Dispersion of Gold

LETTER pubs.acs.org/Langmuir

Logical Regulations of the Aggregation/Dispersion of Gold Nanoparticles via Programmed Chemical Interactions Yulin Li, Xiaogang Han, and Zhaoxiang Deng* CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China

bS Supporting Information ABSTRACT: Nanoparticles that respond to various chemical and physical stimuli form the basis for various conceivable applications including sensors, chemical logic, biomedical imaging, and therapies. In this work, we demonstrate that the electrostatic and chemical (complexing and gold thiol bonding) interactions existing in a gold nanoparticle/Zn2+/dithiothreitol-based ternary chemical system is “programmable” and can be utilized to regulate the aggregation and dispersion of nanoparticles via XOR and INHIBIT logics. The resulting solutions alter their colors according to different input combinations because of the well-controlled aggregation or dispersion of plasmonic gold nanoparticles, opening up new possibilities for the developments of advanced sensors and nanobiomedical devices based on the coupling, gating, and signaling of different chemical stimuli.

1. INTRODUCTION Placing an efficient control on the aggregation and dispersion status of gold nanoparticles (AuNPs) is very important and valuable for a wide range of applications, including plasmonic chemical and biological assays,1 12 surface-enhanced Raman scattering,13 15 activity-tailorable catalysts,16,17 and, more interestingly, nanobiomedical devices capable of targeting and killing cancerous cells.18 Such smart nanosystems are able to self-adjust their physical or chemical behaviors in responding to certain external stimuli. To achieve such a goal, different strategies have been employed, including the use of special protective organic ligands19 21 and biomolecules such as functional DNA.22,23 Yan22 and Liu et al.23 employed either an intact or split DNA i-motif to achieve the pH-tuned aggregation of AuNPs. We have previously reported the use of ethylenediamine as a pH-sensitive electrostatic bridge to regulate the aggregation and dispersion of AuNPs.24 Interestingly, the pH-based control of the aggregation and dispersion of AuNPs has recently been automated by the use of a chemical oscillator,25 which induces alternating pH fluctuations between acidic and basic conditions in a solution. Despite the existence of various systems that have been curiously pursued to fine tune the aggregation and dispersion behaviors of AuNPs, most of these methods use a single stimulus to trigger the state conversions. Developing a nanosystem that reacts to multiple inputs in a combinatorial way is, however, very much desired, which is appealing for advanced sensing and nanobiomedical applications on the basis of the coupling, gating, and signaling of specific chemical and physical stimuli. To construct a functioning system with predictable responses to multiplexed chemical inputs (such as a logic system), it is rational to consider the use of supramolecular and biological r 2011 American Chemical Society

interactions such as programmable DNA base pairings.26 31 Willner29 and Stojanovic et al.27 have demonstrated that functional nucleic acids and their reengineered counterparts are especially powerful for the realization of sophisticated molecular logic. Mao32 and LaBean et al.33 have demonstrated that the interparticle distances of AuNPs could be reliably tuned by bistable DNA complexes. These findings point to the same fact that biomolecules such as DNA seem to be the most suitable choice in placing a rational control on the aggregation behavior of AuNPs.30 Advancements along the line of using sophisticated interactions toward the fine control of nanoparticle assembly reveal the fact that it is essentially very challenging to realize multistimulusbased logical regulations of nanoparticles via readily available small molecular and ionic interactions.21 To address this challenge, we demonstrate the use of extremely simple and commonly existing complexing and ionic bondings for the facile logical regulation of the aggregation and dispersion of AuNPs. This research results in a novel class of smart nanoparticle systems with foreseeable applications in sensing, catalysis, and nanomedical devices upon further elaboration and development.

2. EXPERIMENTAL DETAILS Negatively Charged AuNPs. Gold nanoparticles (AuNPs) with a diameter of 6 nm (based on TEM image analysis) were synthesized by a citrate tannic acid method following published procedures.34,35 Ligand exchange with bis(p-sulfonatophenyl)phenylphosphine Received: May 2, 2011 Revised: July 6, 2011 Published: July 18, 2011 9666

dx.doi.org/10.1021/la201617p | Langmuir 2011, 27, 9666–9670

Langmuir dihydrate dipotassium salt (Strem Chemicals, Newbutyport, MA) was performed to increase the stability of as-synthesized gold nanoparticles.36 38 The resulting AuNPs were negatively charged.24,36 38 Inputs 1 and 2 (50 μL Each). ZnCl2 was dissolved in an ethylenediamine (en) solution with a molar ratio of 1:2 between Zn2+ and en to obtain a [Zn(en)2]Cl2 complex. The input 1 solution contained 2.4 mM [Zn(en)2]Cl2 in 10 mM Tris HCl buffer. Input 2 solution was composed of 4.0 mM DTT (DL-dithiothreitol, Sigma-Aldrich), 0.3 M NaCl, and 10 mM Tris HCl. The input solutions would be diluted 4-fold after being added to 100 μL of an indicator solution. A 50 μL buffer solution was used when input 1 or 2 was “0”. Indicator Solutions (100 μL Each). An XOR indicator contained 134 nM of 6 nm AuNPs in a 10 mM Tris HCl buffer (pH 8.0). An INHIBIT indicator was composed of 134 nM AuNPs, 0.1 M NaCl, and 10 mM Tris HCl. The indicator solutions would be diluted 2-fold in the final 200 μL samples (100 μL indicator, 50 μL for each of two inputs). TEM and Spectroscopic Characterization. Transmission electron microscopy (TEM) imaging was conducted on a JEM2100F field emission transmission electron microscope at an acceleration voltage of 200 kV. Samples were prepared on carboncoated copper grids. Visible absorbance data were collected on a UV757CRT UV vis spectrophotometer (Shanghai Precision Scientific Instrument Co., Ltd., China). In the case of the absorbance measurements, 3.0 mM [Zn(en)2]Cl2 was used for the input 1 solution, which further increased the spectral differences between the “0” and “1” states.

3. RESULTS AND DISCUSSION Figure 1 illustrates the basic mechanism of our strategy. In brief, we took advantage of the electrostatic bridging action of a divalent cation along with a dithiol molecule to induce the crosslinking of AuNPs and thus achieved two mutually related logical controls (i.e., XOR and INHIBIT).39,40 Interestingly, these two logical operations could be executed in a combined way similar to the function of a half-subtractor, thanks to the sharing of exactly the same “inputs” between the two systems (Figure 2a). The results of such regulations could be easily visualized on the basis of the color change of the AuNP solutions from red to purple-blue, which was associated with the size-dependent surface plasmon absorbance of the gold nanoparticle aggregates.24,41 The functioning of our system was a result of highly tunable and strongly associated metal ligand bondings and ionic interactions, which broadly exist among small molecules, ions, and colloidal particles. One attractive advantage of our strategy was that it required neither synthetic efforts toward special multiresponsive supramolecules nor the involvement of elegantly designed and engineered biomolecular conjugates in order to realize such controls. In the case of an XOR control, the core part of the logic was the mutual cancellation between two 1 inputs to produce an output of 0. Divalent cations and dithiol molecules caused Au nanoparticles (AuNPs) to aggregate because of electrostatic and gold thiol bonding interactions.24,42,43 However, the coexistence of Zn2+ (input 1) and DTT (input 2) led to the formation of a very stable complex44 46 between Zn2+ and DTT accompanied by the release of protons into the solution (Figure 1), which reduced the positive charge on Zn2+ and suppressed the gold affinity of the thiol groups simultaneously. Consequently, the cross-linking

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Figure 1. Mechanisms of XOR and INHIBIT regulation of the aggregation and dispersion of gold nanoparticles based on strongly coupled chemical bonding and ionic interactions. Note that both of the XOR and the INHIBIT schemes share exactly the same chemical inputs, which is critical to integrating them further into higher-order logic such as a half subtractor (Figure 2).

Figure 2. Experimental realization of the XOR- and INHIBIT-regulated aggregation/dispersion of 6 nm gold nanoparticles, which together were best exemplified as a half subtractor. (a) Schematic drawing and input/output truth table for a half subtractor. (b) Operation of the half subtractor in microtubes. An output of “1” corresponds to the color change (aggregation) of a gold nanoparticle solution from red to purpleblue. The discrimination between outputs “0” and “1” was very sharp and could be easily judged by the naked eye. Inputs 1 and 2 corresponded to Zn2+ ([Zn(en)2]2+) and DTT, respectively. All experiments were carried out at room temperature.

abilities of the two inputs were canceled by each other, leading to XOR logic. We previously investigated the electrostatic interplay between monovalent and divalent cations in determining the aggregation 9667

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Figure 3. Absorbance spectra of XOR- and INHIBIT-regulated gold nanoparticle solutions (upper panels) and corresponding absorbance ratio (A650 nm/A520 nm) plots (lower panels) characteristic of digitized readouts (0 and 1). A threshold of A650 nm/A520 nm = 0.4 can be chosen for the definitions of 0 and 1 outputs. All of the spectra were normalized at a wavelength of 520 nm for easy comparison.

Figure 4. Typical TEM images corresponding to (a) XOR- and (b) INHIBIT- regulated (refer to Figure 2) aggregation and dispersion of 6 nm gold nanoparticles.

behavior of AuNPs.24 Here, such an interesting phenomenon could be used to help the realization of an INHIBIT logic control. Upon addition of a suitable amount of NaCl to the AuNP indicator solution, XOR logic could be turned into INHIBIT. The existence of NaCl shielded24 (by displacing Zn2+ from the surfaces of AuNPs with Na+ and by counteracting the positive charge of Zn2+ with a relatively large amount of Cl ) the action of Zn2+ as an electrostatic salt bridge during the aggregation of AuNPs (Figure S1), with the gold thiol bonding unaffected. Accordingly, only the Zn2+ input of the XOR gate was inhibited, consistent with INHIBIT logic.

During actual operations, Zn2+ was replaced by [Zn(en)2]2+ (where en represents ethylenediamine) to achieve better stability against hydrolysis at the working pH. Free ethylenediamine molecules would not affect the system at pH 8.0, as shown in our previous publication24 and Figure S5. The complexing ability of en with respect to Zn2+ is much weaker than that of DTT44 46 such that its existence did not interfere with the XOR logic. In addition, the input of DTT was always accompanied by a suitable amount of Na+ to achieve a faster aggregation by reducing the electrostatic repulsions between the negatively charged 6 nm AuNPs (Figures S2 and S3).24 Figure 2 clearly verified the correct 9668


Langmuir functioning of the XOR and INHIBIT regulations. It is noteworthy that all of the results came up in minutes, revealing the fast, sharp response of the system. It is easily seen (Figure 2) that for XOR regulation either the Zn2+ or the DTT input effectively triggered the aggregation of AuNPs according to the scheme described in Figure 1, whereas their coexistence did not result in any color change of the AuNP solution. For INHIBIT logic, the presence of NaCl in the indicator solution successfully suppressed the Zn2+-induced aggregation of AuNPs.24 In the above experiments, the color transitions of gold nanoparticles from red to purple-blue were especially suitable for sensitive judgment by the human eye without the need for any aid from sophisticated instruments. Besides the naked-eye-based signal readout strategy, a more quantitative logic output is pivotal to the standardization of a chemical logic system. To fulfill such a goal, visible absorbance spectra of the gold nanoparticle solutions were obtained, as shown in Figure 3, and exhibited distinctively different spectral “signatures” for the solutions representing the 0 and 1 states. As shown in Figure 3, the absorbance ratios at wavelengths of 650 and 520 nm (i.e., A650 nm/A520 nm) clearly distinguished between the 0 and 1 outputs of the corresponding solutions, consistent with the visual observations. TEM analysis provided complementary evidence for the functioning of the two regulations. As shown in Figure 4, the aggregation and dispersion of AuNPs in the two logic systems were responsive to the different combinations of the two chemical inputs. The TEM data further supporting the color change of the plasmonic gold nanoparticle solutions was a result of forming tightly aggregated nanoparticles, which, along with the spectral characterizations of the nanoparticles, strongly supported the mechanism of our strategy as depicted in Figure 1. The idea of developing a logically controllable nanosystem could be borrowed for the design of novel chemical or biological sensors with enhanced performance. Also, such a concept might be further extended to develop the next generation of nanomedical devices responding to multiple input chemicals possibly existing around a cancerous cell. Different from simple ON/OFF (two state) regulations mostly controlled by a single chemical stimulus, the involvement of multiple inputs manifested the regulation power of our strategy with 2n (n = 2 in the present case) input combinations. This could promise a conceptually interesting chemical sensing platform with increased throughput and enhanced specificity based on the mutual interactions between different chemical analytes through a logic system, benefiting from the existence of a wide range of optional chemical as well as nonchemical interactions. Another appealing feature of the above logic controls (XOR and INHIBIT) was that they shared exactly the same inputs, which made it possible to execute these logic gates in parallel toward a half subtractor (Figure 2) to mimic arithmetic calculations on a binary digit. A half-subtractor performs binary subtraction between two one-bit binary numbers including a minuend and a subtrahend. It generates two outputs, one corresponding to the arithmetic “difference” between the two inputs and the other indicating the happening of a “borrowing” operation (a borrowing output of 1 will be produced in the case where the minuend is smaller than the subtrahend). Figure 2a provides the logic circuit as well as the truth table for a half-subtractor. Although conventional chemical logic is mostly based on molecular systems, the logical regulation of the gold nanoparticles enabled the realization of a half-subtractor with a colloidal system, which should be a

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significant expansion of traditional colloidal science. In this regard, a further exploration of novel colloidal systems for the development of functioning high-order chemical logics under the standards of simplicity, convenience, and low-cost deserves to be pursued in the future. Our work represents a successful example where extremely simple and commonly existing molecular and ionic interactions are successfully utilized to build relatively complicated logic regulation systems with minimal synthesis effort for the logic units. Such an advantage will be especially helpful for a wide adaptation of our scheme to many other situations toward various chemical and nanotechnological applications. Exerting fine control over the aggregation states of colloidal particles by multiple logically combined chemical stimuli has demonstrated an interesting concept of building functional hybrid molecular nanosystems between small molecules/ions and colloidal particles, which definitely deserves further pursuit. Besides Zn2+, Cu2+ could also be used to realize similar regulations (Figure S6). Other divalent or trivalent metal ions, including but not limited to Cd2+, Ni2+, and Pb2+, which form similar complexes with DTT,46 deserve to be researched in the future.

4. CONCLUSIONS We have successfully demonstrated that a gold nanoparticle/ Zn2+/dithiothreitol-based ternary chemical system can be programmed to regulate the aggregation and dispersion behavior of gold nanoparticles via XOR or INHIBIT logic. Apart from previously explored strategies, our system can respond to multiple inputs in a combinatorial way, which is appealing for advanced sensing and nanobiomedical applications. Our research represents a unique example of tunable nanoparticle assembly via rationally programmed chemical interactions broadly existent among small molecules, ions, and colloidal particles. Future research can be envisioned to incorporate a wealth of other chemical or nonchemical interactions, including hydrogen bonding, charge transfer, host guest inclusion, and magnetic interactions to enrich the library of regulatory mechanisms for nanoparticles. The resulting platform can then be further investigated to build smart molecular/nanosystems, which may find important applications in chemical logic, nanosensors, bioimaging, anticancer drug delivery, and targeted photothermal or photodynamic therapy. ’ ASSOCIATED CONTENT

bS

Supporting Information. Extra supporting experiments. This material is available free of charge via the Internet at http:// pubs.acs.org.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected].

’ ACKNOWLEDGMENT This work was supported by the NSFC (grant nos. 20873134 and 91023005), CAS Bairen professorship support, and Fundamental Research Funds for the Central Universities (grant WK2060190007). Prof. H. Yu and Mr. R. Lu are acknowledged for providing us with some experimental materials during our preliminary research. 9669


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Dispersion of Gold

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