Synthesis of Gold Nanoparticles from Au(I) - ACS Publications

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Synthesis of Gold Nanoparticles from Au(I) Ions That Shuttle To Solidify: Application on the Sensor Array Design Yumin Leng,*,†,‡ Kai Jiang,‡ Wentai Zhang,† and Yuhui Wang‡ †

College of Physics and Electronic Engineering, Nanyang Normal University, Nanyang 473061, China Ningbo Institute of Materials Technology & Engineering (NIMTE), Chinese Academy of Sciences, Ningbo 315201, China

‡

S Supporting Information *

ABSTRACT: Metal-mediated interlocking rings won the 2016 Nobel Prize in Chemistry. The metal-directed interlocking rings in macromolecular systems (e.g., proteins) may be similar to the form of Maxwell’s electromagnetic waves; the metal ions may shuttle among the rings in the special environment. To verify this hypothesis, we designed a general approach to synthesize the multicolored gold nanoparticles (GNPs) mediated by Au(I)directed interlocking rings in proteins. The Au(I) ions shuttled among these interlocking rings in the strong alkaline solution. Through the rapid nucleation method, the multicolored GNPs of different morphology and sizes were synthesized in the multiple honeycombed templates. On the basis of the “three-color” principle of Thomas Young, we extracted the red, green, and blue (RGB) alterations of GNPs to fabricate a visual sensor array for protein discrimination. The fingerprints (ΔRGB) were obtained from the target proteins and fed into computer programs. The proposed sensing platform was also applied to detect lysozyme in human tears with satisfactory results. Importantly, we forecasted that lysozyme could be the effective drug for curing dacryocystitis and nasolacrimal duct obstruction diseases.

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molecular shuttle principle,6 the metal ions may shuttle among the rings under the special environment (e.g., strong alkaline solution). To verify this hypothesis, we designed a general approach to synthesize the multicolored gold nanoparticles (GNPs) mediated by Au(I)-directed interlocking rings in proteins. Actually, the Au(I) ions shuttled among the interlocking rings in the strong alkaline solution. Through microwave boiling of the solution, the multicolored GNPs of different morphology, size, and distribution were synthesized in the honeycombed templates. The facile strategy from Au(I) ions that shuttled to solidify to be GNPs with various colors should enable new approaches to color modulation, nanomaterial engineering, and sensing. Owing to the optical characters, GNPs are the natural and promising candidates for visual sensor arrays and have been exploited for a wide detection of heavy metal ions, organic molecules, proteins, and so on.7−12 Recently, GNP-based multichannel sensing devices have been constructed for the pattern recognition analysis of macromolecules (especially proteins).13−18 For example, Rotello et al. developed a series of multichannel sensor arrays for the recognition and analysis of macromolecules (including proteins) based on the fluorescent polymer or protein-modified GNPs.13,14,18 Liu et al. reported a

INTRODUCTION

Professors Sauvage and Stoddart, the winners of the 2016 Nobel Prize in Chemistry, synthesized a series of catenates mediated by metal ions.1−4 For example, the dimetallic catenates were prepared through Cu(I)-template-assisted synthesis.1 Sauvage et al. forecasted that the metal-mediated interlocking rings could, in principle, be extended to polymers4 and that the macromolecular systems incorporating interlocking rings would lead to interesting systems.5 The metaldirected interlocking rings in the macromolecular systems (e.g., proteins) may be similar to the form of Maxwell’s electromagnetic waves, as illustrated in Scheme 1. Inspected by the Scheme 1. Metal-Directed Interlocking Rings in Macromolecular Systems (e.g., Proteins) May be Similar to the Form of Maxwell’s Electromagnetic Waves

Received: April 4, 2017 Revised: May 23, 2017 Published: June 5, 2017 © 2017 American Chemical Society

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DOI: 10.1021/acs.langmuir.7b01150 Langmuir 2017, 33, 6398−6403

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Synthesis of GNPs from Au(I) Ions That Shuttle To Solidify. Inspected by the molecular shuttle principle,6 the metal ions may shuttle among the rings under the special environment (e.g., strong alkaline solution). To demonstrate this hypothesis, we designed an experiment to synthesize the multicolored GNPs that might be produced in the honeycombed templates achieved from Au(I) ions that shuttle to solidify. To prompt the shuttling of Au(I) ions, the synthesized Au(I)−Pep/Try complexes are mixed with other proteins; the Au(I) ions shuttled from Pep/Try to other proteins (see Figure 1). The multiple interlocking rings were formed through Au(I)directed ions (see Figure 1). The strong interactions between the Au(I) ions and the functional groups of proteins (e.g., −NH and −CO) help the Au(I) ions in the rings to be the cores that could be deposited by the free Au(I) ions. Through the rapid nucleation method, the Au(I) ions were reduced by the reductive proteins to be GNPs8 that were synthesized in the honeycombed templates [see transmission electron microscopy (TEM) images in Figures 2 and S3] and show different colors (see Figure 3).

multichannel sensing array for pattern recognition of proteins based on the DNA-sequence-modified GNPs (DNA−GNPs).17 These efforts have made great progress on the development of GNP-based sensing arrays for protein recognition. However, in these GNP-based colorimetric assays, surface modifications are indispensable, which greatly limit their further applications. In our experiment, the synthesis process of multicolored GNPs obviously avoids complicated surface modification. Therefore, we are interested to design a multichannel sensor array for protein discrimination based on the “three-color” principle of Thomas Young, that is, “all colors are mixed by red (R), green (G), and blue (B) in different proportions.” The red, green, and blue (RGB) data were extracted from multicolored GNPs, which correspond to a certain protein, and were further fed into the Multi-Variate Statistical Package (MVSP) computing software.19 Then, the proteins were quantitatively distinguished by using the statistical methods [e.g., hierarchical clustering analysis (HCA) and principal component analysis (PCA)].20,21 Owing to the real application, the proposed sensor array is successfully applied to monitor the level of lysozyme (Lys) in human tears.

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RESULTS AND DISCUSSION Preparation of Au(I)-Directed Interlocking Rings in Protein. As shown in Figure 1, the preparation of Au(I)-

Figure 2. TEM images at different magnifications of typical GNPs distributed in the honeycombed templates. Insets: Interplanar distances of GNPs determined by using the ImageJ software.

The protein templates might be similar to the honeycombed substrates.25,26 The circular protein template was proved by the distribution of the as-synthesized GNPs (see TEM images in Figure 2). The diverse colors of GNPs are attributed to the different sizes and shapes of GNPs synthesized in the multiple

Figure 1. Schematic illustration of the preparation of Au(I)-directed interlocking rings in proteins and the synthesis of GNPs from Au(I) ions that shuttle to solidify. The proteins (e.g., Pep and Try) and Au(III) are first incubated in a strong alkaline solution to generate the Au(I)−protein [e.g., Au(I)−Pep and Au(I)−Try] complex. Addition of the other proteins prompts Au(I) anions to shuttle from Pep/Try to other proteins. The interlocked rings of Au(I)−Pep/Try−protein are subjected to the microwave reaction to synthesize GNPs that are produced in the honeycombed templates.

directed interlocking rings involves the incubation of the protein [e.g., pepsin (Pep) or trypsin (Try)] with Au(III) (e.g., [AuCl4]−) in a strong alkaline solution (see methods)22 to produce the colorless solution. As shown in Figure S1, the maximum absorption wavelength (i.e., 246 nm) of the colorless solution agrees well with that of Au(I) anions (e.g., [AuCl2]−).23,24 The Au(III) complexes are reduced by the protein to be the aqueous Au(I) anions in the alkaline solution.22 According to the principle developed by Professors Sauvage and Stoddart,1−5 the Au(I) ions mediate the amino acid residues present in the protein to be interlocked rings, as shown in Figures 1 and S2. The multiple covalent bonds of Au−O and Au−N are formed between the Au(I) ions and the functional groups of proteins (see Figure S2).

Figure 3. Multicolor GNPs synthesized from Au(I) ions that shuttle to solidify. The Au(I) ions shuttle from (a) Au(I)−Pep (or (b) Au(I)− Try) to other proteins and are reduced by proteins to be multicolored GNPs through microwave boiling. The different sizes and shapes of GNPs are solidified in the multiple honeycombed templates. Note: the tested proteins (40 μg/mL) are BHb, Cat, Glu, Try, bovine albumin (BA), Lys, bovine serum albumin (BSA), collagen (Col), and Pep. 6399

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Langmuir honeycombed templates (see Figures 1, 2, and S3). As shown in the TEM images of GNPs synthesized from Au(I)−Pep in the presence of proteins [e.g., glucoamylase (Glu), bovine hemoglobin (BHb), catalase (Cat), and Try], the sizes of GNPs decrease on the order of 4.8 ± 1.1 nm for GNP−Pep−Glu, 4.6 ± 0.59 nm for GNP−Pep−BHb, 2.7 ± 0.53 nm for GNP− Pep−Cat, and 2.5 ± 0.46 nm for GNP−Pep−Try. The sizes of the as-synthesized GNPs are slightly bigger than that of gold nanoclusters.27−29 The small-sized GNPs of different colors have some advantages in biomedical applications (e.g., drug delivery). The characterization of ultraviolet−visible (UV−vis) absorption spectra was performed to reveal the reason for GNPs exhibiting multicolors. The UV−vis absorption spectra of GNPs are found to be characteristic (see Figure S4). Moreover, the functional groups (e.g., −SH and −NH2) induce proteins to interact with GNPs via Au−S and Au−N interactions; their stretching vibrational modes appear in the region of 250 ± 30 cm−1 (see Figure S5), which are in good agreement with the reported data.30,31 The GNPs are also investigated by using high-resolution TEM (HRTEM), as shown in the insets of Figures 2 and S3. The HRTEM images illustrate clear lattice fringes separated by 0.20 nm, which can be assigned to the interplanar distance of the (200) plane of GNPs with a face-centered cubic structure.32 The strategy to synthesize GNPs is expected to prepare the other noble metal nanoparticles (e.g., platinum, silver, and alloy nanoparticles). Construction of Visual Sensor Arrays for Protein Discrimination. The excellent optical properties of the asprepared GNPs show us that they are the perfect and prospective candidates for visual-sensing applications. Considering that the content of proteins in human body fluids is the most sensitive indicator for early diagnosis of specific diseases,33−37 we are interested in building a portable and a low-cost multichannel sensing device to identify protein balances in human body fluids (e.g., tears). We are also interested to design a multichannel sensor array based on the “three-color” principle of Thomas Young. We extracted the RGB data of the synthesized GNPs, which correspond to a certain protein, and further fed them into the MVSP computing software, which then quantitatively differentiated the proteins by using the statistical methods (e.g., HCA and PCA).19−21 For qualitative comparisons of the color responses of the Au(I)−Pep/Try complexes (as indicators) to the target proteins at a much lower concentration (0.4 μg/mL), a scanner is applied to record digital photographs. As shown in Figure 4, from the color images of the as-developed indicators in the absence (named “before”) and presence (named “after”) of proteins after microwave reaction, the obvious color differences are observed, which correspond to the specific target proteins. The visual sensor arrays seem to be successful at differentiating the target proteins (0.4 μg/mL), as shown in the difference maps, which are obtained by taking the RGB variations from the “before” and “after” images. The unique pattern of difference maps corresponds to a certain protein (see Figure 4). The observations demonstrate that the Au(I)−Pep/Try complexes can potentially determine the target proteins (0.4 μg/mL) by constructing the multichannel visual-sensing array. Quadruplicate data were obtained to evaluate the repeatability of the multichannel visual sensor array to detect the target proteins. As shown in Figure 5, the fingerprints (ΔRGB variations) of nine selected proteins are distinct, suggesting the feasibility of protein identification using the constructed sensor array. The RGB variations of the as-developed indicators in the

Figure 4. Construction of visual sensor array for the discrimination of proteins (0.4 μg/mL). Digital photographs of the Au(I)−Pep and Au(I)−Try complexes in the absence (named “before”) and presence (named “after”) of proteins after microwave reaction. For visualization, the color ranges of these difference maps are expanded from 4 to 8 bits per color (RGB range 4−19 expanded to 0−255).

Figure 5. Fingerprints of nine selected proteins based on the patterns of the ΔR1G1B1 and ΔR2G2B2 values obtained from the Au(I)−Pep/ Try complexes in the presence of the target proteins (0.4 μg/mL) after microwave reaction. All experiments were run in quadruple trials.

absence and presence of nine proteins after microwave reaction are listed in Table S1. The color alterations in the response of most proteins to the Au(I)−Pep complex (ΔR1G1B1) are positive, whereas those alterations to the Au(I)−Try complex (ΔR2G2B2) are negative (see Figure 5 and Table S1). To expose the ΔRGB alterations more clearly, the three-channel response patterns are also explored by PCA, which is a statistical treatment used to reduce multichannel data for easier interpretation.20 The canonical colorimetric response patterns (6 channels × 9 proteins × 4 replicates) are clustered into several groups (see Figure 6a). The resulting 2D canonical score plot (Figure 6a) shows clear clustering of the data using the first two principal components (representing 90.8% of the total variance), with excellent discriminatory capacity. The PCA plots for various proteins are not random but rather follow certain patterns. As shown in Figure 6a, all target proteins (0.4 μg/mL) are separated from each other, demonstrating that they are effectively discriminated by PCA based on the values of both ΔR1G1B1 and ΔR2G2B2. The as-developed indicators in the presence of the nine proteins at 0.4 μg/mL were also 6400

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Figure 6. (a) PCA plot and (b) HCA analysis for the discrimination of proteins at 0.4 μg/mL based on the ΔR1G1B1 and ΔR2G2B2 variations. All experiments were run in quadruple trials.

Figure 7. Constructed visual-sensing array for the detection of Lys in human tears. (a) Images of the Au(I)−Pep/Try complexes before and after exposure to concentrations of Lys in water and human tears after microwave reaction and the color difference maps (RGB range of 4−19 expanded to a range of 0−255). (b) The total EDs vs concentrations of Lys spiked in water. Note: the calculation method for the content of Lys in human tears: YED of tear = 38.77 ± 0.89 = 31.56 + 0.89 × X → X = 8.1 ± 1.0 μg/mL → the content of Lys in human tears = (8.1 ± 1.0) μg/mL × 100 = 0.81 ± 0.10 mg/mL. Note: the human tear is diluted 100 times by the analytical process.

analyzed using HCA, which is a model-free method based on the grouping of the analyte vectors according to their spatial distances (i.e., Euclidean distances) in their full vector space.19,21 All of the 36 cases (9 samples × 4 replicates) are correctly assigned to their respective groups (Figure 6b). It is noteworthy that the as-developed multichannel sensor array can differentiate the target proteins at 0.4 μg/mL, which is quite lower than the discrimination concentrations at 300 μg/ mL and 2 mg/mL acquired by other sensor arrays.9,15 Discrimination of Lys in Human Tears. Considering that the level of Lys in human tears is directly related to the diseases of dacryocystitis and nasolacrimal duct obstruction,33−36 we are interested in testing the performance of the constructed visualsensing device to identify the Lys content in human tears. As shown in Figure 7a, comparing the color responses of the Au(I)−Pep/Try complex to the concentrations of Lys spiked in pure water, the content of Lys in human tears are in the range of 0.7−1.0 mg/mL. The excellent linear relationship between the Euclidean distances (EDs = [ΔR2 + ΔG2 + ΔB2]1/2) and the concentrations of Lys spiked in pure water is shown in Figure 7b. On the basis of the linear relationship and the ED data obtained from human tears, we calculate that the content of Lys in human tears is 0.81 ± 0.10 mg/mL. We compare the result with a laboratory grade standard of UV−vis spectrophotometer, which determines the content of Lys in human tears to be 0.83 ± 0.13 mg/mL (see Table 1 and Figure S6). As listed in Table 1, the obtained data by the as-developed sensing platform are in good agreement with the measured data obtained using UV−vis spectrophotometer and the reported value range,38

Table 1. Determination of Lys in Human Tears by Using the As-Developed Visual-Sensing Platform [Lys] (mg/mL) founda sample

naked eye

sensor array

UV−vis

ref 38

human tear

0.7−1.0

0.89 ± 0.11

0.83 ± 0.13

0.72−1.10

a

Mean ± standard deviation, n = 3.

which strongly prove the high reliability of our designed visual sensor array. Interestingly, it is reported that there was a linear decline of Lys with age,38 forecasting that Lys could be the effective drug for curing the diseases of dacryocystitis and nasolacrimal duct obstruction.

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CONCLUSIONS In summary, we report a conceptually new strategy to synthesize the multicolored GNPs mediated by Au(I)-directed interlocking rings in proteins. The Au(I) ions shuttled among the interlocking rings in the strong alkaline solution. The Au(I)-directed interlocking rings in proteins may be similar to the form of Maxwell’s electromagnetic waves. The GNPs were prepared from Au(I) ions that shuttled to solidify through microwave boiling. The strategy is expected to synthesize the other noble metal nanoparticles (e.g., platinum, silver, and alloy nanoparticles). Moreover, the facile strategy to prepare multicolored GNPs should enable new approaches to nanomaterial engineering, color modulation, and sensing. 6401

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replicates) training matrix. The training matrix was processed using the MVSP, HCA, and PCA.19−21 Lys Detection in Human Tears. The content of Lys in human tears was taken to tentatively test the feasibility of the as-developed sensing array for biomedical diagnostics. To test the unknown content of Lys in human tears, Lys at various concentrations spiked in pure water was prepared at first. Human tears (20 μL) and concentrations of Lys were added to 2 mL of the Au(I)−Pep/Try solution. The mixture was subjected to microwave treatment at 300 W for 90 s, and the multicolored GNPs were synthesized. The color corresponding to human tears was compared with those of the standard Lys samples. The color changes of the sensor array were quantitatively illustrated by the total EDs [ED = (ΔR2 + ΔG2 + ΔB2)1/2]. According to the linear relationship between the EDs and the concentrations of Lys, we obtained the content of Lys in human tears. All experiments were performed in accordance with the guidelines and regulations of Zhenhai Hospital Ethics Committee. Ethics Statement. All experiments and procedures were performed in accordance with the appropriate guidelines. All procedures were approved by Nanyang Normal University and Ningbo Institute of Materials Technology & Engineering (NIMTE). Informed consent was obtained from all volunteers before being enrolled in the study.

The as-proposed multichannel visual-sensing method based on the “three-color” principle of Thomas Young shows the rapid, sensitive, and efficient differentiation analysis of proteins. Compared with the reported sensing arrays, the as-designed visual-sensing array presents the unprecedented advantages. First, the detection does not require complicated modification and expensive instrumentation, which increases the operability and reduces the cost potentially improving the standard of living in resource-constrained areas. Second, the developed sensor array provides a new way to detect the proteins contained in the complex matrix (e.g., blood, urine, and milk), showing a great promise for biomedical diagnostics and milk safety in the future. Significantly, we forecast that Lys would be the effective drug for curing dacryocystitis and nasolacrimal duct obstruction diseases. The calculation to prove the Au(I)directed interlocking rings (see Figure 1) in proteins will be performed in future research.

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EXPERIMENTAL SECTION

Materials and Instruments. Pep, Try, BHb, BA, Lys, and chloroauric acid tetrahydrate (HAuCl4·4H2O) were purchased from Sinopharm Chemical Reagent Co., Ltd (Beijing, China). BSA was obtained from Gibco (Grand Island, USA). Cat, Col, and Glu were purchased from Aladdin Reagent Co. Ltd (Shanghai, China). The 96well plates (Corning 3632) were obtained from Genetimes Technology. For the fabrication of the visual-sensing array, the color images were recorded with a scanner in the 96-well polystyrene plates. The absorption spectra of GNPs were measured using a UV−vis spectrophotometer from PerkinElmer (Lambda 950). TEM samples were prepared on copper-supported carbon grids by depositing a drop of solution and allowing it to dry. TEM images were recorded with a Tecnai F20 instrument operating at an acceleration voltage of 200 kV. FTIR spectroscope images were recorded using a Nicolet 6700 spectrometer. Preparation of Au(I)-Directed Interlocking Rings in Proteins. The proteins (e.g., Pep and Try) and HAuCl4 were incubated at the alkaline pH to produce the colorless solution of Au(I) ions. Au(I) mediated Pep (or Try) to be the interlocking rings.1−5 The final concentrations of Au(I) and NaOH in the mixture are 0.5 mM and 0.5 M, respectively. The optimal concentrations of Pep and Try at 0.4 mg/ mL were used throughout the experiment. The colorless solution of Au(I)−Pep/Try complex was collected and stored at 4 °C for further use. Synthesis of Multicolored GNPs from Au(I) Ions That Shuttle To Solidify. To prompt the shuttling of Au(I) ions, BHb, Cat, Glu, Try, BA, Lys, BSA, Col, and Pep (20 μL, 4 mg/mL) were added to the colorless solution of the Au(I)−Pep/Try complex (2 mL), respectively. To solidify and reduce Au(I) ions, the mixture was subjected to microwave treatment at 300 W for 90 s. Thus, the multicolored GNPs were synthesized in the multiple honeycombed templates. Fabrication of Visual-Sensor Array for Protein Discrimination. Target protein (20 μL of 40 μg/mL) (BHb, Cat, Glu, Try, BA, Lys, BSA, Col, or Pep) was added to the colorless solution of the Au(I)−Pep/Try complex (2 mL). The mixture was subjected to microwave treatment at 300 W for 90 s. The Au(I) ions were reduced by proteins to be GNPs,8 and the multicolored GNPs were synthesized. To construct the visual-sensing array, the Au(I)−Pep/Try complexes in the absence (named “before”) and presence (named “after”) of proteins after microwave reaction were loaded into a 96well polystyrene plate. Later, the “before” and “after” images of GNPs were recorded using a scanner. Difference maps were obtained by extracting the color alterations (ΔRGB) from the “before” and “after” images using the Photoshop software. Four replicates were tested for each protein. The ΔRGB data (fingerprints, see Table S1) were used to generate the 2 × 9 × 4 (two indicators × nine proteins × four

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.langmuir.7b01150. UV−vis absorption spectra of the Au(I)-protein (e.g., Pep and Try) complexes, Au(I)-directed interlocking rings in proteins, TEM images at different magnifications of GNPs synthesized via microwave boiling of the mixture of Au(I)−Pep and BHb/Cat/Try, UV−vis absorption spectra of GNPs synthesized via microwave heating of the mixtures of Au(I)−Pep/Try and other proteins, FTIR spectrum of GNPs interacting with proteins, UV−vis spectrophotometer determination of the concentration of Lys contained in human tears, Database for proteins at 0.4 μg/mL refer to the RGB alterations of the Au(I)−Pep/Try complexes (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected], [email protected]. ORCID

Yumin Leng: 0000-0001-8408-8537 Author Contributions

Y.L. conceived the idea, performed the experiments, analyzed the data, and wrote the manuscript. K.J. characterized GNPs. W.Z. drew Scheme 1 and Figure 1. Y.W. analyzed the data and discussed the paper. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Natural Science Foundation of China (21607083), the Natural Science Foundation of Henan (162300410206), the Technicians Troop Construction Projects of Henan Province (no. C20150029), the Scientific and Technological Project of Henan Province (162102310484), the Natural Science Foundation of Ningbo (2016A610262), and the China Postdoctoral Science Foundation (2015M581970). Y.L. thanks Prof. Jane-Marie Lehn for the 6402

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(18) Rana, S.; Le, N. D. B.; Mout, R.; Duncan, B.; Elci, S. G.; Saha, K.; Rotello, V. M. A Multichannel Biosensor for Rapid Determination of Cell Surface Glycomic Signatures. ACS Cent. Sci. 2015, 1, 191−197. (19) Johnson, R. A.; Wichern, D. W. Applied Multivariate Statistical Analysis, 6th ed.; Hoag, C., Ed.; Prentice Hall: Upper Saddle River, NJ, 2007; Chapter 1, pp 1−47. (20) Jolliffe, I. T. Principal Component Analysis, 2nd ed.; SpringerVerlag: New York, 2002; Chapter 7, pp 150−166. (21) Haswell, S. J. Practical Guide to Chemometrics, 2nd ed.; Gemperline, P., Ed.; CRC Press: New York, 1992; Chapter 4, pp 453−467. (22) Chaudhari, K.; Xavier, P. L.; Pradeep, T. Understanding the Evolution of Luminescent Gold Quantum Clusters in Protein Templates. ACS Nano 2011, 5, 8816−8827. (23) Kunkely, H.; Vogler, A. Photooxidation of Dichloro- and Dibromoaurate(1-) Induced by ds Excitation. Inorg. Chem. 1992, 31, 4539−4541. (24) Weaver, S.; Taylor, D.; Gale, W.; Mills, G. Photoinitiated Reversible Formation of Small Gold Crystallites in Polymer Gels. Langmuir 1996, 12, 4618−4620. (25) Xiao, F.-X.; Zeng, Z.; Liu, B. Bridging the Gap: Electron Relay and Plasmonic Sensitization of Metal Nanocrystals for Metal Clusters. J. Am. Chem. Soc. 2015, 137, 10735−10744. (26) Xiao, F. An Efficient Layer-by-Layer Self-Assembly of MetalTiO2 Nanoring/Nanotube Heterostructures, M/T-NRNT (M = Au, Ag, Pt), for Versatile Catalytic Applications. Chem. Commun. 2012, 48, 6538−6540. (27) Fang, J.; Zhang, B.; Yao, Q.; Yang, Y.; Xie, J.; Yan, N. Recent Advances in the Synthesis and Catalytic Applications of Ligandprotected, Atomically Precise Metal Nanoclusters. Coord. Chem. Rev. 2016, 322, 1−29. (28) Song, X.-R.; Goswami, N.; Yang, H.-H.; Xie, J. Functionalization of Metal Nanoclusters for Biomedical Applications. Analyst 2016, 141, 3126−3140. (29) Xie, J.; Zheng, Y.; Ying, J. Y. Protein-Directed Synthesis of Highly Fluorescent Gold Nanoclusters. J. Am. Chem. Soc. 2009, 131, 888−889. (30) Leng, Y.; Zhang, F.; Zhang, Y.; Fu, X.; Weng, Y.; Chen, L.; Wu, A. A Rapid and Sensitive Colorimetric Assay Method for Co2+ Based on the Modified Au Nanoparticles (NPs): Understanding the Involved Interactions from Experiments and Simulations. Talanta 2012, 94, 271−277. (31) Bartram, M. E.; Koel, B. E. The Molecular Adsorption of NO2 and the Formation of N2O3 on Au(111). Surf. Sci. 1989, 213, 137− 156. (32) Yoshida, H.; Kuwauchi, Y.; Jinschek, J. R.; Sun, K.; Tanaka, S.; Kohyama, M.; Shimada, S.; Haruta, M.; Takeda, S. Visualizing Gas Molecules Interacting with Supported Nanoparticulate Catalysts at Reaction Conditions. Science 2012, 335, 317−319. (33) Hardy, J.; Selkoe, D. J. The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics. Science 2002, 297, 353−356. (34) Giljohann, D. A.; Mirkin, C. A. Drivers of Biodiagnostic Development. Nature 2009, 462, 461−464. (35) Lew, H.; Lee, S.-Y.; Yun, Y.-S. Measurement of pH, Electrolytes and Electrophoretic Studies of Tear Proteins in Tears of Patients with Dacryoliths: A Novel Concept for Dacryoliths. Ophthalmologica 2004, 218, 130−135. (36) Versura, P.; Nanni, P.; Bavelloni, A.; Blalock, W. L.; Piazzi, M.; Roda, A.; Campos, E. C. Tear Proteomics in Evaporative Dry Eye Disease. Eye 2010, 24, 1396−1402. (37) Houtkooper, R. H.; Mouchiroud, L.; Ryu, D.; Moullan, N.; Katsyuba, E.; Knott, G.; Williams, R. W.; Auwerx, J. Mitonuclear Protein Imbalance as a Conserved Longevity Mechanism. Nature 2013, 497, 451−457. (38) Mcgill, J. I.; Liakos, G. M.; Goulding, N.; Seal, D. V. Normal Tear Protein Profiles and Age-Related Changes. Br. J. Ophthalmol. 1984, 68, 316−320.

good suggestions on this paper. Y.L. also thanks Professors Hengwei Lin, Yujie Xiong, Xing Li, and Dr. Ling Zhang for their discussions and Dr. Muhammad Zubair Iqbal for checking the manuscript.

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REFERENCES

(1) Sauvage, J. P.; Weiss, J. Synthesis of biscopper(I) [3]-Catenates: Multiring Interlocked Coordinating Systems. J. Am. Chem. Soc. 1985, 107, 6108−6110. (2) Nierengarten, J. F.; Dietrich-Buchecker, C. O.; Sauvage, J. P. Synthesis of a Doubly Interlocked [2]-Catenane. J. Am. Chem. Soc. 1994, 116, 375−376. (3) Amabilino, D. B.; Dietrich-Buchecker, C. O.; Livoreil, A.; PérezGarcía, L.; Sauvage, J.-P.; Stoddart, J. F. A Switchable Hybrid [2]Catenane Based on Transition Metal Complexation and π-Electron Donor−Acceptor Interactions. J. Am. Chem. Soc. 1996, 118, 3905− 3913. (4) Livoreil, A.; Sauvage, J.-P.; Armaroli, N.; Balzani, V.; Flamigni, L.; Ventura, B. Electrochemically and Photochemically Driven Ring Motions in a Disymmetrical Copper[2]-Catenate. J. Am. Chem. Soc. 1997, 119, 12114−12124. (5) Weidmann, J.-L.; Kern, J.-M.; Sauvage, J.-P.; Geerts, Y.; Muscat, D.; Müllen, K. Poly[2]-catenanes Containing Alternating Topological and Covalent Bonds. Chem. Commun. 1996, 1243−1244. (6) Anelli, P. L.; Spencer, N.; Stoddart, J. F. A Molecular Shuttle. J. Am. Chem. Soc. 1991, 113, 5131−5133. (7) Zhang, J.; Zhang, C.-L.; Yu, S.-H. Tuning Gold Nanoparticle Aggregation through the Inhibition of Acid Phosphatase Bioactivity: A Plasmonic Sensor for Light-Up Visual Detection of Arsenate (AsV). ChemPlusChem 2016, 81, 1147−1151. (8) Leng, Y.; Fu, L.; Ye, L.; Li, B.; Xu, X.; Xing, X.; He, J.; Song, Y.; Leng, C.; Guo, Y.; Ji, X.; Lu, Z. Protein-Directed Synthesis of Highly Monodispersed, Spherical Gold Nanoparticles and their Applications in Multidimensional Sensing. Sci. Rep. 2016, 6, 28900. (9) Liu, H.; Ma, L.; Xu, S.; Hua, W.; Ouyang, J. Using Metal Nanoparticles as a Visual Sensor for the Discrimination of Proteins. J. Mater. Chem. B 2014, 2, 3531−3537. (10) Mao, J.; Lu, Y.; Chang, N.; Yang, J.; Zhang, S.; Liu, Y. Multidimensional Colorimetric Sensor Array for Discrimination of Proteins. Biosens. Bioelectron. 2016, 86, 56−61. (11) Leng, Y.; Li, Y.; Gong, A.; Shen, Z.; Chen, L.; Wu, A. Colorimetric Response of Dithizone Product and Hexadecyl Trimethyl Ammonium Bromide Modified Gold Nanoparticle Dispersion to 10 Types of Heavy Metal Ions: Understanding the Involved Molecules from Experiment to Simulation. Langmuir 2013, 29, 7591−7599. (12) Valentini, P.; Fiammengo, R.; Sabella, S.; Gariboldi, M.; Maiorano, G.; Cingolani, R.; Pompa, P. P. Gold-Nanoparticle-Based Colorimetric Discrimination of Cancer-Related Point Mutations with Picomolar Sensitivity. ACS Nano 2013, 7, 5530−5538. (13) You, C.-C.; Miranda, O. R.; Gider, B.; Ghosh, P. S.; Kim, I.-B.; Erdogan, B.; Krovi, S. A.; Bunz, U. H. F.; Rotello, V. M. Detection and Identification of Proteins Using Nanoparticle−Fluorescent Polymer “Chemical Nose” Sensors. Nat. Nanotechnol. 2007, 2, 318−323. (14) De, M.; Rana, S.; Akpinar, H.; Miranda, O. R.; Arvizo, R. R.; Bunz, U. H. F.; Rotello, V. M. Sensing of Proteins in Human Serum using Conjugates of Nanoparticles and Green Fluorescent Protein. Nat. Chem. 2009, 1, 461−465. (15) Xu, S.; Lu, X.; Yao, C.; Huang, F.; Jiang, H.; Hua, W.; Na, N.; Liu, H.; Ouyang, J. A Visual Sensor Array for Pattern Recognition Analysis of Proteins Using Novel Blue-Emitting Fluorescent Gold Nanoclusters. Anal. Chem. 2014, 86, 11634−11639. (16) Yuan, Z.; Du, Y.; Tseng, Y.-T.; Peng, M.; Cai, N.; He, Y.; Chang, H.-T.; Yeung, E. S. Fluorescent Gold Nanodots Based Sensor Array for Proteins Discrimination. Anal. Chem. 2015, 87, 4253−4259. (17) Sun, W.; Lu, Y.; Mao, J.; Chang, N.; Yang, J.; Liu, Y. Multidimensional Sensor for Pattern Recognition of Proteins Based on DNA−Gold Nanoparticles Conjugates. Anal. Chem. 2015, 87, 3354− 3359. 6403

DOI: 10.1021/acs.langmuir.7b01150 Langmuir 2017, 33, 6398−6403