Ligand-Protected Gold Clusters

Small gold clusters with diameters less than or equal to 2 nm (below approximately 200 atoms) possess geometric and electronic structures different from bulk gold. When these gold clusters are protected by ligands, these clusters can be treated as chemical compounds. This review focuses on gold clusters protected by chalcogenate (thiolate, selenolate, or tellurolate) ligands and describes the methods by which these clusters are synthesized as well as their geometric/electronic structures and physical and chemical properties. Recent findings regarding ligand exchange reactions, which may be used to impart functionality to these compounds, are also described.


Introduction
Small gold clusters with diameters less than or equal to 2 nm (below approximately 200 atoms) possess geometric and electronic structures different from those of bulk gold [1]. The geometric structure often consists of an atomic arrangement, such as an icosahedral structure, that differs from the close-packed structure of bulk gold, as a result of reducing the surface energy. In addition, a discrete electronic structure appears rather than the continuous structure observed in the bulk element. Owing to these characteristics, small gold clusters exhibit fundamental properties and functionalities different from those of bulk gold. In addition, when these gold clusters are protected by ligands, it is possible to treat them as chemical compounds. In early studies, beginning in the 1960s, phosphine was employed as a protective ligand [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Representative phosphine (PR 3 (Figure 1(a)). Unfortunately, these clusters have been found to be unstable in solution, which restricts their practical applications. In contrast, thiolate (SR)-protected gold clusters (Au n (SR) m ), first synthesized by Brust et al. in 1994 (Figure 1(b)) [17], are highly stable both in solution and in the solid state, because the SR ligands form strong bonds with gold atoms. These Au n (SR) m clusters exhibit various physical and chemical properties not shown by bulk gold, such as photoluminescence and catalytic activity. For these reasons, SR ligands have become the most common choice for use with gold clusters . Recently, the synthesis of gold clusters protected by other chalcogenates (selenolate (SeR) or tellurolate (TeR); Figure 1(c)) [41][42][43][44][45][46][47][48][49][50][51], by alkynes [52][53][54], or by two kinds of ligand (Figure 1(d)) [55][56][57][58][59] has also been reported. In this chapter, we focus on gold clusters protected by chalcogenates (Au n (XR) m ; XR = SR, SeR, or TeR) and describe the synthetic procedures, geometric/electronic structures, and physical and chemical properties of these compounds. Moreover, the physical and chemical properties of these gold clusters are greatly affected by the type of functional group of the protecting ligand. The ligand exchange  [2,10,11,29,30,34,47,48,59]). reaction is a very powerful means for introducing the different ligands into the pre-synthesized cluster. Although this type of reaction was discovered nearly 20 years ago [60][61][62][63][64][65], the associated mechanism was not fully understood at that time. Recently, tremendous progress has been made in terms of the precise synthesis and evaluation of metal clusters, and details of these reactions have been elucidated [66,67]. Recent findings regarding these reactions are therefore also included herein.

Synthesis of Au n (XR) m clusters
The method used most frequently to synthesize Au n (XR) m clusters is based on the chemical reduction of gold ions in the presence of ligands in solution ( Figure 2). In this approach, a gold salt and the ligand are mixed in solution to form Au-ligand complexes that are subsequently treated with a reducing agent (normally NaBH 4 ). Au n (XR) m clusters are formed by the aggregation Figure 2. A typical procedure for the synthesis of Au n (SR) m clusters having a well-defined chemical composition. of the resulting gold atoms in conjunction with surface protection by the ligands [18]. In the first report published by Brust et al., dodecanethiolate was used as the ligand [17]. Because a gold salt and dodecanethiolate are soluble in different solvents, Brust transferred the gold salt from an aqueous phase to a ligand-containing toluene phase using a phase-transfer reagent (representing a two-phase system; Figure 2). In contrast, in more recent research, tetrahydrofuran (THF) has often been used as the solvent because it could dissolve both gold salt and ligand [68]. This removes the need for phase transfer of the gold salt and thereby simplifies the synthesis to a one-phase system ( Figure 2). Similarly, when a hydrophilic thiol is used as the ligand, gold clusters can be synthesized in a one-phase system [69][70][71].
The product obtained from this technique is typically a mixture of Au n (XR) m clusters having various numbers of constituent atoms. Because the physical and chemical properties of the clusters are greatly affected by the number of atoms, separation by size or conversion to stable clusters by exposure to severe conditions is required to obtain Au n (XR) m clusters with welldefined physical properties and functions ( Figure 2) [18,72]. Polyacrylamide gel electrophoresis [69][70][71][72], high-performance liquid chromatography [72][73][74][75][76][77], and solvent extraction are the most frequently applied techniques for size separation. It is also common to use an etching reaction for size convergence [72,[78][79][80][81][82]. In addition to these techniques, the ligand exchange method, in which the ligands of a specific Au n (XR) m cluster are replaced with other ligands, is an effective means of generating Au n (XR) m clusters with a specific chemical composition ( Figure 2) [83]. Recent results associated with such ligand exchange reactions are discussed in Section 6. structural analysis has revealed that several Au n (SR) m clusters consist of an Au core covered with multiple dS(R)[dAudS(R)] x d staples (Figure 3(b)) [30,[85][86][87][88]. Based on the geometrical structures determined for Au n (SR) m clusters to date, it can be assumed that almost all small Au n (SR) m clusters have this type of core-shell structure. Single-crystal X-ray structural analysis has also demonstrated that small Au n (SeR) m clusters have core-shell structures similar to those of small Au n (SR) m clusters (Figure 1(c)) [47,48]. The geometrical structure of Au n (TeR) m clusters has not yet been determined experimentally, although theoretical calculations [45,89] have shown that these clusters are also likely to have a similar core-shell structure.

Electronic structures of Au n (XR) m clusters
Unlike bulk gold, small Au n (SR) m clusters have discrete electronic structures. As a result, multiple peak structures can be observed in the optical absorption spectra of these clusters. As an example, Au n (SC 12 H 25 ) m clusters show multiple peak structures across the entire visible range in their optical absorption spectra up to the size of Au 144 (SC 12 H 25 ) 60 ( Figure 4) [75]. Such fine peak structures are not observed in the spectra of larger clusters, although peaks that can be attributed to surface plasmon resonance absorption have been identified at approximately At present, the relationship between cluster size and electronic structure is not well understood for Au n (SeR) m and Au n (TeR) m clusters, because only a small number of such compounds have been studied to date. However, the researches regarding Au 25 (SeR) 18 and Au 38 (SeR) 24 clusters have demonstrated that changing the ligands from SR to SeR reduces the HOMO-LUMO gap of the clusters [42,43] and that this effect becomes more pronounced in the case of clusters containing TeR in the ligand shell [45].

Physical and chemical properties of Au n (XR) m clusters
Au n (SR) m clusters exhibit size-specific electronic structures, and their physical and chemical properties also vary with size. Herein, we first discuss typical physical and chemical characteristics of such Au n (SR) m clusters.

Redox behavior
Au n (SR) m clusters also display redox behavior [20,21]. Figure 6(b) shows a differential pulse voltammogram obtained from Au 25 (SC 2 H 4 Ph) 18 , in which the peaks at À1.9 and À0.3 V originate from [Au 25 (SC 2 H 4 Ph) 18 ] À/2À and [Au 25 (SC 2 H 4 Ph) 18 ] 0/À redox couples, respectively. This redox behavior is not confined to clusters with discrete electronic structures; Au n (SR) m clusters larger than Au 144 (SR) 60 also exhibit redox behavior as a result of quantized double-layer charging [21]. The redox properties of Au n (SR) m clusters could be applied to single-electron transistors [92].

Catalytic activity
Catalytic activity is another typical size-specific property of Au n (SR) m clusters (Figure 6(d)) [22,72]. As an example, Au 25 (SR) 18 catalyzes the oxidation of CO, styrene, benzyl alcohol, cyclohexane, and sulfides. The same cluster also exhibits catalytic activity for the hydrogenation of nitrophenol, aldehydes, and ketones and promotes CdC coupling reactions. As noted, several Au n (SR) m clusters have optical isomers and therefore could potentially function as asymmetric catalysts [96].

Effect of changing ligands
Regarding Au n (SeR) m and Au n (TeR) m clusters, it has been reported that the incorporation of SeR or TeR ligands changes the nature of the bonding between the Au atoms and the ligands [97,98]. In the case of Au n (SeC 12 H 25 ) m clusters, this effect reduces the degree of charge transfer from the Au atoms to the ligands (Figure 7(a)) such that the Audligand bond becomes much more covalent than that in Au n (SC 12 H 25 ) m clusters [41]. Owing to these changes in bonding characteristics, Au 25 (SeR) 18 (R = C 12 H 25 or C 8 H 17 ) exhibits greater resistance to degradation in solution compared with Au 25 (SR) 18 (R = C 12 H 25 or C 8 H 17 ) (Figure 7(b)) [42,99]. In addition to such an improved stability, the use of SeR ligands is expected to improve conductivity between the gold core and the ligands [97,100,101], and future work is likely to demonstrate the conductivity of Au n (SeR) m clusters. Furthermore, recent studies have found that Au 25 (SePh) 18

Ligand exchange reactions
As described above, Au n (SR) m clusters tend to resist degradation. However, this type of metal cluster readily exchanges its ligands with other coexisting ligands in solution (Figure 8(a)). A complete understanding of the associated mechanism would allow these reactions to be controlled, thus permitting synthesis of novel metal clusters with specific functions. Recently, more details regarding exchange reactions between metal clusters and ligands have been reported, and these findings are discussed in this section.

Mechanism
Murray et al. reported the ligand exchange reactions of this type of cluster nearly 20 years ago [60][61][62][63][64][65]. However, their research was conducted using mixtures and did not use advanced techniques such as mass spectrometry and single-crystal X-ray structural analysis to characterize the products. Therefore, a thorough understanding of the details of these reactions was not obtained. More recent research has elucidated the associated mechanism. As an example, Au 25 (SR) 18 has a geometry in which the Au 13 core is covered by six dS(R)d[AudS(R)] 2 d staples (Figure 9(a)). As a result, there are two types of SR units in Au 25 (SR) 18 : those in contact with the Au 13 core (core-site SR; Figure 9(a)) and those at the apex of each staple (apex-site SR; Figure 9 with para-bromobenzenethiol to ascertain which SR was more likely to be exchanged [103]. The results showed that Au 25 (SC 2 H 4 Ph) 16 (p-BBT) 2 (p-BBT = para-bromobenzenethiolate), in which the substitution had occurred at the core-site SR ligands, was obtained (Figure 9(a)), suggesting that the ligand exchange occurred at the core-site SR locations. However, this prior work did not determine whether other structures may have been present in the reaction mixture or not. For this reason, Niihori et al. employed reversed-phase high-performance liquid chromatography to allow the high-resolution separation of the coordination isomers generated by a similar reaction and estimated the distribution of isomers in the product. It was confirmed that the product mixture mainly contained a coordination isomer in which the core-site SR ligands had been substituted (Figure 9(b)) [104]. Fernando and Aikens performed density functional theory (DFT) calculations at approximately the same time, and the results indicated that ligand exchange was likely to occur at core-site SR ligands in Au 25 (SR) 18 [105]. These results demonstrated that ligand exchange preferentially proceeds at core-site SR ligands in Au 25 (SC 2 H 4 Ph) 18 . The research by Hossain et al. has revealed that preferential exchange at core-site SR ligands also occurs in the reaction between [Au 25 (SC 2 H 4 Ph) 18 ] À and other chalcogenides (Figure 9(c)) [106].

Induction of quasi-isomerization
Studies have found that, in addition to ligand exchange, a change in geometry can also take place during reactions with thiol (RSH) (Figure 8(b)). This discovery originated from the prediction of the geometry of Au 24 (SR) 20 20 in 2010 [107], after which Pei and coworkers predicted the geometry of these clusters via DFT calculations based on Au 24 (SCH 3 ) 20 [108]. Thereafter, Jin et al. characterized Au 24 (SCH 2 Ph-t Bu) 20 (SCH 2 Ph-t Bu = 4-tert-butylphenylmethanethiolate) by single-crystal X-ray structural analysis but found that the resulting structure was different from that predicted by Pei's group [109]. This discrepancy prompted Jiang et al. to study the geometric structures of Au 24 (SR) 20 clusters (R = CH 3 , C 2 H 4 Ph, or CH 2 Ph-t Bu) using DFT, leading to the conclusion that the most stable structure of a Au 24 (SR) 20 cluster depends on the ligand [110]. At present, this theory has not been proven experimentally for Au 24 (SR) 20 . However, in 2016, Jin et al. reported that exchanging the ligands of Au 28 (SPh-t Bu) 20 (SPh-t Bu = 4-tert-butylbenzenethiolate) with cyclohexanethiolate (S-c-C 6 H 11 ) altered the skeletal structure of the cluster (Figure 10(a)) [111]. This same work also demonstrated that exchanging the ligands of Au 28 (S-c-C 6 H 11 ) 20 with SPh-t Bu regenerated the original geometry, meaning that the reaction was reversible (Figure 10(a)) [111]. Thus, it has recently been revealed that both ligand exchange and quasi-isomerization (as opposed to true isomerization because the ligand is different) can be induced for a particular Au n (SR) m cluster.

Induction of size transformation
Researches have also shown that the introduction of a significant structural deformation via ligand exchange can result in the formation of Au n (SR) m clusters with different chemical compositions (Figure 8(c)) [102]. An example is the reaction of Au 38 (SC 2 H 4 Ph) 24 clusters (Figure 3(b)) with t Bu-PhSH in solution, from which Au 36 (SPh-t Bu) 24 was generated as the main product (yield~90%) (Figure 10(b)) [112]. This outcome indicates that exchange with a ligand containing a bulky functional group can affect the chemical composition of the cluster. Figure 10. Examples of ligand exchange reactions, including (a) quasi-isomerization and (b) size transformation (these figures were adapted from Refs. [111,112]).
Research regarding the mechanism of such reactions has also been conducted. Jin et al. found that the following four processes occur in the reaction between Au 38 (SC 2 H 4 Ph) 24 and t Bu-PhSH: (I) ligand exchange, (II) structural distortion, (III) disproportionation, and (IV) size focusing conversion together with further ligand exchange (Figure 10(b)) [112]. In the first process, ligand exchange occurs without size or structural transformations, while the structural distortion of the resulting Au 38 (SC 2 H 4 Ph) 24Àm (SPh-t Bu) m (m >~12) is initiated in the second process. During the third process, one Au 38 (SC 2 H 4 Ph) 24-m (SPh-t Bu) m releases two gold atoms to form Au 36 and another Au 38 (SC 2 H 4 Ph) 24-m (SPh-t Bu) m captures these two atoms and two free ligands to form Au 40 (SC 2 H 4 Ph) 24-m (SPh-t Bu) m+2 . In the final process, the Au 40 (SC 2 H 4 Ph) 24Àm (SPh-t Bu) m+2 begins to convert to Au 36 , such that pure Au 36 (SPh-t Bu) 24 is eventually obtained (Figure 1(b)). Au n (SR) m clusters such as Au 28 (SPh-t Bu) 20 , Au 36 (SPh-t Bu) 24 , and Au 36 (S-c-C 5 H 9 ) 24 , none of which can be generated via direct synthesis at atomic precision, have also been synthesized in a size-selective manner by inducing this kind of structural deformation [102].

Relation between ligand structure and outcome
In this way, the outcomes are significantly affected by the bulkiness of the ligand in the ligand exchange reactions. Normally, ligand exchange with alkanethiol or PhC 2 H 4 SH does not result in structural transformation, but simply leads to ligand exchange. Conversely, a bulky ligand such as t Bu-PhSH often leads to structural transformation. At present, these are no clear rules for predicting the final state of the deformed cluster (whether quasi-isomerization or size transformation). The final state seems to be related to the magnitude of the structural transformation and the possibility of isomeric structures with similar stabilities.

Summary
This chapter summarized common methods of fabricating Au n (XR) m clusters and surveyed the various geometric and electronic structures of these compounds, as well as their physical and chemical properties. Recent discoveries regarding ligand exchange reactions capable of enhancing the functionality of these clusters were also described. Although the precise synthesis of such clusters was first reported only 13 years ago at the time of writing, many studies regarding these clusters have been conducted in the interim, all of which have significantly improved our understanding of synthetic methods as well as the structures and functions of the clusters. It is expected that more information related to Au n (XR) m clusters will be gained on the basis of continuing research, leading to the readily synthesis of metal clusters with desired functions in the near future.
Research on Innovative Areas (Coordination Asymmetry) (grant number 17H05385). Funding from the Takahashi Industrial and Economic Research Foundation, Futaba Electronics Memorial Foundation, Iwatani Naoji Foundation, Murata Science Foundation, and Ube Industries Foundation is also gratefully acknowledged. We thank Michael D. Judge, MSc, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Conflict of interest
There are no conflicts to declare.