Mathias Brust

Synthesis of thiol-derivatised gold nanoparticles in a two-phase Liquid–Liquid system

Using two-phase (water–toluene) reduction of AuCl4– by sodium borohydride in the presence of an alkanethiol, solutions of 1–3 nm gold particles bearing a surface coating of thiol have been prepared and characterised; this novel material can be handled as a simple chemical compound.

Spontaneous ordering of bimodal ensembles of nanoscopic gold clusters

The controlled fabrication of very small structures at scales beyond the current limits of lithographic techniques is a technological goal of great practical and fundamental interest. Important progress has been made over the past few years in the preparation of ordered ensembles of metal and semiconductor nanocrystals. For example, monodisperse fractions of thiol-stabilized gold nanoparticles have been crystallized into two- and three-dimensional superlattices. Metal particles stabilized by quaternary ammonium salts can also self-assemble into superlattice structures,. Gold particle preparations with quite broad (polydisperse) size distributions also show some tendency to form ordered structures by a process involving spontaneous size segregation,. Here we report that alkanethiol-derivatized gold nanocrystals of different, well defined sizes organize themselves spontaneously into complex, ordered two-dimensional arrays that are structurally related to both colloidal crystals and alloys between metals of different atomic radii. We observe three types of organization: first, different-sized particles intimately mixed, forming an ordered bimodal array (Fig. 1); second, size-segregated regions, each containing hexagonal-close-packed monodisperse particles (Fig. 2); and third, a structure in which particles of several different sizes occupy random positions in a pseudo-hexagonal lattice (Fig. 3).

Uptake and Intracellular Fate of Surface-Modified Gold Nanoparticles

Understanding and controlling the interactions between nanoscale objects and living cells is of great importance for arising diagnostic and therapeutic applications of nanoparticles and for nanotoxicology studies. Here we report a detailed transmission electron microscopy (TEM) study of the uptake of ca. 16 nm surface-modified gold nanoparticles by human fibroblast cells (HeLa cells). It is demonstrated that the well-established endosomal route of cellular uptake can be bypassed to a significant extent by controlling the uptake mechanism either via the delivery of the nanoparticles by liposomes or by surface modification of the nanoparticles with so-called cell penetrating peptides (CPPs). Successful nuclear targeting is demonstrated using surface modification with a cocktail of CPPs and a peptide acting as a nuclear localization signal (NLS).

Some recent advances in nanostructure preparation from gold and silver particles: a short topical review

Recent developments in nanostructure self-assembly from gold and silver particles are reviewed. A brief historical background of the field is given, followed by a selection of topics which are of particular current interest. An overview of the preparation of thiol-stabilised gold and silver nanoparticles and their spontaneous self-organisation into well-ordered superlattices is presented. Distance-dependent metal insulator transitions in ensembles of nanoparticles are discussed, along with a previously unpublished measurement of optical properties of dithiol-linked thin films of gold nanoparticles. Recent approaches to more complex nano-architectures are reviewed, including the use of various templates and of DNA base pair recognition. Some aspects of nanoscopic surface chemistry of gold particles including the evolution of molecular recognition sites are reviewed. Current and potential future applications are discussed.

Gold--an introductory perspective.

We introduce the collection of reviews in this thematic issue of Chemical Society Reviews that demonstrate and discuss the current cutting edge research in the field of gold chemistry and materials science as it stands today. We also highlight achievements in the fields of gold catalysis, gold nanoparticles and the preparative, structural and theoretical chemistry of gold, and discuss the remaining challenges and opportunities. Our aim is to inspire further discovery in these new and deeply fascinating fields.

Synthesis and reactions of functionalised gold nanoparticles

Stable functionalised gold nanoparticles are prepared by simultaneous reduction of tetrachloroaurate ions and attachment of bifunctional organic thiol molecules to the growing gold nuclei leading to a material whose chemical behaviour is characterised by the vacant functionality of the bifunctional thiol ligand.

From monolayers to nanostructured materials : an organic chemist's view of self-assembly

Abstract Simple methods are described for the production of gold nanoparticles with narrow size distributions by reduction of tetrachloroaurate solutions in the presence of thiol-containing organic compounds which self-assemble on the gold surface. Stable solutions of somewhat larger particles can be produced if the thiol is absent. The thiol-derivatized materials are stable in air over long periods and can be handled in much the same way as simple organic compounds. Using dithiols as the derivatizing spacer units, ways have been developed for the preparation of materials in three dimensional form and as thin films attached to a solid substrate. Such materials show conductivities that mimic the behaviour of semiconductors and that depend markedly on the structure of the dithiol used to link the gold particles together. The increase in conductivity with increasing temperature probably involves activated electron hopping from particle to particle. Surfaces treated with a coating of the materials show electroreflectance changes with applied potential that also differ according to the structure of the dithiol spacer. Unusual effects have been observed on heterogeneous electron transfer from electrode surfaces treated with layers of the gold nanoparticles and dithiol spacers. Applications for these nanostructured materials can be envisaged, which range from submicroelectronic devices and circuitry to electrical modification of the reflectance of glass. Such applications will require a multidisciplinary approach with a substantial organic chemical research input.

A Multidentate Peptide for Stabilization and Facile Bioconjugation of Gold Nanoparticles

Gold nanoparticles of two different sizes stabilized by a 15-mer peptide ligand specifically designed for this purpose have been prepared in aqueous solution and characterized by UV-vis spectroscopy and TEM. The presence of the ligand and its binding mode to the particles via its four cystein thiols is evidenced by FTIR and NMR spectroscopy. Biotinylation of the particles via binding to a freely accessible lysine residue is demonstrated.

Negotiation of Intracellular Membrane Barriers by TAT-Modified Gold Nanoparticles

This paper contributes to the debate on how nanosized objects negotiate membrane barriers inside biological cells. The uptake of peptide-modified gold nanoparticles by HeLa cells has been quantified using atomic emission spectroscopy. The TAT peptide from the HIV virus was singled out as a particularly effective promoter of cellular uptake. The evolution of the intracellular distribution of TAT-modified gold nanoparticles with time has been studied in detail by TEM and systematic image analysis. An unusual trend of particles disappearing from the cytosol and the nucleus and accumulating massively in vesicular bodies was observed. Subsequent release of the particles, both by membrane rupture and by direct transfer across the membrane boundary, was frequently found. Ultimately, near total clearing of particles from the cells occurred. This work provides support for the hypothesis that cell-penetrating peptides can enable small objects to negotiate membrane barriers also in the absence of dedicated transport mechanisms.

Cathepsin L Digestion of Nanobioconjugates upon Endocytosis

Understanding the dynamic fate and interactions of bioconjugated nanoparticles within living cells and organisms is a prerequisite for their use as in situ sensors or actuators. While recent research has provided indications on the effect of size, shape, and surface properties of nanoparticles on their internalization by living cells, the biochemical fate of the nanoparticles after internalization has been essentially unknown. Here we show that, upon internalization in a wide range of mammalian cells, biological molecules attached to the nanoparticles are degraded within the endosomal compartments through peptide cleavage by the protease cathepsin L. Importantly, using bioinformatics tools, we show that cathepsin L is able to cleave more than a third of the human proteome, indicating that this degradation process is likely to happen to most nanoparticles conjugated with peptides and proteins and cannot be ignored in the design of nanomaterials for intracellular applications. Preservation of the bioconjugates can be achieved by a combination of cathepsin inhibition and endosome disruption.