Au nanoparticles (NPs) with protecting organothiolate ligands and core diameters smaller than 2 nm are interesting materials because their size-dependent properties range from metal-like to molecule-like. This Account focuses on the most thoroughly investigated of these NPs, Au(25)L(18). Future advances in nanocluster catalysis and electronic miniaturization and biological applications such as drug delivery will depend on a thorough understanding of nanoscale materials in which molecule-like characteristics appear. This Account tells the story of Au(25)L(18) and its associated synthetic, structural, mass spectrometric, electron transfer, optical spectroscopy, and magnetic resonance results. We also reference other Au NP studies to introduce helpful synthetic and measurement tools. Historically, nanoparticle sizes have been described by their diameters. Recently, researchers have reported actual molecular formulas for very small NPs, which is chemically preferable to solely reporting their size. Au(25)L(18) is a success story in this regard; however, researchers initially mislabeled this NP as Au(28)L(16) and as Au(38)L(24) before correctly identifying it by electrospray-ionization mass spectrometry. Because of its small size, this NP is amenable to theoretical investigations. In addition, Au(25)L(18)'s accessibility in pure form and molecule-like properties make it an attractive research target. The properties of this NP include a large energy gap readily seen in cyclic voltammetry (related to its HOMO-LUMO gap), a UV-vis absorbance spectrum with step-like fine structure, and NIR fluorescence emission. A single crystal structure and theoretical analysis have served as important steps in understanding the chemistry of Au(25)L(18). Researchers have determined the single crystal structure of both its "native" as-prepared form, a [N((CH(2))(7)CH(3))(4)(1+)][Au(25)(SCH(2)CH(2)Ph)(18)(1-)] salt, and of the neutral, oxidized form Au(25)(SCH(2)CH(2)Ph)(18)(0). A density functional theory (DFT) analysis correctly predicted essential elements of the structure. The NP is composed of a centered icosahedral Au(13) core stabilized by six Au(2)(SR)(3) semirings. These semirings present interesting implications regarding other small Au nanoparticle clusters. Many properties of the Au(25) NP result from these semiring structures. This overview of the identification, structure determination, and analytical properties of perhaps the best understood Au nanoparticle provides results that should be useful for further analyses and applications. We also hope that the story of this nanoparticle will be useful to those who teach about nanoparticle science.

Monolayer-protected clusters were prepared by procedures like those yielding Au25L18 (where L=-SCH2CH2Ph=-SC2Ph) but using, instead, mixtures of Au and Pd salts, as starting materials, with the intent of creating and characterizing Au25-xMxL18 clusters. Isolation of small nanoparticle product followed by partial ligand exchange to introduce thiolated poly(ethylene glycol) (SPEG=-S(CH2CH2O)5CH3) into the nanoparticle ligand shell enabled characterization of the Au25-xMxL18 content by positive mode electrospray ionization mass spectrometry (ESI-MS). For synthetic feed mole ratios of Au:Pd of 9:1 and 13:12, electrospray spectra of the PEGylated MPCs showed that the reaction and isolation produce a mixture of Au25(SC2Ph)18 and a mono-Pd nanoparticle Au24Pd(SC2Ph)18. A higher proportion of the mono-Pd nanoparticle is produced by the 13:12 mole ratio, and also when the thiol:metal ratio was lowered, according to ESI-MS and MALDI-TOF-MS. As the nanoparticle mixture is enriched, by solvent fractionations, in Au24Pd(SC2Ph)18 relative to Au25(SC2Ph)18, the distinctive optical and electrochemical signatures of Au25(SC2Ph)18 are replaced by Au24Pd(SC2Ph)18 nanoparticle responses, which are very different, even though only one Au atom is replaced by a Pd atom.

New approaches to electrospray ionization mass spectrometry (ESI-MS)swith exact compositional assignmentssof small (Au25) nanoparticles with uniform and mixed protecting organothiolate monolayers are described. The results expand the scope of analysis and reveal a rich chemistry of ionization behavior. ESI-MS of solutions of phenylethanethiolate monolayer-protected gold clusters (MPCs), Au25(SC2Ph)18, containing alkali metal acetate salts (MOAc) produce spectra in which, for Na + , K + , Rb + , and Cs + acetates, the dominant species are MAu25(SC2Ph)18 2+ and M2Au25(SC2Ph)18 2+ . Li + acetates caused ligand loss. This method was extended to the analysis of Au25 MPCs with mixed monolayers, where thiophenolate (-SPh), hexanethiolate (-SC6), or biotinylated (-S-PEG-biotin) ligands had been introduced by ligand exchange. In negative-mode ESI-MS, no added reagents were needed in order to observe Au25(SC2Ph)18and to analyze mixed monolayer Au25 MPCs prepared by ligand exchange with 4-mercaptobenzoic acid, HSPhCOOH, which gave spectra through deprotonation of the carboxylic acids. Adducts of tetraoctylammonium (Oct4N + ) with -SPhCOOsites were also observed. Mass spectrometry is the only method that has demonstrated capacity for measuring the exact distribution of ligand-exchange products. The possible origins of the different Au25 core charges (1-, 0, 1+, 2+) observed during electrospray ionization are discussed.

A single phase (THF) synthesis of monodisperse [Oct(4)N(+)][Au(25)(SR)(18)(-)] nanoparticles is described that yields insights into pathways by which it is formed from initially produced larger nanoparticles. Including the Oct(4)N(+)Br(-) salt in a reported single phase synthetic procedure enables production of reduced nanoparticles having a fully occupied HOMO molecular energy level (Au(25)(SR)(18)(-), as opposed to a partially oxidized state, Au(25)(SR)(18)(0)). The revised synthesis accommodates several (but not all) different thiolate ligands. The importance of acidity, bromide, and dioxygen on Au(25) formation was also assessed. The presence of excess acid in the reaction mixture steers the reaction toward making Au(25)(SR)(18); while bromide does not seem to affect Au(25) formation, but it may play a role in maintaining the -1 oxidation state. Conducting the nanoparticle synthesis and "aging" period in the absence of dioxygen (under Ar) does not produce small nanoparticles, providing insights into the pathway of reaction product "aging" in the synthesis solvent, THF. The "aging" process favors the Au(25)(-) moiety as an end point and possibly involves degradation of larger nanoparticles by hydroperoxides formed from THF and oxygen.

Electrospray ionization triple-quadrupole mass spectrometry of ca. 1.6 nm diameter thiolate-protected gold nanoparticles has been achieved at higher resolution than in previous reports. The results reveal the presence of nanoparticles with formulas Au(144)L(60) and Au(146)L(59), present in the sample as a mixture. The improved resolution is based on lowering m/z by exchanging multiple [-SC(11)H(22)N(CH(2)CH(3))(3)(+)] ligands into the original [-S(CH(2))(5)CH(3)] ligand shell. The nanoparticles are thus intrinsically cationized and appear as a series of 10+ to 15+ mass spectral peaks. The assigned state of charge was confirmed by a collision-induced dissociation measurement.