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Langmuir 2008, 24, 4026-4031
Modification of the Sto1 ber Process by a Polyazamacrocycle Leading to Unusual Core-Shell Silica Nanoparticles Sylvie Masse,† Guillaume Laurent,† Franc¸ oise Chuburu,‡ Cyril Cadiou,‡ Isabelle De´champs,‡ and Thibaud Coradin*,† Laboratoire de Chimie de la Matie` re Condense´ e de Paris, UniVersite´ Pierre et Marie Curie, Paris 6, CNRS, 75252 Paris cedex 05, France, and Groupe de Recherche en Chimie Inorganique, UniVersite´ Reims-Champagne-Ardenne, UFR Sciences, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2, France ReceiVed July 12, 2007 In the view of designing functional nanoparticles, the encapsulation of 1,4,7,10-tetraazacyclododecane (cyclen) within silica nanoparticles using the Sto¨ber process was studied. In the presence of cyclen and tetraethoxysilane (TEOS), silica particles exhibiting an unusual core-shell structure were obtained. On then basis of TEM, DLS, and NMR data, we suggest that the particle core is constituted of hybrid primary nanoparticles resulting from cyclen-silica interactions, whereas the shell formation results from further condensation of unreacted silica precursors. Control experiments performed with the zinc-cyclen complex and ammonia addition suggest that cyclen-TEOS interactions arise from the activation of the silicon alkoxide hydrolysis with the polyazamacrocycle amine groups. These data are discussed in the context of silica biomineralization mechanisms, where polyamine/silica interactions have been shown to play a major role. Moreover, the possibility to control the size and the structure of these nanoparticles makes them promising materials for pharmaceutical applications.
1. Introduction Due to its relevance in the field of biosilicification, the study of the interactions between (poly)amines and silica precursors has almost become a field of research of its own.1-3 Fundamental approaches involving various silica sources (silicates,4 silicon alkoxides,5 silicon complexes,6 colloidal silica7) and amines (short-chain molecules,8 peptides,9,10 polyamino acids,4,6 proteins,9,11,12 synthetic macromolecules13) have been described, aiming at understanding the possible catalytic activity of diatomor sponge-extracted polymers. In parallel, it was possible to take profit from this ability of polyamines to interact with silica to * Corresponding author. Tel: +33-1-44275517. Fax: +33-1-44274769. E-mail:
[email protected]. † Universite ´ Pierre et Marie Curie. ‡ Universite ´ Reims-Champagne-Ardenne. (1) Patwardhan, S. V.; Clarson, S. J.; Perry, C. C. Chem. Commun. 2005, 1113-1121. (2) Lopez, P. J.; Gautier, C.; Livage, J.; Coradin, T. Curr. Nanosci. 2005, 1, 73-83. (3) Sumper, M.; Brunner, E. AdV. Funct. Mater. 2006, 16, 17-26. (4) (a) Mizutani, T.; Nagase, H.; Ogoshi, H. Chem. Lett. 1998, 133-134 (b) Coradin, T.; Livage, J. Colloids Surf. B 2001, 21, 329-336. (5) (a) Sumper, M.; Kro¨ger, N. J. Mater. Chem. 2004, 14, 2059-2065. (b) Patwardhan, S. V.; Mukherjee, N.; Steinitz-Kannan, M.; Clarson, S. J. Chem. Commun. 2003, 1122-1123. (c) Tomczak, M. M.; Glawe, D. D.; Drummy, L. F.; Lawrence, C. G.; Stone, M. O.; Perry, C. C.; Pochan, D. J.; Deming, T. J.; Naik, R. R. J. Am. Chem. Soc. 2005, 127, 12577-12582. (6) Belton, D.; Paine, G.; Patwardhan, S. V.; Perry, C. C. J. Mater. Chem. 2004, 14, 2231-2241. (7) Coradin, T.; Durupthy, O.; Livage, J. Langmuir 2002, 18, 2331-2336. (8) (a) Delak, K. M.; Sahai, N. Chem. Mater. 2005, 17, 3221-3227. (b) Belton, D. J.; Patwardhan, S. V.; Perry, C. C. J. Mater. Chem. 2005, 15, 4629-4638. (9) Kro¨ger, N.; Deutzmann, R.; Sumper, M. Science 1999, 286, 11229-1132. (10) (a) Naik, R. R.; Whitlock, P. W.; Rodriguez, F.; Brott, L. L.; Glawe, D. D.; Clarson, S. J.; Stone, M. O. Chem. Commun. 2003, 238-239. (b) Knecht, M. R.; Wright, D. W. Chem. Commun. 2003, 3038-3039. (11) Cha, J. N.; Shimizu, K.; Zhou, Y.; Christiansen, S. C.; Chmelka, B. F.; Stucky, G. D.; Morse, D. E. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 361-365. (12) (a) Coradin, T.; Coupe´, A.; Livage, J. Colloids Surf. B 2003, 29, 189196. (b) Coradin, T.; Bah, S.; Livage, J. Colloids Surf. B 2004, 35, 53-58. (13) (a) Cha, J. N.; Stucky, G. D.; Morse, D. E.; Deming, T. J. Nature 2000, 403, 289-292. (b) Knecht, M. R.; Wright, D. W. Langmuir 2004, 20, 47284732. (b) Menzel, H.; Horstmann, S.; Behrens, P.; Ba¨rnreuther, P.; Krueger, I.; Jahns, M. Chem. Commun. 2003, 2994-2295. (c) Annenkov, V. V.; Patwardhan, S. V.; Belton, D.; Danilotseva, E. N.; Perry, C. C. Chem. Commun. 2006, 15211523.
obtain novel materials, such as holographic devices,14 mesoporous materials,15 enzyme encapsulation hosts,16 and nanoparticles for drug delivery.17 Despite this huge amount of data, the nature of the interactions arising between amines and silica precursors is still unclear. Two mechanisms have been proposed that involve either the nitrogen lone pair of electrons or the positive charge of ammonium groups.1,2 Interestingly, these two alternative models also appear to be involved in natural silicification processes, as spongeextracted silicatein bears neutral amine group (histidine),11 whereas diatom-extracted silaffins exhibit positively charged ammonium groups (alkylated lysine).9 In this context, it is interesting to examine the process of formation of silica nanoparticles using the Sto¨ber synthesis.18 This process involves the hydrolysis/condensation of silicon alkoxides in the presence of water, alcohol, and ammonia. Several studies have been devoted to the understanding of the reactions leading to silica nanoparticle growth.19-21 In the Sto¨ber conditions, (14) Brott, L. L.; Naik, R. R.; Pikas, D. J.; Kirkpatrick, S. M.; Tomlin, D. W.; Whitlock, P. W.; Clarson, S. J.; Stone, M. O. Nature 2001, 413, 291-293. (15) Sun, Q.; Vrieling, E. G.; van Santen, R. A.; Sommerdijk, N. A. J. M. Curr. Opin. Solid State Mater. Sci. 2004, 8, 111-120. (16) Luckakrift, H. R.; Spain, J. C.; Naik, R. R.; Stone, M. O. Nature Biotechnol. 2004, 22, 211-213. (17) (a) Boissie`re, M.; Meadows, P. J.; Brayner, R.; He´lary, C.; Livage, J.; Coradin, T. J. Mater. Chem. 2006, 16, 1178-1182. (b) Allouche, J.; Boissie`re, M.; He´lary, C.; Livage, J.; Coradin, T. J. Mater. Chem. 2006, 16, 3120-3125. (18) Sto¨ber, W.; Fink, A.; Bohn, E. J. Colloid Interface Sci. 1968, 26, 62-69. (19) (a) van Blaaderen, A.; van Geest, J.; Vrij, A. J. Colloid Interface Sci. 1992, 154, 481-487. (b) Ohmori, M.; Matijevic, E. J. Colloid Interface Sci. 1993, 160, 288-293. (c) Costa, C. A. R.; Leite, C. A. P.; Souza, E. F.; Galembeck, F. Langmuir 2001, 17, 189-194. (d) Green, D. L.; Lin, J. S.; Lam, Y.-F.; Hu, M. Z.-C.; Schaefer, D. W.; Harris, M. T. J Colloid Interface Sci. 2003, 266, 346358. (e) Nozawa, K.; Gailanou, H.; Raison, L.; Panizza, P.; Ushiki, H.; Sellier, E.; Delville, J. P.; Delville, M. H. Langmuir 2005, 21, 1516-1523. (20) (a) Matsoukas, T.; Gulari, E. J. Colloid Interface Sci.1989, 132, 13-21. (b) Harris, M. T.; Brunson, R. R.; Byers, C. H. J. Non-Cryst. Solids 1990, 121, 397-403. (21) (a) Bogush, G. H.; Zukoski, C. F., IV J. Colloid Interface Sci. 1991, 142, 1-17. (b) Lee, K.; Look, J.; Harris, M. T.; McCormick, A. V. J. Colloid Interface Sci. 1997, 194, 78-88. (c) Boukari, H.; Lin, J. S.; Harris, M. T. J. Colloid Interface Sci. 1997, 194, 311-318. (d) Pontoni, D.; Narayanan, T.; Rennie, A. R. Langmuir 2002, 18, 56-59.
10.1021/la703828v CCC: $40.75 © 2008 American Chemical Society Published on Web 02/28/2008
Unusual Core-Shell Silica Nanoparticles Scheme 1. Chemical Structure of the Cyclen Ligand
the role of ammonia is indeed related to its acid-base properties, leading to OH--catalyzed hydrolysis, and not to its nucleophilicity, since hydroxyl anions are more nucleophilic than NH3. On the basis of these observations, we decided to investigate the effect of polyamine addition on the growth of silica nanoparticles obtained via the Sto¨ber synthesis. Our initial aim was to study the suitability of this process to encapsulate transition metal coordination complexes that may act as optical probes or catalysts. More specifically, we wished to compare a one-step process involving the encapsulation of the metal-ligand complex with a two-step approach relying on the incorporation of the ligand followed by its in situ metalation. With this purpose, we selected the 1,4,7,10-tetraazacyclododecane (cyclen) ligand (Scheme 1), due its well-known coordination chemistry22,23 and the wide diversity of functional derivatives described in the literature.23-26 Moreover, the incorporation of the parent 1,4,8,11-tetraazacyclotetradecane (cyclam) in silica materials has already been extensively studied by Corriu et al., providing suitable comparison data.27 In this work, we show that the presence of cyclen has a strong influence on the growth of silica nanoparticles obtained via the Sto¨ber process. Both the size and the structure of the colloids are affected by increasing the amount of cyclen, until a threshold concentration corresponding to the maximum rate of ligand incorporation within the silica network. These effects were not observed when equivalent amounts of the Zn-cyclen complex or ammonia were added. Evidence is found that cyclen amine groups activate silica formation, leading to the formation of hybrid primary nanoparticles that aggregate to form colloidal silica. These colloids can be further coated by a silica shell, provided that precursors are still available in the surrounding solution, i.e., until a critical cyclen/precursor ratio. Present data not only represent a new example of amine-controlled silica formation process but also lead to nanoparticles exhibiting an unusual coreshell structure. The proposed mechanism of these core-shell nanomaterials should significantly contribute to a better understanding of the still actively debated chemical processes involved in the Sto¨ber synthesis of silica colloids. 2. Materials and Methods 2.1. Nanoparticle Synthesis. The 1,4,7,10-tetraazacyclododecane (cyclen) powder (C8H20N4, 98%, Strem Chemicals) was dissolved (22) Hancock, R. D.; Martell, A. E. Chem. ReV. 1989, 89, 1875-1914. (23) Crown Compounds Towards Future Applications; Cooper, S. R., Ed., VCH Publishers: New York, 1992. (24) The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging; Martell, A. E.; Toth, E., Eds.; Wiley: Chichester, UK, 2001. (25) Kimura, E. Tetrahedron 1992, 48, 6175-6217. (26) Costamagna, J.; Ferraudi, G.; Matsuhiro, B.; Campos-Vallette, M.; Canales, J.; Villagran, M.; Vargas, J.; Aguirre, M. J. Coord. Chem. ReV. 2000, 196, 125164. (27) (a) Dubois, G.; Corriu, R. J. P.; Reye´, C.; Brande`s, S.; Denat, F.; Guilard, R. Chem. Commun. 1999, 2283-2284. (b) Dubois, G.; Reye´, C.; Corriu, R. J. P.; Brande`s, S.; Denat, F.; Guilard, R. Angew. Chem., Int. Ed. 2001, 40, 10871090.
Langmuir, Vol. 24, No. 8, 2008 4027 in 5 mL of ammonia (NH4OH, analytical quality, minimum 2830% NH3, Sigma Aldrich Chemicals) into a closed vessel. This solution was quickly added to a just-prepared solution containing 4 mL of tetraethoxysilane (TEOS) [Si(OC2H5)4, 99%, Fluka] and 100 mL of ethanol (EtOH, Normapur quality 99%, Prolabo). The concentrations of TEOS, NH4OH, and EtOH in the final mixture were 0.164, 1.178, and 15.712 M, respectively. The preparation was stirred at room temperature during 21 h. After the hydrolysiscondensation reaction came to completion, the resulting particles were stabilized in aqueous medium by exchanging ethanol for deionized water at 70 °C with the volume kept constant. Most of this suspension was then freeze-dried to get ca. 400 mg of each specimen that could be examined by solid-state nuclear magnetic resonance (NMR). The remaining sol was used for dynamic light scattering (DLS), transmission electron microscopy (TEM) and liquid-state NMR experiments. Encapsulation of the Zn complexes of cyclen was performed using the same procedure but incorporating Zn-cyclen (ZnC8H20N4(NO3)2, home-prepared, controlled purity) as a precursor. In order to get rid of unencapsulated cyclen, water-exchanged sols were dialyzed twice for 24 h against 1 L of deionized water using a cellulose membrane with a 12-16 kDa molecular weight cutoff (pore size 25 Å). 2.2. Nanoparticle Characterization. The mean particle diameter was estimated before TEM imaging by measuring particle size distribution with DLS using a Brookhaven Zeta Plus instrument (Brookhaven Instruments Corp.). TEM observations were performed in bright field mode with a Philips CM12 electron microscope operating at an accelerating voltage of 120 kV. Both imaging and diffraction modes were employed for specimen characterization. The specimens were dispersed on carbon-coated copper grids by deposition of a drop of a diluted suspension of the particles in ethanol after sonication. SEM observations were performed on a JSM-5500 JEOL instrument at an operating voltage of 20 kV. 2.3. NMR Studies. Solid-state NMR studies were performed on an Avance 300 Bruker spectrometer equipped with a Bruker 7BL CP/MAS probe. Magic angle spinning (MAS NMR) as well as crosspolarization coupled to magic angle spinning (CP-MAS NMR) experiments were undertaken. Freeze-dried samples were finely ground and packed into ZrO2 rotors (7 mm diameter) before spinning at 5 kHz. 29Si MAS NMR experiments were carried out at a frequency of 59.63 MHz with single pulse technique with high-power decoupling during acquisition28 (tppm15, ν1H ) 50 kHz), using 90° pulse and recycle delays of 200 s. Such delays should allow quite complete longitudinal relaxation for the silicium nuclei, as indicated by T1 relaxation measurements. Free induction decays (FIDs were recorded with a dwell time of 24 µs, 2048 data points, and about 300 transients. The FID data were processed using X-WinNMR software, and a line broadening of 50 Hz was applied before Fourier transformation. The experimental MAS spectra were simulated using DmFit modeling software,29 giving access to the relative contributions (%Qn) of the different Qn (n ) 0-4) species to the signal. A condensation degree (D) for the silica network could be calculated using eq 1 which indicates the ratio of Si-O-Si linkages over the D ) [%Q1 + 2(%Q2) + 3(%Q3) + 4(%Q4)]/400
(1)
total Si-O-X bonds constituting the network. Thus, D ) 1 when all Si-OH groups have condensed to form Si-O-Si linkages, as expected for a fully condensed tridimensional SiO2 network, and D ) 0 for unreacted orthosilicic acid Si(OH)4. {1H}-13C CP MAS NMR experiments were carried out at a frequency of 75.48 MHz. The recycle delay was 3 s, the contact time was 1 ms, and usually about 3000 transients were sufficient to obtain a reasonable signal-to-noise ratio. All chemical shifts (δ) were referenced to tetramethylsilane (TMS; δ ) 0 ppm). (28) Bennett, A. E.; Rienstra, C. M.; Auger, M.; Lakshmi, K. V.; Griffin, R. G. J. Chem. Phys. 1995, 103 (16), 6951-6958. (29) Massiot, D.; Fayon; F.; Capron, M.; King, I.; Le Calve´, S.; Alonso, B.; Durand, J. O.; Bujoli, B.; Gan, Z.; Hoatson, G. Magn. Reson. Chem. 2002, 40, 70 (http://crmht-europe.cnrs-orleans.fr).
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Figure 1. Selected TEM micrographs of cyclen-containing silica nanoparticles with Cy/Si ) (a) 0%, (b) 2 wt %, (c) 5 wt %, (d) 10 wt %, (e) 20 wt %, and (f) 40 wt %. Liquid-state NMR experiments were performed with a Avance II 300 Bruker spectrometer equipped with a 5 mm QNP Bruker probehead. A liquid specimen of 500 µL was diluted with 200 µL of D2O. 13C NMR experiments were carried out at a frequency of 75.48 MHz with single-pulse technique using 30° pulse and recycle delays of 2 s. The number of transients varied from 2300 to 17 000, depending on the cyclen content in the supernatant of the sol.
3. Results The size of the silica nanoparticles obtained in the presence of cyclen was studied by TEM and DLS. Selected TEM micrographs are shown in Figure 1 and corresponding nanoparticle size are gathered in Figure 2. From a relatively monodispersed sol of colloids 50 nm in diameter, the addition of an increasing amount of cyclen up to Cy/Si ) 15 wt % leads to the growth of larger nanoparticles up to 140 nm with an increase in size distribution. Above this value, the particle diameter fluctuates between 150 and 400 nm, reflecting a large polydispersity in size of the resulting colloids. In parallel, an evolution of the nanoparticle internal structure was observed (Figure 1). Whereas silica colloids obtained in the absence of cyclen present a homogeneous structure, some core granular nanoparticles (4-5 nm in diameter) are observed for Cy/Si ) 2 wt % surrounded by a continuous silica shell ca. 20 nm in thickness. As the amount of cyclen increases, the granular core enlarges to the detriment of the shell until this outer layer appears to completely disappear for Cy/Si ) 15 wt % and above. Also shown in Figure 2 is the size evolution monitored by DLS. A good agreement with TEM data was observed up to Cy/Si ) 15%, whereas particles ca. 450 nm in diameter are found in solution above this value, suggesting nanoparticle aggregation. These data suggest that added cyclen interacts with TEOS and becomes incorporated within the silica nanoparticles, until a limiting value where excess ligand does not modify further the growth process. Noticeably, these structures and the existence of a critical Cy/Si value were also confirmed by investigating the effect of sonication of silica sols on particle
Figure 2. Nanoparticle size evolution with increasing cyclen amount as obtained from TEM (open squares) and DLS (dark diamonds) experiments.
degradation via SEM imaging (Figure 3). Whereas all assynthesized nanoparticles showed a plain spherical morphology (Figure 3a), sonication induces the formation of hollow spheres at low cyclen content (Figure 3b), whereas no evident change in nanoparticle structure was observed for Cy/Si g 15 wt % (Figure 3c). In the former case, the breaking of the silica shell might have occurred, leading to core particle release in the solution, whereas in the latter case, those particles that have been degraded by the sonication process should have led to the dispersion of nanofragments that cannot be observed by SEM. The nanoparticle powder was also studied by 29Si MAS and {1H}-13C CP MAS solid-state NMR. The 29Si spectra of the pure silica colloids indicate the presence of Q2 (-90 ppm), Q3 (-100 ppm), and Q4 (-110 ppm) species in a 1:30:69 ratio (Figure 4). As the amount of added cyclen increases, the Q4 signal intensity decreases relatively to Q3 and Q2 and then remains
Unusual Core-Shell Silica Nanoparticles
Langmuir, Vol. 24, No. 8, 2008 4029
Figure 5. Evolution of {1H}-13C CP-MAS NMR spectra of assynthesized nanoparticles with increasing cyclen amount.
Figure 3. SEM micrographs of cyclen-containing silica nanoparticles (a) before sonication for Cy/Si ) 10 wt % and after sonication for (b) Cy/Si ) 10 wt % and (c) 20 wt %. Arrows indicate hollow particles.
Figure 4. Evolution of 29Si MAS NMR spectra of as-synthesized nanoparticles with increasing cyclen amount. Bottom line: deconvolution of the Cy/Si ) 0% spectrum.
constant, with a Q2:Q3:Q4 ratio at Cy/Si ) 20 wt % to 5:40:55 (Figure 4). From these data the condensation degree (D) of the silica network can be calculated that decreases from 0.93 ( 0.01
to 0.87 ( 0.01 when increasing Cy/Si up to 15 wt % and then remain constant for higher cyclen amounts. 13C NMR data provide additional insight on the effect of cyclen addition. The spectra of the pure silica nanoparticles exhibit two main bands at 18 and 58 ppm, corresponding respectively to the carbon atoms of the terminal CH3 groups and internal CH2O groups of nonhydrolyzed ethoxy groups of TEOS (Figure 5). For the lowest cyclen amount, another peak centered at 45 ppm appears, corresponding to the carbon atoms of the ligand backbone. With increasing Cy/Si ratio, this signal grows in intensity, whereas the two peaks corresponding to ethoxy groups are attenuated and totally disappear for Cy/Si ) 20 wt % and above. Comparison of these two sets of data therefore suggests that cyclen enhances TEOS hydrolysis but interferes with its condensation process. In agreement with TEM data, this influence is apparently effective up to a threshold value above which no significant modification of the system is observed. To estimate the cyclen encapsulation rate, 13C liquid-state NMR studies were undertaken on as-prepared sols. As the entrapped cyclen exhibits a restricted mobility, only the organic molecules remaining in the solution should be detected. In fact, no significant signal could be obtained for Cy/Si e 15 wt %. Above this concentration, 13C NMR cyclen peaks were detected whose intensity increases proportionally to the amount of cyclen (SI). In a step further, as-prepared sols were dialyzed against deionized water and the recovered freeze-dried nanoparticles studied by {1H}-13C CP MAS solid-state NMR. As an example, comparison of spectra of as-synthesized and dialyzed sols at Cy/Si ) 50 wt % are shown in Figure 6. The spectrum of the as-synthesized sol exhibits an asymmetric peak that can be deconvoluted in two components, at 44.3 and 48.4 ppm, respectively. After dialysis, only the 44.3 ppm signal is obtained, suggesting that it corresponds to encapsulated cyclen, whereas the 48.4 ppm is attributed to nonencapsulated molecules. This
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Figure 6. {1H}-13C CP-MAS NMR spectra of as-synthesized (a) and dialyzed (b) nanoparticles obtained for Cy/Si ) 50 wt % to be compared with as-synthesized nanoparticles obtained for Cy/Si ) 10% (c).
is confirmed by the NMR spectrum of as-synthesized sols obtained at Cy/Si ) 10 wt % that only shows the 44.3 ppm peak. Overall these data indicate that the cyclen encapsulation is total up to Cy/Si ) 15 wt %, corresponding to the maximum loading of the silica nanoparticles, whereas above this concentration, the excess cyclen remains in the solution. To get a better understanding of the effect of cyclen addition, different reference experiments were performed. First, the Zncyclen complex was added instead of the pure ligand while the Cy/Si ratios were kept in the initial solution unchanged. From TEM imaging, it was observed that the presence of the complex did not strongly influence the size of the nanoparticles that exhibit an average diameter of 50 nm, being thus comparable to the pure silica system (Figure 7a). However, TEM suggested that these nanoparticles exhibit a higher tendency to form aggregates, a fact that was confirmed by DLS measurements (not shown). Moreover, 13C liquid-state NMR study of the as-prepared sols obtained for Cy/Si ) 15% indicates that only traces of the complex remains in solution, suggesting its efficient encapsulation within the silica nanoparticles (Supporting Information). In parallel, an excess of ammonia was added instead of cyclen while the amount of added amine groups was kept equivalent to previous Cy/Si ratios (i.e., added [NH3] ) 4[cyclen]). In similarity with Zn-cyclen addition, the silica nanoparticle size was observed to be constant (ca. 50 nm), even for ratios equivalent to Cy/Si ) 30% (Figure 7b). In both systems, 29Si NMR studies shows that the condensation degree is independent of the amount of added Zn-cyclen/ ammonia and close to 0.90 (Supporting Information). It therefore seems that when nitrogen atoms are involved in a coordination bond or when they are present as monoamines, they do not interfere with the Sto¨ber silica formation process.
4. Discussion The influence of cyclen on the formation of silica nanoparticles via the Sto¨ber process can be summarized as follows. Below a certain Cy/Si ratio, cyclen molecules interact with the alkoxide precursors, leading to an increase in their hydrolysis rate. At the same time, they are incorporated within the growing colloids, leading to hybrid nanoparticles, as suggested by the granular aspect of the particle core observed by TEM. By doing so, they limit the possibility for particle core densification, decreasing the silica network condensation degree. Above the critical Cy/Si
Figure 7. TEM micrographs of silica nanoparticles formed in the presence of (a) 10 wt % Zn-cyclen and (b) 30% amine equivalent ammonia (inserts scale bar ) 25 nm).
ratio, unencapsulated cyclen is detected in the solution, corresponding to the excess of ligand that did not react with TEOS. Under these conditions, the hybrid nanoparticle size and composition remains constant with increasing cyclen amount. However, such particles have a strong tendency to aggregate, probably due to the increase in particle size together with the presence of the neutral ligand within the silica network, which decreases the nanoparticle surface charge density. It is now necessary to examine the underlying mechanisms. A first possibility would lie in a nonactive incorporation of cyclen, meaning that the ligand is chemically inert toward TEOS and becomes trapped in the growing nanoparticles as part of the initial solution. This situation is illustrated by Zn-cyclen addition that leads to the incorporation of the complex within the silica colloids. However, in this case, neither the silica nanoparticle size nor the silica degree of condensation showed significant variation with the initial Zn-cyclen amount, even if comparable Cy/Si are found in the recovered hybrid colloids. Therefore, some kind of interactions should exist between the macrocycle amines and the silicon alkoxide. Cyclen shows two nitrogen atoms with high basicity (pKa ≈ 11 and 10) and two others with low basicity (pKa< 2).30 Although pH measurements using a standard electrode are not fully reliable because the reaction media mainly consist of ethanol, the initial solution shows an apparent pH above 12. Therefore, introduction of cyclen as a free base in the ethanol/TEOS/ammonia mixture should not induce significant protonation of the ligand amine (30) Koike, T.; Kajitani, S.; Nakamura, I.; Kimura, E.; Shiro, M. J. Am. Chem. Soc. 1995, 117, 1210-1219.
Unusual Core-Shell Silica Nanoparticles
groups and is not expected to influence the solution pH, in agreement with our observations. Moreover, it was observed that ammonia addition in comparable amounts does not modify the nanoparticle growth. Thus, the observed effect of cyclen addition cannot be attributed to pH modifications. Overall, it suggests that TEOS should interact with the lone pairs of electrons of the nitrogen atoms of cyclen (that are no longer available for Zn-cyclen) and that the fact that the ligand is a polyamine (and not a monoamine like ammonia) also play a role in nanoparticle formation. The first conclusion is supported by the observed increase of TEOS hydrolysis progress with increasing cyclen addition. The second aspect is in agreement with previous reports on silica formation activation by polyamines resulting in the entrapment of the additives within the silica network.1-10 Interestingly, the largest dimension of the cyclen molecule is ca. 5 Å, with a nitrogen-nitrogen shortest distance of ca. 3 Å.31 In comparison, the average Si-Si distance in a silica gel is also on the order of 3 Å.32 This suggests that cyclen nitrogen atoms may act cooperatively with two TEOS molecules and favor their condensation, as already proposed.7 Such a phenomenon would favor the nucleation of silica primary nanoparticles. The growth process would then proceed by aggregation of these hybrid primary nanoparticles. In addition, it is interesting to note that a maximum loading of Cy/Si ) 15% by weight corresponds to a cyclen:SiO2 molar ratio of 0.05 so that each cyclen molecule is associated with 20 “SiO4” groups. It might therefore be suggested that these “cyclen-SiO2” associations constitute the building blocks that form the primary nanoparticles. It is worth noting that DLS investigations of reaction mixtures in the absence of TEOS did not show any evidence for the formation of cyclen supramolecular assembly, ruling out the possibility for a contribution of such self-assembled systems to the control of silica formation. The mechanisms involved in the Sto¨ber process are still a matter of debate.19 On the one hand, it was proposed that, following TEOS hydrolysis, primary nanoparticles are first formed and then grow by addition of soluble monomers.20 On the other hand, it was suggested that the nucleation occurs continuously during the reaction and that the growth process proceeds by primary nanoparticle aggregation.21 Some authors also indicated that both mechanisms may occur at different stages of the reaction, first with a controlled aggregation of the primary nanoparticles, followed by further coating by soluble monomers.19d In our system, above a certain Cy/Si ratio, an excess of ligand is found in the colloidal solution and the nanoparticle size and structure remain constant. This suggests that all available TEOS molecules have been consumed by their interaction with cyclen. Thus, it is very unlikely that a mixture of primary nanoparticles and monomers would cohabitate if cyclen is still present in the solution. Thus, the controlled-aggregation process alone may explain the formation of the silica nanoparticles. On the contrary, when the Cy/Si ratio is below this critical value, it can be suggested that hybrid primary nanoparticles are also first formed by TEOS/ cyclen interactions but are further coated by available monomers. This is in agreement with the observed core-shell structure of the nanoparticles and the progressive decrease of the shell thickness with increasing amount of cyclen. (31) Kimura, E.; Aoki, S.; Koike, T.; Shiro, M. J. Am. Chem. Soc. 1997, 119, 2038-3076. (32) Iler, R. K. The Chemistry of Silica; Wiley-Interscience: New York, 1979.
Langmuir, Vol. 24, No. 8, 2008 4031 Scheme 2. Schematic Illustration of the Formation of Silica Core-Shell Nanoparticlesa
a Condensation of TEOS is activated by cyclen, leading to hybrid primary nanoparticles that aggregate to form the particle core. Unreacted precursors, if available, condense on the core surface to form an external silica shell.
5. Conclusion Several inorganic complexes,33 including Ru(2,2′-bipyridine) and porphyrin,34,35 have been encapsulated within Sto¨ber silica particles. In these systems, organic ligands usually bear several amino groups. However, to the best of our knowledge, the possible influence of these ligands on the formation and structure of resulting silica colloids has not been studied so far. Therefore, the here-observed process of formation and the structure of resulting hybrid colloids is rather uncommon when compared to traditional Sto¨ber synthesis and is summarized in Scheme 2. First, cyclen molecules interact with a very limited amount of silicate species in a way that can be pictured as a supramolecular assembly of silica oligomers surrounding the organic molecules. These hybrid primary nanoparticles are then aggregated to form a granular core. In the presence of unreacted TEOS, a silica layer can then be deposited, resulting in an unusual core-shell structure. From a fundamental point of view, it is now necessary to study the effect of other polyazamacrocycles such as cyclam (1,4,8,11-tetraazacyclodecane) to confirm the here-proposed mechanism of hybrid core-shell silica nanoparticles. In parallel, it should be interesting to take advantage of these unusual structures and of our ability to control the shell thickness via cyclen incorporation to evaluate their potential as controlledrelease systems. Supporting Information Available: Evolution of the intensity of the 13C liquid-state NMR signal of cyclen versus cyclen content, 13C liquid-state NMR spectrum of the 10 wt % Zn-cyclen/silica sample, evolution of the 29Si MAS NMR spectra of Zn-cyclen/silica samples with increasing Zn-cyclen content, and evolution of the 29Si MAS NMR spectra of ammonia-silica samples with increasing ammonia content. This material is available free of charge via the Internet at http://pubs.acs.org. LA703828V (33) Smith, J. E.; Wang, L.; Tan, W. Trends Anal. Chem. 2006, 25, 848-855. (34) Rossi, L. M.; Shi, L.; Quina, F. H.; Rosenzweig, Z. Langmuir 2005, 21, 4277-4280. (35) Papacidero, A. T.; Rocha, L. A.; Caetano, B. L.; Molina, E.; Sacco, H. C.; Nassar, E. J.; Martinelli, Y.; Mello, C.; Nakagaki, S.; Ciuffi, K. J. Colloids Surf. A 2006, 275, 27-35.
