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Stable oligomeric clusters of gold nanoparticles: preparation, size distribution, derivatization, and physical and biological properties.

Smithies O, Lawrence M, Testen A, Horne LP, Wilder J, Altenburg M, Bleasdale B, Maeda N, Koklic T - Langmuir (2014)

Bottom Line: The crude oligocluster preparations have narrow size distributions, and for most purposes do not require fractionation.The oligoclusters do not aggregate after ∼300-fold centrifugal-filter concentration, and at this high concentration are easily derivatized with a variety of thiol-containing reagents.Unlike conventional glutathione-capped nanoparticles of comparable gold content, large oligoclusters derivatized with glutathione do not aggregate at high concentrations in phosphate-buffered saline (PBS) or in the circulation when injected into mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, and ‡Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.

ABSTRACT
Reducing dilute aqueous HAuCl4 with NaSCN under alkaline conditions produces 2-3 nm diameter yellow nanoparticles without the addition of extraneous capping agents. We here describe two very simple methods for producing highly stable oligomeric grape-like clusters (oligoclusters) of these small nanoparticles. The oligoclusters have well-controlled diameters ranging from ∼5 to ∼30 nm, depending mainly on the number of subunits in the cluster. Our first ["delay-time"] method controls the size of the oligoclusters by varying from seconds to hours the delay time between making the HAuCl4 alkaline and adding the reducing agent, NaSCN. Our second ["add-on"] method controls size by using yellow nanoparticles as seeds onto which varying amounts of gold derived from "hydroxylated gold", Na(+)[Au(OH4-x)Clx](-), are added-on catalytically in the presence of NaSCN. Possible reaction mechanisms and a simple kinetic model fitting the data are discussed. The crude oligocluster preparations have narrow size distributions, and for most purposes do not require fractionation. The oligoclusters do not aggregate after ∼300-fold centrifugal-filter concentration, and at this high concentration are easily derivatized with a variety of thiol-containing reagents. This allows rare or expensive derivatizing reagents to be used economically. Unlike conventional glutathione-capped nanoparticles of comparable gold content, large oligoclusters derivatized with glutathione do not aggregate at high concentrations in phosphate-buffered saline (PBS) or in the circulation when injected into mice. Mice receiving them intravenously show no visible signs of distress. Their sizes can be made small enough to allow their excretion in the urine or large enough to prevent them from crossing capillary basement membranes. They are directly visible in electron micrographs without enhancement, and can model the biological fate of protein-like macromolecules with controlled sizes and charges. The ease of derivatizing the oligoclusters makes them potentially useful for presenting pharmacological agents to different tissues while controlling escape of the reagents from the circulation.

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Schematics of delay-time reaction (A)and add-on reaction (B).(A) Delay-time reaction. After HAuCl4 is made alkaline,species that are able to nucleate (blue ●) are progressivelyconverted by hydrolysis into species that are unable to nucleate (red○) but are able to add on to existing particles. Addition ofSCN– initiates the nucleation and growth processes.In reactions with delay times less than 5 s, almost all species presentare able to nucleate, and the reduction/growth processes continueuntil all of the gold is reduced and the particles reach the stablesize (●), characteristic of the reduction of gold chlorideby NaSCN under alkaline conditions. In reactions with longer delaytimes, nucleation-unable species are present, which can only be reducedby catalysis resulting from contact with already existing nucleationcenters or fully formed nanoparticles. All subunits, including thoseformed by contact catalysis (○), can catalyze the formationand growth of additional subunits using any unreduced gold remainingin the mix. The number of oligoclusters formed (N) decreases with longer delay times, because hydrolysis decreasesthe amount of nucleation-able species present when the NaSCN reductionis initiated. The number of subunits in the resulting oligoclusters(n) depends on the total amount of blue “●”plus red “○” present in the reaction mix. Becausethis is normally kept fixed at 1 mM, N × n is constant regardless of the delay time. (B) Add-on reaction.In this reaction, the hydrolytic process is separated from the reduction/growthprocesses. Preformed nanoparticles, “●”, areused as seeds. Fully hydrolyzed nucleation-unable species, red “○”,are used as sources of additional gold that by contact catalysis canform additional subunits, “○”. Thus, the numberof oligoclusters, N, formed is determined by thenumber of seeds present in the reaction mix, while the number of subunitsin the resulting oligoclusters, n, increases as N decreases, since the total amount of gold in the reactionmix is kept constant.
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fig9: Schematics of delay-time reaction (A)and add-on reaction (B).(A) Delay-time reaction. After HAuCl4 is made alkaline,species that are able to nucleate (blue ●) are progressivelyconverted by hydrolysis into species that are unable to nucleate (red○) but are able to add on to existing particles. Addition ofSCN– initiates the nucleation and growth processes.In reactions with delay times less than 5 s, almost all species presentare able to nucleate, and the reduction/growth processes continueuntil all of the gold is reduced and the particles reach the stablesize (●), characteristic of the reduction of gold chlorideby NaSCN under alkaline conditions. In reactions with longer delaytimes, nucleation-unable species are present, which can only be reducedby catalysis resulting from contact with already existing nucleationcenters or fully formed nanoparticles. All subunits, including thoseformed by contact catalysis (○), can catalyze the formationand growth of additional subunits using any unreduced gold remainingin the mix. The number of oligoclusters formed (N) decreases with longer delay times, because hydrolysis decreasesthe amount of nucleation-able species present when the NaSCN reductionis initiated. The number of subunits in the resulting oligoclusters(n) depends on the total amount of blue “●”plus red “○” present in the reaction mix. Becausethis is normally kept fixed at 1 mM, N × n is constant regardless of the delay time. (B) Add-on reaction.In this reaction, the hydrolytic process is separated from the reduction/growthprocesses. Preformed nanoparticles, “●”, areused as seeds. Fully hydrolyzed nucleation-unable species, red “○”,are used as sources of additional gold that by contact catalysis canform additional subunits, “○”. Thus, the numberof oligoclusters, N, formed is determined by thenumber of seeds present in the reaction mix, while the number of subunitsin the resulting oligoclusters, n, increases as N decreases, since the total amount of gold in the reactionmix is kept constant.

Mentions: The cartoon in Figure 9 summarizes our observations.The sizes of the oligoclusters depend on the number of subunits (n) that they contain. The number of oligoclusters formed(N) is a reflection of the number of discrete nucleationcenters that form in the delay-time reaction, or are added as seedsin the add-on reaction. The total number of subunits formed (N × n) is determined by the totalamount of gold present in the reaction, which is kept constant. Thetwo methods provide different ways of controlling the number of effectivenucleation centers (the number of oligoclusters) and thence the numberof subunits that they contain.


Stable oligomeric clusters of gold nanoparticles: preparation, size distribution, derivatization, and physical and biological properties.

Smithies O, Lawrence M, Testen A, Horne LP, Wilder J, Altenburg M, Bleasdale B, Maeda N, Koklic T - Langmuir (2014)

Schematics of delay-time reaction (A)and add-on reaction (B).(A) Delay-time reaction. After HAuCl4 is made alkaline,species that are able to nucleate (blue ●) are progressivelyconverted by hydrolysis into species that are unable to nucleate (red○) but are able to add on to existing particles. Addition ofSCN– initiates the nucleation and growth processes.In reactions with delay times less than 5 s, almost all species presentare able to nucleate, and the reduction/growth processes continueuntil all of the gold is reduced and the particles reach the stablesize (●), characteristic of the reduction of gold chlorideby NaSCN under alkaline conditions. In reactions with longer delaytimes, nucleation-unable species are present, which can only be reducedby catalysis resulting from contact with already existing nucleationcenters or fully formed nanoparticles. All subunits, including thoseformed by contact catalysis (○), can catalyze the formationand growth of additional subunits using any unreduced gold remainingin the mix. The number of oligoclusters formed (N) decreases with longer delay times, because hydrolysis decreasesthe amount of nucleation-able species present when the NaSCN reductionis initiated. The number of subunits in the resulting oligoclusters(n) depends on the total amount of blue “●”plus red “○” present in the reaction mix. Becausethis is normally kept fixed at 1 mM, N × n is constant regardless of the delay time. (B) Add-on reaction.In this reaction, the hydrolytic process is separated from the reduction/growthprocesses. Preformed nanoparticles, “●”, areused as seeds. Fully hydrolyzed nucleation-unable species, red “○”,are used as sources of additional gold that by contact catalysis canform additional subunits, “○”. Thus, the numberof oligoclusters, N, formed is determined by thenumber of seeds present in the reaction mix, while the number of subunitsin the resulting oligoclusters, n, increases as N decreases, since the total amount of gold in the reactionmix is kept constant.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4230385&req=5

fig9: Schematics of delay-time reaction (A)and add-on reaction (B).(A) Delay-time reaction. After HAuCl4 is made alkaline,species that are able to nucleate (blue ●) are progressivelyconverted by hydrolysis into species that are unable to nucleate (red○) but are able to add on to existing particles. Addition ofSCN– initiates the nucleation and growth processes.In reactions with delay times less than 5 s, almost all species presentare able to nucleate, and the reduction/growth processes continueuntil all of the gold is reduced and the particles reach the stablesize (●), characteristic of the reduction of gold chlorideby NaSCN under alkaline conditions. In reactions with longer delaytimes, nucleation-unable species are present, which can only be reducedby catalysis resulting from contact with already existing nucleationcenters or fully formed nanoparticles. All subunits, including thoseformed by contact catalysis (○), can catalyze the formationand growth of additional subunits using any unreduced gold remainingin the mix. The number of oligoclusters formed (N) decreases with longer delay times, because hydrolysis decreasesthe amount of nucleation-able species present when the NaSCN reductionis initiated. The number of subunits in the resulting oligoclusters(n) depends on the total amount of blue “●”plus red “○” present in the reaction mix. Becausethis is normally kept fixed at 1 mM, N × n is constant regardless of the delay time. (B) Add-on reaction.In this reaction, the hydrolytic process is separated from the reduction/growthprocesses. Preformed nanoparticles, “●”, areused as seeds. Fully hydrolyzed nucleation-unable species, red “○”,are used as sources of additional gold that by contact catalysis canform additional subunits, “○”. Thus, the numberof oligoclusters, N, formed is determined by thenumber of seeds present in the reaction mix, while the number of subunitsin the resulting oligoclusters, n, increases as N decreases, since the total amount of gold in the reactionmix is kept constant.
Mentions: The cartoon in Figure 9 summarizes our observations.The sizes of the oligoclusters depend on the number of subunits (n) that they contain. The number of oligoclusters formed(N) is a reflection of the number of discrete nucleationcenters that form in the delay-time reaction, or are added as seedsin the add-on reaction. The total number of subunits formed (N × n) is determined by the totalamount of gold present in the reaction, which is kept constant. Thetwo methods provide different ways of controlling the number of effectivenucleation centers (the number of oligoclusters) and thence the numberof subunits that they contain.

Bottom Line: The crude oligocluster preparations have narrow size distributions, and for most purposes do not require fractionation.The oligoclusters do not aggregate after ∼300-fold centrifugal-filter concentration, and at this high concentration are easily derivatized with a variety of thiol-containing reagents.Unlike conventional glutathione-capped nanoparticles of comparable gold content, large oligoclusters derivatized with glutathione do not aggregate at high concentrations in phosphate-buffered saline (PBS) or in the circulation when injected into mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, and ‡Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.

ABSTRACT
Reducing dilute aqueous HAuCl4 with NaSCN under alkaline conditions produces 2-3 nm diameter yellow nanoparticles without the addition of extraneous capping agents. We here describe two very simple methods for producing highly stable oligomeric grape-like clusters (oligoclusters) of these small nanoparticles. The oligoclusters have well-controlled diameters ranging from ∼5 to ∼30 nm, depending mainly on the number of subunits in the cluster. Our first ["delay-time"] method controls the size of the oligoclusters by varying from seconds to hours the delay time between making the HAuCl4 alkaline and adding the reducing agent, NaSCN. Our second ["add-on"] method controls size by using yellow nanoparticles as seeds onto which varying amounts of gold derived from "hydroxylated gold", Na(+)[Au(OH4-x)Clx](-), are added-on catalytically in the presence of NaSCN. Possible reaction mechanisms and a simple kinetic model fitting the data are discussed. The crude oligocluster preparations have narrow size distributions, and for most purposes do not require fractionation. The oligoclusters do not aggregate after ∼300-fold centrifugal-filter concentration, and at this high concentration are easily derivatized with a variety of thiol-containing reagents. This allows rare or expensive derivatizing reagents to be used economically. Unlike conventional glutathione-capped nanoparticles of comparable gold content, large oligoclusters derivatized with glutathione do not aggregate at high concentrations in phosphate-buffered saline (PBS) or in the circulation when injected into mice. Mice receiving them intravenously show no visible signs of distress. Their sizes can be made small enough to allow their excretion in the urine or large enough to prevent them from crossing capillary basement membranes. They are directly visible in electron micrographs without enhancement, and can model the biological fate of protein-like macromolecules with controlled sizes and charges. The ease of derivatizing the oligoclusters makes them potentially useful for presenting pharmacological agents to different tissues while controlling escape of the reagents from the circulation.

Show MeSH
Related in: MedlinePlus