Christopher J. Ackerson

A unified view of ligand-protected gold clusters as superatom complexes

Synthesis, characterization, and functionalization of self-assembled, ligand-stabilized gold nanoparticles are long-standing issues in the chemistry of nanomaterials. Factors driving the thermodynamic stability of well documented discrete sizes are largely unknown. Herein, we provide a unified view of principles that underlie the stability of particles protected by thiolate (SR) or phosphine and halide (PR3, X) ligands. The picture has emerged from analysis of large-scale density functional theory calculations of structurally characterized compounds, namely Au102(SR)44, Au39(PR3)14X6−, Au11(PR3)7X3, and Au13(PR3)10X23+, where X is either a halogen or a thiolate. Attributable to a compact, symmetric core and complete steric protection, each compound has a filled spherical electronic shell and a major energy gap to unoccupied states. Consequently, the exceptional stability is best described by a “noble-gas superatom” analogy. The explanatory power of this concept is shown by its application to many monomeric and oligomeric compounds of precisely known composition and structure, and its predictive power is indicated through suggestions offered for a series of anomalously stable cluster compositions which are still awaiting a precise structure determination.

Inhibition of HIV fusion with multivalent gold nanoparticles.

The design and synthesis of a multivalent gold nanoparticle therapeutic is presented. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diameter gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small molecules on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics.

Structural and theoretical basis for ligand exchange on thiolate monolayer protected gold nanoclusters.

Ligand exchange reactions are widely used for imparting new functionality on or integrating nanoparticles into devices. Thiolate-for-thiolate ligand exchange in monolayer protected gold nanoclusters has been used for over a decade; however, a firm structural basis of this reaction has been lacking. Herein, we present the first single-crystal X-ray structure of a partially exchanged Au(102)(p-MBA)(40)(p-BBT)(4) (p-MBA = para-mercaptobenzoic acid, p-BBT = para-bromobenzene thiol) with p-BBT as the incoming ligand. The crystal structure shows that 2 of the 22 symmetry-unique p-MBA ligand sites are partially exchanged to p-BBT under the initial fast kinetics in a 5 min timescale exchange reaction. Each of these ligand-binding sites is bonded to a different solvent-exposed Au atom, suggesting an associative mechanism for the initial ligand exchange. Density functional theory calculations modeling both thiol and thiolate incoming ligands postulate a mechanistic pathway for thiol-based ligand exchange. The discrete modification of a small set of ligand binding sites suggests Au(102)(p-MBA)(44) as a powerful platform for surface chemical engineering.

Synthesis and Bioconjugation of 2 and 3 nm-Diameter Gold Nanoparticles

By adjustment of solvent conditions for synthesis, virtually monodisperse 4-mercaptobenzoic acid (p-MBA) monolayer-protected gold nanoparticles, 2 and 3 nm in diameter, were obtained. Large single crystals of the 2 nm particles could be grown from the reaction mixture. Uniformity was also demonstrated by the formation of two-dimensional arrays and by quantitative high-angle annular dark-field scanning transmission electron microscopy. The 2 and 3 nm particles were spontaneously reactive for conjugation with proteins and DNA, and further reaction could be prevented by repassivation with glutathione. Conjugates with antibody Fc fragment could be used to identify TAP-tagged proteins of interest in electron micrographs, through the binding of a pair of particles to the pair of protein A domains in the TAP tag.

Chiral Phase Transfer and Enantioenrichment of Thiolate-Protected Au102 Clusters

The Au102(p-MBA)44 cluster (p-MBA: para-mercaptobenzoic acid) is observed as a chiral compound comprised of achiral components in its single-crystal structure. So far the enantiomers observed in the crystal structure are not isolated, nor is the circular dichroism spectrum known. A chiral phase transfer method is presented which allows partial resolution of the enantiomers by the use of a chiral ammonium bromide, (-)-1R,2S-N-dodecyl-N-methylephedrinium bromide ((-)-DMEBr). At sufficiently low concentration of (-)-DMEBr, the phase transfer from water to chloroform is incomplete. Both the aqueous and organic phases show optical activity of near mirror image relationship. Differences in the spectra are ascribed to the formation of diastereomeric salts. At high concentrations of (-)-DMEBr, full phase transfer is observed. The organic phase, however, still displays optical activity. We assume that one of the diastereomers has very strong optical activity, which overrules the cancelation of the spectra with opposite sign. Comparison with computations further corroborates the experimental data and allows a provisional assignment of handedness of each fraction.

Optical Properties and Electronic Energy Relaxation of Metallic Au144(SR)60 Nanoclusters

Electronic energy relaxation of Au144(SR)60(q) ligand-protected nanoclusters, where SR = SC6H13 and q = -1, 0, +1, and +2, was examined using femtosecond time-resolved transient absorption spectroscopy. The observed differential transient spectra contained three distinct components: (1) transient bleaches at 525 and 600 nm, (2) broad visible excited-state absorption (ESA), and (3) stimulated emission (SE) at 670 nm. The bleach recovery kinetics depended upon the excitation pulse energy and were thus attributed to electron-phonon coupling typical of metallic nanostructures. The prominent bleach at 525 nm was assigned to a core-localized plasmon resonance (CLPR). ESA decay kinetics were oxidation-state dependent and could be described using a metal-sphere charging model. The dynamics, emission energy, and intensity of the SE peak exhibited dielectric-dependent responses indicative of Superatom charge transfer states. On the basis of these data, the Au144(SR)60 system is the smallest-known nanocluster to exhibit quantifiable electron dynamics and optical properties characteristic of metals.

Superatom Paramagnetism Enables Gold Nanocluster Heating in Applied Radiofrequency Fields

The Au102(pMBA)44 nanocluster becomes a superatom paramagnet after chemical oxidation. Solutions of paramagnetic Au102(pMBA)44 heat in an oscillating magnetic field component of an RF field, but not in the electric component. Combined, these experiments suggest that paramagnetic Au102(pMBA)44 heats through interactions of spin magnetic moment with an external oscillating magnetic field. These results may clarify some current controversy regarding gold nanoparticle heating in radiofrequency fields.

Ligand symmetry-equivalence on thiolate protected gold nanoclusters determined by NMR spectroscopy

The Au(144)(SR)(60) nanocluster has been a subject of structural conjecture since its initial description over a decade ago as a 29 kDa compound, yet a decisive empirical structure is elusive. Herein we show that (1)H NMR spectroscopy can provide a detailed view of ligand-layer equivalence for thiolate protected gold nanoclusters. We show that Au(25)(SR)(18), Au(38)(SR)(24) and Au(102)(SR)(44) nanoclusters have (1)H NMR spectra where the number of distinct chemical environments for the R-groups is equivalent to the number of symmetry environments of the sulfur headgroups, which anchor each ligand. We also show that the Au(144)(SR)(60)(1)H NMR spectrum is consistent with a previously published DFT-derived structural model for Au(144)(SR)(60). We suggest that this analysis may be extended to other structurally obscure nanoclusters, such as a ∼59 kDa compound for which we observe up to four symmetry environments.

Structural Basis for Ligand Exchange on Au25(SR)18

The single-crystal X-ray structure of Au25(SC2H4Ph)16(pBBT)2 is presented. The crystallized compound resulted from ligand exchange of Au25(SC2H4Ph)18 with pBBT as the incoming ligand, and for the first time, ligand exchange is structurally resolved on the widely studied Au25(SR)18 compound. A single ligand in the asymmetric unit is observed to exchange, corresponding to two ligands in the molecule because of the crystallographic symmetry. The ligand-exchanged Au25 is bonded to the most solvent-exposed Au atom in the structure, making the exchange event consistent with an associative mechanism. The apparent nonexchange of other ligands is rationalized through possible selective crystallization of the observed product and differential bond lengths.

Site-specific biomolecule labeling with gold clusters.

Site-specific labeling of biomolecules in vitro with gold clusters can enhance the information content of electron cryomicroscopy experiments. This chapter provides a practical overview of well-established techniques for forming biomolecule/gold cluster conjugates. Three bioconjugation chemistries are covered: linker-mediated bioconjugation, direct gold-biomolecule bonding, and coordination-mediated bonding of nickel(II) nitrilotriacetic acid (NTA)-derivatized gold clusters to polyhistidine (His)-tagged proteins.