Although gold is the subject of one of the most ancient themes of investigation in science, its renaissance now leads to an exponentially increasing number of publications, especially in the context of emerging nanoscience and nanotechnology with nanoparticles and self-assembled monolayers (SAMs). We will limit the present review to gold nanoparticles (AuNPs), also called gold colloids. AuNPs are the most stable metal nanoparticles, and they present fascinating aspects such as their assembly of multiple types involving materials science, the behavior of the individual particles, size-related electronic, magnetic and optical properties (quantum size effect), and their applications to catalysis and biology. Their promises are in these fields as well as in the bottom-up approach of nanotechnology, and they will be key materials and building block in the 21st century. Whereas the extraction of gold started in the 5th millennium B.C. near Varna (Bulgaria) and reached 10 tons per year in Egypt around 1200-1300 B.C. when the marvelous statue of Touthankamon was constructed, it is probable that “soluble” gold appeared around the 5th or 4th century B.C. in Egypt and China. In antiquity, materials were used in an ecological sense for both aesthetic and curative purposes. Colloidal gold was used to make ruby glass 293 Chem. Rev. 2004, 104, 293−346

Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology.

Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchemical beginnings, gold nanoparticles exhibit physical properties that are truly different from both small molecules and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This critical review will provide insights into the design, synthesis, functionalization, and applications of these artificial molecules in biomedicine and discuss their tailored interactions with biological systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnology-enabled biomedicine is not simply an act of ‘gilding the (nanomedicinal) lily’, but that a new ‘Golden Age’ of biomedical nanotechnology is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chemical and physical methods of functionalizing gold nanoparticles with compounds that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biological systems and their long-term term effects on human health and reproduction (472 references).

The golden age: gold nanoparticles for biomedicine

Much progress has been made over the past ten years on the synthesis of monodisperse spherical nanocrystals. Mechanistic studies have shown that monodisperse nanocrystals are produced when the burst of nucleation that enables separation of the nucleation and growth processes is combined with the subsequent diffusion-controlled growth process through which the crystal size is determined. Several chemical methods have been used to synthesize uniform nanocrystals of metals, metal oxides, and metal chalcogenides. Monodisperse nanocrystals of CdSe, Co, and other materials have been generated in surfactant solution by nucleation induced at high temperature, and subsequent aging and size selection. Monodisperse nanocrystals of many metals and metal oxides, including magnetic ferrites, have been synthesized directly by thermal decomposition of metal-surfactant complexes prepared from the metal precursors and surfactants. Nonhydrolytic sol-gel reactions have been used to synthesize various transition-metal-oxide nanocrystals. Monodisperse gold nanocrystals have been obtained from polydisperse samples by digestive-ripening processes. Uniform-sized nanocrystals of gold, silver, platinum, and palladium have been synthesized by polyol processes in which metal salts are reduced by alcohols in the presence of appropriate surfactants.

Synthesis of monodisperse spherical nanocrystals.

Atomically precise pieces of matter of nanometer dimensions composed of noble metals are new categories of materials with many unusual properties. Over 100 molecules of this kind with formulas such as Au25(SR)18, Au38(SR)24, and Au102(SR)44 as well as Ag25(SR)18, Ag29(S2R)12, and Ag44(SR)30 (often with a few counterions to compensate charges) are known now. They can be made reproducibly with robust synthetic protocols, resulting in colored solutions, yielding powders or diffractable crystals. They are distinctly different from nanoparticles in their spectroscopic properties such as optical absorption and emission, showing well-defined features, just like molecules. They show isotopically resolved molecular ion peaks in mass spectra and provide diverse information when examined through multiple instrumental methods. Most important of these properties is luminescence, often in the visible–near-infrared window, useful in biological applications. Luminescence in the visible region, especially by clusters prot...

Atomically Precise Clusters of Noble Metals: Emerging Link between Atoms and Nanoparticles

Small gold clusters (∼1 nm) protected by molecules of a tripeptide, glutathione (GSH), were prepared by reductive decomposition of Au(I)−SG polymers at a low temperature and separated into a number of fractions by polyacrylamide gel electrophoresis (PAGE) Chemical compositions of the fractionated clusters determined previously by electrospray ionization (ESI) mass spectrometry (Negishi, Y et al J Am Chem Soc 2004, 126, 6518) were reassessed by taking advantage of freshly prepared samples, higher mass resolution, and more accurate mass calibration; the nine smallest components are reassigned to Au10(SG)10, Au15(SG)13, Au18(SG)14, Au22(SG)16, Au22(SG)17, Au25(SG)18, Au29(SG)20, Au33(SG)22, and Au39(SG)24 These assignments were further confirmed by measuring the mass spectra of the isolated Au:S(h-G) clusters, where h-GSH is a homoglutathione It is proposed that a series of the isolated Au:SG clusters corresponds to kinetically trapped intermediates of the growing Au cores The relative abundance of

Glutathione-Protected Gold Clusters Revisited: Bridging the Gap between Gold(I)−Thiolate Complexes and Thiolate-Protected Gold Nanocrystals

A simple method is proposed to control the size of alkanethiol-protected Au nanoparticles by heat treatment in the solid state. The mean diameter of the Au nanoparticles prepared by Brust's two-phase method (∼1.5 nm) was evolved to 3.4−9.7 nm by heating to 150−250 °C in air. The uniform growth of nanoparticles was not observed when tetraoctylammonium bromide (TOAB), which was used as a phase-transfer agent during the preparation of Au nanoparticles, was removed before the particle growth process. The crystal structures of Au nanoparticles and alkanethiol ligand structures on Au nanoparticles were characterized before and after the heat treatment. The size-evolution mechanism was discussed on the basis of the thermodynamic model. The heat-treated Au nanoparticles easily formed self-assembled 2D superlattices with hexagonal packing, where the alkanethiol protective agents with an all-trans conformation were estimated to interpenetrate each other.

Size Evolution of Alkanethiol-Protected Gold Nanoparticles by Heat Treatment in the Solid State

For fabrication of a planar array of 1D chains of gold nanoparticles prepared by a chemical process, the faceted (110) planes of sodium chloride crystals were used as templates to produce nanoscale ridge-and-valley structured carbon layers by a vacuum process. When these carbon layers loaded on copper grids were dipped in toluene solution of 3.4 nm gold nanoparticles followed by natural dry, a planar array of 1D chains of gold nanoparticles were formed on carbon layers, where the nanoparticles were immobilized predominantly in valleys and partly on ridges of carbon layers.

Takami Shimizu

Papers

Size Evolution of Alkanethiol-Protected Gold Nanoparticles by Heat Treatment in the Solid State

Planar array of 1D gold nanoparticles on ridge-and-valley structured carbon.