Little Adjustments Significantly Improve the Turkevich Synthesis of

Aug 15, 2014 - The key features of the improved protocol are the control of the pH by using a citrate buffer instead of a citrate solution as the redu...
0 downloads 3 Views 5MB Size
Download PDF
Subscriber access provided by Western Michigan University

Article

Little Adjustments Significantly Improve the Turkevich Synthesis of Gold Nanoparticles. Florian Schulz, Torge Homolka, Neus G Bastús, Víctor F. Puntes, Horst Weller, and Tobias Vossmeyer Langmuir, Just Accepted Manuscript • DOI: 10.1021/la503209b • Publication Date (Web): 15 Aug 2014 Downloaded from http://pubs.acs.org on August 18, 2014

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Langmuir is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Little Adjustments Significantly Improve the Turkevich Synthesis of Gold Nanoparticles. Florian Schulz,*,† Torge Homolka,† Neus G. Bastús,‡ Victor Puntes,‡ Horst Weller†,ǁ and Tobias Vossmeyer*,† †

Institute for Physical Chemistry, University of Hamburg, Grindelallee 117, 20146 Hamburg, Germany ‡ Institut Català de Nanociència i Nanotecnologia (ICN2), Campus UAB, 08193 Bellaterra, Barcelona, Spain

ǁ Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia

Supporting Information Placeholder ABSTRACT: In this report we show how the classical and widely-used Turkevich synthesis can be improved significantly by simple adjustments. The gold nanoparticles produced with the optimized protocol have a much narrower size distribution (5-8 % standard deviation) and their diameters can be reproduced with unrivaled little variation (< 3 %). Moreover, large volumes of these particles can be produced in one synthesis; we routinely synthesize 1000 ml of ~3.5 nM AuNPs. The key features of the improved protocol are the control of the pH by using a citrate buffer instead of a citrate solution as the reducing agent/stabilizer and optimized mixing of reagents. Further, the shape uniformity of the particles can be improved by addition of 0.02 mM EDTA. While the proposed protocol is as straightforward as the original Turkevich protocol, it is more tolerant against variations of the precursor concentration.

Introduction Gold nanoparticles (AuNPs) are among the most widely used and studied nanomaterials and have numerous applications in nanomedicine, biotechnology, microelectronics, 1–8 9 optics and catalysis. The Turkevich protocol for the synthesis of citrate-stabilized AuNPs is considered most popular for several reasons. The procedure is very straightforward and reliably produces AuNPs with diameters from 5 to 150 10 nm which are nontoxic and well stabilized by citrate ions. The citrate stabilizer can easily be exchanged by ligands with higher affinity to gold, especially thiols, allowing for (multi)functionalization of the AuNPs. The mechanism of the Turkevich synthesis is much more complex than the simple procedure might suggest and until today studies aim at a better understanding of the mecha11–20 nism to assist optimization of the protocol. Regarding such optimization, improvements of the size distribution, indicated by a low coefficient of variation (CV), uniformity, reproducibility and control of the AuNP-diameter were ad-

dressed by most studies, but scaling up has also gained inter21–28 est. The state of the art in the synthesis of AuNPs was 10 reviewed recently. To understand the influence of the various parameters on the outcome of the synthesis it is helpful to consider separately the chemical reactions and processes involved on the one hand and the mechanisms of particle nucleation and growth on the other hand. These are presented in Figure 1. It can be considered consensus that a fast nucleation in the Turkevich synthesis leads to AuNPs with narrow size distri10,14,23,27 bution. A fast nucleation can be achieved by increasing the reactivity of the precursor or by increasing the concentration of the intermediate acetondicarboxylate [ADC] 14,23,27 (Figure 1). [ADC] can be increased easily by reversing the reagent addition of the original Turkevich protocol, i.e., injecting the Au precursor into a boiling aqueous solution of sodium citrate. This inverse addition of reagents promotes the thermal oxidation of sodium citrate (SC) and the subsequent formation of ADC, which results in a faster nucleation 23 and an improved dispersity of the final AuNPs. This method is referred to herein as inverse method. The following key parameters for the synthesis can be identified based on available literature: the concentrations of precursor, [HAuCl4], sodium citrate, [SC], and acetondicarboxylate, [ADC], the electrolyte concentration, the tempera9,13–16,18,23,27,28 ture and heating time and the pH. Among these, the pH seems to be the essential parameter in the synthesis, but due to the complex interplay of parameters, its role can be conflicting. Especially interesting is the work of Peng's group who studied the pH-dependent reactivity of the Au 14 precursor. Similarly, Puntes' group reported the interplayed 23 role of [ADC], solution pH and the AuNPs' CV. In another study, Xia et al. reduced the buffer effect of the citrate (leading to an increase in pH) by fast mixing of the reagents and catalysis of ADC formation with silver(I)-ions to obtain uni27 form AuNPs with low CV.

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 12

ethylenediaminetetraacetate (EDTA). With optimal conditions, 1000 ml of ~3.5 nM quasispherical AuNPs with high uniformity and a CV as low as 5-6 % were synthesized in a highly reproducible manner. The relative standard deviation (SDrel) of the mean diameter, d ~12 nm, of several batches was < 3 %. To our best knowledge, this is the lowest CV and the best reproducibility of citrate-stabilized AuNPs in this size regime demonstrated so far, which are also superior to all commercially available AuNPs. At the same time the protocol is very straightforward and robust and can be easily implemented by researchers to synthesize large quantities of high quality AuNPs. This is a great advantage for any research objective and application that benefits from high reproducibility and comparability of different batches and for improved quantification of surface-related parameters like ligand coverage and catalytic activity. Also, for the comparison of experiment and theory, e.g. in the field of plasmonics, for their use as a standard for calibration and for the selfassembly of highly ordered superstructures well-defined particles are highly desirable.

Methods Materials. Tetrachloroauric(III) acid (≥99.9 % trace metals basis) and trisodium citrate dihydrate (≥99.0 %) were ordered from Sigma Aldrich. Ethylenediaminetetraacetic acid tetrasodium salt hydrate (EDTA) and citric acid monohydrate (≥99.5 %) was from Merck. α-Methoxypoly(ethylene glycol)-ω-(11-mercaptoundecanoate) (PEGMUA) was synthe30 sized as described previously. Ultrapure water (18.2 MΩ∙cm, Millipore) was used for all procedures. 23

Figure 1. Mechanism of the Turkevich synthesis and pH 9,14–16,27,29 influence. a.) The Redox-reaction of citrate and the Au(III)-precursor yields Au(I)-ions and acetonedicarboxylate (ADC). b.) ADC organizes Au(I)-ions in polymolecular complexes to yield high local Au(I)-concentrations, which allow c.) disproportionation of Au(I) to Au(0) and Au(III) and d.) the nucleation and growth of Au(0) to AuNPs. The pH influences not only the protonation of citrate and therefore the electrostatic stabilization of the growing and final AuNPs but also the reactivity of the precursor and thus the rate and extent of nucleation. A fast nucleation and good stabilization promote a narrow size distribution of the AuNPs, whereas slow nucleation and low stabilization result in a broad size distribution of the AuNPs due to temporal overlap of nucleation and growth and aggregative growth. Here, we show that in fact at high [SC]/[HAuCl4]-ratios AuNPs with very low CV can be synthesized by controlling the pH at a rather low value of ~5.5. At this low pH, the dispersity was further improved by optimizing the mixing conditions. Interestingly, the shape uniformity of the AuNPs was significantly improved by the addition of small amounts

Syntheses of AuNPs. INVERSE METHOD. 97.1 mg (0.33 mmol) trisodium citrate dihydrate (SC) were dissolved in 150 ml water (c = 2.2 mM) and the solution was heated to reflux in a 250 ml three-necked flask equipped with a Dimrothcondenser. The boiling time before precursor-addition was ∆t = 15 min unless noted otherwise. 1 ml precursor solution (HAuCl4∙3H2O in water, c = 25 mM) was then quickly injected under rapid stirring. When the color-change of the solution to the characteristic wine-red indicated formation of AuNPs, the heating-mantle was switched off but not removed until the solution´s temperature was ~70 °C. INVERSE METHOD WITH pH OPTIMIZATION. pH optimization by addition of hydrochloric acid: The inverse method was performed as described but with addition of 100 µl 2 M hydrochloric acid before precursor addition. pH optimization by use of citric acid/sodium citrate buffer: 2.2 mM solutions of sodium citrate (SC) and citric acid (CA) were mixed to yield molar ratios SC/CA of 90/10, 75/25 or 50/50 and used for the inverse method as described. PROTOCOL FOR OPTIMIZED MIXING AND SCALE UP. 800 ml 2.75 mM citrate buffer (SC/CA: 75/25) in a 2000 ml beaker was heated to boiling point on a hot plate magnetic stirrer. The beaker can be covered to minimize evaporation of water but the synthesis is not affected by evaporation, so covering the beaker is not critical. Meanwhile, 200 ml precursor solution (HAuCl4∙3H2O in water, c = 812.5 µM) was heated to 90-100 °C to avoid a temperature drop during subsequent mixing. The boiling time of the citrate buffer before precursor-addition was ∆t = 15 min unless noted otherwise. The precursor solution was then quickly added under rapid

ACS Paragon Plus Environment

Page 3 of 12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

stirring (800 rpm, stirring bar 40 x 8 mm, cylindrical) to the citrate buffer solution. [Caution! Danger of scalding. Hot liquids have to be handled with appropriate protective gear.] After color-change of the solution it was heated to boiling for another 20 minutes before the hot plate was switched off to let the solution cool down to ~70 °C. The solution was then transferred into a glass bottle for storage. Variations of this protocol, e.g. the addition of EDTA, are detailed in Table S1. Characterization. TRANSMISSION ELECTRON MICROSCOPY (TEM). TEM measurements were performed using a Jeol JEM-1011 operating at 100 kV. All AuNPs were functionalized with PEGMUA before TEM sample prepara30 tion as described previously. 500 µl AuNPs (~2-5 nM) were thoroughly mixed with 50 µl aqueous PEGMUA (c = 1 mM). The solution was centrifuged (20,000 g, 15-20 min) and 500 µl supernatant replaced with water. 10 µl of this solution was then drop-casted onto a carbon-coated copper grid, which was placed on a glass slide, and left drying for at least 24 h. ANALYSIS OF SIZE DISTRIBUTIONS. Quantitative analyses of AuNP size distributions based on TEM measurements were done using the software ImageJ (version 1.43u). The Images were converted into binary images and scaled to allow automated counting and measurement of the imaged particles´ areas. Edges can be excluded by the software, other sources of error like the scale bar, adjacent particles which were not distinguished by the algorithm and particles which were not correctly binarized were removed manually. Particles strongly deviating from the mean, coalesced particles, unusual geometries etc. were not removed. Exemplative TEM images, original and processed for analysis, for all AuNP batches are provided in Tables S2-S4. ANALYSIS OF CIRCULARITY. To analyze the circularity, the binarized images were smoothed ten times. The software -2 calculates the circularity as circ = 4π[area][perimeter] , so circ = 1 corresponds to a perfect circle, whereas circ = 0 corresponds to an infinitely elongated polygon. The binarization of the TEM images results in more or less irregular boundaries of the AuNP-projections depending on the contrast in the according region (Figure S4). If no smoothing is applied, these irregularities lead to strong deviations in the perimeters, too much smoothing affects the shapes, though. We found ten iterations of smoothing to be a good compromise of smooth boundaries and maintained shape-information. After smoothing, the images were binarized again to allow automated analysis with the software. The smoothing can create new merged AuNP-projections, so the images were carefully controlled before analysis.

Results and Discussion The statistical evaluation of 41 syntheses is presented herein, which are summarized in Figure 2 while detailed information for each batch are provided as Supporting Information, Tables S1-S4. Exemplative absorbance spectra and results of dynamic light scattering (DLS) measurements are provided as Supporting Information Figure S1. Size distributions of AuNPs synthesized with the inverse method and with optimal conditions are presented in Figure 3 to illustrate the significantly improved dispersity.

Figure 2. Diameter and CV of AuNP-batches synthesized with the inverse method, the inverse method with pH optimization and with the pH and mixing optimized protocol as indicated. The reproducibility of the diameter with the pH and mixing optimized protocol is very good, even though the batches represented by the data points were synthesized with several variations of the protocol as detailed in the text and Supporting Information. The optimized protocol for the synthesis of citrate stabilized AuNPs with d ~12 nm is based on the inverse method 23 described previously. With this protocol, relatively small AuNPs (d ~8-12 nm) with CVs from 10 to 12 % can be obtained, but some batches also yielded larger particles with higher CVs up to 17 % (Figure 2, inverse method). The reason for this lack of reproducibility is not clear but we assume that the pH of the solution plays a critical role, which cannot be controlled perfectly with this protocol. In the relevant range from 5.5-7.5 where the reaction takes place, the pH responds very sensitively to any change of ionic concentrations. All involved reagents interact with the pH (Figure 1) and the exact concentration of the hygroscopic gold precursor is hard to control accurately. Additionally, the temperature and heating profiles affect [SC] and [ADC] via their decomposi16,23,27 thereby affecting the pH. Consequently, tion rates, reproductions of the AuNP diameter and CV are difficult, especially in different settings (quality of reagents, water supply, experimental setup, etc.). A simple way to control the pH is the use of citrate/citric acid buffer instead of citrate solution and we found that a mixture of 75 % SC and 25 % citric acid (CA) is optimal for the synthesis of AuNPs with low CV (Figure S2). By using the citrate buffer with 75 % citrate and a total concentration of all citrate species ctotal = 2.2 mM, the CV of the AuNPs was reproducible at ~11% and the reproducibility of the mean diameter was improved (SDrel = 6 %, Figure 2, pH optimized protocol). The diameters of the AuNPs were in the range 14-17 nm.

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 12

flask resulted in a faster nucleation, beginning after ~20 s, but had no effect on the diameter and dispersity (Table S1 and S4, batches 25-28). The preheating time ∆t before precursor addition and the addition of different amounts of EDTA had no significant effect on the mean diameter but some effects on the uniformity and CV which are discussed below. It is important to note, that in Figure 2 the batches with all these variations are included. Also the protocol was tested by different scientists in different laboratories and using different reagents (water supply, batches, supplier etc.). The high reproducibility of the diameter (SDrel < 3 %) was not affected by these variations and the CV of all batches was ≤ 8 %, underlining the robustness of the protocol.

Figure 3. Normalized size distributions of AuNPs synthesized with the inverse method or with the pH and mixing optimized method in the presence of 0.02 mM EDTA (optimized method) as indicated. The mean diameter of these batches were d = 12.0 ± 1.5 nm (inverse method, CV = 12.5 %, batch 7 in Table S2) and d = 11.7 ± 0.7 nm (optimized method, CV = 6.0 %, batch 19 in Table S4). A section of a representative TEM image for the batch synthesized with the optimized method is shown in the inset. To scale up the pH-optimized procedure, the final volume of the reaction mixture was increased to V = 1000 ml. A larger volume of precursor solution (VPr = 200 ml) was used to improve the initial mixing of the reagent solutions. The final precursor concentration was similar to the inverse method. Accordingly, VSC = 800 ml of 2.75 mM citrate buffer (75 %) was used to yield 2.20 mM in the final mixture. With this simple adjustments, not only scaling up was achieved but the dispersity of the resulting AuNPs was also significantly improved. The CVs were 8 % and lower and the reproducibility of the diameter, d ~12 nm, was excellent (SDrel < 3 %, Figure 2, protocol for optimized pH and mixing). The AuNP concentrations were in the range from 3-5 nM and the deviations are mainly due to solvent evaporation during the syntheses. The AuNP concentrations were determined using their ab31 sorbance at 450 nm as described by Haiss et al. When a citrate solution was used instead of citrate buffer in the protocol for optimized mixing, very polydisperse AuNPs were obtained (Figure S3). Apparently, at low pH (pH 5.5 of the final AuNP solution) the protocol allows scaling up and improvement of the dispersity at the same time, whereas this is not the case at high pH (pH 6.7 of the final AuNP solution synthesized with just citrate, Table S1). The reason for this observation is not clear but it should be related to the reactivity of the precursor, the completeness of its conversion in the nucleation step and the speed of nucleation, which is considerably lower at higher pH. In this regard, the beginning of nucleation is observable by bare eye as a first change of the solution’s color after 30-40 s at low pH but at high pH it takes longer, ~7 min, until it can be observed (Table S1). To test its robustness we varied the protocol for optimized pH and mixing regarding the amount of precursor. The concentration of the hygroscopic precursor was tested because it is hard to control accurately. The concentration [HAuCl4] was varied from 125.0 µM to 200.0 µM (±23 %) without significant effect on diameter and dispersity. Syntheses in a baffled

All AuNPs were functionalized with a poly(ethylene glycol) 30 ligand for TEM analysis as described previously. Occasionally, self-assembly of the monodisperse AuNPs into highly ordered superlattices was observed as shown in Figure 4. This self-assembly is favored by the very narrow size distri32,33 butions of the AuNPs.

Figure 4. Areas of AuNPs self-assembled on a TEM-grid. A region with 3 layers is detailed in the upper picture. In the lower picture, from the lower left to the upper right, 3, 2 and 1 layers of self-assembled AuNPs can be seen. The protocol with optimized pH and mixing yields AuNPs with very low CV, but these AuNPs contain up to several % of triangular prismatic particles. Since it is well-known, that the underpotential deposition of metal ions like Ag(I) can affect 34 the growth of AuNPs, we first assumed that trace contaminations by Zn(II) or Cu(II) may promote anisotropic growth of some AuNPs. To minimize the effect of such ions, we added small amounts of EDTA to the reaction. Indeed we found, that the number of triangular prismatic particles can be reduced to practically zero by addition of suitable amounts of EDTA, as shown in Figure 5. To characterize the uniformity of the AuNPs, the circularity was analyzed as described in the method section and in Figure S4. Both, uniformity and dispersity can be optimized by addition of suitable amounts of EDTA and the same trend and optimum was found for both parameters (Figure 5 and Figure S5).

ACS Paragon Plus Environment

Page 5 of 12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Optimal results in terms of uniformity and dispersity were obtained with ∆t = 15 minutes in combination with addition of EDTA to a concentration of 0.02 mM into the boiling citrate buffer before precursor addition. With these conditions, CVs as low as 5-6 % and very uniform quasispherical AuNPs were obtained in quantitative yield (details regarding additional characterization and determination of the yield are provided as Supporting Information, p. 14).

vant for the ongoing discussion of a suitable approach – continuous flow or batch synthesis – for large-scale produc36 tion of AuNPs. The question of size control was not addressed in this study since robust protocols for the seeded growth of citrate-stabilized AuNPs with diameters > 15 nm 37,38 and CVs < 10 % are available. While the AuNPs presented in this study can be used as seeds, we note that the strategy of using a citric-acid buffer could not be transferred to a complete seeded-growth protocol (Figure S10). By addition of EDTA the uniformity of the quasispherical AuNPs is clearly improved and the underlying mechanism of this influence of EDTA on anisotropic growth is an interesting subject for more detailed studies. The addition of EDTA is not mandatory in the presented protocol, but AuNPs with exceptionally low CVs of ~5 % and excellent uniformity were obtained in the presence of 0.02 mM EDTA.

ASSOCIATED CONTENT Supporting Information

Figure 5. Exemplative TEM-images and circularitydistributions for AuNP-batches synthesized in the absence and in the presence of 0.02 mM EDTA as indicated. The preheating time ∆t was 15 min. However, at this point the hypothetical influence of contaminating ions on the particle shape and the effect of masking these contaminants by EDTA could not be confirmed experimentally. The intentional addition of Zn(II) and Cu(II) to the reaction mixture without EDTA addition did not result in more triangular prismatic AuNPs. A recent detailed analysis of the citrate-layer on AuNPs provides an indication of another possible mechanism for the formation of some trian35 gular prismatic AuNPs and the effect of EDTA at low pH, namely the pH-dependent stabilization of some crystal facets of the AuNPs. A detailed discussion of this hypothesis and the observation that EDTA suppresses anisotropic growth is provided as Supporting Information (Supporting Information, pages 16-19, Figures S4-S9). Although the exact role of EDTA in suppressing the formation of triangular prismatic AuNPs still remains to be explored in more detail, we emphasize that the observed beneficial effect is quantifiable and highly reproducible (Figure S5).

Conclusion In conclusion we presented a variation of the Turkevich synthesis that is as straightforward as the original protocol but yields AuNPs with significantly improved dispersity and excellent size reproducibility. Significant variations of the precursor concentration are tolerated by the protocol underlining its robustness. At the same time the synthesis is scaled up by a factor of ~7. Even higher scale-up factors seem possible but were not tested in this study. Our findings are rele-

Additional observations for the optimized protocol, TEM data for all batches presented, DLS and UV-vis characterization and determination of the yield, TEM results addressing the influence of pH on the inverse method, TEM data for AuNP synthesized with optimized mixing but with citrate solution instead of citrate buffer, discussion and experimental data addressing the role of EDTA, TEM data for AuNP synthesized with a seeded growth method at low pH. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Author Florian Schulz [email protected] Tobias Vossmeyer [email protected]

Notes The authors declare no competing financial interests.

ACKNOWLEDGMENT V.P. and N.G.B. acknowledge financial support from Spanish MICINN (MAT2012-33330). N.G.B. thanks the Spanish MICINN for the financial support through the Juan de la Cierva program and the European Commission for the Career Integration Grants (CIG)—Marie Curie Action. The authors thank Niklas Lucht for assistance with experimental work and Dr. Frank Meyberg and his team (University of Hamburg) for graphit furnace atomic absorption spectrometry measurements.

REFERENCES (1)

(2)

Boisselier, E.; Astruc, D. Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem. Soc. Rev. 2009, 38, 1759–1782. Daniel, M.-C.; Astruc, D. Gold Nanoparticles: Assembly, Supramolecular Chemistry, Quantum-Size-Related Properties, and Applications toward Biology, Catalysis, and Nanotechnology. Chem. Rev. 2004, 104, 293–346.

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(3)

(4)

(5)

(6) (7)

(8)

(9)

(10)

(11)

(12)

(13)

(14)

(15)

(16)

(17)

(18)

(19)

(20)

(21)

(22)

Dreaden, E. C.; Alkilany, A. M.; Huang, X.; Murphy, C. J.; El-Sayed, M. A. The golden age: gold nanoparticles for biomedicine. Chem. Soc. Rev. 2012, 41, 2740–2779. Ghosh, P.; Han, G.; De, M.; Kim, C. K.; Rotello, V. M. Gold nanoparticles in delivery applications. Adv. Drug Delivery Rev. 2008, 60, 1307–1315. Giljohann, D. A.; Seferos, D. S.; Daniel, W. L.; Massich, M. D.; Patel, P. C.; Mirkin, C. A. Gold Nanoparticles for Biology and Medicine. Angew. Chem. Int. Ed. 2010, 49, 3280–3294. Haruta, M.; Date, M. Advances in the catalysis of Au nanoparticles. Appl. Catal., A 2001, 222, 427–437. Kamat, P. V. Photophysical, photochemical and photocatalytic aspects of metal nanoparticles. J. Phys. Chem. B 2002, 106, 7729–7744. Saha, K.; Agasti, S. S.; Kim, C.; Li, X.; Rotello, V. M. Gold Nanoparticles in Chemical and Biological Sensing. Chem. Rev. 2012, 112, 2739–2779. Turkevich, J.; Stevenson, P. C.; Hillier, J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss. Faraday Soc. 1951, 11, 55–75. Zhao, P.; Li, N.; Astruc, D. State of the art in gold nanoparticle synthesis. Coord. Chem. Rev. 2013, 257, 638– 665. Biggs, S.; Chow, M. K.; Zukoski, C. F.; Grieser, F. The role of colloidal stability in the formation of gold sols. J. Colloid Interface Sci. 1993, 160, 511–13. Chow, M. K.; Zukoski, C. F. Gold sol formation mechanisms: role of colloidal stability. J. Colloid Interface Sci. 1994, 165, 97–109. Frens, G. Controlled Nucleation for the Regulation of the Particle Size in Monodisperse Gold Suspensions. Nature Phys. Sci. 1973, 241, 20–22. Ji, X.; Song, X.; Li, J.; Bai, Y.; Yang, W.; Peng, X. Size control of gold nanocrystals in citrate reduction: The third role of citrate. J. Am. Chem. Soc. 2007, 129, 13939–13948. Kimling, J.; Maier, M.; Okenve, B.; Kotaidis, V.; Ballot, H.; Plech, A. Turkevich Method for Gold Nanoparticle Synthesis Revisited. J. Phys. Chem. B 2006, 110, 15700–15707. Kumar, S.; Gandhi, K. S.; Kumar, R. Modeling of Formation of Gold Nanoparticles by Citrate Method. Ind. Eng. Chem. Res. 2007, 46, 3128–3136. Mikhlin, Y.; Karacharov, A.; Likhatski, M.; Podlipskaya, T.; Zubavichus, Y.; Veligzhanin, A.; Zaikovski, V. Submicrometer intermediates in the citrate synthesis of gold nanoparticles: New insights into the nucleation and crystal growth mechanisms. J. Colloid Interface Sci. 2011, 362, 330–336. Ojea-Jimenez, I.; Campanera, J. M. Molecular Modeling of the Reduction Mechanism in the Citrate-Mediated Synthesis of Gold Nanoparticles. J. Phys. Chem. C 2012, 116, 23682–23691. Polte, J.; Ahner, T. T.; Delissen, F.; Sokolov, S.; Emmerling, F.; Thuenemann, A. F.; Kraehnert, R. Mechanism of Gold Nanoparticle Formation in the Classical Citrate Synthesis Method Derived from Coupled In Situ XANES and SAXS Evaluation. J. Am. Chem. Soc. 2010, 132, 1296–1301. Pong, B.-K.; Elim, H. I.; Chong, J.-X.; Ji, W.; Trout, B. L.; Lee, J.-Y. New insights on the nanoparticle growth mechanism in the citrate reduction of gold(III) salt: Formation of the Au nanowire intermediate and its nonlinear optical properties. J. Phys. Chem. C 2007, 111, 6281–6287. Li, C.; Li, D.; Wan, G.; Xu, J.; Hou, W. Facile synthesis of concentrated gold nanoparticles with low size-distribution in water: temperature and pH controls. Nanoscale Res. Lett. 2011, 6, 440. Liu, X.; Xu, H.; Xia, H.; Wang, D. Rapid Seeded Growth of Monodisperse, Quasi-Spherical, Citrate-Stabilized Gold

(23)

(24)

(25)

(26)

(27)

(28)

(29) (30)

(31)

(32)

(33)

(34)

(35)

(36)

(37)

(38)

Page 6 of 12

Nanoparticles via H2O2 Reduction. Langmuir 2012, 28, 13720–13726. Ojea-Jimenez, I.; Bastus, N. G.; Puntes, V. Influence of the Sequence of the Reagents Addition in the Citrate-Mediated Synthesis of Gold Nanoparticles. J. Phys. Chem. C 2011, 115, 15752–15757. Sivaraman, S. K.; Kumar, S.; Santhanam, V. Monodisperse sub-10 nm gold nanoparticles by reversing the order of addition in Turkevich method - The role of chloroauric acid. J. Colloid Interface Sci. 2011, 361, 543–547. Uppal, M. A.; Kafizas, A.; Ewing, M. B.; Parkin, I. P. The effect of initiation method on the size, monodispersity and shape of gold nanoparticles formed by the Turkevich method. New J. Chem. 2010, 34, 2906–2914. Uppal, M. A.; Kafizas, A.; Lim, T. H.; Parkin, I. P. The extended time evolution size decrease of gold nanoparticles formed by the Turkevich method. New J. Chem. 2010, 34, 1401–1407. Xia, H.; Bai, S.; Hartmann, J.; Wang, D. Synthesis of Monodisperse Quasi-Spherical Gold Nanoparticles in Water via Silver(I)-Assisted Citrate Reduction. Langmuir 2010, 26, 3585–3589. Zabetakis, K.; Ghann, W. E.; Kumar, S.; Daniel, M.-C. Effect of high gold salt concentrations on the size and polydispersity of gold nanoparticles prepared by an extended Turkevich-Frens method. Gold Bull. 2012, 45, 203–211. Turkevich, J.; Stevenson, P. C.; Hillier, J. The Formation of Colloidal Gold. J. Phys. Chem. 1953, 57, 670–673. Schulz, F.; Vossmeyer, T.; Bastús, N. G.; Weller, H. Effect of the Spacer Structure on the Stability of Gold Nanoparticles Functionalized with Monodentate Thiolated Poly(ethylene glycol) Ligands. Langmuir 2013, 29, 9897–9908. Haiss, W.; Thanh, N. T. K.; Aveyard, J.; Fernig, D. G. Determination of Size and Concentration of Gold Nanoparticles from UV-Vis Spectra. Anal. Chem. 2007, 79, 4215–4221. Pazos-Perez, N.; Abajo, F. J. Garcia de; Fery, A.; AlvarezPuebla, R. A. From Nano to Micro: Synthesis and Optical Properties of Homogeneous Spheroidal Gold Particles and Their Superlattices. Langmuir 2012, 28, 8909–8914. Sun, S.; Murray, C. B.; Weller, D.; Folks, L.; Moser, A. Monodisperse FePt Nanoparticles and Ferromagnetic FePt Nanocrystal Superlattices. Science 2000, 287, 1989–1992. Grzelczak, M.; Pérez-Juste, J.; Mulvaney, P.; Liz-Marzán, L. M. Shape control in gold nanoparticle synthesis. Chem. Soc. Rev. 2008, 37, 1783–1791. Park, J.-W.; Shumaker-Parry, J. S. Structural Study of Citrate Layers on Gold Nanoparticles: Role of Intermolecular Interactions in Stabilizing Nanoparticles. J. Am. Chem. Soc. 2014, 136, 1907–1921. Zhang, L.; Xia, Y. Scaling up the Production of Colloidal Nanocrystals: Should We Increase or Decrease the Reaction Volume? Adv. Mater. 2014, 26, 2600–2606. Bastus, N. G.; Comenge, J.; Puntes, V. Kinetically Controlled Seeded Growth Synthesis of Citrate-Stabilized Gold Nanoparticles of up to 200 nm: Size Focusing versus Ostwald Ripening. Langmuir 2011, 27, 11098–11105. Ziegler, C.; Eychmüller, A. Seeded Growth Synthesis of Uniform Gold Nanoparticles with Diameters of 15-300 nm. J. Phys. Chem. C 2011, 115, 4502–4506.

ACS Paragon Plus Environment

Page 7 of 12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

TOC-Figure

ACS Paragon Plus Environment

7

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

150x282mm (300 x 300 DPI)

ACS Paragon Plus Environment

Page 8 of 12

Page 9 of 12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

57x40mm (300 x 300 DPI)

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

71x50mm (300 x 300 DPI)

ACS Paragon Plus Environment

Page 10 of 12

Page 11 of 12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

75x115mm (300 x 300 DPI)

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

71x63mm (300 x 300 DPI)

ACS Paragon Plus Environment

Page 12 of 12