Perspective: Exchange reactions in thiolate-protected metal clusters Open Access

It has recently become possible to synthesize metal clusters protected by organic ligands, like thiolates and phosphines, with atomic precision.^1–10 The geometric structures of such precise metal clusters can be determined via single-crystal X-ray structural analysis. Therefore, our knowledge of the geometry of metal clusters protected by organic ligands is currently improving rapidly. In addition, experimental and theoretical studies on precise metal clusters have furthered our understanding of their size-specific physical properties, including photoluminescence,¹¹ magnetic properties,¹² and redox behavior,^12–14 as well as the origins of their appearances.

These ligand-protected metal clusters also exhibit several interesting features in their chemical properties. One representative example is the catalytic effect.¹⁵ For example, the thiolate (RS)-protected Au₂₅ cluster [Au₂₅(SR)₁₈]⁻ exhibits catalytic activity in the oxidation of carbon monoxide, styrene, benzyl alcohol, cyclohexane, and sulfides. Moreover, [Au₂₅(SR)₁₈]⁻ also catalyzes the hydrogenation of 4-nitrophenol and ketones as well as C–C coupling.

In addition to this catalytic activity, exchange reactions with other substances also illustrate the remarkable chemical properties shown by ligand-protected metal clusters. For example, RS-protected gold clusters (Au_n(SR)_m) can exchange ligands, metal atoms, and metal–ligand complexes with coexisting ligands, complexes, and metal clusters. The physical and chemical properties of these metal clusters vary depending on the ligand structure^2,3 and metal core composition.^4,7 Thus, the use of these exchange reactions enables us to produce metal clusters with new physical and chemical properties. Although the occurrence of such reactions was recognized nearly 20 years ago,^16–18 they were not well understood. Techniques for the precise synthesis of metal clusters and their characterization methods have substantially progressed recently and, as a consequence, the details of these reactions are being clarified. In this perspective, focusing on the most-studied Au_n(SR)_m clusters,^19,20 we provide a summary of recent findings as well as future expectations concerning these exchange reactions.

When Au_n(SR)_m clusters are mixed with RSH in solution, ligand exchange can occur (Fig. 1(a)). Murray et al.¹⁶ reported such a ligand exchange nearly 20 years ago. However, their research was conducted on mixtures, and methods such as mass spectrometry and single-crystal X-ray structural analysis were not used to characterize the products. Therefore, a deep understanding of the details of this reaction was not obtained. However, recent research has revealed the mechanism of ligand exchange. For example, Au₂₅(SR)₁₈ has a geometry in which the Au₁₃ core is covered by six units of the –SR–[Au–SR–]₂ staple (Fig. 2(a)).⁵ Therefore, there are two types of SR in Au₂₅(SR)₁₈; namely, SR in contact with the Au₁₃ core (core-site SR; Fig. 2(a)), and SR at the apex of the staple (apex-site SR; Fig. 2(a)). Ackerson et al.²¹ performed single-crystal X-ray structural analysis of the product obtained from the reaction of Au₂₅(SC₂H₄Ph)₁₈ (SC₂H₄Ph = 2-phenylethanethiolate) with para-bromobenzenethiol to investigate which SR is likely to be exchanged. Consequently, Au₂₅(SC₂H₄Ph)₁₆(p-BBT)₂ (p-BBT = para-bromobenzenethiolate) where the substitution occurred at the core-site SR was observed (Fig. 2(a)). This suggests that ligand exchange is likely to occur at the core-site SR in the reaction between these two compounds. However, the obtained geometric structure may be only one of the multiple products present. Therefore, we used reversed-phase high-performance liquid chromatography to separate the product generated by a similar reaction with high resolution according to coordination isomer and estimated the distribution of coordination isomers in the product.²² We confirmed that the main product contained the coordination isomer substituted at the core-site SR (Fig. 2(b)).²³ Similarly, Aikens and colleagues performed density functional theory (DFT) calculations at the same time as our research, which showed that ligand exchange is likely to occur at the core-site SR in Au₂₅(SR)₁₈.²⁴ These results indicate that ligand exchange preferentially occurs at the core-site SR in Au₂₅(SC₂H₄Ph)₁₈. Our research revealed that preferential exchange at the core-site SR also occurs in the reaction between [Au₂₅(SC₂H₄Ph)₁₈]⁻ and other chalcogenides (Fig. 2(c)).²⁵ 

In addition, it has recently been found that a change in geometry could also occur in reactions with RSH in addition to ligand replacement (Fig. 1(b)). This discovery originates from the prediction of the geometry of Au₂₄(SR)₂₀. Jin et al.²⁶ precisely synthesized Au₂₄(SC₂H₄Ph)₂₀ in 2010. Pei and co-workers predicted the geometry of the synthesized clusters through DFT calculations of Au₂₄(SCH₃)₂₀.²⁷ Thereafter, Jin et al.²⁸ characterized Au₂₄(SCH₂Ph-^tBu)₂₀ (SCH₂Ph-^tBu = 4-tert-butylphenylmethanethiolate) by single-crystal X-ray structural analysis. However, the obtained geometric structure was different from that predicted by Pei’s group. Interested in this question, Jiang et al.²⁹ studied the geometric structure of Au₂₄(SR)₂₀ (R = CH₃, C₂H₄Ph, or CH₂Ph-^tBu) via DFT calculations and predicted that the stable structure of Au₂₄(SR)₂₀ depends on the ligand structure. Currently, this phenomenon has not been proven experimentally for Au₂₄(SR)₂₀. However, in 2016, Jin et al.³⁰ reported that when the ligands of Au₂₈(SPh-^tBu)₂₀ (SPh-^tBu = 4-tert-butylbenzenethiolate) were exchanged with 1-cyclohexanethiolate (S-c-C₆H₁₁), the skeletal structure of the cluster was altered (Fig. 3(a)). They further revealed that when the ligands of Au₂₈(S-c-C₆H₁₁)₂₀ were exchanged with SPh-^tBu, the original geometry was resumed; the reaction was therefore reversible (Fig. 3(a)). Thus, it has recently been revealed that not only ligand exchange but also quasi-isomerization (this is not an isomerization because the ligand is different) is induced for a particular Au_n(SR)_m cluster.

It has also been revealed that when a larger structural deformation is induced by the exchange ligand, the change is not limited to slight geometric deformation and instead results in the formation of Au_n(SR)_m clusters with different chemical compositions (Fig. 1(c)).⁵ For example, when Au₃₈(SC₂H₄Ph)₂₄ reacts with ^tBu-PhSH in solution, Au₃₆(SPh-^tBu)₂₄ is formed as the main product (yield ∼90%) (Fig. 3(b)).⁵ This indicates that when the exchange ligand contains a bulky functional group, changes in the chemical composition of the cluster are induced through ligand exchange. Research on the mechanism of such a reaction has also been conducted. For example, Jin et al.⁵ found that the following four processes occur in the reaction between Au₃₈(SC₂H₄Ph)₂₄ and ^tBu-PhSH: (I) ligand exchange, (II) structural distortion, (III) disproportionation, and (IV) size focusing (Fig. 3(b)). In the first process (I), ligand exchange occurs without the size or structure transformation. The structural distortion of Au₃₈(SC₂H₄Ph)_24−m(SPh-^tBu)_m (m < ∼12) starts to occur in the second process (II). This distortion becomes larger in the third process (III) (m > ∼12), and one Au₃₈(SC₂H₄Ph)_24−m(SPh-^tBu)_m releases two gold atoms to form Au₃₆ and another Au₃₈(SC₂H₄Ph)_24−m(SPh-^tBu)_m captures two released gold atoms and two free ^tBu-PhSH to form Au₄₀(SC₂H₄Ph)_26−m(SPh-^tBu)_m. In the final process (IV), the ligand exchange occurs to completion, and the Au₄₀(SC₂H₄Ph)_26−m(SPh-^tBu)_m species start to convert to Au₃₆, and eventually molecular pure Au₃₆(SPh-^tBu)₂₄ is obtained (Fig. 3(b)).⁵ Au_n(SR)_m clusters such as Au₂₈(SPh-^tBu)₂₀, Au₃₆(SPh-^tBu)₂₄, and Au₃₆(S-c-C₅H₉)₂₄, which have not been obtained via direct synthesis, have been synthesized in a size-selective manner by inducing this kind of structural deformation.⁵ 

In these ligand exchange reactions, the kinds of outcomes are strongly related to the bulkiness of the ligand. Normally, the ligand exchange with alkanethiol or PhC₂H₄SH do not cause the structural transformation and result in the mere ligand exchange. On the other hand, that with bulky ligands, such as ^tBu-PhSH, often causes the structural transformation.^5,30 At the present, a clear rule has not been established for the final fate of the deformed cluster. The final fate of the deformed cluster (quasi-isomerization or size transformation) seems to be determined by the magnitude of structural transformation, and the existence or nonexistence of isomer structures with similar stability in the subjected cluster.^5,30

When thiolate-protected metal clusters are mixed with metal thiolate complexes in solution, metal exchange can occur (Fig. 4(a)). This exchange has already been observed in the studies of early stage.¹⁷ However, the details of this type of exchange reaction were elucidated recently. In 2015, Zhu et al. reacted [Au₂₅(SC₂H₄Ph)₁₈]⁻ with Ag^ISC₂H₄Ph complex and obtained [Au_25−xAg_x(SC₂H₄Ph)₁₈]⁻ in which some Au atoms are replaced by Ag. Furthermore, when [Au₂₅(SC₂H₄Ph)₁₈]⁻ reacted with a Cu^II(SC₂H₄Ph)₂ complex in the presence of a reducing agent, [Au_25−xCu_x(SC₂H₄Ph)₁₈]⁻ formed. Reactions between [Au₂₅(SC₂H₄Ph)₁₈]⁻ and a Hg^II(SC₂H₄Ph)₂ or Cd^II(SC₂H₄Ph)₂ complex gave [Au₂₄Hg(SC₂H₄Ph)₁₈]⁰ and [Au₂₄Cd(SC₂H₄Ph)₁₈]⁰, respectively.³¹ The obtained alloy clusters have a geometric structure similar to that of [Au₂₅(SC₂H₄Ph)₁₈]⁻ (Fig. 5(a)).³¹ These results show that when [Au₂₅(SR)₁₈]⁻ is used as a template, some of its metal atoms are replaced with other metals while retaining the number of metal atoms and ligands, and geometric structure. Zhu and colleagues and our studies revealed that similar reactions also occur between bimetallic/trimetallic alloy clusters and metal thiolate complexes (Fig. 5(b)).^32,33

Such metal exchange progresses similarly even when a metal salt is used as the metal source (Fig. 4(b)).^34,36 Wu et al. reported that when Au₂₅(SC₂H₄Ph)₁₈ is mixed with AgNO₃, Hg(NO₃)₂, or Cd(NO₃)₂ in solution, some Au atoms are replaced with Ag, Hg, or Cd to form Au_25−xAg_x(SC₂H₄Ph)₁₈, Au₂₄Hg(SC₂H₄Ph)₁₈,³⁶ or Au₂₄Cd(SC₂H₄Ph)₁₈, respectively. Bakr’s group found that similar metal exchange occurs in the reaction of metal clusters containing Ag as a base element, e.g., [Ag₂₄Pd(SPhMe₂)₁₈]²⁻ (SPhMe₂ = 2,4-dimethylbenzenethiolate), with AuPPh₃Cl.³⁷ 

Metal exchange can also occur between metal clusters (Fig. 4(c)).¹⁸ Knowledge of intercluster metal exchange has drastically improved recently. For example, Pradeep et al.³⁸ reported that the alloy clusters formed by the reaction between [Au₂₅(SC₂H₄Ph)₁₈]⁻ and [Ag₄₄(SPhF)₃₀]⁴⁻ (SPhF = 4-fluorobenzenethiolate) have the same number of metal atoms and ligands as [Au₂₅(SC₂H₄Ph)₁₈]⁻ or [Ag₄₄(SPhF)₃₀]⁴⁻. This means that when using stable clusters like [Au₂₅(SC₂H₄Ph)₁₈]⁻ or [Ag₄₄(SPhF)₃₀]⁴⁻ as a precursor, metal exchange occurs while maintaining the number of metal atoms and ligands (Fig. 6(a)) as in the case of the other two reactions considered (Figs. 4 and 5). Bürgi and co-workers studied the reaction of Au₃₈(SC₂H₄Ph)₂₄ with Au_38−xAg_x(SC₂H₄Ph)₂₄ and found that metal exchange occurs via direct collision of Au₃₈(SC₂H₄Ph)₂₄ with Au_38−xAg_x(SC₂H₄Ph)₂₄ (Fig. 6(b)).³⁸ This metal exchange occurs instantaneously in solution.^39,40 For example, Pradeep et al. reported that in the reaction between [Au₂₅(SC₂H₄Ph)₁₈]⁻ and [Ag₂₅(SPhMe₂)₁₈]⁻, [Ag₂₅Au₂₅(SPhMe₂)₁₈(SC₂H₄Ph)₁₈]²⁻ consisting of both clusters forms within 2 min, and then the exchange of metallic elements begins between the two clusters.⁴⁰ 

An interesting feature of these metal exchange reactions is that both the number of constituent atoms and ligands are maintained when some metal atoms are replaced by others. Thus, using precisely synthesized metal clusters as templates, it is possible to synthesize alloy clusters with a controlled number of metal atoms and ligands. Furthermore, this reaction can also be used to synthesize alloy clusters composed of elements with quite different standard redox potentials,^31,36 unlike the case of simultaneous reduction of multiple types of metal ions (simultaneous reduction method⁴¹). Compared with the simultaneous reduction method, it is also possible to introduce a larger number of heteroatoms using metal exchange. To date, the alloy clusters, such as Au_25−xAg_x(SR)₁₈ (x = 1–8), Au_25−xCu_x(SR)₁₈ (x = 1–9), Au₂₄Cd(SR)₁₈, Au₂₄Hg(SR)₁₈, Au_24−xAg_xCd(SR)₁₈ (x = 2–6), Au_24−xAg_xPd(SR)₁₈ (x = 1–6), Au_24−x−yAg_xCuyPd(SR)₁₈ (x = 1–3, y = 1, 2), Au_24−xAg_xHg(SR)₁₈ (x = 1–8), Ag_25−xAu_x(SR)₁₈ (x = 1, 2), Ag_24−xAu_xPt(SR)₁₈ (x = 1, 2, 4–9), and Au_38−xAg_x(SR)₂₄ (x = 1–11), have been synthesized using metal exchange reactions.^{31–33,35,37,39}

Recently, an understanding of the exchange reactions between metal clusters and other substances has improved considerably. Regarding ligand exchange, in addition to the elucidation of preferential exchange sites, it has been revealed that quasi-isomerization and changes in chemical composition can be induced by modulating the structure of the exchange ligand. In metal exchange, it has been revealed that when using stable clusters as templates, metal atoms can be exchanged without affecting the number of metal atoms and ligands. Based on these findings, the formation of metal clusters with controlled isomer structure,²³ metal clusters difficult to obtain via direct synthesis,⁵ and alloy clusters difficult to produce via the simultaneous reduction method^31,33 have been accessed.

It is expected that many experimental and theoretical studies will be conducted on the following points regarding these reactions in the future. The first is the elucidation of the correlation between the structure of the functional group and the preferential exchange site in ligand exchange. Pengo et al.⁴² recently reported that ligand exchange occurs preferentially at the apex-site SR when 4-fluorobenzylthiol is used as the incoming ligand, contrary to the previous reports.^21,23–25 Thus, the preferential exchange site is expected to depend on the ligand functional group. The preference of 4-fluorobenzylthiol for the apex site is only about three times higher than that for the core site.⁴² We expect that the correlation between the functional group of the exchange ligand and preferential site will soon be understood in a greater depth. Such an understanding would enable the selective introduction of an incoming ligand at the apex site, and thereby the selection of introduction site according to the intended application of the cluster.

We also expect that more research will be conducted on the mechanism of metal exchange. Currently, the origin of the metal exchange between Au_n(SR)_m clusters and metal thiolate complexes or metal salts has not been clarified, although several mechanisms have been proposed.^31,36 Although Cd can be exchanged for the central atom of the Au₂₅(SR)₁₈ cluster,³¹ it is unclear why similar central exchange does not occur for Pd and Pt, which also prefer the central position.⁴¹ In addition, in this type of Cd exchange, the exchange site (center or edge) depends on the metal source (Cd^II(SC₂H₄Ph)₂ complex or Cd(NO₃)₂).^31,43 However, the underlying reason for this dependence on metal source is unknown. Further experimental and theoretical studies should reveal the origin of these phenomena. This endeavor will improve the understanding of interchangeable elements and exchange sites and allow the type of heteroelements and exchange sites to be selected according to the intended application.

With regard to metal exchange, a technique to control the number of exchanges is also expected. The electronic structure of metal clusters depends on the number of exchanged atoms.⁴⁴ Therefore, to strictly control the electronic structure of an alloy cluster and its related physical/chemical properties, it is essential to precisely regulate the number of exchanged atoms. Currently, strict control of the number of exchanged atoms is difficult to achieve except in the case of a few elements (Cd, Hg).^31,36,43 For example, the number of Ag atoms in Au_25−xAg_x(SR)₁₈ produced by metal exchange usually has a distribution.³¹ One way to obtain Au_25−xAg_x(SR)₁₈ with a controlled number of exchanged atoms might be to separate the obtained mixture with high resolution according to the number of exchanged atoms. However, we also anticipate that methods involving rigorous control of the number of exchanged atoms via reaction control will be developed.

If these problems are resolved, in addition to achieving a deeper understanding of the exchange reactions of metal clusters, these reactions will probably enable a finer control of their physical and chemical properties. This is expected to lead to the establishment of methodology to freely create metal clusters that possess desired functions.

This work was supported by JSPS KAKENHI Grant Nos. JP15H00763, 15H00883, and JP16H04099.