Reversible Self-Assembly of Glutathione-Coated Gold Nanoparticle

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Reversible self-assembly of glutathione-coated gold nanoparticle clusters via pH-tunable interactions Ehsan Moaseri, Jonathan A Bollinger, Behzad Changalvaie, Lindsay Johnson, Joseph Schroer, Keith P. Johnston, and Thomas M. Truskett Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.7b02446 • Publication Date (Web): 06 Oct 2017 Downloaded from http://pubs.acs.org on October 9, 2017

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Reversible self-assembly of glutathione-coated gold nanoparticle clusters via pH-tunable interactions

Ehsan Moaseri†, Jonathan A. Bollinger†#, Behzad Changalvaie‡, Lindsay Johnson†, Joseph Schroer†, Keith P. Johnston†,‡, and Thomas M. Truskett†,§ †

McKetta Department of Chemical Engineering, ‡Texas Materials Institute, §Department of Physics; University of Texas at Austin, Austin, TX 78712, USA

#

Center for Integrated Nanotechnologies, Sandia National Laboratories, Albuquerque, NM 87185, USA

Abstract Nanoparticle (NP) clusters with diameters ranging from 20 to 100 nm are reversibly assembled from 5nm gold (Au) primary particles coated with glutathione (GSH) in aqueous solution as a function of pH in the range of 5.4 to 3.8. As the pH is lowered, the GSH surface ligands become partially zwitterionic and form interparticle hydrogen bonds that drive the self-limited assembly of metastable clusters in less than one minute. While clusters up to 20 nm in size are stable against cluster-cluster aggregation for up to one day, clusters up to 80 nm in size can be stabilized over this period via addition of citrate to the solution in equal molarity with GSH molecules. The cluster diameter may be cycled reversibly by tuning pH to manipulate the colloidal interactions; however, modest background cluster-cluster aggregation occurs during cycling. Cluster sizes can be stabilized for at least one month via addition of PEG-thiol as a grafted steric stabilizer, where PEG-grafted clusters dissociate back to starting primary nanoparticles at pH 7 in less than 3 days. Whereas the presence of excess citrate has little effect

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on the initial size of the metastable clusters, it is necessary for both the cycling and dissociation to mediate the GSH-GSH hydrogen bonds. In summary, these metastable clusters exhibit significant characteristics of equilibrium self-limited assembly between primary particles and clusters at timescales where cluster-cluster aggregation is not present.

1. Introduction Metal nanoclusters (NCs) composed of aggregated primary nanoparticles (NPs) are of great interest for technological applications,

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subsurface reservoir characterization.7,

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catalytic properties

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including biomedical imaging,3,

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catalysis,5,

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and

The optical (e.g., surface plasmon resonance)4,

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and

can be tuned by virtue of the way the small primary NPs are spatially

organized within the NCs. To facilitate the use of clusters for precise in situ detection and other applications such as controlled release—and, more broadly, to generate functional NP-based materials via “bottom-up” self-assembly routes11—it is desirable to control the kinetics, temporal stability, and morphology (e.g., size, shape) of NC aggregation as a function of external conditions such as pH, temperature, salinity, etc..12 In this vein, NCs would be fully reorganizable, with aggregate states existing in thermodynamic equilibrium (or at least stable on long timescales), and with readily reversible transitions between primary NPs and aggregated NCs. Novel design rules and nanoparticle surface chemistries are needed to advance these challenging goals.13 Aggregation of colloids, whether NPs or larger micron-sized particles, has been observed and characterized across a diverse array of organic and inorganic NP core materials, surface coatings, and solvents; crucially, the vast majority of these systems exhibit irreversible, non-

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equilibrium growth, with little control over cluster size or morphology.14, 15 Broadly speaking, such non-equilibrium assembly is initiated by inducing strong net attractions between primary particles or, equivalently, reducing energetic (e.g., electrostatic) barriers that otherwise stabilize the dispersed phase. Depending on the surface chemistry or coating of the particles (and the properties of the suspending medium), these driving forces for aggregation can be initiated by altering pH16, 17 or ionic strength,9, 18, 19, 20 or by introducing components such as polymers that can destabilize primary particles via entropic depletion forces.21 In turn, if these net attractions lead particles to become permanently trapped in deep energetic minima (e.g., contact minima due to van der Waals (VdW) attractions), assembly will continue uncontrollably until all NPs are incorporated into extremely large aggregates that precipitate out of solution22 or—depending on the assembly route—persist in gel states.23 Depending on system chemistry and concentration, characteristic timescales for growth can range from seconds to days, but by and large such assemblies grow continuously at all times after initiation.9, 24 In contrast, during the past decade, numerous investigators have generated stable colloidal cluster phases composed of reversible finite-sized aggregates in thermodynamic equilibrium, but this type of behavior has mainly been observed via computer simulations of idealized systems25 and in experiments on non-metallic primary particles. Beginning with Stradner, et. al.,26 proteins27,

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equilibrium cluster phases have been reported for monomers including and polymer-based particles31,

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with primaries (and thus aggregates)

ranging from several nanometers to microns in diameter. Typically, such equilibrium clustering behavior can be attributable to strong attractions between monomers that drive aggregation (as above), which are frustrated by weak, longer-ranged repulsive interactions—almost universally attributed to screened electrostatic forces—that grow progressively with cluster size and

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ultimately arrest nanocluster growth.34 For example, a recent study by Lotfizadeh et al.35 reports tunable aggregation of amino silane-coated silica NCs between dispersed primary NPs, clusters, and fully percolated gels as a function of pH, where reducing pH deprotonates the amino silane groups; this allows the weak underlying VdW forces between silica cores to drive NP association while providing collective electrostatic stabilization, with aggregation reversible at all but the lowest pH values. However, despite the above phenomenological framework and thermodynamic models36,

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that can predict cluster size based on generalized Derjaguin-Landau-Verwey-

Overbeek (DLVO) interactions between monomers,39 it remains difficult to precisely tune terminal cluster size and morphology with respect to variables like pH. Meanwhile, there has been limited success in realizing such thermodynamic stability for cluster phases composed of metallic NPs, where the difficulty of generating competitive interparticle forces has generally meant that finite-sized aggregates can only be assembled at the cost of reversibility or via multi-step protocols for (dis-)assembly. For metallic NPs, arresting and reversing assembly is challenging because the strong VdW attractions between even small primaries can permanently trap particles in the clustered state in the absence of sufficient competitive electrostatic and/or steric stabilization. If the repulsion is too strong, the intracluster particle spacing may be too large to achieve the amount of coupling required in certain functional properties, e.g., optical properties such as shifts in the surface plasmon resonance.4 Meanwhile, there remain basic outstanding questions about how the intersection of these various forces—conventionally rationalized within the long-standing pairwise DLVO framework—truly plays out for small closely-packed NPs (e.g., with diameters d < 100 nm), making it difficult to apply broad principles in designing such systems.40

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Despite these challenges, there are examples of self-limited cluster formation for metallic (or semi-conducting) particles: Guo et al. reported the first reversible colorimetric DNA sensors based on target DNA binding. This binding actuates an abrupt change in the particle spacing of gold nanoparticle dimers which causes a detectible red shift.41 Kumacheva et al. showed reversible ensembles of anisotropic metal nanoparticles, with varying geometries (side-side/endend), can be made with hydrophilic nanorods and amphiphilic triblock copolymers that adsorb on the rod ends.42 Xia et al. generated monodisperse finite-sized supra-particle clusters of cadmium selenide (CdSe) nanoparticles, though the aggregation was irreversible.5 More morphologicallycomplex clusters have been also been reported for mixtures of cytochrome C and cadium telluride (CdTe)6 and one-component systems composed of cadmium sulfide (CdS), the latter of which can form viral-capsid-like nanoshells.43 For chemically-simpler systems, homogeneous aggregates of Au NPs were irreversibly assembled as a function of co-solute (3mercaptopropionate co-linker) concentration.44 On the other hand, reversible Au NCs have been assembled at various sizes via quenching with PLA-b-PEG-b-PLA copolymer, with dissociation back to primary NPs occurring within 24 hrs upon biodegradation of the PLA segments.45,

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Likewise, Au NPs coated with binary ligand mixtures (e.g. thioctic acid zwitterion (TAZ) and citrate (Cit)) have been used to form reversible clusters.4 Meanwhile, Grzybowski and co-authors have used externally-applied energy—exposure to light—to control the reversible self-assembly of nanoparticles capped with photo-switchable ligands, where aggregation is tuned by increasing or decreasing the complementary ratio of capping agents on the surfaces of the primaries.47, 48 However, to the best of our knowledge, reversible assembly of size-tunable metallic NCs as a continuous function of solution conditions in aqueous media (e.g. pH, salinity, concentration), without any externally applied forces, is quite rare for metallic NPs.

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In this article, we report the rapid and reversible formation of aqueous Au NCs with tunable size. Specifically, 5 nm Au NPs capped with GSH (GSH) may be converted from stable primary particles to self-limited NCs with characteristic diameters ranging from 20 to 100 nm as the pH window is lowered from 5.6 to 3.8. Consistent with previous studies of related systems,49, 50

rapid assembly of Au NCs is initiated by pH-driven transitions of GSH from its anionic state

(at high pH) to zwitterionic form (lower pH). At low pH, GSH forms hydrogen bonds with itself—though these aggregates are not in themselves stable against irreversible aggregation at longer time scales and continuously grow until exhaustion. Thus, we identify a short time scale for assembly of the nanoclusters on the order of seconds and a much longer time (on the order of tens to hundreds of minutes) for aggregation of the nanoclusters.

However, we find that

stoichiometric excess Cit in solution can act as a competitive inhibitor against aggregation of these clusters for up to 24 hours or more by increasing their stability ratio. The diameter of clusters in the presence of Cit may be cycled reversibly multiple times by varying the pH, although with a modest amount of background growth. Furthermore, the NCs are stabilized against cluster-cluster aggregation with a constant hydrodynamic diameter for a month with the addition of PEG-thiol as a steric stabilizer. An advantage of this technique is that the initial cluster formation may be controlled without the need for a polymer, peptide or DNA thus simplifying the process and the composition of the final particles.

2. Experimental Methods Materials

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Tetrachloroauric acid (HAuCl4·3H2O) was purchased from Acros Chemicals (Morris Plains, NJ). Sodium borohydride (NaBH4), GSH, and sodium citrate (Na3C6H5O7·2H2O) were obtained from Fisher Chemical (Fair Lawn, NJ).

Synthesis of primary Cit-capped nanoparticles and ligand exchange Cit-capped ∼5 nm primary nanoparticles were synthesized via a previously reported procedure.45, 51 First, 30 mL of a 25.4 mM HAuCl4.3H2O solution was slowly added to 3 L of DI water at 95 °C under vigorous stirring. Next, 30 mL of a 34.0 mM Na3C6H5O7·2H2O solution was added to the boiling solution to initiate the reduction of the gold ions. Approximately one minute later as the solution started darkening, an additional 30 mL of 34.0 mM Na3C6H5O7·2H2O was immediately added to aid particle stabilization along with 19.8 mM NaBH4 for complete Au3+ reduction, resulting in a bright red color. The solution was then cooled in an ice bath before centrifugation at 14,000 rcf for 10 min to remove large aggregates. To achieve a final Au solution concentration of 3 mg/mL, the supernatant was then concentrated using tangential flow filtration (TFF), with a 10 kD PES filter to a final volume of ~200 mL, followed by centrifugation of 15 mL batches with 30 kD PES Millipore filter centrifuge tubes at 6000 rpm for 5 min. The retentates were combined to give a final solution volume of ~10 mL. Finally, approximately 20 mL of DI water (pH 6.90) was added to the retentate to achieve a final Au concentration of ~3 mg/mL. The pH of the solution was 6.60. Ligand place exchange was conducted according to a previously described method.4 Briefly, a solution of 1% (w/v) GSH in deionized water was freshly prepared and the pH was set to 7 to completely dissolve the ligand powder and then added to dispersions of Cit-capped Au nanoparticles at ambient temperature. The initial amount of Cit coated on the Au nanoparticles

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was ~4% w/w Cit, measured by thermogravimetric analysis (TGA). Given an Au concentration of 3 mg/ml, measured by Flame Atomic Absorption Spectroscopy (FAAS), the Cit concentration was thus ~0.12 mg/ml. In a typical experiment for a full exchange of Cit with GSH molecules, 195 µL (feed ratio of 10/1 GSH/Cit) of this solution was added to 1 mL of a 3 mg/mL Cit-capped Au nanoparticle dispersion, and the mixture was stirred at room temperature for overnight. After the ligand exchange, the sample was washed by deionized water five times using centrifugal filters (30,000 kDa). Based on the proton nuclear magnetic resonance measurements, the surface of the Au NPs were almost fully coated with GSH molecules (with a ratio of 98:1 GSH:Cit) after the exchange process (Supporting Information).

Characterization of nanoparticles Nanoparticles were diluted to ~0.03 mg/mL Au and filtered through a 200 nm polyethersulfone (PES) syringe filter prior to dynamic light scattering (DLS), zeta potential, and UV-vis-NIR measurements. As reported previously,9 hydrodynamic size distributions were measured on a Brookhaven ZetaPALS instrument using a 90° detection angle using a nonnegatively constrained least squares multiple pass (NNLS) method and an auto-fit slope analysis option. The autocorrelation functions had flat baselines and were fit automatically for all particles where the first peak was smaller than 200nm. This protocol was found to yield hydrodynamic diameters that were in agreement with the TEM number average diameters as shown in Supporting Information. The zeta potentials were measured using the Brookhaven ZetaPALS instrument in the ZetaPALS mode at various pHs within an hour after setting the pH. The gold concentration of the measured samples was 0.03 mg/mL. Even at this low concentration, the primary particles

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formed clusters particularly at lower pHs. A minimum of five runs were performed for each sample with 10 cycles with an average applied electric field of ~ 9 V/cm. All values reported assume the Debye-Hückel model. UV-vis-NIR spectroscopy was obtained with a Varian Cary 60 spectrophotometer with a sample path length of 1 cm. Extinction peaks were normalized to 1 for clarity of comparison. Thermogravimetric analysis (TGA) measurements were made with a Mettler Toledo TGA/DSC 1 STAR. Samples were dried under desiccated air. The final sample was heated from 25 °C to 900 °C at a rate of 10 °C/min under nitrogen flow. Gold concentrations were determined through flame atomic absorption spectroscopy (FAAS) using a GBC 908AA analyzer (GBC Scientific Equipment Pty Ltd.) with an air/acetylene flame at a wavelength of 242.8 nm. Samples were prepared by dissolving a known volume of nanoparticles in an Aqua Regia (3:1 HCl:HNO3, v/v) solution overnight before exposing them to the flame. The absorbance data were then related to a set of Au standards of known mass to determine the sample concentration.

Nanocluster formation and characterization: The nanoparticle solutions were diluted to their respective concentrations with DI water. To first determine the volume of 0.1 N HCl required to achieve a desired pH, 0.5 mL of the 0.6 mg/ml Au solution and 0.5 mL of DI water were added in no specific order to a clean Fisherbrand glass vial to achieve a 0.3 mg/ml Au solution. Using a Mettler Toledo InLab micro pH probe, the pH was measured as 0.1 N HCl was added to reduce the solution pH to the desired value and the volume of acid was recorded. Then, the required acid volume for each desired pH was added to 0.5 mL of DI water in a fresh vial under vigorous stirring. Next, 0.5 mL of the

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respective gold nanoparticles (0.6 mg/ml) was added to this dilute acid solution to yield the final gold concentration of 0.3 mg/ml. For dissociation and cycling experiments, 0.1 N NaOH was used to raise the pH. To cap the clusters with PEG-SH, a solution of 10 mg/ml 10K g/mol PEGSH was prepared and added to the 0.3 mg/ml solution of clusters at a weight ratio of 1:1 polymer:Au. Nanocluster samples underwent DLS and UV-vis-NIR measurements. Certain samples also underwent TEM analysis after both DLS and UVvis- NIR were complete. TEM samples were prepared by placing a 10 µL drop of a given sample onto a 200-mesh carbon Type-A grid (Ted Pella, Redding, CA). The majority of the drop was then wicked off using a Kim-Wipe to form a thin liquid film on the grid which was then immersed in liquid nitrogen and lyophilized overnight at -40 °C using a VirTis AdVantage tray lyophilizer (VirTis, Gardiner, NY). The samples were then examined using an FEI TECNAI G2 F20 X-TWIN TEM with a high-angle annular dark-field detector with an accelerating voltage of 80 kV. The TEM sizing was carried out by using ImageJ software and manually sizing the longest dimension of the clusters. At least 100 clusters were sized for each condition.

3. Results & Discussion Self-assembling nanoclusters of Cit- or GSH-capped AuNPs Fig. 1 shows the chemical structure and the titration curves (i.e., charge-states) of Cit and GSH, which are critical for understanding the distinct assembly trends of Cit- and GSH-capped AuNPs as a function of pH, shown in Figs. 2 and 3. By way of context, we first consider the assembly behavior of Cit-capped AuNPs (prior to ligand exchange for GSH), a simple and wellcharacterized colloidal system that shifts directly from a charge-stabilized dispersed primary

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state toward uncontrolled aggregation as pH is lowered.9, 14 These AuNPs are highly stable, with no aggregation for months, above pH 4 due to the strong repulsion between the negatively charged Cit groups, as plotted in Figs. 1(a-b). Below pH 4 (around pH 3.8), an increasing fraction of the carboxylate groups becomes protonated and the electrostatic repulsion is weakened, as is evident based on the zeta potentials (measured at more dilute conditions of 0.03 mg/ml) in Fig. 3. This drives the Cit-capped AuNPs to assemble into clusters due to VdWdominated attractions between NP surfaces.52 As shown in Fig. 2, we directly observe via DLS measurements that upon changing pH from 9 to target values below 4, Cit-capped AuNPs form small clusters in less than a minute. At pH 3.7 the clusters are stable for a day, but with decreasing pH, the initial clusters become larger and their temporal stability decreases. The kinetics of cluster growth for the Cit-capped AuNPs are characterized by the reference lines in Fig. 2(a): the measured size profiles at various pH values serially span predicted growth trends corresponding to reaction-limited (slow) and diffusion-limited (fast) cluster aggregation (denoted RLCA and DLCA, respectively), which have well-established characteristic growth rates.

14, 24, 53, 54, 55, 56

Here, the reference line for DLCA behavior is given

by the expression DH = At0.53, with time elapsed t given in minutes and prefactor A = 80.5 nm. RLCA behavior is given by DH = Bexp(t/τ) with B = 7.0 nm and time constant τ = 4320 min (i.e., 72 hours). In both cases, parameter combinations correspond to initial hydrodynamic sizes of 7.0 nm. As shown in Fig. 2(b), after complete ligand-exchange and the removal (washing) of Cit, cluster growth trends of the GSH-capped AuNPs qualitatively resemble that of the Cit-capped particles in Fi. 2(a) (i.e., ranging from RLCA to DLCA limits), but over a shifted and expanded pH-range. The GSH-capped AuNPs remain electrostatically-stabilized and dispersed above pH 6,

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where GSH exists primarily in the anionic state (Fig. 1(d)). In turn, as GSH groups become protonated and increasingly zwitterionic at lower pH (Figs. 1(c-d)), primaries readily aggregate in less than a minute into metastable clusters. The timescale for formation of the initial clusters is unknown given the limitations in the time resolution of the experiment, where the first measurement was at ~ 60 s, but based on the collision rate it could be < 1 s. At pH 5.4, the initial metastable clusters were stable for 1 day, which is >103-fold longer than the first measured time point indicating self-limited growth. However, temporal stability rapidly decreases as the pH is lowered, which also corresponds with larger cluster sizes at the first observation time. Assembly of the GSH-capped AuNPs assembly may be attributed to two complementary phenomena: first, as above, decreasing surface charge (Fig. 2(d)) reduces electrostatic barriers to close monomer-monomer contacts. The second—and likely more important—driving force is favorable hydrogen-bonding between GSH molecules that are bonded to neighboring NPs. Indeed, the zwitterionic form of GSH is understood to form multiple types of strong hydrogen bonds (HBs) with both zwitterionic and anionic GSH,57

58

Stobiecka et al.50 used molecular

dynamics simulations and quantum mechanical calculations to show that single, double and triple hydrogen bonds may be formed between two GSH molecules via coupling of COOH– COOH and COOH–NH2 groups. Despite similar shapes of the growth profiles in Figs. 2(a) and (b) for Cit- and GSH-coated particles, initial DH values for the latter increase more slowly with decreasing pH; thus, the net strengths of the particle-particle attractions in the GSH-capped systems evidently grow more slowly with respect to pH. Meanwhile, the average electrostatic repulsion between GSH-capped particles is relatively weaker at a given pH compared to Citcapped particles, as evidenced by the relative trends in zeta potential (Fig. 3(b)).

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Fig. 1: Panels (a) and (b) show chemical structure and titration curves for bulk aqueous citrate (Cit) and panels (c) and (d) show the same for aqueous glutathione (GSH). In (a) and (c), dashed circles identify titratable sites on the molecules.59 Unfilled circles denote sites that are protonated in the pH range where clusters can be stabilized, while filled circles denote deprotonated sites in this range (with darker colors corresponding to sites with higher pKa values). Partially filled circles denote sites that exhibit co-extant (de-)protonated states in the same range. Green shaded regions in (b) and (d) shows pH-range where stable clusters can be assembled. Values of z in (b) and (d) indicate net (integer) charge corresponding to each species profile. Panel (e) illustrates

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the reversible self-assembly of the GSH-capped AuNPs in the presence of aqueous Cit, where cluster size increases with decreasing solution pH.

Fig. 2 Hydrodynamic diameter DH versus elapsed time after adjusting solution from pH=9 to target pH-values (printed by respective data sets) for different AuNP coatings and concentrations of excess aqueous Cit. Note that pH ranges under inspection differ from panel (a) to panels (b-c), and that errors bars in panel (a) for pH < 3.7 and in panels (b-c) for pH < 5.4 are smaller than the symbol sizes. Panel (a) shows predicted assembly behaviors under diffusion- and reactionlimited cluster aggregation, respectively denoted DLCA and RLCA (see text).

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Fig. 3 (a) Hydrodynamic diameters DH for particles or aggregates (depending on pH) and (b) zeta potentials measured at t=1 min as a function of pH for Cit-capped AuNPs, GSH-capped AuNPs, and GSH-capped AuNPs with excess Cit. Shaded regions schematically indicate conditions where primary particles remain stable and dispersed.

Stabilizing nanoclusters of GSH-capped AuNPs via excess Cit As schematically illustrated in Fig. 1(e), addition of only 30mM Cit to the solution prior to the transition to target pH raises the stability of the GSH-capped AuNP clusters from less than about an hour to up to 24 hrs for pH values down to 4.1 and cluster diameters from 20 to 80 nm. As shown in Figs. 2(c) and 3(a), upon lowering pH (over a range of 5.4 to 3.8), the primary NPs immediately (t < 1 min) assemble into clusters with sizes almost identical to the clusters formed in the absence of excess Cit (Fig. 1(d)). Eventually, as shown in Fig. 2(c), secondary aggregation

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between the clusters leads to further growth in DH starting after 24 hours. The 30mM Cit in the solution of 0.3 mg/ml GSH-capped AuNPs corresponds to a ratio of 1:1 Cit:GSH. The results did not change for higher Cit:GSH ratios, whereas lower ratios were found to be inadequate to mediate GSH-GSH interactions and stabilize the clusters after the first hour (see Supporting Information). We also tested how the size and stability of the clusters is affected as a function of excess free GSH in the solution, the overall Au concentration, and the AuNP core size. As the excess amounts of GSH increased (for a given amount of Cit), the size of the clusters increased and the colloidal stability decreased due to intensified GSH-GSH interactions (see Supporting Information). Here, it is understood that the free GSH molecules in solution can act as linkers between GSH molecules bound to nearby NPs50 increasing the number of opportunities for cluster growth and secondary cluster-cluster interactions. Hence, the hypothesis of GSH-GSH driving the initially assembly and Cit mediating the GSH interactions to prolong the stability of the clusters was further reinforced by these results with excess Cit or free GSH in the solution.55 The effects of Au concentration (Fig. S4) and the AuNP core size (Fig. S5) on the assembly of the NPs were also tested in the presence of free Cit (1:1 Cit:GSH). As the Au concentration was increased from 0.03 to 3 mg/ml, the size of the clusters increases at a given pH, as may be expected from mass action. As the size of the primary particles was increased from 8 to 12 nm (Fig. S5) the cluster DH increases given the stronger VdW forces.

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Fig. 4 (Top) TEM images of stabilized clusters and (bottom) corresponding histograms of cluster sizes determined from TEM images at different pH values. Scale bars are the same for all TEM images. The reported size distributions are weight-normalized and multiple grids/samples have been used for the sizing. Note that the horizontal axis of TEM sizes for pH 7.0 in (a) differs in scale from (b-f). In the lower panels, average sizes obtained from TEM and DLS are listed, with the DLS sizes marked by vertical arrows.

In Fig. 4, representative TEM images of the GSH-capped NCs with excess Cit (samples in Fig. 2(c)) are shown versus pH, along with corresponding histograms of aggregate sizes that are each based on 100 individual clusters (see also Figs. S7-S11 for additional TEM images). As is evident from the TEM images, the clusters from pH 5.4 to 3.9 are relatively compact55, as would be expected for reaction-limited cluster aggregation. For pH values of 5.4, 4.9, 4.7, 4.1, and 3.9, the longest dimensions (average ± standard deviation) of the clusters are respectively 25±6, 37±10, 56±8, 71±12 and 96±15 nm. These average sizes are quite similar to the effective spherical diameters from DLS also indicated in each panel. This similarity suggests the TEM sample preparation did not cause much aggregation, and that it is reasonable to determine an

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effective spherical diameter with DLS, given that the deviations from spherical behavior were only modest. In Fig. 5, the UV-NIR absorbance of the various-sized aggregates are shown as a function of pH and lag time. The absorbance curves exhibit distinct peak positions across the pH-range of interest, and the curves as a function of time reinforce the findings above (see Fig. 2) regarding the temporal stability of the clusters. As can be seen in Fig. 5(a), the absorbance of the nanoclusters measured just after assembly show monotonic, but small, shifts to longer wavelengths at lower pH values where larger aggregates form. As seen previously,49, 60 as the number of interacting monomers inside a cluster increases, the surface plasmon resonance of the clusters shifts to higher wavelengths. For two AuNPs at very small separation, the oscillating electrons produce instantaneous dipoles and multipoles that cause a large red shift.61 For nanoclusters, the red shift increases as the spacing between the primary particles decreases and the aggregation number increases.62 In order to achieve large shifts, the edge-to-edge spacing should be < ~10 % of the particle diameter.63 (For example, for AuNPs stabilized by homocysteine (0.7nm), the SPR bands shifts to 800 nm for aggregates of 30 nm AuNPs, but only to 650 nm for 11 nm particles.60) Given the fairly large size of a GSH molecule (1.2 nm50) for a 5 nm gold core, only minor red shifts are expected for the clusters as seen in the spectra in Fig. 5.4, 63, 64, 65

In Fig. 5(b-c), the absorbance spectra are shown to be consistent at fixed pH for periods

up to 24 hours. This timescale is consistent with the temporal DLS measurements in Fig. 2, and demonstrates the uniformity and stability of the cluster aggregates for times much larger than the times for initial rapid assembly. Interestingly, the absorbance spectra of the nanoclusters are found to be able to go through cycles similar to the size of the clusters (not shown) which further verify the moderate cyclability of the clusters.

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Fig. 5 UV curves of self-limited GSH-capped AuNP clusters in the presence of 30mM Cit: (a) UV spectra at different pHs after 10 min from formation, (b-c) UV spectra over time at a specific pH (the curves are shifted vertically for visual clarity).

Mechanisms of cluster stabilization We now consider the possible mechanism(s) by which Cit effectively stabilizes large GSHcapped AuNP clusters for up to one day with minimal effect on their initial formation, where we first determine that a simple explanation based solely on electrostatic stabilization (due to absorption of the charged Cit molecules) is inappropriate. As shown in Fig. 3(b), the zeta

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potential measurements reveal that the excess Cit slightly increases the magnitude of the surface charges on the GSH-capped clusters formed at short times, as is expected if Cit does indeed adsorb onto the cluster surfaces. However, such a modest change in net charge would not be sufficient in itself to stabilize AuNP clusters up to 80-100nm in diameter: the zeta potentials of the GSH-capped systems in the presence of excess Cit at pH < 5.4 only marginally approach the magnitudes associated with stabilization of GSH- or Cit-capped primary particles that, given their size, are subject to considerably weaker VdW attractions. Instead, we propose that the role of Cit in providing stabilization can be primarily explained by two complementary non-DLVO-type interactions: adsorbed Cit molecules (1) mediate (i.e., inhibit) attractive GSH-GSH interactions; and (2) provide additional steric stabilization. Over the pH range from 5.4 to 3.8, Cit molecules become increasingly protonated, with at least one or two protonated carboxylate group(s) (see Figs. 1(a-b)). In turn, Cit can interact with both the zwitterionic and carboxylate groups of GSH (see Figs. 1(c-d)) to form Hbonds50, which—if modestly preferential compared to H-bonding between GSH ligands—would hinder the favorable underlying GSH-GSH interactions between two assembled clusters. (A longstanding model of H-bonding between base and its conjugate acid groups due to Wood demonstrates that this behavior would be sharply pH-dependent.66) This balance evidently breaks down for pH values below 3.8, where the GSH-capped AuNPs exhibit fast uncontrollable aggregation and subsequent precipitation. Under these conditions, GSH molecules are less charged (see Fig. 1(d)), further weakening any electrostatic stabilization relative to attractive HBs between GSH ligands on neighboring NPs. In addition, Cit is increasingly protonated (see Fig. 1(b)) and thus less disruptive to GSH-GSH binding. Meanwhile, the other relevant nonDLVO interaction is the steric repulsion generated by the surface molecules. As illustrated in

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Fig. 1 (which is drawn to scale), the attachment of GSH on the surface of the AuNPs and further adsorption of Cit can add a stablilizing shell of ~2 nm in thickness around individual NPs or clusters.

Fig. 6 Size of the self-limited clusters (GSH-capped Au NPs with 30mM Cit in the solution) going through (a) cycles between various pHs (see labels in vertical stripes) and (b) alternating between pH-values of 4.9 and 5.4.

Reversibility of nanoclusters with GSH and excess Cit In Fig. 6, we demonstrate that the aggregation states of the GSH-capped AuNPs in the presence of 30mM Cit can be serially tuned by varying the pH. The dashed lines indicate the expected size of clusters formed from initially stable individual primary NPs (i.e., beginning with the solution at pH > 7.0) according to Fig. 2. We observe that the cluster diameters may be increased and decreased through multiple cycles, reaching the expected sizes in less than an hour. All cluster

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growth events upon decreasing pH proceed quickly to stable sizes (less than a minute), whereas all decreases in cluster size with an increase in pH are much slower, taking up to an hour. This is expected given that the (layer-by-layer) dissociation of primary nanoparticles from the surface of a cluster requires overcoming close-range VdW attractions and hydrogen bonds from multiple neighboring cluster neighbors. Additionally, Fig. 6(b) shows while cluster sizes can be tuned between two specific pH values for a few cycles, deviations from the expected sizes are observed after a few cycles, with a bias toward larger clusters. Indeed, such samples were allowed to sit for longer times (results not shown here) to see if they ultimately dissociate back to the expected size in longer times, but after three to four cycles the clusters did not shrink to the desired size and did not fully dissociate upon raising pH. This background growth, or secondary clustercluster aggregation, was present beyond the shorter-timescale processes of primary particle (dis)association that connect the quasi-equilibrium cluster sizes at various pH values.

Nanoclusters stabilized with PEG-thiol with and without excess Cit As shown in Fig. 7, we exploit the separation of time-scales between initial formation (24 hrs) of clusters of GSH-coated NPs in excess Cit to greatly extend the long-term stability of the clusters (up to 30 days) by adding polymer chains to generate additional steric stabilization.. One hour after forming clusters with the same protocol as in Fig. 2(c), 10k thiolated polyethylene glycol (PEG-SH) chains were added to the solution, which graft to the AuNPs via thiol bonds. (The grafted chains increase the diameters of the clusters by a few nanometers.) As shown in Fig. 7(a), the DH values of the PEG-capped clusters were found to be stable for at least 30 days, relative to approximately 24 hrs without PEG-SH (see Fig. 2(c)). Next, we considered the dissociation of the PEG-capped clusters formed at the

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various pH values in Fig. 7(a) at pH 7, where the pH was adjusted by adding 0.1 N NaOH. As shown in Fig. 7(b), dissociation of the PEG-capped clusters is slower compared to those without PEG (as in Fig. 6), with the clusters fully dissociating on timescales of up to 3 days. Therefore, the addition of the PEG-SH chains can be an effective way of (perhaps indefinitely) prolonging the half-life of the assembled clusters while allowing clusters to remain fundamentally dissociable. However, these systems cannot be reliably reassembled upon lowering pH because the PEG chains remain covalently bonded to primary AuNPs after cluster dissociation, presumably distributed only on those surfaces previously exposed by the clusters during polymer additions. Thus, upon lowering pH, these PEG chains sterically hinder AuNP association unevenly across individual AuNPs, which leads to polydisperse cluster phases. We also considered the stabilization and dissociation of GSH-capped AuNPs without excess Cit (see Fig. S12). These clusters were stable for at least 30 days at pH range of 3.9-5.4, similar to the clusters with excess Cit. However, if pH is raised to 7.0, these clusters only modestly dissociate over timescales of up to 30 days, and we do not observe full dissociation back to dispersed primary particles as is seen with excess Cit. Thus, excess Cit not only allows for a separation of aggregation timescales—allowing PEG-grafting to be implemented up to 24 hours after initial cluster assembly—but also facilitates complete cluster dissociation after the PEG stabilization is reversed at high pH. A summary of behavior of the four compositions of clusters with the various combinations GSH, citrate and PEG-SH is presented in Table S3 with regard to size control, degree of dissociation, cyclability, and stability against cluster-cluster aggregation. From the stability ratio calculations and the data, it is evident that long-term stability against cluster-cluster aggregation >> 1 day was only achieved with the PEG-SH. However, for time scales up to one

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day, metastable clusters were observed for the 20 nm GSH clusters at pH 5.4, and the 20 to 80 nm GSH clusters with excess citrate (pH 5.4 to 3.8) in Figs. 2b and 2c. Furthermore, the clusters fully dissociated with an increase in pH and could be cycled with pH indicating significant reversibility when excess citrate was present. Together the results may suggest that these systems might have some aspects of equilibrium self-limited assembly providing (meta)stable states for a time scale up to one day.

Fig 7. Hydrodynamic diameter (DH) of the clusters versus elapsed time after adding 10k PEG-SH to the clusters solution at each target pH-values (printed by respective data sets) (a) and the dissociation of the PEG-capped clusters at pH 7 over time (b).

Generality of Cit stabilization for alternative GSH-capped NPs Finally, we briefly note that the assembly of GSH-capped NPs in the presence of free Cit (1:1 Cit:GSH) was tested for another type of core to validate the generality and universality of this technique. Copper sulfide NPs (CuS NPs) were synthesized with a size of 4nm following

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established literature protocols67 and thioglycolic acid groups were exchanged with GSH following the process described in the experimental section for AuNPs. As can be seen in Fig. S6, while the primary NPs were stable at pH above 6, clusters of CuS NPs with the sizes in the range of 50-210 nm were formed in the pH window of 3.9-5.3 at a CuS concentration of 0.5 mg/ml. Interestingly, the clusters were found to remain the same size for one full day, similar to the behavior for the AuNP clusters. This supports the idea that the assembly technique developed here is applicable for various metallic NP cores.

4. Conclusions We demonstrate the reversible self-assembly of nanoclusters in the size range of 20 to 100 nm from 5nm GSH-capped primary AuNPs in the pH window from 5.4 to 3.8. As the pH is lowered the anionic GSH ligands become partially zwitterionic and rapidly form GSH-GSH hydrogen bonds that drive assembly into clusters in less than a minute. Addition of Cit to the solution has a negligible effect on the initial assembly size of the clusters, but it stabilizes the rapidly-formed clusters against cluster-cluster aggregation for up to 24 hrs. This stability is demonstrated by both hydrodynamic diameters (DLS) and UV-NIR absorbance spectra. TEM micrographs indicate relatively compact cluster morphologies, with average sizes that are similar to the effective spherical hydrodynamic diameters measured via DLS. The temporal stabilities of clusters in the pH range of 3.9-5.4 are increased up to one month by adding 10k PEG-SH chains to sterically stabilize the clusters against secondary cluster-cluster aggregation. The PEG-capped clusters with excess Cit fully dissociate to primary particles in 3 days upon raising the pH to 7,

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whereas dissociation is largely incomplete without excess Cit. This Cit-controlled stabilization process was also tested on GSH-capped CuS nanoparticles and similar behavior was observed, which demonstrates the applicability to different types of cores. We direct the interested reader to Table S3 for a summary of cluster assembly responses—in terms of size control, temporal stability, reversibility, and cyclability—with respect to the various combinations GSH, Cit, and PEG-SH examined here. Taken altogether, the results here point to a relatively generic approach for generating clusters of metallic NPs in quasi-equilibrium (i.e., resembling monodisperse equilibrium phases) up to timescales of one day. Looking forward, it is desirable to better understand how physical models for clustering, such as those of Kegel36 that consider balances between short-range attractions, surface charges, etc. to describe equilibrium self-limiting growth, that may be useful in explaining the highly-arrested states considered here. Based on zeta potential measurements of the clusters and previous studies by molecular spectroscopy58 and simulation50 we propose that while pH dependent GSH-GSH hydrogen bonding drives the aggregation of AuNPs, the excess Cit binds to the GSH ligands on the AuNP surfaces (via modestly preferential hydrogen bonding) and mainly inhibits intercluster GSH-GSH interactions. However, the lack of precise knowledge on the strengths of the various hydrogen bonds between GSH-GSH and GSH-Cit—along with the molecular-scale structure and steric impacts of the GSH-Cit shells—currently precludes quantitative model predictions. Better characterizing these mechanisms and effective interactions, which span both DLVO and non-DLVO contributions, should allow such models to be adapted for describing the stabilization effects observed here.

Acknowledgments

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This work was partially supported by the National Science Foundation (1247945) and CPRIT (RP 170314). K.P.J. and T.M.T acknowledge support from the Welch Foundation (F-1319 and F-1696, respectively).

References: 1. Wilcoxon, J.; Abrams, B. Synthesis, structure and properties of metal nanoclusters. Chemical Society Reviews 2006, 35 (11), 1162-1194. 2. Aiken, J. D.; Finke, R. G. A review of modern transition-metal nanoclusters: their synthesis, characterization, and applications in catalysis. Journal of Molecular Catalysis A: Chemical 1999, 145 (1), 1-44. 3. Van Haute, D.; Longmate, J. M.; Berlin, J. M. Controlled assembly of biocompatible metallic nanoaggregates using a small molecule crosslinker. Advanced Materials 2015, 27 (35), 5158-5164. 4. Moaseri, E.; Stover, R. J.; Changalvaie, B.; Cepeda, A. J.; Truskett, T. M.; Sokolov, K.; Johnston, K. P. Control of Primary Particle Spacing in Gold Nanoparticle Clusters for Both High NIR Extinction and Full Reversibility. Langmuir 2017. 5. Xia, Y. S.; Nguyen, T. D.; Yang, M.; Lee, B.; Santos, A.; Podsiadlo, P.; Tang, Z. Y.; Glotzer, S. C.; Kotov, N. A. Self-assembly of self-limiting monodisperse supraparticles from polydisperse nanoparticles. Nature Nanotechnology 2011, 6 (9), 580-587. 6. Park, J. I.; Nguyen, T. D.; de Queirós Silveira, G.; Bahng, J. H.; Srivastava, S.; Zhao, G.; Sun, K.; Zhang, P.; Glotzer, S. C.; Kotov, N. A. Terminal supraparticle assemblies from similarly charged protein molecules and nanoparticles. Nat Commun 2014, 5. 7. Iqbal, M.; Lyon, B. A.; Ureña-Benavides, E. E.; Moaseri, E.; Fei, Y.; McFadden, C.; Javier, K. J.; Ellison, C. J.; Pennell, K. D.; Johnston, K. P. High temperature stability and low adsorption of sub-100nm magnetite nanoparticles grafted with sulfonated copolymers on Berea sandstone in high salinity brine. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2017, 520, 257-267. 8. Ureña-Benavides, E. E.; Lin, E. L.; Foster, E. L.; Xue, Z.; Ortiz, M. R.; Fei, Y.; Larsen, E. S.; Kmetz, A. A.; Lyon, B. A.; Moaseri, E.; Bielawski, C. W.; Pennell, K. D.; Ellison, C. J.; Johnston, K. P. Low Adsorption of Magnetite Nanoparticles with Uniform Polyelectrolyte Coatings in Concentrated Brine on Model Silica and Sandstone. Industrial & Engineering Chemistry Research 2016. 9. Stover, R. J.; Moaseri, E.; Gourisankar, S.; Rahbar, N.; Changalvaie, B.; Iqbal, M.; Truskett, T. M.; Johnston, K. P. Formation of small gold nanoparticle chains with high NIR extinction through bridging with calcium ions. Langmuir 2016. 10. Piccolo, L.; Henry, C. R. Reactivity of metal nanoclusters: nitric oxide adsorption and CO+ NO reaction on Pd/MgO model catalysts. Applied surface science 2000, 162, 670-678.

27


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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 28 of 40

11. Jain, A.; Bollinger, J. A.; Truskett, T. M. Inverse methods for material design. AIChE Journal 2014, 60 (8), 2732-2740. 12. Woodward, R. T.; Hight, C.; Yildiz, U.; Schaeffer, N.; Valliant, E. M.; Jones, J. R.; Stevens, M. M.; Weaver, J. V. Reversible aggregation of responsive polymer-stabilized colloids and the pH-dependent formation of porous scaffolds. Soft Matter 2011, 7 (16), 7560-7566. 13. Kotov, N. A. Particle self-assembly: Superstructures simplified. Nature Nanotechnology 2016. 14. Weitz, D.; Oliveria, M. Fractal structures formed by kinetic aggregation of aqueous gold colloids. Physical Review Letters 1984, 52 (16), 1433. 15. Glotzer, S.; Solomon, M.; Kotov, N. A. Self-assembly: From nanoscale to microscale colloids. AIChE Journal 2004, 50 (12), 2978-2985. 16. Zakaria, H. M.; Shah, A.; Konieczny, M.; Hoffmann, J. A.; Nijdam, A. J.; Reeves, M. Small molecule-and amino acid-induced aggregation of gold nanoparticles. Langmuir 2013, 29 (25), 7661-7673. 17. Olivier, B.; Sorensen, C. Variable aggregation rates in colloidal gold: kernel homogeneity dependence on aggregant concentration. Physical Review A 1990, 41 (4), 2093. 18. Enustun, B. V.; Turkevich, J. Coagulation of Colloidal Gold. J. Am. Chem. Soc. 1963, 85 (21), 3317-3328. 19. Kim, T.; Lee, C.-H.; Joo, S.-W.; Lee, K. Kinetics of gold nanoparticle aggregation: Experiments and modeling. Journal of Colloid and Interface Science 2008, 318 (2), 238-243. 20. Baalousha, M.; Nur, Y.; Römer, I.; Tejamaya, M.; Lead, J. R. Effect of monovalent and divalent cations, anions and fulvic acid on aggregation of citrate-coated silver nanoparticles. Science of The Total Environment 2013, 454–455, 119-131. 21. Israelachvili, J. N. Intermolecular and Surface Forces; 3 ed. ed.; Academic Press: Burlington, MA, 2011. 22. Mani, E.; Lechner, W.; Kegel, W. K.; Bolhuis, P. G. Equilibrium and non-equilibrium cluster phases in colloids with competing interactions. Soft Matter 2014, 10 (25), 4479-4486. 23. Lu, P. J.; Zaccarelli, E.; Ciulla, F.; Scholfield, A. B.; Sciortino, F.; Weitz, D. A. Gelation of particles with short-range attraction. Nature 2008, 453, 499-504. 24. Weitz, D. A.; Huang, J. S.; Lin, M. Y.; Sung, J. Limits of the Fractal Dimension for Irreversible Kinetic Aggregation of Gold Colloids. Physical Review Letters 1985, 54 (13), 14161419. 25. Zhuang, Y.; Charbonneau, P. Recent advances in the theory and simulation of model colloidal microphase formers. arXiv preprint arXiv:1605.09718 2016. 26. Stradner, A.; Sedgwick, H.; Cardinaux, F.; Poon, W. C. K.; Egelhaaf, S. U.; Schurtenberger, P. Equilibrium cluster formation in concentrated protein solutions and colloids. Nature 2004, 432 (7016), 492-495. 27. Porcar, L.; Falus, P.; Chen, W.-R.; Faraone, A.; Fratini, E.; Hong, K.; Baglioni, P.; Liu, Y. Formation of the dynamic clusters in concentrated lysozyme protein solutions. The Journal of Physical Chemistry Letters 2009, 1 (1), 126-129. 28. Liu, Y.; Porcar, L.; Chen, J.; Chen, W.-R.; Falus, P.; Faraone, A.; Fratini, E.; Hong, K.; Baglioni, P. Lysozyme protein solution with an intermediate range order structure. The Journal of Physical Chemistry B 2010, 115 (22), 7238-7247.

28


Page 29 of 40

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

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29. Johnston, K. P.; Maynard, J. A.; Truskett, T. M.; Borwankar, A. U.; Miller, M. A.; Wilson, B. K.; Dinin, A. K.; Khan, T. A.; Kaczorowski, K. J. Concentrated Dispersion of Equilibrium Protein Nanoclusters That Reversibly Dissociate Into Active Monomers. ACS Nano 2012, 6 (2), 13571369. 30. Yearley, E. J.; Godfrin, P. D.; Perevozchikova, T.; Zhang, H.; Falus, P.; Porcar, L.; Nagao, M.; Curtis, J. E.; Gawande, P.; Taing, R. Observation of small cluster formation in concentrated monoclonal antibody solutions and its implications to solution viscosity. Biophysical journal 2014, 106 (8), 1763-1770. 31. Campbell, A. I.; Anderson, V. J.; van Duijneveldt, J. S.; Bartlett, P. Dynamical arrest in attractive colloids: The effect of long-range repulsion. Physical review letters 2005, 94 (20), 208301. 32. Klix, C. L.; Royall, C. P.; Tanaka, H. Structural and dynamical features of multiple metastable glassy states in a colloidal system with competing interactions. Physical review letters 2010, 104 (16), 165702. 33. Zhang, T. H.; Klok, J.; Tromp, R. H.; Groenewold, J.; Kegel, W. K. Non-equilibrium cluster states in colloids with competing interactions. Soft Matter 2012, 8 (3), 667-672. 34. Sciortino, F.; Mossa, S.; Zaccarelli, E.; Tartaglia, P. Equilibrium cluster phases and lowdensity arrested disordered states: the role of short-range attraction and long-range repulsion. Physical review letters 2004, 93 (5), 055701. 35. Lotfizadeh, S.; Aljama, H.; Reilly, D.; Matsoukas, T. Formation of Reversible Clusters with Controlled Degree of Aggregation. Langmuir 2016, 32 (19), 4862-4867. 36. Groenewold, J.; Kegel, W. K. Anomalously Large Equilibrium Clusters of Colloids. Journal of Physical Chemistry B 2001, 105, 11702-11709. 37. Groenewold, J.; Kegel, W. K. Colloidal cluster phases, gelation and nuclear matter. Journal of Physics-Condensed Matter 2004, 16 (42), S4877-S4886. 38. Bollinger, J. A.; Truskett, T. M. Fluids with competing interactions. II. Validating a free energy model for equilibrium cluster size. The Journal of Chemical Physics 2016, 145 (6), 064903. 39. Derjaguin, B. Theory of the stability of strongly charged lyophobic sols and the adhesion of strongly charged particles in solutions of electrolytes. Acta Physicochim. USSR 1941, 14, 633662. 40. Batista, C. A. S.; Larson, R. G.; Kotov, N. A. Nonadditivity of nanoparticle interactions. Science 2015, 350 (6257), 1242477. 41. Guo, L.; Ferhan, A. R.; Chen, H.; Li, C.; Chen, G.; Hong, S.; Kim, D. H. Distance-Mediated Plasmonic Dimers for Reusable Colorimetric Switches: A Measurable Peak Shift of More than 60 nm. Small 2013, 9 (2), 234-240. 42. Nie, Z.; Fava, D.; Kumacheva, E.; Zou, S.; Walker, G. C.; Rubinstein, M. Self-assembly of metal–polymer analogues of amphiphilic triblock copolymers. Nature materials 2007, 6 (8), 609-614. 43. Yang, M.; Chan, H.; Zhao, G.; Bahng, J. H.; Zhang, P.; Král, P.; Kotov, N. A. Self-assembly of nanoparticles into biomimetic capsid-like nanoshells. Nature Chemistry 2016. 44. Zhang, C.; Pansare, V. J.; Prud'homme, R. K.; Priestley, R. D. Flash nanoprecipitation of polystyrene nanoparticles. Soft Matter 2012, 8, 86-93.

29


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Page 30 of 40

45. Murthy, A. K.; Stover, R. J.; Borwankar, A. U.; Nie, G. D.; Gourisankar, S.; Truskett, T. M.; Sokolov, K. V.; Johnston, K. P. Equilibrium Gold Nanoclusters Quenched with Biodegradable Polymers. ACS Nano 2013, 7 (1), 239-251. 46. Tam, J. M.; Murthy, A. K.; Ingram, D. R.; Nguyen, R.; Sokolov, K. V.; Johnston, K. P. Kinetic Assembly of Near-IR-Active Gold Nanoclusters Using Weakly Adsorbing Polymers to Control the Size. Langmuir 2010, 26 (11), 8988-8999. 47. Klajn, R.; Bishop, K. J.; Grzybowski, B. A. Light-controlled self-assembly of reversible and irreversible nanoparticle suprastructures. Proceedings of the National Academy of Sciences 2007, 104 (25), 10305-10309. 48. Wei, Y.; Han, S.; Kim, J.; Soh, S.; Grzybowski, B. A. Photoswitchable catalysis mediated by dynamic aggregation of nanoparticles. J. Am. Chem. Soc. 2010, 132 (32), 11018-11020. 49. Lim, I.-I. S.; Mott, D.; Ip, W.; Njoki, P. N.; Pan, Y.; Zhou, S.; Zhong, C.-J. Interparticle interactions in glutathione mediated assembly of gold nanoparticles. Langmuir 2008, 24 (16), 8857-8863. 50. Stobiecka, M.; Coopersmith, K.; Hepel, M. Resonance elastic light scattering (RELS) spectroscopy of fast non-Langmuirian ligand-exchange in glutathione-induced gold nanoparticle assembly. Journal of Colloid and Interface Science 2010, 350, 168-177. 51. Tam, J. M.; Murthy, A. K.; Ingram, D. R.; Nguyen, R.; Sokolov, K. V.; Johnston, K. P. Kinetic Assembly of Near-IR Active Gold Nanoclusters Using Weakly Adsorbing Polymers to Control the Size. Langmuir 2010, 26 (11), 8988-8999. 52. Hiemenz, P. C.; Rajagopalan, R. Principles of colloid and surface chemistry; 3rd ed.; Marcel Dekker: New York, 1997. p xix, 650 p. 53. Golub, N. V.; Markossian, K. A.; Sholukh, M. V.; Muranov, K. O.; Kurganov, B. I. Study of kinetics of thermal aggregation of mitochondrial aspartate aminotransferase by dynamic light scattering: protective effect of α-crystallin. European Biophysics Journal 2009, 38 (5), 547-556. 54. Shima, P.; Philip, J.; Raj, B. Role of microconvection induced by Brownian motion of nanoparticles in the enhanced thermal conductivity of stable nanofluids. Applied Physics Letters 2009, 94 (22), 223101. 55. Du, C.-R.; Thomas, H. M.; Ivlev, A. V.; Konopka, U.; Morfill, G. E. Agglomeration of microparticles in complex plasmas. Physics of Plasmas 2010, 17 (11), 113710. 56. Murphy, R. J.; Pristinski, D.; Migler, K.; Douglas, J. F.; Prabhu, V. M. Dynamic light scattering investigations of nanoparticle aggregation following a light-induced p H jump. The Journal of chemical physics 2010, 132 (19), 194903. 57. Ni, W.; Mosquera, R. A.; Pérez-Juste, J.; Liz-Marzán, L. M. Evidence for hydrogenbonding-directed assembly of gold nanorods in aqueous solution. The Journal of Physical Chemistry Letters 2010, 1 (8), 1181-1185. 58. Huckerby, T. N.; Tudor, A. J.; Dawber, J. G. Acid–base studies of glutathione (L-γglutamyl-L-cysteinyl-L-glycine) by one-and two-dimensional nuclear magnetic resonance spectroscopy. Journal of the Chemical Society, Perkin Transactions 2 1985, (6), 759-763. 59. Vila-Viçosa, D.; Teixeira, V. H.; Santos, H. A.; Machuqueiro, M. Conformational study of GSH and GSSG using constant-pH molecular dynamics simulations. The Journal of Physical Chemistry B 2013, 117 (25), 7507-7517.

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60. Lim, I. I. S.; Ip, W.; Crew, E.; Njoki, P. N.; Mott, D.; Zhong, C.-J.; Pan, Y.; Zhou, S. Homocysteine-Mediated Reactivity and Assembly of Gold Nanoparticles. Langmuir 2007, 23 (2), 826-833. 61. Halas, N. J.; Lal, S.; Chang, W.-S.; Link, S.; Nordlander, P. Plasmons in Strongly Coupled Metallic Nanostructures. Chemical Reviews 2011, 111, 3913-3961. 62. Nordlander, P.; Oubre, C.; Prodan, E.; Li, K.; Stockman, M. Plasmon hybridization in nanoparticle dimers. Nano Lett. 2004, 4 (5), 899-903. 63. Khlebtsov, B. N.; Khanadeyev, V. A.; Ye, J.; Mackowski, D. W.; Borghs, G.; Khlebtsov, N. G. Coupled plasmon resonances in monolayers of metal nanoparticles and nanoshells. Physical Review B 2008, 77 (3), 035440. 64. Khlebtsov, N.; Dykman, L.; Krasnov, Y. M.; Mel'nikov, A. Light absorption by the clusters of colloidal gold and silver particles formed during slow and fast aggregation. Colloid J 2000, 62 (6), 765-779. 65. Khlebtsov, B.; Zharov, V.; Melnikov, A.; Tuchin, V.; Khlebtsov, N. Optical amplification of photothermal therapy with gold nanoparticles and nanoclusters. Nanotechnology 2006, 51675179. 66. Wood, J. L. pH-controlled hydrogen-bonding. Biochemical Journal 1974, 143 (3), 775777. 67. Ma, G.; Zhou, Y.; Li, X.; Sun, K.; Liu, S.; Hu, J.; Kotov, N. A. Self-assembly of copper sulfide nanoparticles into nanoribbons with continuous crystallinity. ACS Nano 2013, 7 (10), 90109018.

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Fig. 1: Panels (a) and (b) show chemical structure and titration curves for bulk aqueous citrate (Cit) and panels (c) and (d) show the same for aqueous glutathione (GSH). In (a) and (c), dashed circles identify titratable sites on the molecules.54 Unfilled circles denote sites that are protonated in the pH range where monodisperse clusters can be stabilized, while filled circles denote deprotonated sites in this range (with darker colors corresponding to sites with higher pKa values). Partially filled circles denote sites that exhibit co-extant (de-)protonated states in the same range. Green shaded regions in (b) and (d) shows pH-range where stable clusters can be assembled. Panel (e) illustrates the reversible self-assembly of the GSH-capped AuNPs in the presence of aqueous citrate, where there is a negative correlation between solution pH and cluster size. 79x124mm (96 x 96 DPI)


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Fig. 2 Hydrodynamic diameter DH versus elapsed time after adjusting solution from pH=9 to target pHvalues (printed by respective data sets) for different AuNP coatings and concentrations of excess aqueous Cit. Note that pH ranges under inspection differ from panel (a) to panels (b-c), and that errors bars in panel (a) for pH < 3.7 and in panels (b-c) for pH < 5.4 are smaller than the symbol sizes. Panel (a) shows predicted assembly behaviors under diffusion- and reaction-limited cluster aggregation, respectively denoted DLCA and RLCA (see text). 162x63mm (96 x 96 DPI)


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Fig. 3 (a) Hydrodynamic diameters DH for particles or aggregates (depending on pH) and (b) zeta potentials measured at t=1 min as a function of pH for Cit-capped AuNPs, GSH-capped AuNPs, and GSH-capped AuNPs with excess Cit. Shaded regions schematically indicate conditions where primary particles remain stable and dispersed. 103x119mm (240 x 240 DPI)


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Fig. 4 (Top) TEM images of stabilized clusters and (bottom) corresponding histograms of cluster sizes determined from TEM images at different pH values. Scale bars are the same for all TEM images. The reported size distributions are weight-normalized and multiple grids/samples have been used for the sizing. Note that the horizontal axis of TEM sizes for pH 7.0 in (a) differs in scale from (b-f). In the lower panels, average sizes obtained from TEM and DLS are listed, with the DLS sizes marked by vertical arrows. 206x84mm (240 x 240 DPI)


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Fig. 5 UV curves of self-limited GSH-capped AuNP clusters in the presence of 30mM Cit: (a) UV spectra at different pHs after 10 min from formation, (b-c) UV spectra over time at a specific pH (the curves are shifted vertically for visual clarity). 103x119mm (240 x 240 DPI)


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Fig. 6 Size of the self-limited clusters (GSH-capped Au NPs with 30mM Cit in the solution) going through (a) cycles between various pHs (see labels in vertical stripes) and (b) alternating between pH-values of 4.9 and 5.4. 103x119mm (240 x 240 DPI)


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Fig 7. Hydrodynamic diameter (DH) of the clusters versus elapsed time after adding 10k PEG-SH to the clusters solution at each target pH-values (printed by respective data sets) (a) and the dissociation of the PEG-capped clusters at pH 7 over time (b). 103x82mm (240 x 240 DPI)


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Reversible Self-Assembly of Glutathione-Coated Gold Nanoparticle

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