolecular system. The lack of cooperativity could be due to the failure of the reactants to bring the mutually reactive groups sufficiently close to each other. The dendrimer molecules are perhaps too flexible to stabilize the near attack conformation (NAC) in which the reactive groups should be held next to each other. “Incorrect” alignment of the reactive groups or the strain of the reaction products could also slow the reaction. Although examples of mechanistic studies in multifunctional compounds are extremely rare, the evidence for the lack of cooperativity in such systems can be found in the literature.20 Ester Methanolysis. Interestingly, ester methanolysis occurred via different mechanistic pathways for nanoparticles 1b and free ligand 1a. Fitting the experimental kinetic data for the reaction of ligand 1a with amines 2a or 2b showed zeroth order with respect to the concentration (16) Chechik, V.; Stirling, C. J. M. Langmuir 1998, 14, 99. (17) Ruzicka, L.; Brugger, W.; Pfeiffer, M.; Schinz, H.; Stoll, M. Helv. Chim. Acta 1926, 9, 499. DeTar, D. F.; Luthra, N. P. J. Am. Chem. Soc. 1980, 102, 4505. Page, M. I.; Jencks, W. P. Gazz. Chim. Ital. 1987, 117, 455. Bruice, T. C.; Benkovic, S. J. Biochemistry 2000, 39, 6267. (18) Mengen, F. M. Acc. Chem. Res. 1985, 18, 128. (19) Mesecar, A. D.; Stoddard, B. L.; Koshland, D. E. Science 1997, 277, 202. (20) Zhang, W.; Tichy, S. E.; Perez, L. M.; Maria, G. C.; Lindahl, P. A.; Simanek, E. E. J. Am. Chem. Soc. 2003, 125, 5086.
of the amine. This was attributed to the intramolecular base-catalyzed solvolysis with a six-membered cyclic transition state.
The intramolecular general base catalysis for the hydrolysis of 3-aminopropanoate and 2-aminobenzoic esters has been reported in the literature.21 Typical EM values for these reactions are of the order of 20. These values, however, vary substantially depending on the structure of the reagents. Our data are therefore consistent with the intramolecular catalysis being strongly favored within the range of concentrations used in this study. The calculated rate constants kB are in Table 1. Comparison of the reaction rates shows that dendritic Michael addition product 7b reacts slower than parent monofunctional compound 7a, probably due to steric hindrance. We did not observe any rate enhancement for the reaction of dendritic product, which one might have expected for a multifunctional molecule where a high local concentration of the amine groups could facilitate intramolecular catalysis. Importantly, however, the same reaction on nanoparticles 1b was much slower and showed first kinetic order with respect to the concentration of the amine (second overall order, Table 1). The errors in calculating this rate constant were quite substantial, mostly due to the small amount of the product formed (due to the slow rate of this reaction). Even with the large error, however, it is clear from Table 1 that the second-order rate constants are almost concentration-independent in a fairly large range of concentrations. This confirms the second overall order and clearly demonstrates that the intramolecular catalytic reaction is completely suppressed. Methanolysis is thus catalyzed intermolecularly. This unusual behavior leads to substantial differences in the composition of reaction mixtures of Au nanoparticles 1b and ligand 1a. For ligand 1a, the rate of methanolysis is comparable to that of the Michael addition. Therefore, the yield of the addition product 7a (acrylate/amine ratio of 1/1.9) reaches only 45% (Figure 4a). For the reaction of nanoparticles 1b, however, methanolysis is substantially slower, and the Michael addition product can be obtained in good yield, either with butylamine 2a or with dendrimer 2b. For example, product 7c (acrylate/amine ratio of 1/1.6) is obtained in 75% yield and adduct 7d (acrylate/amine ratio of 1/1.4) in 83% yield. Data in Table 1, which show the (21) Kirby, A. J.; Lloyd, G. J. J. Chem. Soc., Perkin Trans. 2 1976, 1748. Fife, T. H.; Singh, R.; Bembi, R. J. Org. Chem. 2002, 67, 3179.
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ratio of the two reaction products at 90% conversion of the starting material, further illustrate this point. The reason for the suppression of the intramolecular catalytic pathway is not clear. The ligand chains on the nanoparticle surface certainly create some steric hindrance, but they do not pack closely due to the high curvature of the surface of small Au nanoparticles used in this study. Molecular models show that the transition state for the intramolecularly catalyzed reaction is not very bulky. However, it involves a sideway attack of the nucleophile. Thus, for the intramolecular reaction to occur on the nanoparticles, the nucleophile (MeOH) molecules must align almost perpendicular to the particle surface. We believe that the steric strain caused by this alignment makes the intramolecular catalysis unfavorable. Alternatively, reduced basicity of the nanoparticle-attached secondary amine groups (e.g., due to the network of H-bonds connecting them to each other) could explain the lack of intramolecular catalysis. Conclusions We have studied the reaction of acrylate-terminated Au nanoparticles and a model monofunctional compound with mono- and multifunctional amines. The rate of the first step (Michael addition) was independent of the structure of both reagents. We did not therefore observe any cooperative effect in the reaction between multifunctional compounds. It appears that simply creating a high local concentration of reactive functional groups in a supramolecular system has a minimal impact on the reaction kinetics; substantially enhanced reaction rates typical of some intramolecular cyclizations and enzymatic reactions can only be achieved by the accurate positioning of the functional groups. Our results suggest therefore that application of supramolecular systems to biomimicry can only be made successful by carefully designing and controlling the distance between reactive functionalities. Interestingly, we observed that methanolysis of the Michael adduct occurs via different mechanistic pathways with free and nanoparticle-immobilized ligands. Intramolecular general base catalysis, typical for the reactions in the bulk, was completely suppressed on the nanoparticles. We attribute this mechanistic behavior to the steric hindrance of the organic layer adsorbed on the Au surface. Steric effects play therefore a major role in determining the reactivity in supramolecular assemblies, and our study illustrates how attaching the reagents to the nanoparticle surface can substantially shift the balance in competing reactions. Experimental Section Materials. All solvents (Fisher), 11-bromoundecanol (Lancaster), thiourea (Lancaster), acryloyl chloride (Aldrich), hydrogen tetrachloroaurate (Aldrich), tetraoctylammonium bromide (ABCR), sodium borohydride (Aldrich), n-butylamine (Lancaster), and DAB-Am-8 polypropylenimine octaamine dendrimer Generation 2 (Aldrich) were used without further purification except from CH2Cl2 and triethylamine (Aldrich) which were distilled over calcium hydride prior to use. Thin-layer chromatography was carried out using commercially available Merck Silica Gel 60 F254. Column chromatography was performed using silica gel supplied by BDH. 11-Mercaptoundecanol (5) was synthesized from 11-bromoundecanol (3) and thiourea by adapting the method described in the literature.22,23 11,11′-Dihydroxydiundecyl di(22) Spivak, D.; Shea, K. J. J. Org. Chem. 1999, 64, 4627. (23) Poirier, D.; Auger, S.; Merand, Y.; Simard, J.; Labrie, F. J. Med. Chem. 1994, 1115.
Koenig and Chechik sulfide (6) was synthesized according to a standard oxidation procedure with iodine.24 Methods. 1H and 13C NMR spectra were recorded on a JEOLE270 instrument. IR spectra were recorded on an ATI Mattson Genesis Series FT-IR spectrometer. Melting points were measured on a Bibby Stuart Scientific SMP3 melting point apparatus and were uncorrected. UV-visible absorption spectra were recorded on a Hitachi U-3000 spectrophotometer. Mass spectra were recorded on a Fisons Analytical (VG) Autospec spectrometer. Transmission electron microscopy was performed using a JEOL 1200 EX instrument operated at 120 kV. Synthesis. 11,11′-Dithiodiundecyl dipropenoate (1a) was synthesized using a method adapted from the literature (Scheme 2).25 11,11′-Dihydroxydiundecyl disulfide 6 (1 g, 2.46 mmol) was dissolved in dry CH2Cl2 (50 mL) under N2. Acryloyl chloride (0.706 g, 7.80 mmol) and NEt3 (0.498 g, 4.92 mmol) were added to this solution at 0 °C. After stirring in the dark at room temperature for 18 h, a 3% aqueous HCl solution (5.1 mL) was added to the colorless reaction mixture followed by CH2Cl2 (50 mL) and water (50 mL). The organic phase was washed with water (100 mL, then 50 mL). Brine was used to break the emulsion. The CH2Cl2 phase was then dried (Na2SO4) and evaporated to give the crude product as a white sticky solid (0.854 g, 67% yield). The product was purified by column chromatography (SiO2, CH2Cl2/hexane 10:1), which afforded the pure product (0.302 g, 27% yield) as a colorless liquid that crystallized in the refrigerator. Mp: 31-32 °C. TLC: Rf ) 0.35 (CH2Cl2/hexane 10:1). 1H NMR (CDCl3, 270 MHz): δ 6.42 (dd, 2H, J ) 1.5 and 17 Hz, Ha), 6.12 (dd, 2H, J ) 10 and 17 Hz, Hc), 5.82 (dd, 2H, J ) 1.5 and 10.5 Hz, Hb), 4.14 (t, 4H, J ) 6.5 Hz, CH2O), 2.67 (t, 4H, J ) 7 Hz, CH2S), 1.71-1.59 (m, 10 H, CH2CH2S), 1.3 [broad m, (CH2)8]. 13C NMR (CDCl3, 68 MHz): δ 166.3 (CdO), 130.4 (CdCH2), 128.6 (Cd CH2), 64.8 (CH2O), 39.1 (CH2S), 29.4-28.5 [m, (CH2)8], 25.9 (CH2CH2CH2O). IR (CHCl3): ν 2929 m (C-H), 2855 m (C-H), 1717 m (CdO), 1640 w and 1623 w (CdC). MS (CI): m/z 515 [(M + H)+, 3], 532 [(M + NH4+), 39], 276 [(S(CH2)11OCOCHCH2 + NH4+), 100], 259 [r.a.: 15]. Au nanoparticles coated with 11,11′-dithiodiundecyl dipropenoate (1b) were synthesized by a modified literature procedure (see Scheme 2).8 A 28.74 mM aqueous solution of HAuCl4 (13.5 mL) was stirred vigorously with a toluene solution (39 mL) of tetraoctylammonium bromide (1.06 g, 1.94 mmol) until the organic phase turned dark red. A solution of 11,11′-dithiodiundecyl dipropenoate 1a (100 mg, 194 µmol) in toluene (10 mL) was added to the two-phase system with vigorous stirring, followed by an aqueous solution (12 mL) of NaBH4 (176 mg, 4.66 mmol). After 20 s, the phases were separated. The organic phase was washed with an aqueous 1 M HCl solution (40 mL), a saturated aqueous solution of NaHCO3 (40 mL), and finally with water (40 mL). The resulting organic phase was then poured into MeOH (900 mL) and stored overnight in the freezer to allow the particles to precipitate. The dark brown product (132 mg) was collected by centrifugation, and washed several times with cold MeOH to purify it from the transfer agent. 1H NMR (CDCl3, 270 MHz): δ 6.36 (broad m, 1H, Ha), 6.11 (broad m, 1H, Hc), 5.82 (broad m, 1H, Hb), 4.13 (broad m, 2H, CH2OCO), 0.75-1.96 (broad m, 32H, CH2CH2S, CH2). Kinetic Study. The reaction conditions for Michael addition were adapted from the literature.26 A solution of the acrylate compound (1a or 1b) in CDCl3 (0.5 mL, 1 equiv of acrylate) was mixed with a solution of amine (n-butylamine 2a or dendrimer 2b) in CD3OD (0.5 mL). The reaction mixture was kept in an NMR tube (amber NMR tube for the reactions involving nanoparticles) at 22 °C and analyzed by 1H NMR at regular intervals. The spectra were integrated relative to the residual CHCl3 peak. The concentration of reagents was calculated from the initial amine concentration, integral values of the reagent peaks, and the reference peak of the amine (CH3 triplet at 0.84 ppm and (24) Cheng, J.; Miller, C. J. J. Phys. Chem. B 1997, 101, 1058. Zong, K.; Brittain, S. T.; Wurm, D. B.; Kim, Y.-T. Synth. Commun. 1997, 27, 157. (25) Porter, N.; Chang, V. H.-T. J. Am. Chem. Soc. 1987, 109, 4976. (26) Dvornic, P. R.; De Leuze-Jallouli, A. M.; Owen, M. J.; Perz, S. V. Macromolecules 2000, 33, 5366. Mu¨h, E.; Marquardt, J.; Klee, J. E.; Frey, H.; Mu¨lhaupt, R. Macromolecules 2001, 34, 5778.
Reactivity of Au Nanoparticles CH2N multiplet at 2.38 ppm for the ligand reaction with butylamine or dendrimer; CH2NH2 triplet at 2.57 ppm and CH2NH2 triplet at 2.61 ppm for the reaction of nanoparticles with butylamine or dendrimer, respectively). The concentrations of individual components of the reaction mixture were determined as follows: (a) starting material (acrylate 1a or 1b) from the acrylic protons signals (5.7-6.4 ppm), (b) Michael addition products 7a, 7b, 7c, and 7d from the CH2O peaks at 3.9-4.1 ppm corrected for the contribution of the starting material (as calculated from the intensity of the acrylic peaks), (c) alcohols 8a and 8b from the CH2OD triplet at 3.45 ppm, and (d) methyl esters 9a and 9b from the CHDCH2NH doublet at 2.75 ppm. Both Michael addition product and methyl ester contribute to this signal. For the reaction of ligand 1a, its intensity was corrected for the Michael addition products 7a and 7b. For the reaction of nanoparticles with amine 2a, the NMR peak of the particle-immobilized Michael addition product is broadened, which allowed the methyl ester peak to be integrated separately. For the reaction of dendrimer with acrylate-terminated nanoparticles, the CHDCH2N doublet signal overlapped other peaks. This peak was therefore ignored in data analysis. The concentrations of these reagents at different time intervals were fitted to kinetic models using DynaFit software.14 The following set of differential equations was used to model reaction of butylamine with the ligand 1a.
d[1a]/dt ) -kA[1a][2a] d[2a]/dt ) -kA[1a][2a]
Langmuir, Vol. 19, No. 22, 2003 9517 Reaction of dendrimer 2b with nanoparticles 1b was modeled with the following set of differential equations.
d[1b]/dt ) -kA[1b][2b] d[2b]/dt ) -kA[1b][2b] - kB[2b][7d] d[7d]/dt ) kA[1b][2b] - kB[2b][7d] d[8b]/dt ) kB[2b][7d] d[9b]/dt ) kB[2b][7d] The products of the reaction of the ligand with amines were further characterized by 13C NMR and MS. A typical 13C NMR spectrum recorded after the reaction of ligand 1a with butylamine 2a gave the following peaks. 13C NMR (CDCl3, 67 MHz): δ 173.22 (CdO, 9a), 172.89 (CdO, 7a), 64.58 (CH2OCO, 7a), 62.83 (CH2OH, 8a), 51.55 (CH3O, 9a), 49.43 (CO(CH2)2NHCH2, 7a + 9a), 45.04 (CO(CH2)2CH2NH, 7a), 44.98 (CO(CH2)2CH2NH, 9a), 39.13 and 39.10 (SCH2, 8a + 7a), 34.63 (COCH2, 7a), 34.42 (COCH2, 9a), 32.78 (CH2CH2OH, 8a), 32.05 (NHCH2CH2CH2CH3, 9a + 7a), 29.53, 29.44, and 29.17 (CH2 in chain, 8a + 7a), 28.56 (SCH2CH2, 8a), 28.46 (SCH2CH2, 7a), 25.86 (CH2CH2CH2OCO, 7a), 25.73 (CH2CH2CH2OH, 8a), 20.39 (NH(CH2)2CH2CH3, 7a + 9a), 13.95 (NH(CH2)3CH3, 7a + 9a). MS m/z (EI): 660 [7a], 406 [8a], 330 [one branch of disulfide 7a], 185 [one branch of disulfide 8a - H2O], 159 [9a].
d[8a]/dt ) kB[7a]
Acknowledgment. We thank Dr. David Vaughan for TEM micrographs and Dr. Trevor A. Dransfield for running MS spectra. The funding for this work was provided by the EPSRC (Grant Number GR/R54675/01).
d[9a]/dt ) kB[7a]
LA035132V
d[7a]/dt ) kA[1a][2a] - kB[7a]
