Quantitative analysis of thiolated ligand exchange on gold nanoparticles monitored by 1H NMR spectroscopy.

We use nuclear magnetic resonance spectroscopy methods to quantify the extent of ligand exchange between different types of thiolated molecules on the surface of gold nanoparticles. Specifically, we determine ligand density values for single-moiety ligand shells and then use these data to describe ligand exchange behavior with a second, thiolated molecule. Using these techniques, we identify trends in gold nanoparticle functionalization efficiency with respect to ligand type, concentration, and reaction time as well as distinguish between functionalization pathways where the new ligand may either replace the existing ligand shell (exchange) or add to it ("backfilling"). Specifically, we find that gold nanoparticles functionalized with thiolated macromolecules, such as poly(ethylene glycol) (1 kDa), exhibit ligand exchange efficiencies ranging from 70% to 95% depending on the structure of the incoming ligand. Conversely, gold nanoparticles functionalized with small-molecule thiolated ligands exhibit exchange efficiencies as low as 2% when exposed to thiolated molecules under identical exchange conditions. Taken together, the reported results provide advances in the fundamental understanding of mixed ligand shell formation and will be important for the preparation of gold nanoparticles in a variety of biomedical, optoelectronic, and catalytic applications.

[1]  R. Murray,et al.  Dynamics of Place-Exchange Reactions on Monolayer-Protected Gold Cluster Molecules , 1999 .

[2]  S. Reed,et al.  Improved Synthesis of Small (dCORE ≈ 1.5 nm) Phosphine-Stabilized Gold Nanoparticles , 2000 .

[3]  F. Stellacci,et al.  Nucleation and island growth of alkanethiolate ligand domains on gold nanoparticles. , 2012, ACS nano.

[4]  L. Reven,et al.  The Effect of Terminal Hydrogen Bonding on the Structure and Dynamics of Nanoparticle Self-Assembled Monolayers (SAMs): An NMR Dynamics Study. , 1998, Advanced materials.

[5]  H. Häkkinen,et al.  Solvation chemistry of water-soluble thiol-protected gold nanocluster Au₁₀₂ from DOSY NMR spectroscopy and DFT calculations. , 2014, Nanoscale.

[6]  Haitao Liu,et al.  Conversion Reactions of Cadmium Chalcogenide Nanocrystal Precursors , 2013 .

[7]  R. Murray,et al.  Nanometer Gold Clusters Protected by Surface-Bound Monolayers of Thiolated Poly(ethylene glycol) Polymer Electrolyte , 1998 .

[8]  Lee L Yu,et al.  Quantification of ligand packing density on gold nanoparticles using ICP-OES , 2012, Analytical and Bioanalytical Chemistry.

[9]  George M. Whitesides,et al.  Formation of monolayers by the coadsorption of thiols on gold: variation in the head group, tail group, and solvent , 1989 .

[10]  L. Demers,et al.  Structure and Chain Dynamics of Alkanethiol-Capped Gold Colloids , 1996 .

[11]  Marc D. Porter,et al.  Alkanethiolate Gold Cluster Molecules with Core Diameters from 1.5 to 5.2 nm: Core and Monolayer Properties as a Function of Core Size , 1998 .

[12]  Chad A Mirkin,et al.  The bio-barcode assay for the detection of protein and nucleic acid targets using DTT-induced ligand exchange , 2006, Nature Protocols.

[13]  Jesse V Jokerst,et al.  Nanoparticle PEGylation for imaging and therapy. , 2011, Nanomedicine.

[14]  Younan Xia,et al.  Quantifying the coverage density of poly(ethylene glycol) chains on the surface of gold nanostructures. , 2012, ACS nano.

[15]  G. Whitesides,et al.  Self-assembled monolayers of thiolates on metals as a form of nanotechnology. , 2005, Chemical reviews.

[16]  L. Demers,et al.  Gold−Sulfur Interactions in Alkylthiol Self-Assembled Monolayers Formed on Gold Nanoparticles Studied by Solid-State NMR , 1997 .

[17]  J. Hillier,et al.  A study of the nucleation and growth processes in the synthesis of colloidal gold , 1951 .

[18]  Olena V. Zenkina,et al.  Ultra stable self-assembled monolayers of N-heterocyclic carbenes on gold. , 2014, Nature chemistry.

[19]  R. Murray,et al.  Water-Soluble, Isolable Gold Clusters Protected by Tiopronin and Coenzyme A Monolayers , 1999 .

[20]  L. Demers,et al.  Structure and Dynamics in Alkanethiolate Monolayers Self-Assembled on Gold Nanoparticles: A DSC, FT-IR, and Deuterium NMR Study , 1997 .

[21]  N. Halas,et al.  Determining the conformation of thiolated poly(ethylene glycol) on Au nanoshells by surface-enhanced Raman scattering spectroscopic assay. , 2006, Analytical chemistry.

[22]  M. Samant,et al.  Formation of an ordered self-assembled monolayer of docosaneselenol on gold(111). Structure by surface x-ray diffraction , 1992 .

[23]  Younan Xia,et al.  Chemical synthesis of novel plasmonic nanoparticles. , 2009, Annual review of physical chemistry.

[24]  G. Frens.  Controlled nucleation for the regulation of the particle size in monodisperse gold solutions , 1973 .

[25]  E. Weiss,et al.  The Effect of a Common Purification Procedure on the Chemical Composition of the Surfaces of CdSe Quantum Dots Synthesized with Trioctylphosphine Oxide , 2010 .

[26]  George M. Whitesides,et al.  Comparison of the Structures and Wetting Properties of Self-Assembled Monolayers of n- Alkanethiols on the Coinage Metal Surfaces, Cu, Ag, Au' , 1991 .

[27]  Kyung Tae Kim,et al.  Fabrication and enhanced thermoelectric properties of alumina nanoparticle-dispersed Bi 0.5 Sb 1.5 Te 3 matrix composites , 2013 .

[28]  R. Murray,et al.  Ligand heterogeneity on monolayer-protected gold clusters. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[29]  G. Frens.  Controlled Nucleation for the Regulation of the Particle Size in Monodisperse Gold Suspensions , 1973 .

[30]  A. Katz,et al.  Steady-State Fluorescence-Based Investigation of the Interaction between Protected Thiols and Gold Nanoparticles , 2002 .

[31]  H. Häkkinen,et al.  The gold-sulfur interface at the nanoscale. , 2012, Nature chemistry.

[32]  H. Jiang,et al.  Preparation of poly(N-isopropylacrylamide)-monolayer protected gold clusters: synthesis methods, core size and thickness of monolayer , 2003 .

[33]  G. Whitesides,et al.  Formation of monolayer films by the spontaneous assembly of organic thiols from solution onto gold , 1989 .

[34]  P. Weiss,et al.  Comparison of Oligo(ethylene glycol)alkanethiols versus n-Alkanethiols: Self-Assembly, Insertion, and Functionalization , 2011 .

[35]  S. Pennycook,et al.  The possibility and implications of dynamic nanoparticle surfaces. , 2013, ACS nano.

[36]  O. Konovalov,et al.  Real-time observation of structural and orientational transitions during growth of organic thin films. , 2006, Physical review letters.

[37]  Vincent M Rotello,et al.  Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. , 2004, Bioconjugate chemistry.

[38]  Paul S. Weiss,et al.  Patterning self-assembled monolayers , 2004 .

[39]  Suntharampillai Thevuthasan,et al.  PEGylated inorganic nanoparticles. , 2011, Angewandte Chemie.

[40]  Z. Hens,et al.  Utilizing self-exchange to address the binding of carboxylic acid ligands to CdSe quantum dots. , 2010, Journal of the American Chemical Society.

[41]  Francesco Stellacci,et al.  Determination of monolayer-protected gold nanoparticle ligand–shell morphology using NMR , 2012, Nature Communications.

[42]  D. Allara,et al.  Phase Separation of Mixed-Composition Self-Assembled Monolayers into Nanometer Scale Molecular Domains , 1994 .

[43]  J. M. Harris,et al.  Poly(Ethylene Glycol) Chemistry , 1992 .

[44]  C. Mirkin,et al.  Making sense of the mayhem behind shape control in the synthesis of gold nanoparticles. , 2013, Journal of the American Chemical Society.

[45]  Jonathan S. Owen,et al.  Ligand exchange and the stoichiometry of metal chalcogenide nanocrystals: spectroscopic observation of facile metal-carboxylate displacement and binding. , 2013, Journal of the American Chemical Society.

[46]  Catherine J. Murphy,et al.  Sensing strategy for lithium ion based on gold nanoparticles , 2002 .

[47]  M. Morris,et al.  PEGylated gold nanoparticles: polymer quantification as a function of PEG lengths and nanoparticle dimensions , 2013 .

[48]  I. Moreels,et al.  In situ observation of rapid ligand exchange in colloidal nanocrystal suspensions using transfer NOE nuclear magnetic resonance spectroscopy. , 2009, Journal of the American Chemical Society.

[49]  George M. Whitesides,et al.  Self-assembled monolayers of alkanethiols on gold: comparisons of monolayers containing mixtures of short- and long-chain constituents with methyl and hydroxymethyl terminal groups , 1992 .

[50]  R. V. Van Duyne,et al.  Localized surface plasmon resonance spectroscopy and sensing. , 2007, Annual review of physical chemistry.

[51]  Nicolaas Bloembergen,et al.  Proton Relaxation Times in Paramagnetic Solutions , 1957 .

[52]  Anabel E. Lanterna,et al.  When nanoparticle size and molecular geometry matter: Analyzing the degree of surface functionalization of gold nanoparticles with sulfur heterocyclic compounds , 2012 .

[53]  A. Ulman,et al.  Structure and binding of alkanethiolates on gold and silver surfaces: implications for self-assembled monolayers , 1993 .

[54]  N. Anderson,et al.  Soluble, Chloride-Terminated CdSe Nanocrystals: Ligand Exchange Monitored by 1H and 31P NMR Spectroscopy , 2013 .

[55]  E. Weiss,et al.  Chemical, Structural, and Quantitative Analysis of the Ligand Shells of Colloidal Quantum Dots , 2013 .

[56]  Alaaldin M. Alkilany,et al.  Gold nanoparticles in biology: beyond toxicity to cellular imaging. , 2008, Accounts of chemical research.

[57]  I. Solomon.  Relaxation Processes in a System of Two Spins , 1955 .

[58]  G. Poirier,et al.  The Self-Assembly Mechanism of Alkanethiols on Au(111) , 1996, Science.

[59]  T. Prohaska,et al.  Quantifying Thiol Ligand Density of Self-Assembled Monolayers on Gold Nanoparticles by Inductively Coupled Plasma–Mass Spectrometry , 2013, ACS nano.