Nadiia I. Gumerova

Polyoxometalates (POMs) offer unique physicochemical properties for radiopharmaceutical design, yet their integration with clinically relevant radionuclides remains largely unexplored. Here we report the isolation and comprehensive solid‐state and solution characterization of the gallium‐substituted Keggin phosphotungstate cesium salt, Cs ₄ [Ga(H ₂ O)PW ₁₁ O ₃₉ ]·8H ₂ O ( CsGaPW ₁₁ ), including single‐crystal and powder X‐ray diffraction, multinuclear NMR ( ³¹ P, ⁷¹ Ga, ¹⁸³ W), IR spectroscopy, ESI‐MS, elemental analysis, and TGA. The radiolabeled analogue Cs ⁶⁸ GaPW ₁₁ (45–55 MBq, >96% radiochemical purity) was synthesized in under 60 min, dictated by the 68 min half‐life of ⁶⁸ Ga, and retained full structural integrity after radioactive decay. In CHO‐K1 cells, Cs ⁶⁸ GaPW ₁₁ shows higher cellular uptake than ⁶⁸ GaCl ₃ and ⁶⁸ Ga‐oxine, with radioactivity progressively shifting from the cell membrane to the intracellular compartment over 60 min. Together with low cytotoxicity (>90% viability at 100 µM), these findings identify the membrane‐permeable Keggin anion as a viable inorganic platform for PET cell tracking.

ZUSAMMENFASSUNG: Polyoxometallate (POMs) haben viele verschiedene physikochemische Eigenschaften, welche für radiopharmazeutische Zwecke verwendet werden können. Jedoch ist das Potential einer Kombination aus POMs und klinisch relevanten Nukliden noch unausgeschöpft. In diesem Artikel zeigen wir die Isolierung und Charakterisierung des Cäsiumsalzes des galliumsubstituierten Keggin Phosphowolframats Cs ₄ [Ga(H ₂ O)PW ₁₁ O ₃₉ ]·8H ₂ O ( CsGaPW ₁₁ ). Dabei wurden Einkristall‐ und Pulver‐Röntgen‐ Strukturanalyse, Multikern NMR ( ³¹ P, ⁷¹ Ga, ¹⁸³ W), IR Spektroskopie, ESI‐MS, Elementaranalyse und eine totale gravimetrische Analyse angewendet. Das radioaktive Analog Cs ⁶⁸ GaPW ₁₁ (45–55 MBq, >96 % Reinheit) wurde in 60 min, unter Beachtung der 68 min Halbwertszeit, synthetisiert und blieb nach radioaktivem Zerfall strukturell intakt. In CHO‐K1 Zellen zeigte Cs ⁶⁸ GaPW ₁₁ eine höhere intrazelluläre Aufnahme als ⁶⁸ GaCl ₃ and ⁶⁸ Ga‐Oxin. Dabei bewegte sich das radioaktive Signal zeitabhängig von der Zellmembran in das Innere der Zelle, selbst bei einem niedrigen Zytotoxizität Effekt (>90 % Viabilität bei 100 µM). Somit kann ein membrangängiges Keggin‐Anion als geeignete anorganische Plattform für PET‐Tracer zur Zell‐Markierung etabliert werden.

Polyoxometalates (POMs) are promising antiviral agents, yet systematic structure–activity relationships remain scarce and biological stability is rarely assessed. Here we report the antiviral activity, cytotoxicity, and solution speciation of 11 Keggin-type POMs spanning three compositional series─PVxW12–x, PVxMo12–x, and SiMoxW12–x (x = 0–3)─alongside lacunary derivatives, and simple metal salt controls. Multinuclear NMR spectroscopy (31P, 51V, 183W) in cell culture medium under assay conditions revealed a direct correlation between cluster integrity and antiviral potency: compounds that decompose are uniformly inactive while structurally stable or partially transformed clusters show concentration-dependent inhibition. The silicomolybdotungstate series proved most promising, with [SiW12O40]4– and [SiMoW11O40]4– achieving IC50 values of 26.0 and 24.9 μM against HCoV-OC43. Antiviral potency correlates with overall cluster charge, with 4– anions consistently outperforming their 3– and 6– analogues─an observation rationalized through the superchaotropic ion concept.

We studied the speciation, protein binding, biotransformation, and cytotoxicity of the dioxidovanadium(V) lactate complex Cs2[VV2O4(lact)2]·2H2O and compared the results with those obtained for the analogous malate compound. 51V NMR and ESI-MS results show that Cs2[VV2O4(lact)2]·2H2O forms [VVO2]+, [H2VVO4]−, [H2VV2O7]2–, [VV2O4(lact)2]2–, [VV3O7(lact)2]3–, [VV4O12]4–, [VV5O15]5–, [VVO2(lact)(H2O)]−, [VVO2(lact)(OH)]2–, and [VV10O28]6– species in aqueous solution. In the presence of lysozyme, the amounts of [VV10O28]6– and [VVO2(lact)(H2O)]− significantly decrease and protein adducts with [VV2O4(lact)2]2– and [VVO(lact)2]− are detected by ESI-MS. X-ray structures of the adducts show noncovalent binding of [VIVO]2+, [VVO2]+, [VV2O4(lact)2]2–, cyclic [VV3O9]3–, and [VV3O7(lact)2]3– to lysozyme. Cs2[VV2O4(lact)2]·2H2O and Cs2[VV2O4(mal)2]·2H2O exhibit higher cytotoxicity than cisplatin on PC-3 cancer cells (IC50 values are 5.9 ± 0.3 and 5.0 ± 0.3 μM, respectively), while they are less active than cisplatin against HeLa cells and less selective against BALB/c-3T3 and HaCaT cells. In systems containing [VV2O4(lact)2]2– and biological reductants, EPR studies demonstrate the formation of hydroxyl radicals, supporting a mechanism in which redox cycling between VV and VIV contributes to the oxidative stress that accounts for the observed biological activity.

ZUSAMMENFASSUNG: Polyoxometallate (POMs; molekulare Metall–Oxo‐Cluster) werden typischerweise in wässrigen Medien untersucht und verwendet, in denen allgegenwärtige Puffer darüber bestimmen, welche Cluster sich bilden, bestehen bleiben oder weiter reagieren. Tris(hydroxymethyl)aminomethan (Tris) ist ein allgegenwärtiger Puffer nahe des physiologischen pH‐Wertes und sein Einsatz hat zu Resultaten geführt, die sich allein durch dessen pH‐Kontrolle nicht erklären ließen. Dies wirft eine einfache Frage mit weitreichenden Konsequenzen auf: Was genau bewirkt Tris bei POMs? Quantitative Untersuchungen anhand mehrerer POM‐Archetypen zeigen, dass eine weniger strenge Pufferung zu längeren Lebensdauern intakter Anionen, zur Bildung von Tris‐spezifischen Addukten und zu einer durch die Ionenstärke steuerbaren Stabilität führt. Wir beschreiben drei molekulare Funktionen von Tris: Erstens wirkt Tris als Alkoxydonor, der μ‐O–CH ₂ ‐Einheiten in POM‐Gerüste einbettet. Zweitens fungiert Tris als Chelator, der die anfängliche Wolfram–Oxo‐Kondensation hemmt und ein kleines Isopolywolframat stabilisiert. Drittens dient Tris als strukturleitendes Medium, da ein Chrom‐inkorporiertes Kegginion, welches ein Single‐Ion‐Magnet‐Verhalten zeigt, nur in Gegenwart von Tris bei pH 7,5 gebildet wird. Für zukünftige Arbeiten plädieren wir für einen „Speciation‐First“‐Arbeitsablauf, der den erreichten pH‐Wert protokolliert, die Pufferidentität, Konzentration und Ionenstärke angibt und die vorliegenden Spezies mittels orthogonaler spektroskopischer, kristallographischer und computergestützter Methoden verifiziert. Die Bedeutung der hier dargestellten Ergebnisse reicht weit über die POM‐Chemie hinaus: In der Katalyse, der Elektrochemie und in Biomaterialien können Puffer und Aminzusätze die Speziation steuern, den Redoxzugang verändern und Kinetiken verzerren.

Polyoxometalates (POMs, molecular metal–oxo clusters) are typically studied and applied in aqueous media, where routine buffers determine which clusters form, persist, or react. Tris(hydroxymethyl)aminomethane (Tris) is a ubiquitous buffer near physiological pH and has produced outcomes that pH control alone could not explain, prompting a simple question with large consequences: What does Tris actually do to POMs? Quantification across several POM families shows that this loose buffering correlates with longer lifetimes of intact anions, the formation of Tris‐specific adducts, and tunable stability through ionic‐strength adjustment. We describe three molecular roles of Tris. First, Tris acts as an alkoxy donor that embeds μ‐O─CH ₂ units within POM scaffolds. Second, Tris functions as a chelator that arrests early tungsten‐oxo condensation and stabilizes a minimal isopolytungstate. Third, Tris serves as a structure‐directing medium, since a chromium‐incorporated Keggin forms only in Tris buffer at pH 7.5 and displays single‐ion‐magnet behavior. We advocate a speciation‐first workflow that logs attained pH, reports buffer identity, concentration, and ionic strength, and verifies species by orthogonal spectroscopic, diffraction, and computational methods. The implication extends well beyond POM chemistry: in catalysis, electrochemistry, and biomaterials, buffers and amine additives can redirect speciation, alter redox access, and bias kinetics.

Keggin-type polyoxometalates deliver membrane-impermeable phalloidin into living colorectal carcinoma cells. Single-atom molybdenum substitution improves intracellular delivery efficiency.

We present a validated, openly accessible workflow and spectral database charting the solution speciation of molybdenum browns. These redox-active polyoxometalates are central to catalysis and increasingly explored for bioinspired transformations and nanomedicine, making their solution behavior critical for both mechanistic understanding and practical use. Two archetypal Keplerate-type polyoxometalates, {Mo ₇₂ V ₃₀ } and {W ₇₂ V ₃₀ }, were investigated under 69 systematically varied aqueous conditions. Complementary ⁵¹ V/ ³¹ P nuclear magnetic resonance, resonance Raman, electrospray ionization mass spectrometry, and ultraviolet-visible spectroscopy interrogate the effects of pH, buffer identity, temperature, and incubation time on Keplerate integrity. Substituting Mo with W changes redox potential and hard/soft metal balance, yielding distinct stability patterns: {Mo ₇₂ V ₃₀ } breaks into fragments under all tested conditions whereas {W ₇₂ V ₃₀ } remains intact in fresh solutions and retains structural integrity up to pH 4 after 24 hours. All raw spectra, processed data, and stepwise protocols are deposited in a FAIR (findable, accessible, interoperable, reusable) repository, providing an open resource to accelerate catalytic and biological applications of polyoxometalates.