Characterization of New Specific Copper Chelators as Potential Drugs for the Treatment of Alzheimer’s Disease

The non‐controlled redox‐active metal ions, especially copper, in the brain of patients with Alzheimer disease (AD) should be considered at the origin of the intense oxidative damage in the AD brain. Several bis(8‐aminoquinoline) ligands, such as 1 and PA1637, are able to chelate Cu²⁺ with high affinity, and are specific chelators of copper with respect to iron and zinc. They are able to efficiently extract Cu²⁺ from a metal‐loaded amyloid. In addition, these tetradentate ligands are specific for the chelation of Cu²⁺ compared with Cu⁺. Consequently, the copper ion is easily released from the bis(8‐aminoquinoline) ligand under reductive conditions, and can be trapped again by a protein having some affinity for copper such as human serum albumin (HSA) proteins. In addition, the copper is not efficiently released from [Cu(CQ)₂] in reductive conditions. The catalytic production of H₂O₂ by [Cu²⁺‐Aβ_1?28]/ascorbate is inhibited in vitro by the bis(8‐aminoquinoline) 1 , suggesting that 1 should be able to play a protective role against oxidative damages induced by copper‐loaded amyloids.     

Organoplatinum‐Substituted Polyoxometalate Inhibits β‐amyloid Aggregation for Alzheimer's Therapy

Aggregated β‐amyloid (Aβ) is widely considered as a key factor in triggering progressive loss of neuronal function in Alzheimer's disease (AD), so targeting and inhibiting Aβ aggregation has been broadly recognized as an efficient therapeutic strategy for curing AD. Herein, we designed and prepared an organic platinum‐substituted polyoxometalate, (Me₄N)₃[PW₁₁O₄₀(SiC₃H₆NH₂)₂PtCl₂] (abbreviated as Pt^II‐PW₁₁) for inhibiting Aβ₄₂ aggregation. The mechanism of inhibition on Aβ₄₂ aggregation by Pt^II‐PW₁₁ was attributed to the multiple interactions of Pt^II‐PW₁₁ with Aβ₄₂ including coordination interaction of Pt²⁺ in Pt^II‐PW₁₁ with amino group in Aβ₄₂, electrostatic attraction, hydrogen bonding and van der Waals force. In cell‐based assay, Pt^II‐PW₁₁ displayed remarkable neuroprotective effect for Aβ₄₂ aggregation‐induced cytotoxicity, leading to increase of cell viability from 49 % to 67 % at a dosage of 8 μm . More importantly, the Pt^II‐PW₁₁ greatly reduced Aβ deposition and rescued memory loss in APP/PS1 transgenic AD model mice without noticeable cytotoxicity, demonstrating its potential as drugs for AD treatment.     

Reoxidation of Transition‐metal Catalysts with O2

Transition‐metal catalyzed oxidation reactions are central components of organic chemistry. On behalf of green and sustainable chemistry, molecular oxygen (O₂) has been considered as an ideal oxidant due to its natural, inexpensive, and environmentally friendly characters, and therefore offers attractive academic and industrial prospects. In recent years, some powerful organic oxidation methods have been continuously developed. Among them, the use of molecular oxygen (O₂) as a green and sustainable oxidant has attracted considerable attentions. However, the development of new transition metal‐catalyzed protocols using O₂ as an ideal oxidant is highly desirable but very challenging because of the low standard electrode potential of O₂ to reoxidize the transition‐metal catalysts. In this Account, we highlight some of our progress toward the use of transition‐metal catalyzed aerobic oxidation reactions. Through the careful selection of ligand and the acidic additives, we have successfully realized the reoxidation of Cu, Pd, Mn, Fe, Ru, Rh, and bimetallic catalysts under O₂ or air atmosphere (1 atm) for the oxidative coupling, oxygenation reactions, oxidative C‐H/C‐C bond cleavage, oxidative annulation, and olefins difunctionalization reactions. Most of the reactions can tolerate a range of functional groups. These methods provide new strategies for the green synthesis of alkynes, (α ‐keto)amides/esters, ketones/diones, O/N‐heterocycles, β ‐azido alcohols, and nitriles. The high efficiency, low cost, and simple operation under air make these methodologies very attractive and practical. We will also discuss the mechanisms of these reactions which might be useful to promote the new type of aerobic oxidative reaction design.     

Alleviating Cellular Oxidative Stress through Treatment with Superoxide‐Triggered Persulfide Prodrugs

Overproduction of superoxide anion (O₂^.?), the primary cellular reactive oxygen species (ROS), is implicated in various human diseases. To reduce cellular oxidative stress caused by overproduction of superoxide, we developed a compound that reacts with O₂^.? to release a persulfide (RSSH), a type of reactive sulfur species related to the gasotransmitter hydrogen sulfide (H₂S). Termed SOPD‐NAC , this persulfide donor reacts specifically with O₂^.?, decomposing to generate N‐acetyl cysteine (NAC) persulfide. To enhance persulfide delivery to cells, we conjugated the SOPD motif to a short, self‐assembling peptide (Bz‐CFFE‐NH₂) to make a superoxide‐responsive, persulfide‐donating peptide ( SOPD‐Pep ). Both SOPD‐NAC and SOPD‐Pep delivered persulfides/H₂S to H9C2 cardiomyocytes and lowered ROS levels as confirmed by quantitative in vitro fluorescence imaging studies. Additional in vitro studies on RAW 264.7 macrophages showed that SOPD‐Pep mitigated toxicity induced by phorbol 12‐myristate 13‐acetate (PMA) more effectively than SOPD‐NAC and several control compounds, including common H₂S donors.     

Assembly of a New 3D Octamolybdate‐based Compound: Using the Flexible Bis(triazole) ligand with a –(CH2)6– Spacer

Through utilizing the flexible bis(triazole) ligand 1, 6‐bis(1, 2, 4‐triazol‐1‐yl)hexane (btx), a new octamolybdate‐based compound, [Cu₂(btx)₄(β‐Mo₈O₂₆)] · H₂O ( 1 ), was synthesized under hydrothermal conditions. It was characterized by single‐crystal X‐ray diffraction, elemental analyses, IR spectroscopy, thermogravimetric analysis, and cyclic voltammetry. In compound 1 , the [β‐Mo₈O₂₆]^4– anion acts as a bi‐connected inorganic linkage to connect the Cu‐btx moieties. The Cu1‐btx moiety linked by the [β‐Mo₈O₂₆]^4– anions exhibits a 2D layer, while the Cu2‐btx moiety also shows a similar 2D layer. Furthermore, these two 2D moieties construct a 3D framework through sharing the same N7‐containing btx ligands.     

A new inorganic–organic hybrid: tetra­imid­azolium octa­molyb­date(VI) containing the β‐form of the [Mo8O26]4− anion

The title compound, (C₃H₅N₂)₄[β‐Mo₈O₂₆], has been prepared from imidazole octamolybdate, (C₃H₅N₂)₄[(C₃H₄N₂)₂(γ‐Mo₈O₂₆)], which was described previously. The γ→β conversion is produced in the presence of Cu(NO₃)₂·3H₂O and is reported for the first time in this work. The X‐ray structure analysis confirmed the presence of the [Mo₈O₂₆]^4? anion. The structure consists of β‐Mo₈O₂₆ polyanions and imidazolium cations. These cations are linked to the terminal and bridging O atoms of the anion by hydrogen bonds.     

3β,7α,12α‐Tri­formyl­oxy‐24‐nor‐5β‐chol‐22‐ene

The title compound, alternatively called 24‐nor‐5β‐chol‐22‐ene‐3β,7α,12α‐triyl triformate, C₂₆H₃₈O₆, has a cis junction between two of the six‐membered rings. All three of the six‐membered rings have chair conformations that are slightly flattened and the five‐membered ring has a 13β,14α‐half‐chair conformation. The 3β, 7α and 12α ring substituents are axial and the 17β group is equatorial. The 3β‐formyl­oxy group is involved in one weak intermol­ecular C—H⋯O bond, which links the mol­ecules into dimers in a head‐to‐head fashion.     

Michael-Addition Reaction of Malononitrile with α,β-Unsaturated Cycloketones Catalyzed by KF／Al2O3

A series of KF/Al2O3 catalyzed Michael-addition reactions between malononitrile and α,β-unsaturated cycloketones in DMF solution were studied. At room temperature, 2-cyano-3-aryl-3-(1,2,3,4-tetrahydronaphthalen-1-one-2-yl) propionitrile derivatives were synthesized by the reaction between 2-arylmethylidene-1,2,3,4-tetra-hydronaphthalen-1-one and malononitrile. However, if the temperature was increased to 80℃, 2-amino-3-cyano-4-aryl-4H-benzo[h]chromene derivatives were obtained in high yields. When the α,β-unsaturated ketones were replaced by 2,6-biarylmethylidenecyclohexanone or 2,5-biarylmethylidenecyclopentanone, another series of 2-amino-3-cyano-4H-pyran derivatives was isolated successfully. The structures of the products were confirmed by X-ray diffraction analysis.     

Anthraquinone Redox Relay for Dye‐Sensitized Photo‐electrochemical H2O2 Production

Anthraquinone (AQ) redox mediators are introduced to metal‐free organic dye sensitized photo‐electrochemical cells (DSPECs) for the generation of H₂O₂. Instead of directly reducing O₂ to produce H₂O₂, visible‐light‐driven AQ reduction occurs in the DSPEC and the following autooxidation with O₂ allows H₂O₂ accumulation and AQ regeneration. In an aqueous electrolyte, under 1 sun conditions, a water‐soluble AQ salt is employed with the highest photocurrent of up to 0.4 mA cm^?2 and near‐quantitative faradaic efficiency for producing H₂O₂. In a non‐aqueous electrolyte, under 1 sun illumination, an organic‐soluble AQ is applied and the photocurrent reaches 1.8 mA cm^?2 with faradaic efficiency up to 95 % for H₂O₂ production. This AQ‐relay DSPEC exhibits the highest photocurrent so far in non‐aqueous electrolytes for H₂O₂ production and excellent acid stability in aqueous electrolytes, thus providing a practical and efficient strategy for visible‐light‐driven H₂O₂ production.     

Attenuation of the Aggregation and Neurotoxicity of Amyloid‐β Peptides by Catalytic Photooxygenation

Alzheimer’s disease (AD), a progressive severe neurodegenerative disorder, is currently incurable, despite intensive efforts worldwide. Herein, we demonstrate that catalytic oxygenation of amyloid‐β peptides (Aβ) might be an effective approach to treat AD. Aβ1–42 was oxygenated under physiologically‐relevant conditions (pH 7.4, 37 °C) using a riboflavin catalyst and visible light irradiation, with modifications at the Tyr¹⁰, His¹³, His¹⁴, and Met³⁵ residues. The oxygenated Aβ1–42 exhibited considerably lower aggregation potency and neurotoxicity compared with native Aβ. Photooxygenation of Aβ can be performed even in the presence of cells, by using a selective flavin catalyst attached to an Aβ‐binding peptide; the Aβ cytotoxicity was attenuated in this case as well. Furthermore, oxygenated Aβ1–42 inhibited the aggregation and cytotoxicity of native Aβ.     

Kinetic Magnetic‐Field Effect Involving the Small Biologically Relevant Inorganic Radicals NO and O2.−

Oxidation of dihydrorhodamine 123 (DHR) to rhodamine 123 (RH) by oxoperoxonitrite (ONOO^?), formed through recombination of NO and O₂^.? radicals resulting from thermal decomposition of 3‐morpholinosydnonimine (SIN‐1) in buffered aerated aqueous solution at pH 7.6, represents a kinetic model system of the reactivity of NO and O₂^.? in biochemical systems. A magnetic‐field effect (MFE) on the yield of RH detected in this system is explored in the full range of fields between 0 and 18 T. It is found to increase in a nearly linear fashion up to a value of 5.5±1.6 % at 18 T and 23 °C (3.1±0.7 % at 40 °C). A theoretical framework to analyze the MFE in terms of the magnetic‐field‐enhanced recombination rate constant k_rec of NO and O₂^.? due to magnetic mixing of T₀ and S spin states of the radical pair by the Δg mechanism is developed, including estimation of magnetic properties (g tensor and spin relaxation times) of NO and O₂^.? in aqueous solution, and calculation of the MFE on k_rec using the theoretical formalism of Gorelik at al. The factor with which the MFE on k_rec is translated to the MFE on the yield of ONOO^? and RH is derived for various kinetic scenarios representing possible sink channels for NO and O₂^.?. With reasonable assumptions for the values of some unknown kinetic parameters, the theoretical predictions account well for the observed MFE.     

Zu den Kristallstrukturen der Übergangsmetall(II)‐Dodekahydro‐closo‐Dodekaborat‐Hydrate Cu(H2O)5,5[B12H12]·2,5 H2O und Zn(H2O)6[B12H12]·6 H2O

On the Crystal Structures of the Transition‐Metal(II) Dodecahydro‐closo‐Dodecaborate Hydrates Cu(H₂O)_5.5[B₁₂H₁₂]·2.5 H₂O and Zn(H₂O)₆[B₁₂H₁₂]·6 H₂O By neutralization of an aqueous solution of the free acid (H₃O)₂[B₁₂H₁₂] with basic copper(II) carbonate or zinc carbonate, blue lath‐shaped single crystals of the octahydrate Cu[B₁₂H₁₂]·8 H₂O (≡ Cu(H₂O)_5.5[B₁₂H₁₂]·2.5 H₂O) and colourless face‐rich single crystals of the dodecahydrate Zn[B₁₂H₁₂]·12 H₂O (≡ Zn(H₂O)₆[B₁₂H₁₂]·6 H₂O) could be isolated after isothermic evaporation. Copper(II) dodecahydro‐closo‐dodecaborate octahydrate crystallizes at room temperature in the monoclinic system with the non‐centrosymmetric space group Pm (Cu(H₂O)_5.5[B₁₂H₁₂]·2.5 H₂O: a = 768.23(5), b = 1434.48(9), c = 777.31(5) pm, β = 90.894(6)°; Z = 2), whereas zinc dodecahydro‐closo‐dodecaborate dodecahydrate crystallizes cubic in the likewise non‐centrosymmetric space group F23 (Zn(H₂O)₆[B₁₂H₁₂]·6 H₂O: a = 1637.43(9) pm; Z = 8). The crystal structure of Cu(H₂O)_5.5[B₁₂H₁₂]·2.5 H₂O can be described as a monoclinic distortion variant of the CsCl‐type arrangement. As characteristic feature the formation of isolated [Cu₂(H₂O)₁₁]⁴⁺ units as a condensate of two corner‐linked Jahn‐Teller distorted [Cu(H₂O)₆]²⁺ octahedra via an oxygen atom of crystal water can be considered. Since “zeolitic” water of hydratation is also present, obviously both classical H–O^δ?···^+δH–O and non‐classical B–H^δ?···^+δH–O hydrogen bonds play a significant role for the stabilization of the structure. A direct coordinative influence of the quasi‐icosahedral [B₁₂H₁₂]^2? anions on the Cu²⁺ cations has not been determined. The zinc compound Zn(H₂O)₆[B₁₂H₁₂]·6 H₂O crystallizes in a NaTl‐type related structure. Two crystallographically different [Zn(H₂O)₆]²⁺ octahedra are present, which only differ in their relative orientation within the packing of the [B₁₂H₁₂]^2? anions. The stabilization of the crystal structure takes place mainly via H–O^δ?···^+δH–O hydrogen bonds, since again the hydrogen atoms of the [B₁₂H₁₂]^2? anions have no direct coordinative influence on the Zn²⁺ cations.     

Synthesis,Crystal Structure,and Magnetic Properties of {[Cu(phen)]2(C4H2O4)2} · 4.5H2O with C4H4O4 = Maleic Acid

Reaction of CuCl₂ · 2H₂O, phenanthroline, maleic acid and NaOH in CH₃OH/H₂O (1:1 v/v) at pH = 7.0 yielded blue {[Cu(phen)]₂(C₄H₂O₄)₂} · 4.5H₂O, which crystallizes in the monoclinic space group C2/c (no. 15) with cell dimensions: a = 18.127(2)Å, b = 12.482(2)Å, c = 14.602(2)Å, β = 103.43(1)°, U = 3213.5(8)ų, Z = 4. The crystal structure consists of the centrosymmetric dinuclear {[Cu(phen)]₂(C₄H₂O₄)₂} complex molecules and hydrogen bonded H₂O molecules. The Cu atoms are each square‐pyramidally coordinated by two N atoms of one phen ligand and three carboxyl O atoms of two maleato ligands with one carboxyl O atom at the apical position (d(Cu‐N) = 2.008, 2.012Å, equatorial d(Cu‐O) = 1.933, 1.969Å, axial d(Cu‐O) = 2.306Å). Two square‐pyramids are condensed via two apical carboxyl O atoms with a relatively larger Cu···Cu separation of 3.346(1)Å. The dinuclear complex molecules are assembled via the intermolecular π—π stacking interactions into 1D ribbons. Crossover of the resulting ribbons via interribbon π—π stacking interactions forms a 3D network with the tunnels occupied by H₂O molecules. The title complex behaves paramagnetically between 5—300 K, following the Curie‐Weiss law _χm(T—θ) = 0.435 cm³ · mol^—1 · K with θ = 1.59 K.     

The Astounding Chemistry of a 2‐Amino‐1,2‐dihydroisoquinoline Derivative

The cycloadducts of isoquinolinium N‐phenyl imide 2 with C=C bonds are derivatives of 2‐amino‐1,2‐dihydroisoquinoline. Their N^β‐vinylphenylhydrazine system is amenable to an acid‐catalyzed [3,3]‐sigmatropic shift; the formation of pentacyclic aminals is exemplified by 6 → 8 . The dimethyl maleate adduct 11 , C₂₁H₂₀N₂O₄, is exceptional by being converted on treatment with acid to bright‐yellow crystals, C₂₄H₂₂N₂O₆ (additional C₃H₂O₂). X‐Ray crystal‐structure analysis and NMR spectra reveal structure 13 , and mechanistic studies indicated an initial β‐elimination at the N−N bond of 11 to yield 18 ; this step is followed by a retro‐Mannich‐type cleavage that gives methyl isoquinoline‐1‐acetate ( 14 ) and methyl 2‐(phenylimino)acetate ( 15 ), according to the sequence C₂₁H₂₀N₂O₄ ( 11 )→ 18 →C₁₂H₁₁NO₂ ( 14 )+C₉H₉NO₂ ( 15 ). In the second act of the drama, electrophilic attack by 15 ‐H⁺ on the ene‐hydrazine group of a second molecule of 11 furnishes 13 by a polystep intramolecular redox reaction. All rate constants must be fine‐tuned in this reaction cascade to give 13 in yields of up to 78% with an overall stoichiometry: 2 C₂₁H₂₀N₂O₄ ( 11 )→C₂₄H₂₂N₂O₆ ( 13 )+C₁₂H₁₁NO₂ ( 14 )+aniline. Interception and model experiments confirmed the above pathway. A by‐product, C₃₃H₃₁N₃O₆ ( 62 ), arises from an acid‐catalyzed dimerization of 11 and subsequent elimination of 15 .     

Unusual O‐coordination of caffeine in tetra­kis(μ‐3,5‐dinitro­benzoato‐κ2O:O′)bis­[(caffeine‐κO)copper(II)]

The title compound {systematic name: tetra­kis(μ‐3,5‐dinitro­benzoato‐κ²O:O′)bis­[(3,7‐dihydro‐1,3,7‐trimethyl‐1H‐purine‐2,6‐dione‐κO²)copper(II)]}, [Cu₂(C₇H₃N₂O₆)₄(C₈H₁₀N₄O₂)₂], consists of paddle‐wheel dimeric tetra­kis(μ‐3,5‐dinitro­benzoato‐κ²O:O′)dicopper(II) units with O‐coordinated caffeine mol­ecules in both apical positions. The entire dimeric mol­ecule lies on a tetra­gonal inversion axis, and thus one nitro­benzoate anion with one Cu atom in a special position belong to the independent part of the mol­ecule. The caffeine ligand bonded to the Cu atom is disordered on a local twofold non‐crystallographic axis coincident with the axis. A π–π stacking inter­action is observed between the caffeine rings and adjacent symmetry‐related benzene rings of the 3,5‐dinitro­benzoate anions.     

A Bicapped α‐Keggin Unit‐Supported Transition Metal Complex: Hydrothermal Synthesis and Characterization of [Cu(en)2(H2O)]2[Cu(en)2]0.5[Mo8V7O42{Cu(en)2}]

A new metal‐oxo cluster supported transition metal complex, [Cu(en)₂(H₂O)]₂[Cu(en)₂]_0.5[Mo^VI₈V^IV₆V^VO₄₂{Cu(en)₂}], has been synthesized under hydrothermal conditions. Its structure was determined by single‐crystal X‐ray diffraction. The compound crystallizes in the triclinic system, space group (No. 2), a = 12.245(5), b = 12.669(5), c = 20.949(8) Å, α = 77.120(13), β = 78.107(17), γ = 65.560(14)°, V = 2860(2) ų, Z = 2. The metal‐oxo cluster contains a novel bicapped a‐Keggin structure unit and a [Cu(en)₂]²⁺ unit covalently bonded to the [Mo₈V₇O₄₂]^7? cluster.     

Comparison of two polymeric transition metal complexes with 1,4‐benzenedicarboxylate ions as bridging ligands, [Co(C8H4O4)(C12H8N2)(H2O)] and [Cu(C8H4O4)(C10H9N3)]·H2O

The title complexes, catena‐poly[[aqua(1,10‐phenanthroline‐κ²N,N′)­cobalt(II)]‐μ‐benzene‐1,4‐di­carboxyl­ato‐κ²O¹:O⁴], [Co(C₈H₄O₄)(C₁₂H₈N₂)(H₂O)], (I), and catena‐poly[[[(di‐2‐pyridyl‐κN‐amine)copper(II)]‐μ‐benzene‐1,4‐di­carboxyl­ato‐κ⁴O¹,O^1′:O⁴,O^4′] hydrate], [Cu(C₈H₄O₄)(C₁₀H₉N₃)]·H₂O, (II), take the form of zigzag chains, with the 1,4‐benzene­di­carboxyl­ate ion acting as an amphimonodentate ligand in (I) and a bis‐bidentate ligand in (II). The Co^II ion in (I) is five‐coordinate and has a distorted trigonal–bipyramidal geometry. The Cu^II ion in (II) is in a very distorted octahedral 4+2 environment, with the octahedron elongated along the trans O—Cu—O bonds and with a trans O—Cu—O angle of only 137.22 (8)°.     

Versatile Fluorescent Probes for Imaging the Superoxide Anion in Living Cells and In Vivo

The superoxide anion (O₂^.?) is widely engaged in the regulation of cell functions and is thereby intimately associated with the onset and progression of many diseases. To ascertain the pathological roles of O₂^.? in related diseases, developing effective methods for monitoring O₂^.? in biological systems is essential. Fluorescence imaging is a powerful tool for monitoring bioactive molecules in cells and in vivo owing to its high sensitivity and high temporal‐spatial resolution. Therefore, increasing numbers of fluorescent imaging probes have been constructed to monitor O₂^.? inside live cells and small animals. In this minireview, we summarize the methods for design and application of O₂^.?‐responsive fluorescent probes. Moreover, we present the challenges for detecting O₂^.? and suggestions for constructing new fluorescent probes that can indicate the production sites and concentration changes in O₂^.? as well as O₂^.?‐associated active molecules in living cells and in vivo.     

Additive‐Free,Robust H2 Production from H2O and DMF by Dehydrogenation Catalyzed by Cu/Cu2O Formed In Situ

Hydrogen production from organic/inorganic hydrides is a promising strategy for the development of novel clean energy resources to replace fossil fuels and satisfy ever‐increasing energy demands. Most current processes involve small flammable chemicals and are catalyzed by noble metals in basic media with the release of the greenhouse gas CO₂. Herein, we describe an alternative pathway for highly efficient and robust H₂ production through a dehydrogenation reaction between water and N ,N ‐dimethylformamide catalyzed by Cu/Cu₂O catalysts formed in situ. The catalysts exhibit high and robust activity for H₂ production. Importantly, the formation of H₂ as the sole gas and the valuable by‐product N ,N ‐dimethylaminoformic acid make this process clean and valuable with 100 % atom economy.     

Modified polyoxometalate: a novel monocapped bi‐supporting and reduced α‐Keggin structure {PMo12O40[Cu(2,2′‐bpy)]}[Cu(2,2′‐bpy)(en)(H2O)]2

A novel modified polyoxometalate, {PMo₁₂O₄₀[Cu(2,2′‐bpy)]}[Cu(2,2′‐bpy)(en)(H₂O)]₂ [2,2′‐bpy is 2,2′‐bipyridyl (C₁₀H₈N₂) and en is ethylenediamine (C₂H₈N₂)], has been synthesized hydrothermally and structurally characterized by elemental analysis, TG, IR, XPS and single‐crystal X‐ray diffraction. The structural analysis reveals that the compound contains the reduced Keggin polyanion [PMo₁₂O₄₀]^6? as the parent unit, which is monocapped by [Cu(2,2′‐bpy)]²⁺ fragments via four bridging O atoms on an {Mo₄O₄} pit and bi‐supported by two [Cu(2,2′‐bpy)(en)(H₂O)]²⁺ coordination cations simultaneously. There exist strong intramolecular π–π stacking between the capping and supporting units, which play a stabilizing role during the crystallization of the compound. Adjacent POM clusters are further aggregated to form a three‐dimensional supramolecular network through noncovalent forces, hydrogen bonding and π–π stacking interactions. In addition, the photocatalytic properties were investigated in detail, and the results indicated that the compound can be used as a photocatalyst towards the decomposition of the organic pollutant methylene blue (MB).