Gold was initially considered to be catalytically inactive for a long time [1,2]. This changed when gold was seen in the context of the nanometric scale, which has indeed shown it to have excellent catalytic activity as a homogeneous or a heterogeneous catalyst [3-12]. The comprehensive reviews and books about gold nanoparticles as catalysts have appeared, which cover many important aspects related to preparation of gold catalysts and their catalytic properties [13-19]. However, almost all of the current studies only give rise to an ensemble average of the catalytic performance due to the structural polydispersity and heterogeneity of conventional nanoparticles catalysts. Although significant efforts have been invested in preparing well defined nanoparticles, fundamental nanocatalysis research still lags significantly behind. Due to the size dispersity of conventional nanoparticles, it is not possible to achieve an in-depth understanding of the origin of the size-dependence of nanogold catalysts; moreover, it is impossible to identify the catalytically active species in nanoparticle catalysis.

Therefore, it is of paramount importance to attain atomically precise gold nanoparticles and use such nanoparticles as well defined catalysts. By solving their atomic structure of the nanoparticles, one will be able to precisely correlate the catalytic properties with the exact atomic structure of the nanoparticles and to learn what controls the surface activation, surface active site structure and catalytic mechanism. Atomically monodisperse gold nanoclusters (referred to as Au_n, n = number of metal atom in particle, n ranging from a dozen to hundreds) are ideally composed of an exact number of gold atoms and are unique and vastly different from their larger counterparts—gold nanocrystals (typically 3–100 nm). Small Au_n nanoclusters (n < 100) behave like molecules and exhibit strong quantum confinement effects; relatively larger ones (100 < n <200) exhibit intermediate properties between molecular behavior and metallic properties [20]. Overall, the non-metallic behavior of Au_n in both size regimes is particularly important for nanocatalysis. More importantly, on the basis of their atom packing structures and unique electronic properties, one could indeed study a precise correlation of structural properties with catalytic properties, identify the catalytically active sites on the gold particle and unravel the nature of gold catalysis [21-27]. This has long been an important task in nanocatalysis [28-36].

The emphasis of the review will be on the preparation of monodisperse gold nanocluster catalysts and precise structure-catalytic activity relationships, the investigation of which is currently being actively pursued.

The atom packing structures of Au_n nanoclusters are critical for understanding the catalytic properties of nanoclusters and theoretical modeling of mechanistic steps. The synthesis of gold nanoclusters in solution phase has been developed, including the electrophoretic separation [37,38], the kinetic control approach [39,40], and the thiol etching method [41,42]. Interestingly, these structures of Au_n nanoclusters do not resemble the face-centered cubic (fcc) structure of their larger counterparts: gold nanocrystals or bulk gold. Firstly, the structural model emerged from the density functional calculation provides a glimpse into a prevailing structural concept with an atomically Au/ligand interface and compact gold core [43-57].

The early theoretical studies confirmed that Au₁₆ and Au₂₀ clusters have tetrahedral structures. Au₂₀ cluster contains a prolate Au₈ core and four level-3 extended staple motifs -RS-Au-RS-Au-RS-Au-RS-. This highly stable cluster may represent a structural evolution of thiolate protected gold clusters from the homoleptic core-free structure to the core-stacked structure (Figure 1) [58]. The geometry of Au₁₆ is derived from the T_d-symmetric Au₂₀ by removing the four vertex atoms and allowing for an outward relaxation of the 4 face-centered atoms [59]. Au₃₄ cluster has been predicted for a C₃ structure constructured from a more symmetric C_3v geometry via a twist (see Figure 2) [60]. Au₃₉ cluster has an approximate D3 point group symmetry, with the gold atoms forming a hexagonal antiprismatic cage, filled by one bulk-coordinated gold atom (Figure 3) [61].

The true monodispersity of Au_n nanoclusters allows us to grow single crystals and determines their total structures by X-ray crystallography [62-65]. By carefully controlling the experimental conditions of the nanocluster synthesis, a specific chemical environment is created, which leads to exclusive formation of atomically precise, one-sized Au_n nanoclusters in high yield and high purity. The experimental breakthroughs focus on the crystal structures of three Au_n(SR)_m nanoclusters, including Au₁₀₂(S-C₆H₄-p-COOH)₄₄, Au₂₅(SC₂H₄Ph)₁₈, and Au₃₈(SC₂H₄Ph)₂₄. We start with the smallest Au₂₅(SR)₁₈ cluster. The control kinetics toward the synthesis of one-sized Au₂₅ cluster involves two steps (Figure 4): (i) the reduction of Au(III) to Au(I) by thiols, forming an intermediate of Au-(I):SR complexes; and (ii) further reduction of Au(I) to Au(0) by a strong reducing agent (NaBH₄). The control over the reaction temperature (0 °C) and stirring condition can generate a particular aggregation state of the Au(I):SR intermediates that leads to the exclusive formation of Au₂₅ nanoclusters [39].

X-ray crystallographic analysis shows that the Au₂₅ nanocluster features a centered icosahedral Au₁₃ core (Figure 5(A)), further capped by a second shell comprised of the remaining 12 Au atoms [64]. Viewed along the three mutually perpendicular C₂ axes of the icosahedron, the 12 exterior Au atoms form six pairs and are situated around the ±x, ±y, and ±z axes, respectively (Figure 5(B)). Another view of the Au₂₅(SR)₁₈ structure is an Au₁₃ icosahedral kernel capped by six staple motifs of –S(R)–Au–S(R)–Au–S(R)– along the ±x, ±y, and ±z axes (Figure 5(C)). Apparently, the 12 exterior Au atoms form an open shell on the Au₁₃ icosahedron. An icosahedron has 20 triangular faces (Au₃), but only 12 of them are face-capped, which leaves eight Au₃ triangular faces uncapped. The entire Au₂₅ cluster is protected by 18 −SR ligands. The charge state (q = −1, 0) of [Au₂₅(SR)₁₈]^q does not affect the atomic structure of the cluster [66,67].

The next size is the 38-atom Au₃₈(SR)₂₄ [65,68]. The high yield synthesis of monodisperse Au₃₈ nanoclusters involves two main steps (Figure 6): first, glutathionate (-SG) protected polydisperse Au_n clusters (n ranging from 38 to 102) are synthesized by reducing Au(I)-SG in acetone; subsequently, the size-mixed Au_n clusters react with excess phenylethylthiol (PhC₂H₄SH) for 40 h at 80 °C, which leads to Au₃₈(SC₂H₄Ph)₂₄ clusters of molecular purity.

The core of Au₃₈(SR)₂₄ is a face-fused biicosahedral Au₂₃ (13 + 13 − 3 = 23) (Figure 7(A)) [65]. The fusion of the two icosahedra occurs along a common C₃ axis. Note that the way the structure is anatomized does not necessarily mean the real growth mechanism of the cluster. The Au₂₃ rod is structurally strengthened by three monomeric -SR-Au-RS- staples (Figure 7(C)). Then, the top icosa-hedron is further capped by three -SR-Au-SR-Au-RS- dimeric staples, which are arranged in a rotative fashion, resembling a tri-blade “fan” or “propeller” (Figure 7(D) and (E)). A similar arrangement of the other three staples is found on the bottom icosahedron, but the bottom “propeller” rotates by approximately 60° relative to the top one, forming a staggered dual-propeller configuration. In fact, the entire cluster is chiral due to the rotative arrangement of the dimeric staples. A larger Au_n(SR)_m nanocluster is Au₁₀₂(SR)₄₄ [62,69]. The gold particles were coated with p-MBA and crystallized from a solution containing 40% methanol, 300 mM sodium chloride, and 100 mM sodium acetate, at pH 2.5. Interestingly, this cluster has a truncated Au₄₉ Marks decahedral kernel (Figure 8B and C), which is based on a fivefold symmetric 19-atom kernel (Figure 8(A)). The Au₄₉ kernel is further capped by two 15-atom caps at the top/bottom, respectively (Figure 8(D) and (E)). The resultant Au₇₉ kernel is capped by five -SR-Au-SR- monomeric staples on the top and another five at the bottom, and nine monomers and two dimers (-SR-Au-SR-Au-SR-) at the waist. The arrangement of 13 gold atoms at the waist (from nine monomers and two dimers, 9 + 2 × 2 = 13) destroys the fivefold symmetry of the entire Au₁₀₂ cluster, so Au₁₀₂ cluster has two chiral isomers.

Such nanoclusters provide a new opportunity for unraveling catalysis at an atomic level. The catalytic activity has been explained by various complementary mechanisms, such as charging effects, geometric fluxionality, particle-size-dependent metal-insulator transition and electronic quantum size effects [70-76]. The theoretical investigations of the catalytic activity of these small gold nanoclusters (up to a few tens of atoms) were studied a decade ago [29,75]. Density functional calculations showed that the gold particle sizes fall into a region where quantum size effects are expected to dominate the reactivity of gold. Hakkinen et al. showed, by considering a series of structurally well-defined gold clusters with diameter between 1.2 and 2.4 nm, that electronic quantum size effects, particularly the magnitude of HOMO-LUMO energy gap, have a decisive role in activated-form of the nanocatalysts [70].

The experiments have given strong indications of the catalytic activity of supersmall well-defined gold clusters. Recently, Turner et al. [77] reported the selective oxidation of styrene with O₂ by nanocatalysts derived from solution phase protected Au₅₅ clusters and found the activity of Au₅₅ nanocatalyst was super to that of Au nanocrystals (>3 nm). A sharp size threshold in catalytic activity was found such that that, when fed with O₂ alone, the catalytic activity is quenched for Au particles with diameters greater than or equal to 2 nm (Figure 10(d)). Since the crystal structure of Au₅₅ cluster has been utterly unknown so far, it is not easy to correlate structural properties with catalytic properties.

Tsukuda et al. studied the effect of electronic structures of Au clusters on aerotic oxidation catalysis [78-80]. The catalytic activity is enhanced with increasing electron density on the Au core. They proposed that electron transfer from the anionic gold core into LUMO(π*) of O₂ forms superoxo- or peroxo-like species, which may play an essential role in the oxidation of alcohol (Figure 11). This work provides a principle for the synthesis of aerobic oxidation catalysts based on the electronic structures of Au clusters and more electronic charge should be deposited into the high-lying orbitals of Au clusters by doping with electropositive elements or by interaction with nucleophilic sites of stabilizing molecules.

Recently, Jin et al. reported the Au_n(SR)_m nanocluster catalysts for selective oxidation of styrene using three robust supersmall Au_n nanoclusters, including Au₂₅ (1.0 nm), Au₃₈ (1.3 nm) and Au₁₄₄ (1.6 nm) [23,26]. The catalytic activity of Au_n nanocluster catalysts exhibits a strong dependence on size (n); the smaller Au_n(SR)_m nanoclusters give rise to a much higher catalytic activity. Among the three sizes, Au₂₅ nanocluster catalyst shows the highest conversion of styrene, followed by Au₃₈ and Au₁₄₄. The effect of thiolate ligands was investigated and found that the ligands do not affect the catalytic activity and selectivity. Therefore, the catalysis of Aun(SR)m nanoclusters are mainly determined by the gold core rather than by ligands shell. A mechanism has been proposed for selective oxidation of styrene catalyzed by Au₂₅(SR)₁₈ nanoclusters (Figure 12) [26]. The three oxidant systems were investigated: (a) TBHP (tert-butyl hydroperoxide) as the oxidant; (b) TBHP as an initiator and O₂ as the main oxidant; (c) O₂ as the oxidant [26]. The three different oxidant systems can undergo different reaction pathways to activate the oxidants and generate a common peroxyformate intermediate Au₂₅-O_2(ad) (species D). In the case of TBHP as the oxidant, interaction of anionic Au₂₅ (species A) with TBHP forms a hydroperoxy species B, and then species B loses one H₂O molecule and rearranges to form the Au₂₅-O_2(ad) species D. In the case of TBHP as an initiator and O₂ as a main oxidant, initiation of TBHP forms species BuO*/*OH and hence activates O₂ to form the superoxo- like O₂*. The O₂* is proposed to adsorb via a side-on fashion to the gold surface with two partial Au-O bonds to produce a low-barrier transition state species C, and then the peroxo-like species C transforms to the Au₂₅-O_2(ad) species D. In the case of sole O₂ as oxidant, O₂ may directly attack the Au₁₃ core to form the Au₂₅-O_2(ad) species D. The presence of partial positive charges on the surface gold atoms of the Au₁₂ shell should greatly facilitate activation of the nucleophilic C=C group of styrene (species E) since the positive Au atoms at the shell are electrophilic. Then the activated C=C bond reacts with the O_2(ad) species through side-by-side interaction on the Au₂₅ surface sites, leading to species F. Subsequently, the catalytic selectivity is triggered by the dissociation and rearrangement in three competing pathways that lead to the three products. The formation of benzaldehyde is from the breaking of the C–C bond (species G); the epoxide is created by the transfer of oxygen to the olefinic bond to form a metalloepoxy intermediate (species H); and acetophenone is produced by the breaking of the C–O bond (species I). Finally, the oxidized [Au₂₅(SR)₁₈]⁰ catalyst can be reduced to the anionic [Au₂₅(SR)₁₈]⁻ by gaining an electron when the C=C bond leaves the Au₂₅ cluster, hence, one catalytic cycle is completed [26].

Tsukuda et al. [22] immobilized Au₂₅(SR)₁₈ nanoclusters on a hydroxyapatite support for the selective oxidation of styrene in toluene solvent. They achieved a 100% conversion of styrene and 92% selectivity to the epoxide product. These results demonstrate that atomically monodisperse Au_n nanocluster catalysts exhibit excellent catalytic activity in the selective oxidation processes.

Au_n nanolcusters catalysts have also made significant advances in selective hydrogenation processes. Herein, Au₂₅ nanocluster is chosen as a model for a discussion of selective hydrogenation. The crystal structures of [Au₂₅(SR)₁₈]^q (q = −1, 0) show a core–shell type structure: a Au₁₃ icosahedral core and an exterior Au₁₂ shell. The charge distribution on the Au₁₃ core and the Au₁₂ shell is quite different: the Au₁₃ core possesses eight (when q = −1) or seven (q = 0) delocalized valence electrons originated from Au(6s). These electrons are primarily distributed within the Au₁₃ core, whereas the Au₁₂ shell bears positive charges due to bonding with thiolates and electron transfer from gold to sulfur. The electron-rich Au₁₃ core should facilitate electrophilic bands activation, such as C=O, accompanied by conversion of [Au₂₅(SR)₁₈]⁻ to neutral [Au₂₅(SR)₁₈]⁰. An Au₁₂ shell with low-coordination charater should adsorpt and dissociate H₂.

Selective hydrogenation of α,β-unsaturated ketones/aldehydes, conventional supported gold nanoparticle catalysts have been demonstrated to be capable of selective hydrogenation of α,β-unsaturated ketones to produce predominant α,β-unsaturated alcohols but with side products of saturated ketones from C=C hydrogenation as well as saturated alcohols from further hydrogenation. Although conventional gold nanoparticles can achieve high conversion and selectivity of the unsaturated alcohol in the hydrogenation of α,β-unsaturated ketones, a ∼100% selectivity for the unsaturated alcohol has not been achieved [21]. Using Au₂₅(SR)₁₈ nanoclusters as hydrogenation catalysts, selective hydrogenation of the C=O bond in α,β-unsaturated ketones (or aldehydes) with 100% selectivity for α,β-unsaturated alcohols can be obtained. The extraordinary selectivity and activity of Au₂₅ catalysts correlate with the electronic structure of the Au₂₅ nanocluster and its nonclosed Au₁₂ exterior shell. The volcano-like eight uncapped Au₃ faces of the icosahedron from the exposure of Au₁₃ core should favor adsorption of the C=O group by interaction of the active site with the O atom of the C=O group (see Figure 13). Subsequently, the weakly nucleophilic hydrogen attacks the activated C=O group, and then form the unsaturated alcohol product. The surface Au atoms with low-coordination character, coordination number N = 3, should provide a favorable environment for the adsorption and dissociation of H₂, and H₂ dissociation should occur on the gold atoms of the exterior shell (Figure 13) [21]. The electron-rich Au₁₃ core has no ability to active C=C bond in α,β- unsaturated ketone at mild temperatures, therefore there are no side products from the hydrogenation of C=C in α,β-unsaturated ketone.

These Au_n catalyst examples demonstrate the huge power of atomically precise Au_n nanocatalysts for achieving super selective oxidation and hydrogenation performance and atomically precise structure-property relationships. Au_n nanoclusters possess a unique core-shell structure—an electron-rich core with delocalized valence electrons and an electron-deficient shell. Such nanoclusters will not only provide further insight into the nature of gold nanocatalysis at an atomic level, but also promote the exploration of new chemical processes with Au_n as well-defined, highly efficient catalysts. Au_n nanocluster catalysts will ultimately bring gold nanocatalysis to an exciting new level.