Structural Characterization of the Complex between Hen Egg‐White Lysozyme and ZrIV‐Substituted Keggin Polyoxometalate as Artificial Protease

Successful co‐crystallization of a noncovalent complex between hen egg‐white lysozyme (HEWL) and the monomeric Zr^IV‐substituted Keggin polyoxometalate (POM) (Zr1 K1), (Et₂NH₂)₃[Zr(PW₁₁O₃₉)] ( 1 ), has been achieved, and its single‐crystal X‐ray structure has been determined. The dimeric Zr^IV‐substituted Keggin‐type polyoxometalate (Zr1 K2), (Et₂NH₂)₁₀[Zr(PW₁₁O₃₉)₂] ( 2 ), has been previously shown to exhibit remarkable selectivity towards HEWL hydrolysis. The reported X‐ray structure shows that the hydrolytically active Zr^IV‐substituted Keggin POM exists as a monomeric species. Prior to hydrolysis, this monomer interacts with HEWL in the vicinity of the previously identified cleavage sites found at Trp28‐Val29 and Asn44‐Arg45, through water‐mediated H‐bonding and electrostatic interactions. Three binding sites are observed at the interface of the negatively charged Keggin POM and the positively charged regions of HEWL at: 1) Gly16, Tyr20, and Arg21; 2) Asn44, Arg45, and Asn46; and 3) Arg128.     

Molecular Origin of the Hydrolytic Activity and Fixed Regioselectivity of a ZrIV‐Substituted Polyoxotungstate as Artificial Protease

A multitechnique approach has been applied in order to identify the thermodynamic and kinetic parameters related to the regioselective hydrolysis of human serum albumin (HSA) promoted by the Wells–Dawson polyoxometalate (POM), K₁₅H[Zr(α₂‐P₂W₁₇O₆₁)₂]. Isothermal titration calorimetry (ITC) studies indicate that up to four POM molecules interact with HSA. While the first interaction site is characterized by a 1:1 binding and an affinity constant of 2×10⁸ M ^?1, the three remaining sites are characterized by a lower global affinity constant of 7×10⁵ M ^?1. The higher affinity constant at the first site is in accordance with a high quenching constant of 2.2×10⁸ M ^?1 obtained for fluorescence quenching of the Trp214 residue located in the only positively charged cleft of HSA, in the presence of K₁₅H[Zr(α₂‐P₂W₁₇O₆₁)₂]. In addition, Eu^III luminescence experiments with an Eu^III‐substituted POM analogue have shown the replacement of water molecules in the first coordination sphere of Eu^III due to binding of the metal ion to amino acid side chain residues of HSA. All three interaction studies are in accordance with a stronger POM dominated binding at the positive cleft on the one hand, and interaction mainly governed by metal anchoring at the three remaining positions, on the other hand. Hydrolysis experiments in the presence of K₁₅H[Zr(α₂‐P₂W₁₇O₆₁)₂] have demonstrated regioselective cleavage of HSA at the Arg114?Leu115, Ala257?Asp258, Lys313?Asp314 or Cys392?Glu393 peptide bonds. This is in agreement with the interaction studies as the Arg114?Leu115 peptide bond is located in the positive cleft of HSA and the three remaining peptide bonds are each located near an upstream acidic residue, which can be expected to coordinate to the metal ion. A detailed kinetic study has evidenced the formation of additional fragments upon prolonged reaction times. Edman degradation of the additional reaction products has shown that these fragments result from further hydrolysis at the initially observed cleavage positions, indicating a fixed selectivity for K₁₅H[Zr(α₂‐P₂W₁₇O₆₁)₂].     

POSS end‐linked peptide‐functionalized poly(ɛ‐caprolactone)s and their inclusion complexes with α‐cyclodextrin

In this report, we have synthesized organic/inorganic hybrid peptide–poly(?‐caprolactone) (PCL) conjugates via ring opening polymerization (ROP) of ?‐caprolactone (CL) in the presence of two sequence defined peptide initiators, namely POSS‐Leu‐Aib‐Leu‐NH₂ (POSS: polyhedral oligomeric silsesquioxane; Leu: Leucine; Aib: α‐aminoisobutyric acid) and OMe‐Leu‐Aib‐Leu‐NH₂. Covalent attachment of peptide segments with the PCLs were examined by ¹H and ²⁹Si NMR spectroscopy, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS) and FTIR spectroscopy. Supramolecular inclusion complexations of synthesized peptide‐PCL conjugates with α‐cyclodextrin (α‐CyD) were studied to understand the effect of POSS/OMe‐peptide moieties at the PCL chain ends. Inclusion complexation of peptide‐PCL conjugates with α‐CyD produced linear polypseudorotaxane, confirmed by ¹H NMR, FTIR, powder X‐ray diffraction (PXRD), polarized optical microscopy (POM) and differential scanning calorimetry (DSC). Extent of α‐CyD threading onto the hybrid peptide‐PCL conjugated polymers is less than that of α‐CyD threaded onto the linear PCL. Thus, PCL chains were not fully covered by the host α‐CyD molecules due to the bulky POSS/OMe‐peptide moieties connected with the one edge of the PCL chains. PXRD experiment reveals channel like structures by the synthesized inclusion complexes (ICs). Spherulitic morphologies of POSS/OMe‐peptide‐PCL conjugates were fully destroyed after inclusion complexation with α‐CyD and tiny nanoobjects were produced. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3643–3651.     

Synthesis of α‐Dawson‐Type Silicotungstate [α‐Si2W18O62]8− and Protonation and Deprotonation Inside the Aperture through Intramolecular Hydrogen Bonds

The design of structurally well‐defined anionic molecular metal–oxygen clusters, polyoxometalates (POMs), leads to inorganic receptors with unique and tunable properties. Herein, an α‐Dawson‐type silicotungstate, TBA₈[α‐Si₂W₁₈O₆₂] ? 3 H₂O ( II ) that possesses a ?8 charge was successfully synthesized by dimerization of a trivacant lacunary α‐Keggin‐type silicotungstate TBA₄H₆[α‐SiW₉O₃₄] ? 2 H₂O ( I ) in an organic solvent. POM II could be reversibly protonated (in the presence of acid) and deprotonated (in the presence of base) inside the aperture by means of intramolecular hydrogen bonds with retention of the POM structure. In contrast, the aperture of phosphorus‐centered POM TBA₆[α‐P₂W₁₈O₆₂]?H₂O ( III ) was not protonated inside the aperture. The density functional theory (DFT) calculations revealed that the basicities and charges of internal μ₃‐oxygen atoms were increased by changing the central heteroatoms from P⁵⁺ to Si⁴⁺, thereby supporting the protonation of II . Additionally, II showed much higher catalytic performance for the Knoevenagel condensation of ethyl cyanoacetate with benzaldehyde than I and III .     

Hydrogels Composed of Organic Amphiphiles and α‐Cyclodextrin: Supramolecular Networks of Their Pseudorotaxanes in Aqueous Media

Mixtures of N‐alkyl pyridinium compounds [py‐N‐(CH₂)_nOC₆H₃‐3,5‐(OMe)₂]⁺(X^?) ( 1b Cl: n=10, X=Cl; 1c Br: n=12, X=Br) and α‐cyclodextrin (α‐CD) form supramolecular hydrogels in aqueous media. The concentrations of the two components influences the sol–gel transition temperature, which ranges from 7 to 67 °C. Washing the hydrogel with acetone or evaporation of water left the xerogel, and ¹³C CP/MAS NMR measurements, powder X‐ray diffraction (XRD), and scanning electron microscopy (SEM) revealed that the xerogel of 1b Cl (or 1c Br) and α‐CD was composed of pseudorotaxanes with high crystallinity. ¹³C{¹H} and ¹H NMR spectra of the gel revealed the detailed composition of the components. The gel from 1b Cl and α‐CD contains the corresponding [2]‐ and [3]pseudorotaxanes, [ 1b? (α‐CD)]Br and [ 1b? (α‐CD)₂]Br, while that from 1c Br and α‐CD consists mainly of [3]pseudorotaxane [ 1c? (α‐CD)₂]Br. 2D ROESY ¹H NMR measurements suggested intermolecular contact of 3,5‐dimethoxyphenyl and pyridyl end groups of the axle component. The presence of the [3]pseudorotaxane is indispensable for gel formation. Thus, intermolecular interaction between the end groups of the axle component and that between α‐CDs of the [3]pseudorotaxane contribute to formation of the network. The supramolecular gels were transformed into sols by adding denaturing agents such as urea, C₆H₃‐1,3,5‐(OH)₃, and [py‐N‐nBu]⁺(Cl^?).     

Reversible Light‐Driven Polymerization of Polyoxometalate Tethered with Coumarin Molecules

A new photosensitive polyoxometalate (POM) organic–inorganic hybrid compound has been prepared by covalently tethering coumarin moieties onto a Mn–Anderson cluster. This compound has been fully characterized by ¹H NMR, ¹³C NMR, FTIR, and UV/Vis spectroscopy, and ESI‐MS. This organic–inorganic hybrid compound can undergo reversible light‐driven polymerization and this process has been characterized in detail.     

Visible‐Light‐Induced Water Oxidation Mediated by a Mononuclear‐Cobalt(II)‐Substituted Silicotungstate

A mononuclear‐cobalt(II)‐substituted silicotungstate, K₁₀[Co(H₂O)₂(γ‐SiW₁₀O₃₅)₂] ? 23 H₂O (POM‐ 1 ), has been evaluated as a light‐driven water‐oxidation catalyst. With in situ photogenerated [Ru(bpy)₃]³⁺ (bpy=2,2′‐bipyridine) as the oxidant, quite high catalytic turnover number (TON; 313), turnover frequency (TOF; 3.2 s^?1), and quantum yield (Φ_QY; 27 %) for oxygen evolution at pH 9.0 were acquired. Comparison experiments with its structural analogues, namely [Ni(H₂O)₂(γ‐SiW₁₀O₃₅)₂]^10? (POM‐ 2 ) and [Mn(H₂O)₂(γ‐SiW₁₀O₃₅)₂]^10? (POM‐ 3 ), gave the conclusion that the cobalt center in POM‐ 1 is the active site. The hydrolytic stability of the title polyoxometalate (POM) was confirmed by extensive experiments, including UV/Vis spectroscopy, linear sweep voltammetry (LSV), and cathodic adsorption stripping analysis (CASA). As the [Ru(bpy)₃]²⁺/visible light/sodium persulfate system was introduced, a POM–photosensitizer complex formed within minutes before visible‐light irradiation. It was demonstrated that this complex functioned as the active species, which remained intact after the oxygen‐evolution reaction. Multiple experimental parameters were investigated and the catalytic activity was also compared with the well‐studied POM‐based water‐oxidation catalysts (i.e., [Co₄(H₂O)₂(α‐PW₉O₃₄)₂]^10? (Co₄‐POM) and [Co^IIICo^II(H₂O)W₁₁O₃₉]^7? (Co₂‐POM)) under optimum conditions.     

Self‐Assembly of a Giant Tetrahedral 3 d–4 f Single‐Molecule Magnet within a Polyoxometalate System

A giant tetrahedral heterometallic polyoxometalate (POM) [Dy₃₀Co₈Ge₁₂W₁₀₈O₄₀₈(OH)₄₂(OH₂)₃₀]^56?, which shows single‐molecule magnet (SMM) behavior, is described. This hybrid contains the largest number of 4f ions of any polyoxometalate (POM) reported to date and is the first to incorporate two different 3d–4f and 4f coordination cluster assemblies within same POM framework.     

Activity of α‐Chymotrypsin in Cationic and Nonionic Micellar Media: Ultraviolet and Fluorescence Spectroscopic Approach

α‐Chymotrypsin (α‐CT) activity was measured in aqueous buffer with the following alkyltriphenylphosphonium bromide surfactants in the series cetyl, tetradecyl, and dodecyl as a tail length. For the sake of comparison with mixed micellar investigation on activity of α‐CT, cationic cetyltriphenylphosphonium bromide (CTPB) and nonionic surfactant Triton X‐100, Brij‐56, Brij‐35, Tween 20, and Igepal Co‐210 have been used. The p‐nitrophenyl acetate (PNPA) hydrolysis rate was determined at the surfactant concentration of both cationic and mixed micellar systems by a UV–vis spectrophotometer. The catalytic reaction follows the Michaelis–Menten mechanism, and the catalytic efficiency (k_cat/K_M) was evaluated for both homogeneous and mixed‐micellar media. The maximum catalytic efficiency was observed at 5 mM concentration of CTPB, but the highest catalytic efficiency, 572 M^?1 s^?1, was measured in the presence of mixed micellar (7.5 mM CTPB + 2.5 mM Tween‐20). The fluorescence (FL) spectra showed the differences of α‐CT conformations in the presence of cationic surfactants. The FL results suggest that the influence of cationic surfactant on proteolysis arises from the interaction with the α‐CT. The binding constant, k_sv, of α‐CT with cationic aggregates was determined in the buffer using the Stern–Volmer equation by the fluorescence spectroscopic approach.     

Core–Shell α‐Fe2O3@α‐MoO3 Nanorods as Lithium‐Ion Battery Anodes with Extremely High Capacity and Cyclability

α‐Fe₂O₃ nanoparticles are uniformly coated on the surface of α‐MoO₃ nanorods through a two‐step hydrothermal synthesis method. As the anode of a lithium‐ion battery, α‐Fe₂O₃@α‐MoO₃ core–shell nanorods exhibit extremely high lithium‐storage performance. At a rate of 0.1 C (10 h per half cycle), the reversible capacity of α‐Fe₂O₃@α‐MoO₃ core–shell nanorods is 1481 mA h g^?1 and a value of 1281 mA h g^?1 is retained after 50 cycles, which is much higher than that retained by bare α‐MoO₃ and α‐Fe₂O₃ and higher than traditional theoretical results. Such a good performance can be attributed to the synergistic effect between α‐Fe₂O₃ and α‐MoO₃, the small size effect, one‐dimensional nanostructures, short paths for lithium diffusion, and interface spaces. Our results reveal that core–shell nanocomposites have potential applications as high‐performance lithium‐ion batteries.     

Probing Polyoxometalate–Protein Interactions Using Molecular Dynamics Simulations

The molecular interactions between the Ce^IV‐substituted Keggin anion [PW₁₁O₃₉Ce(OH₂)₄]^3? ( CeK ) and hen egg‐white lysozyme (HEWL) were investigated by molecular dynamics simulations. The analysis of CeK was compared with the Ce^IV‐substituted Keggin dimer [(PW₁₁O₃₉)₂Ce]^10? ( CeK₂ ) and the Zr^IV‐substituted Lindqvist anion [W₅O₁₈Zr(OH₂)(OH)]^3? ( ZrL ) to understand how POM features such as shape, size, charge, or type of incorporated metal ion influence the POM???protein interactions. Simulations revealed two regions of the protein in which the CeK anion interacts strongly: cationic sites formed by Arg21 and by Arg45 and Arg68. The POMs chiefly interact with the side chains of the positively charged (arginines, lysines) and the polar uncharged residues (tyrosines, serines, aspargines) via electrostatic attraction and hydrogen bonding with the oxygen atoms of the POM framework. The CeK anion shows higher protein affinity than the CeK₂ and ZrL anions, because it is less hydrophilic and it has the right size and shape for establishing interactions with several residues simultaneously. The larger, more negatively charged CeK₂ anion has a high solvent‐accessible surface, which is sub‐optimal for the interaction, while the smaller ZrL anion is highly hydrophilic and cannot efficiently interact with several residues simultaneously.     

Multinuclear Diffusion NMR Spectroscopy and DFT Modeling: A Powerful Combination for Unraveling the Mechanism of Phosphoester Bond Hydrolysis Catalyzed by Metal‐Substituted Polyoxometalates

A detailed reaction mechanism is proposed for the hydrolysis of the phosphoester bonds in the DNA model substrate bis(4‐nitrophenyl) phosphate (BNPP) in the presence of the Zr^IV‐substituted Keggin type polyoxometalate (Et₂NH₂)₈[{α‐PW₁₁O₃₉Zr(μ‐OH) (H₂O)}₂] ? 7 H₂O (ZrK 2:2) at pD 6.4. Low‐temperature ³¹P DOSY spectra at pD 6.4 gave the first experimental evidence for the presence of ZrK 1:1 in fast equilibrium with ZrK 2:2 in purely aqueous solution. Moreover, theoretical calculations identified the ZrK 1:1 form as the potentially active species in solution. The reaction intermediates involved in the hydrolysis were identified by means of ¹H/³¹P NMR studies, including EXSY and DOSY NMR spectroscopy, which were supported by DFT calculations. This experimental/theoretical approach enabled the determination of the structures of four intermediate species in which the starting compound BNPP, nitrophenyl phosphate (NPP), or the end product phosphate (P) is coordinated to ZrK 1:1. In the proposed reaction mechanism, BNPP initially coordinates to ZrK 1:1 in a monodentate fashion, which results in hydrolysis of the first phosphoester bond in BNPP and formation of NPP. EXSY NMR studies showed that the bidentate complex between NPP and ZrK 1:1 is in equilibrium with monobound and free NPP. Subsequently, hydrolysis of NPP results in P, which is in equilibrium with its monobound form.     

Carbon Monoxide Oxidation by Polyoxometalate‐Supported Gold Nanoparticulate Catalysts: Activity,Stability, and Temperature‐ Dependent Activation Properties

Nanoparticulate gold supported on a Keggin‐type polyoxometalate (POM), Cs₄[α‐SiW₁₂O₄₀]?n H₂O, was prepared by the sol immobilization method. The size of the gold nanoparticles (NPs) was approximately 2 nm, which was almost the same as the size of the gold colloid precursor. Deposition of gold NPs smaller than 2 nm onto POM (Au/POM) was essential for a high catalytic activity for CO oxidation. The temperature for 50 % CO conversion was ?67 °C. The catalyst showed extremely high stability for at least one month at 0 °C with full conversion. The catalytic activity and the reaction mechanism drastically changed at temperatures higher than 40 °C, showing a unique behavior called a U‐shaped curve. It was revealed by IR measurement that Au^δ+ was a CO adsorption site and that adsorbed water promoted CO oxidation for the Au/POM catalyst. This is the first report on CO oxidation utilizing Au/POMs catalysts, and there is a potential for expansion to various gas‐phase reactions.     

Assessing the Influence of Mutation on GTPase Transition States by Using X‐ray Crystallography, 19F NMR,and DFT Approaches

We report X‐ray crystallographic and ¹⁹F NMR studies of the G‐protein RhoA complexed with MgF₃⁻, GDP, and RhoGAP, which has the mutation Arg85′Ala. When combined with DFT calculations, these data permit the identification of changes in transition state (TS) properties. The X‐ray data show how Tyr34 maintains solvent exclusion and the core H‐bond network in the active site by relocating to replace the missing Arg85′ sidechain. The ¹⁹F NMR data show deshielding effects that indicate the main function of Arg85′ is electronic polarization of the transferring phosphoryl group, primarily mediated by H‐bonding to O^3G and thence to P^G. DFT calculations identify electron‐density redistribution and pinpoint why the TS for guanosine 5′‐triphosphate (GTP) hydrolysis is higher in energy when RhoA is complexed with RhoGAP_Arg85′Ala relative to wild‐type (WT) RhoGAP. This study demonstrates that ¹⁹F NMR measurements, in combination with X‐ray crystallography and DFT calculations, can reliably dissect the response of small GTPases to site‐specific modifications.     

Modification of Glassy Carbon Electrode With Single‐Walled Carbon Nanotubes and α‐Silicomolybdate: Application to Sb(III) Detection

A simple procedure was developed to prepare a glassy carbon (GC) electrode modified with single‐walled carbon nanotubes (SWCNTs) and polyoxometalate. With immersing SWCNTs modified GC electrode in silicon polyoxomolybdate (α‐SiMo₁₂O₄₀^4?) solution (direct deposition) for a short period of time (2–10 s) oxoanion adsorbed strongly and irreversibly on SWCNTs. Cyclic voltammograms of the α‐SiMo₁₂O₄₀^4? incorporated‐SWCNTs indicates three well‐defined and reversible redox couples with surface confined characteristic at wide pH range (1–7). The surface coverage (Γ) of α‐SiMo₁₂O₄₀^4? immobilized on SWCNTs was 2.14 (±0.11)×10^?9 mol cm^?2 indicating high loading ability of SWCNTs for polyoxometalate. The charge transfer rate constant (k_s) of three redox couples of adsorbed α‐SiMo₁₂O₄₀^4? were 9.20 (±0.20), 8.02 (±0.20), and 3.70 (±0.10) s^?1, respectively, indicate great facilitation of the electron transfer between α‐SiMo₁₂O₄₀^4? and CNTs. In this research the attractive mechanical and electrical characteristics of CNTs and unique properties and reactivity of polyoxometalates were combined. The modified electrode in buffer solution containing Sb(III) shows a new redox system at 0.38 V in pH 1. The voltammetric peak current increased with increasing Sb(III) concentration. The differential pulse voltammetry (DPV) technique was used for detection micromolar concentration of antimony. Furthermore, the interference effects various electroactive compounds on voltammetric response of Sb(III) were negligible. Finally the ability of the modified electrode for antimony detection in real samples was evaluated.     

Assessing the Influence of Mutation on GTPase Transition States by Using X‐ray Crystallography, 19F NMR,and DFT Approaches

We report X‐ray crystallographic and ¹⁹F NMR studies of the G‐protein RhoA complexed with MgF₃⁻, GDP, and RhoGAP, which has the mutation Arg85′Ala. When combined with DFT calculations, these data permit the identification of changes in transition state (TS) properties. The X‐ray data show how Tyr34 maintains solvent exclusion and the core H‐bond network in the active site by relocating to replace the missing Arg85′ sidechain. The ¹⁹F NMR data show deshielding effects that indicate the main function of Arg85′ is electronic polarization of the transferring phosphoryl group, primarily mediated by H‐bonding to O^3G and thence to P^G. DFT calculations identify electron‐density redistribution and pinpoint why the TS for guanosine 5′‐triphosphate (GTP) hydrolysis is higher in energy when RhoA is complexed with RhoGAP_Arg85′Ala relative to wild‐type (WT) RhoGAP. This study demonstrates that ¹⁹F NMR measurements, in combination with X‐ray crystallography and DFT calculations, can reliably dissect the response of small GTPases to site‐specific modifications.     

Generation of Photocurrent by Visible‐Light Irradiation of Conjugated Dawson Polyoxophosphovanadotungstate–Porphyrin Copolymers

Four hybrid polyoxometalate–porphyrin copolymer films were obtained by the electrooxidation of zinc octaethylporphyrin in the presence of four different Dawson‐type polyoxometalates bearing two pyridyl groups (POM(py)₂) with various spacers. The POM monomers were designed around 1,3,5‐trisubstituted benzene rings. Two of the substituents of the benzene ring are linked to the pyridyl groups, and the third is connected to the POM subunit. The four monomers vary in the relative positions of the nitrogen atoms of the pyridine rings or in the distance from the carbonyl group. The monomers were fully characterized by ¹H, ³¹P, and ¹³C NMR spectroscopy, electrospray mass spectrometry, IR and UV/Vis spectroscopy, and electrochemistry. The copolymers were characterized by UV/Vis spectroscopy, X‐ray photoelectron spectroscopy, electrochemistry, and AFM. Their photovoltaic performance under visible light irradiation was investigated by photocurrent transient measurements under visible illumination.     

Polyoxometalate Ionic Liquids as Self‐Repairing Acid‐Resistant Corrosion Protection

Corrosion is a global problem for any metallic structure or material. Herein we show how metals can easily be protected against acid corrosion using hydrophobic polyoxometalate‐based ionic liquids (POM‐ILs). Copper metal disks were coated with room‐temperature POM‐ILs composed of transition‐metal functionalized Keggin anions [SiW₁₁O₃₉TM(H₂O)]^n? (TM=Cu^II, Fe^III) and quaternary alkylammonium cations (C_nH_{2 n+1})₄N⁺ (n=7–8). The corrosion resistance against acetic acid vapors and simulated “acid rain” was significantly improved compared with commercial ionic liquids or solid polyoxometalate coatings. Mechanical damage to the POM‐IL coating is self‐repaired in less than one minute with full retention of the acid protection properties. The coating can easily be removed and recovered by rinsing with organic solvents.     

Synthesis,Structural Characterization,and Thermoresponsivity of Hybrid Supramolecular Dendrimers Bearing a Polyoxometalate Core

A series of cationic dendrons bearing triethylene glycol monomethyl ether terminal groups of different generations have been synthesized and used to encapsulate an inorganic polyanionic cluster [K_12.5Na_1.5(NaP₅W₃₀O₁₁₀)] through electrostatic interactions. The resulting dendritic cation–encapsulated polyoxometalate (POM) complexes, cluster–dendrimers, are soluble in water and exhibit lower critical solution temperatures (LCST). The thermoresponsivities of these complexes in aqueous solutions were studied by turbidimetry and variable‐temperature ¹H NMR spectroscopy. The observed cloud points show a remarkable dependence on the generation of the dendrons. Complexes composed of first‐generation dendrons exhibit no obvious thermoresponsive properties, but for complexes bearing second‐generation dendrons, the LCST decreases as the number of dendritic cations around the POM cluster increases. Complexes composed of third‐generation cations underwent reversible aggregation and disaggregation upon heating and cooling, respectively. This thermally induced self‐aggregation was characterized by DLS and TEM. In addition, the effects of salt and solvent on the LCST were investigated. This research demonstrates a new type of thermoresponsive dendritic organic–inorganic hybrid complex and provides a general route to the endowment of POMs with temperature‐sensitive properties through electrostatic interactions.