Exploring bio-activity of polyoxometalates

Applicant: Nadiia Gumerova, PhD (Post-doctoral fellow, Department of Biophysical Chemistry, University of Vienna, Austria) National cooperation partner: Prof. Annette Rompel (Head of the Department of Biophysical Chemistry, University of Vienna, Austria) Polyoxometalates (POMs), discrete polynuclear metal-oxo anions with a fascinating variety of structures and unique chemical and physical properties. Their full potential can be optimized by enhancing their biocompatibility through organic functionalization with bioactive moieties. In recent years, POMs emerged as a promising group of protein crystallization additives. Protein crystallography is the most widely used method for determining the molecular structure of proteins and obtaining structural information on proteinligand complexes at the atomic level. As the structure determines the functions and properties of a protein, crystallography is of immense importance for nearly all research fields related to biochemistry. The general aim of the proposed project is the synthesis and characterization of inorganic and hybrid organic-inorganic polynuclear metal-oxo anions to investigate their potential application in the field of protein crystallography and as antibacterial agents as well as to shed light on the mechanism of their interaction with biopolymers. The innovativeness and unique character of the project lies in the target-oriented design of novel hybrid POMs with enhanced stability and biological activity, which will be applied in different biological systems. The combination of organic molecules, which may adopt different conformations, and inorganic polyanions with fairly rigid cagelike structures will improve the interaction between the macromolecules which is very often the basis for successful crystal formation.

Polyoxometalates (POMs) - molecular metal-oxo coordination compounds of W, Mo, V and main-group elements-offer a uniquely programmable platform at the interface of chemistry, biology and materials science. This FWF project advanced POM science from empirical discovery toward rules, maps and data resources that make behavior predictable and designable. We combined solution-speciation surveys, structural chemistry, and bio-interface studies with open datasets and data-centric perspectives to deliver broadly useful insights and tools. A central outcome is a "speciation-first" view of POM chemistry. Through systematic experiments and collaborative studies, we showed how acidity, concentration, ionic strength and buffer identity dictate what POM actually exists in water-and therefore what function is possible. Highlights include a high-impact Speciation Atlas of polyoxometalates in aqueous solutions (Science Advances, 2023) and complementary mechanistic case studies on buffer and co-crystallization effects, including TRIS-stabilized minimal polyoxotungstate motifs and protein co-crystallization of transition-metal-substituted Keggin silicotungstates (Inorg. Chem., 2021). Follow-on work mapped the interplay of concentration, ionic strength and buffer composition (Frontiers in Chemical Biology, 2024), while accessible crystallographic reports expanded reliable structural anchors (Acta Cryst. C/E, 2021-2022). We translated these foundations into function. On the biology side, we elucidated how defined POM species engage targets across membranes and proteins. Studies with collaborators revealed inhibition of SERCA/PMCA Ca-ATPases and broad overviews of polyoxidovanadate-protein interactions (J. Inorg. Biochem., Coord. Chem. Rev., 2021-2022), agonistic actions of Preyssler-type POMs on purinergic P2 receptors (J. Inorg. Biochem., 2024), mushroom tyrosinase inhibition by Wells-Dawson phosphotungstates via speciation-aware design (Scientific Reports, 2021), and anti-quorum sensing, antibiofilm and antiviral activities (Biology, 2022). We also demonstrated that entirely inorganic POMs can act as superchaotropic membrane carriers, transporting across lipid barriers without organic appendages (Advanced Materials, 2023). In materials and energy contexts, we immobilized Co-containing POMs for photocatalytic oxygen evolution (ACS Materials Au, 2022) and developed Ni-substituted, amino-acid-functionalized sandwich tungstobismuthates with antibacterial activity (Inorg. Chem., 2023). To enable reproducibility and future discovery, we released a Curated Polyoxometalate Formula Dataset (Data, 2024) and articulated a forward-looking framework in Data-Driven Polyoxometalate Chemistry (Chem. Eur. J., 2025): community datasets + speciation maps + mechanism-guided design. Reviews in ACS Inorganic Chemistry, ACS Org/Inorg Au and Coordination Chemistry Reviews helped codify best practices and unify terminology across subfields. Together, these outputs establish practical design rules-choose solvent conditions first, verify the operating species, then match structure to task-and provide open resources that lower the barrier to entry. The project leaves a durable legacy of maps, methods and data that researchers in catalysis, medicine and materials can immediately use to engineer safer, more effective POM-based solutions.