Recent Advances of Ti/Zr-Substituted Polyoxometalates: From Structural Diversity to Functional Applications

Polyoxometalates (POMs), a large family of anionic polynuclear metal–oxo clusters, have received considerable research attention due to their structural versatility and diverse physicochemical properties. Lacunary POMs are key building blocks for the syntheses of functional POMs due to their highly active multidentate O-donor sites. In this review, we have addressed the structural diversities of Ti/Zr-substituted POMs based on the polymerization number of POM building blocks and the number of Ti and Zr centers. The synthetic strategies and relevant catalytic applications of some representative Ti/Zr-substituted POMs have been discussed in detail. Finally, the outlook on the future development of this area is also prospected.


Introduction
Polyoxometalates (POMs), as anionic metal-oxide clusters with diverse nuclearities, elemental compositions and physicochemical properties, have usually been constructed through the self-assembly of reactive oxometallate precursors in aqueous or organic reaction systems. [1][2][3][4] POMs can serve as crucial intermediates in the reaction pathway from water-soluble metal ions to insoluble metal oxides, and isolation of these molecular intermediates enable insightful elucidation on the formation mechanism and control over reaction pathways. POMs exhibit special characteristics of high negative charges, rich redox properties, good thermal stability, and readily available organic grafting [5,6], leading to wide applications in catalysis [7], magnetism [8], material science [9], electrochemistry [10], luminescence [11], etc.
As an important derivative of plenary POMs, lacunary POMs can be easily formed by removing one to several [MO 6 ] (M = Mo, W) building blocks from prototypal architectures such as the Keggin or Wells-Dawson type POMs [12]. These lacunary POMs usually show high coordination reactivity and oxidative and thermal stability. Their high negative charge and nucleophilic oxygen-enriched surfaces render them suitable inorganic, diamagnetic, multidentate nucleophilic ligands toward the electrophilic center. Transition metals (TM) or lanthanide (Ln) cations can be easily incorporated into the defect sites of lacunary POM ligands to construct metal-substituted POMs, which can exhibit unique physicochemical properties depending on the types of incorporated metal ions [13][14][15][16][17][18][19][20]. Metal-substituted POMs (MSPs) typically possess a higher negative charge density than that of the plenary POMs due to the substitution of a high oxidation state M 6+ ion (e.g., W 6+ , Mo 6+ ) with a low oxidation state M n+ ion (usually n = 1-3) [21]. To date, a wide variety of MSPs have been prepared, especially by the transition metals like manganese, iron, cobalt, nickel, copper and zinc in the fourth period and the lanthanides in the sixth period of the periodic table [22,23]. In contrast, the research on the syntheses of titanium-and zirconium-substituted POMs is still in a very early stage, which could be mainly attributed to the following two reasons: (a) the easy hydrolysis of Ti 4+ /Zr 4+ salts in Compared to Ti-substituted POMs, the exploration of Zr-containing POMs has seldom been studied. In 1985, Chauveau et al. reported a compound of Zr-containing POM, [ZrW5O19H2] 2− , which was considered as the Lindqvist-type structure. However, it is still doubted about the exact structure given the presented low signal-to-noise ratio and incorrect intensity ratio of 183 W NMR data [33]. Subsequently, Villanneau et al. has been unambiguously determined the structure as [W5O18Zr(H2O)3] 2− by using EXFAS data [34,35]. Meanwhile, the same group also reported a similar compound with the structural formula of [{W5O18Zr(μ-OH)}2] 6    Compared to Ti-substituted POMs, the exploration of Zr-containing POMs has seldom been studied. In 1985, Chauveau et al. reported a compound of Zr-containing POM, [ZrW5O19H2] 2− , which was considered as the Lindqvist-type structure. However, it is still doubted about the exact structure given the presented low signal-to-noise ratio and incorrect intensity ratio of 183 W NMR data [33]. Subsequently, Villanneau et al. has been unambiguously determined the structure as [W5O18Zr(H2O)3] 2− by using EXFAS data [34,35]. Meanwhile, the same group also reported a similar compound with the structural formula of

Ti/Zr-Substituted Dimeric POMs
In addition to the monomeric POMs, some presentative Ti/Zr-substituted dimeric POMs have also been reviewed herein in detail. In 1993, Finke et al. reported the first hexa-   (Figure 3d). The polyoxoanion was constructed with two tri-Ti-substituted protonated Wells−Dawson subunits "[P 2 W 15 Ti 3 O 60 (OH) 2 ] 10− " bridged by the two organometallic Cp*Rh 2+ groups [43]. Additionally, they also reported the first tetra-  [48]. Subsequently, they synthesized a similar structure using mono-lacunary Dawson precursor K 10 Figure 3h) containing dissimilar copper under hydrothermal condition. The resulting organic-inorganic hybrid assemblies contained a rare corner-sharing double-Keggin type POM architecture in the Ti-POM species, which was further connected with the butterfly-type [Cu II Lo] units to form a 1-D chain and a square plane, respectively [50].

Ti/Zr-Substituted Trimeric POMs
In contrast to the dimeric POM structures, the syntheses of Ti/Zr-substituted trimeric POMs have rarely been reported. The early reported Zr-substituted trimeric POM is Zr 6 O 2 (OH) 4 (Figure 5f) was reported that contains a hexacalcium cluster cation, one carbonate anion, and one calcium cation assembled on a trimeric tri-Ti-substituted Wells-Dawson polyoxometalates. This complex was obtained through the reaction of calcium chloride with the monomeric trititanium(IV)-substituted Wells−Dawson POM species "[P 2 W 15 Ti 3 O 59 (OH) 3 ] 9− ". During the synthesis, the [Ca 6 (CO 3 )(µ 3 -OH)(OH 2 ) 18 ] 9+ cluster cation, composed of six calcium cations linked by one µ 6 -carbonato anion and one µ 3 -OHanion, assembled with one calcium ion, a trimeric "[P 2 W 15 Ti 3 O 59 (OH) 3 ] 9− " species to form the target product. The compound is an unprecedented POM species containing an alkaline-earth-metal cluster cation, and it is also the first example of alkaline-earth-metal ions clustered around a Ti-substituted POM [85].

Ti/Zr-Substituted Tetrameric POMs
In this section, a number of Ti/Zr-substituted tetrameric POMs will be briefly introduced. The early example is a dodeca-Ti-substituted Dawson-type tetrameric, [{Ti3P2W15O57.5(OH)3}4] 24− (Figure 6a), representing a supramolecular phosphotungstate reported by Kortz's group in 2003 [86]. The polyoxoanion was composed of four lacunary [P2W15O56] 12− Well-Dawson building blocks linked with terminal Ti-O bonds, resulting in a structure with Td symmetry. The {Ti12O46} core of the polyoxoanion is composed of four groups of three edge-shared, corner-linked TiO6 octahedra. Such a rare arrangement resembles one set of the four corner-shared faces of an octahedron, described as a "reversed Keggin structure", which is very similar to the [As4Mo12O50] 8− geometry reported by Sasaki and Nishikawa [87]. Apart from this Ti12 cluster, they also discovered another deca-Tisubstituted tetrameric species

Ti/Zr-Substituted Tetrameric POMs
In this section, a number of Ti/Zr-substituted tetrameric POMs will be briefly introduced.
The early example is a dodeca-Ti-substituted Dawson-type tetrameric, [{Ti 3 P 2 W 15 O 57.5 (OH) 3 } 4 ] 24− (Figure 6a), representing a supramolecular phosphotungstate reported by Kortz's group in 2003 [86]. The polyoxoanion was composed of four lacunary [P 2 W 15 O 56 ] 12− Well-Dawson building blocks linked with terminal Ti-O bonds, resulting in a structure with T d symmetry. The {Ti 12 O 46 } core of the polyoxoanion is composed of four groups of three edge-shared, corner-linked TiO 6 octahedra. Such a rare arrangement resembles one set of the four corner-shared faces of an octahedron, described as a "reversed Keggin structure", which is very similar to the [As 4 Mo 12 O 50 ] 8− geometry reported by Sasaki and Nishikawa [87]. Apart from this Ti 12 cluster, they also discovered another deca-Ti-substituted tetrameric species [{Ti 3 P 2 W 15 O 57.5 (OH) 3 } 2 {Ti 2 P 2 W 16 O 60 (OH)} 2 ] 26− containing two {Ti 3 P 2 W 15 } and two {Ti 2 P 2 W 16 } fragments, therefore resulting in a structure with C 2v symmetry. Meanwhile, Nomiya et al. also reported two multi-Ti-substituted tetrameric POMs. The first one is a giant "tetrapod"-shaped dodeca-Ti-substituted Dawson-type tetrameric phosphotungstate, [(α-1,2,3-P 2 W 15 Ti 3 O 60.5 ) 4 Cl] 37− (Figure 6b), which contains the four Wells-Dawson units fused together through Ti-O-Ti bonds. The structure exhibits an approximately T d symmetry, where the four Ti 3 O 6 facets of "P 2 W 15 Ti 3 " occupied four alternate facets of an octahedron, and the one Clion was encapsulated in the central octahedral cavity [88]. It is noted that a similar structure [(P 2 W 15 Ti 3 O 60.5 ) 4 (NH 4 )] 35− was also reported in 2011, except that Clwas replaced by NH 4 + [89]. The other example belongs to a "tetrapod"-shaped Ti 16 (Figure 6d) assembly under mild, one-pot reaction conditions. The polyoxoanion is composed of four {β-Ti 2 SiW 10 O 39 } Keggin fragments bridged with Ti-O-Ti bonds, leading to a cyclic assembly. The successful preparation of this compound provides future possibilities for preparing even larger wheel-shaped polyoxotungstates and other discrete nanomolecular objects of similar size, structure, and function as those made with polyoxometalates [92]. Then, Kortz's group also successfully prepared a hepta-Ti substituted arsenotungstate [Ti 6 (TiO 6 )(AsW 9 O 33 ) 4 ] 20− (Figure 6e) in 2014 using a simple one-pot procedure. The polyoxoanion contains a novel Ti 7 -core consisting of a central TiO 6 octahedron surrounded by six TiO 5 square pyramids, which was further capped by four trilacunary {As III W 9 } fragments, leading to an assembly with T d point-group symmetry [93].  [95].
In addition to these Ti-substituted POMs, some Zr-substituted tetrameric POMs have also been actively investigated. For instance, a Zr 4 2 12− (Figure 7a), has been firstly constructed using {α-SeW 9 } building blocks. Such a tetrameric structure can be divided into two same subunits, each containing a dimer sandwich-type structure that consists of a well-known trivacant Keggin-type {α-SeW 9 O 34 } building blocks [96]. Then, Yang's group continuously reported eight tetrameric Zr-substituted POMs. The first example represents a new tetra-Zr-substituted tungstophosphate, {Zr 2 [SbP 2 W 4 (OH) 2 (Figure 6f) under hydrothermal conditions, which represents the highest number of Ti centers in Keggin-type poly(POM) family to date. In this structure, two types of novel chiral trivacant [GeW9O36] 14− (A-α-1,3,5-GeW9O36 and A-α-2,3,4-GeW9O36) fragments have been first discovered in POM chemistry, and four [GeW9O36] 14− fragments are alternately connected by two Ti2O and two Ti4O4 cores to form a ring-shaped poly(POM) [95].   (Figure 7a), has been firstly constructed using {α-SeW9} building blocks. Such a tetrameric structure can be divided into two same subunits, each containing a dimer sandwich-type structure that consists of a well-known trivacant Keggin-type {α-SeW9O34} building blocks [96]. Then, Yang's group continuously reported eight tetrameric Zr-substituted POMs. The first example represents a new tetra-Zr-substituted tungstophosphate

Ti/Zr-Substituted Multimeric POMs
Compared to those mono-, di-, tri-and tetrameric POM structures, there are very few reports on the preparation of multimeric Ti/Zr-substituted POMs. To date, only two related compounds have been reported. The first example belongs to an octa-Tisubstituted Dawson-type supramolecular polyoxoanion reported by Kortz's group in 2003 [86]. However, the polyoxoanion was described by the preliminary and incomplete formula "Ti 8 P 12 W 84 " or "(Ti 2 P 2 W 15 ) 2 (Ti 2 P 2 W 16 ) 2 (P 2 W 11 ) 2 " (Figure 8a) due to the poor quality of the crystallographic data. The second representative example is the gigantic Zr 24 -clustersubstituted Keggin-type germanotungstates [Zr 24 O 22 (OH) 10  Catalytic experiments also showed that this compound worked as a good catalyst for the oxygenation of thioethers to sulfoxides/sulfones in the presence of H 2 O 2 , which could be attributed to the unique redox property of oxygen-enriched polyoxotungstate fragments as well as the Lewis acidity of the Zr 24 cluster. Although the synthesis of multimeric POMs is rather difficult, these pioneering works provide some insights and future direction for the exploration of this specific research area.

Ti/Zr-Substituted Multimeric POMs
Compared to those mono-, di-, tri-and tetrameric POM structures, there are very few reports on the preparation of multimeric Ti/Zr-substituted POMs. To date, only two related compounds have been reported. The first example belongs to an octa-Ti-substituted Dawson-type supramolecular polyoxoanion reported by Kortz's group in 2003 [86]. However, the polyoxoanion was described by the preliminary and incomplete formula "Ti8P12W84" or "(Ti2P2W15)2(Ti2P2W16)2(P2W11)2" (Figure 8a) due to the poor quality of the crystallographic data. The second representative example is the gigantic Zr24-cluster-substituted Keggin-type germanotungstates [Zr24O22(OH)10(H2O)2(W2O10H)2(GeW9O34)4(GeW8O31)2] 32− (Figure 8b) reported by Yang's group in 2014 [102]. The polyoxoanion was successfully synthesized under hydrothermal conditions, which contains the largest [Zr24O22(OH)10(H2O)2] cluster among all reported Zr-based poly(polyoxometalate)s to date. Detailed structural analyses of this complex showed that the centrosymmetric Zr24-cluster-based hexamer contained two symmetryrelated [Zr12O11(OH)5(H2O)(W2O10H)(GeW9O34)2(GeW8O31)] 16− trimers linked via six μ3-oxo bridges, which were further encapsulated by different POM fragments including B-α-GeW9O34, B-α-GeW8O31, and W2O10. Catalytic experiments also showed that this compound worked as a good catalyst for the oxygenation of thioethers to sulfoxides/sulfones in the presence of H2O2, which could be attributed to the unique redox property of oxygenenriched polyoxotungstate fragments as well as the Lewis acidity of the Zr24 cluster. Although the synthesis of multimeric POMs is rather difficult, these pioneering works provide some insights and future direction for the exploration of this specific research area.

The Applications of Representative Ti/Zr-Substituted POMs
It is well known that transition-metal clusters are a unique area in inorganic chemistry, considering their vital contribution to the blossom of modern chemistry as well as their potential application as structural models for various industrial and biological catalytic processes [103][104][105][106]. To date, the Ti/Zr-substituted POMs have been widely investigated as catalysts for the oxidation of organic substrates.

The Applications of Representative Ti/Zr-Substituted POMs
It is well known that transition-metal clusters are a unique area in inorganic chemistry, considering their vital contribution to the blossom of modern chemistry as well as their potential application as structural models for various industrial and biological catalytic processes [103][104][105][106] O 39 ] and found that protonated titanium peroxo complex has a higher redox potential, which can improve the catalytic performance [109]. In the same year, Ti(IV)-monosubstituted Keggin-type POMs were reported to exhibit excellent catalytic oxidation properties with H 2 O 2 [110][111][112]. Subsequently, Kholdeeva et al. also reported the epoxidation of a range of alkenes easily proceeds with aqueous H 2 O 2 as oxidant and the dititanium-containing 19-tungstodiarsenate (III) as catalyst [113]. In 2012, the same group also published two works on alkene oxidation by Ti-containing POMs. They claimed that the energy barrier for the heterolytic oxygen transfer from the reactive Ti hydroperoxo intermediate was significantly reduced by the protonated Ti-containing POM, as revealed by the kinetic and DFT studies, thereby greatly enhancing the activity and selectivity of alkene oxidation [114,115] [32,116,117]. Based on the research of alkene epoxidation catalysis, Kholdeeva et al. also revealed the mechanism of thioether oxidation of Ti-substituted POMs by kinetic modeling and DFT calculations. Two possible models regarding the active group were proposed: (1) the active group is the terminal Ti−OH group for the mononuclear, and (2) the active group is the bridging Ti 2 (µ-OH) moiety for the multinuclear [118]. Subsequently, Yang's group also reported two cases of the catalytic oxidation of thioethers using Ti 7 -and Ti 12 -substituted POMs, respectively, which both exhibited good catalytic properties [94,95]. In addition, Li's group investigated the photocatalytic degradation of MB with Ti 2 -substituted POM units under UV irradiation, which proved that Ti-substituted Keggin-type POMs showed better photocatalytic activities than that of typical Keggin-type POMs [50]. Some Ti-substituted POMs have also been reported with good electrocatalytic properties [119].
reported a protonated titanium peroxo complex [Bu4N]4[HPTi(O2)W11O39] and found that protonated titanium peroxo complex has a higher redox potential, which can improve the catalytic performance [109]. In the same year, Ti(IV)-monosubstituted Keggin-type POMs were reported to exhibit excellent catalytic oxidation properties with H2O2 [110][111][112]. Subsequently, Kholdeeva et al. also reported the epoxidation of a range of alkenes easily proceeds with aqueous H2O2 as oxidant and the dititanium-containing 19-tungstodiarsenate (III) as catalyst [113]. In 2012, the same group also published two works on alkene oxidation by Ti-containing POMs. They claimed that the energy barrier for the heterolytic oxygen transfer from the reactive Ti hydroperoxo intermediate was significantly reduced by the protonated Ti-containing POM, as revealed by the kinetic and DFT studies, thereby greatly enhancing the activity and selectivity of alkene oxidation [114,115] [32,116,117]. Based on the research of alkene epoxidation catalysis, Kholdeeva et al. also revealed the mechanism of thioether oxidation of Ti-substituted POMs by kinetic modeling and DFT calculations. Two possible models regarding the active group were proposed: (1) the active group is the terminal TiOH group for the mononuclear, and (2) the active group is the bridging Ti2(μ-OH) moiety for the multinuclear [118]. Subsequently, Yang's group also reported two cases of the catalytic oxidation of thioethers using Ti7-and Ti12-substituted POMs, respectively, which both exhibited good catalytic properties [94,95]. In addition, Li's group investigated the photocatalytic degradation of MB with Ti2-substituted POM units under UV irradiation, which proved that Ti-substituted Keggin-type POMs showed better photocatalytic activities than that of typical Keggin-type POMs [50]. Some Ti-substituted POMs have also been reported with good electrocatalytic properties [119]. Compared with the applications of Ti-substituted POMs, a part of Zr-substituted POMs also exhibited good catalytic oxidation of thioether, electrocatalytic and nonlinear optical properties, etc. For example, Yang's groups reported a few works on the oxidation of sulfide using Zr2-, Zr4-, Zr7-and Zr8-substituted POMs, respectively [76,[99][100][101]. These compounds showed remarkable heterogeneous catalysts for the catalytic oxidation of sulfides into the corresponding sulfones with H2O2. The same groups also reported several Chiral Zr-substituted POMs which have excellent nonlinear optical properties [75,77]. In addition, transition-metal-substituted POMs are air-and water-stable Lewis acids that were often used in organic reactions [120], and in the last two decades, most Zr-substituted POMs also were reported to be used as optimal Lewis acid catalysts to hydrolyze the O = C-NH-bonds in proteins or peptides (Scheme 2), leading to the formation of amino acids [121][122][123][124][125][126]. These works implied the potential applications of Zr-substituted POMs in biological systems. Compared with the applications of Ti-substituted POMs, a part of Zr-substituted POMs also exhibited good catalytic oxidation of thioether, electrocatalytic and nonlinear optical properties, etc. For example, Yang's groups reported a few works on the oxidation of sulfide using Zr 2 -, Zr 4 -, Zr 7 -and Zr 8 -substituted POMs, respectively [76,[99][100][101]. These compounds showed remarkable heterogeneous catalysts for the catalytic oxidation of sulfides into the corresponding sulfones with H 2 O 2 . The same groups also reported several Chiral Zr-substituted POMs which have excellent nonlinear optical properties [75,77]. In addition, transition-metal-substituted POMs are air-and water-stable Lewis acids that were often used in organic reactions [120], and in the last two decades, most Zr-substituted POMs also were reported to be used as optimal Lewis acid catalysts to hydrolyze the O = C-NH-bonds in proteins or peptides (Scheme 2), leading to the formation of amino acids [121][122][123][124][125][126]. These works implied the potential applications of Zr-substituted POMs in biological systems.

Conclusions and Perspectives
In summary, this review has mainly addressed the development of Ti/Zr-substituted POMs with an emphasis on structural diversity, synthetic approaches, and potential catalytic applications. According to the overview of these reported Ti/Zr-substituted POMs, Scheme 2. Schematic diagram of hydrolysis of GG in the Presence of POMs.

Conclusions and Perspectives
In summary, this review has mainly addressed the development of Ti/Zr-substituted POMs with an emphasis on structural diversity, synthetic approaches, and potential catalytic applications. According to the overview of these reported Ti/Zr-substituted POMs, we can conclude that (1) the solution-based synthetic approach is an effective method for the syntheses of Ti/Zr-substituted POMs; (2) interesting and attracting POM structures could be often obtained via the hydrothermal synthetic strategy. These successful synthetic strategies and the persistent and dedicated efforts of chemists over the past decades have greatly contributed to the vast and beautiful array of Ti/Zr-substituted POMs. However, there are still bottlenecks in Ti/Zr-substituted POM chemistry with respect to the controllable assembly of target POM structures, the exploration of novel synthetic approaches, as well as the insightful understanding of catalytic mechanisms using Ti/Zr-substituted POM catalysts. Therefore, we believe that the development of other synthetic methods, for instance, the mixed solvent diffusion method, ionothermal approach, templated modular assembly method or the combination with existing solution/hydrothermal approaches, would provide new blood to the synthetic chemistry of Ti/Zr-substituted POMs. Moreover, the ground-breaking exploration of new catalytic functionalities of these Ti/Zr-substituted POMs should also be strengthened in the future. Finally, we hope this critical review could provide research insights into the controllable design and syntheses of Ti/Zr-substituted POMs derivatives and, in the meantime, attract more researchers to join the research community of POM Chemistry or the related interdisciplinary research areas.