Polyoxometalates (POMs) are an emerging class of inorganic metal oxides, which over the last decades demonstrated promising biological activities by the virtue of their great diversity in structures and properties. They possess high potential for the inhibition of various tumor types; however, their unspecific interactions with biomolecules and toxicity impede their clinical usage. The current focus of the field of biologically active POMs lies on organically functionalized and POM‐based nanocomposite structures as these hybrids show enhanced anticancer activity and significantly reduced toxicity towards normal cells in comparison to unmodified POMs. Although the antitumor activity of POMs is well documented, their mechanisms of action are still not well understood. In this Review, an overview is given of the cytotoxic effects of POMs with a special focus on POM‐based hybrid and nanocomposite structures. Furthermore, we aim to provide proposed mode of actions and to identify molecular targets. POMs are expected to develop into the next generation of anticancer drugs that selectively target cancer cells while sparing healthy cells.

Polyoxometalates (POMs) are, mostly anionic, metal oxide compounds that span a wide range of tunable physical and chemical features rendering them very interesting for biological purposes, an continuously emerging but little explored field. Due to their biological and biochemical effects, including antitumor, -viral and -bacterial properties, POMs and POM-based systems are considered as promising future metallodrugs. In this article, we focus on the antibacterial activity of POMs and their therapeutic potential in the battle against bacteria and their increasing resistance against pharmaceuticals. Recent advances in the synthesis of POMs are highlighted, with emphasis on the development and properties of biologically active POM-based hybrid and nanocomposite structures. By analysing the antibacterial activity and structure of POMs, putative mode of actions are provided, including potential targets for POM–protein interactions, and a structure–activity-relationship was established for a series of POMs against two bacteria, namely Helicobacter pylori and Streptococcus pneumoniae.

Polyphenol oxidases (PPOs) contain the structurally similar enzymes tyrosinases (TYRs) and catechol oxidases (COs). Two cDNAs encoding pro-PPOs from tomato (Solanum lycopersicum) were cloned and heterologously expressed in Escherichia coli. The two pro-PPOs (SlPPO1-2) differ remarkably in their activity as SlPPO1 reacts with the monophenols tyramine (k_cat = 7.94 s⁻¹) and phloretin (k_cat = 2.42 s⁻¹) and was thus characterized as TYR, whereas SlPPO2 accepts only diphenolic substrates like dopamine (k_cat = 1.99 s⁻¹) and caffeic acid (k_cat = 20.33 s⁻¹) rendering this enzyme a CO. This study, for the first time, characterizes a plant TYR and CO originating from the same organism. Moreover, X-ray structure analysis of the latent holo- and apo-SlPPO1 (PDB: 6HQI and 6HQJ) reveals an unprecedented high flexibility of the gatekeeper residue phenylalanine (Phe270). Docking studies showed that depending on its orientation the gatekeeper residue could either stabilize and correctly position incoming substrates or hinder their entrance into the active site. Furthermore, phloretin, a substrate of SIPPO1 (K_m = 0.11 mM), is able to approach the active centre of SlPPO1 with both phenolic rings. Kinetic and structural results indicate that phloretin could act as a natural substrate and connote the participation of PPOs in flavonoid-biosynthesis.

Polyoxometallate (POMs) haben großes Potenzial, verschiedene Tumorarten zu inhibieren; ihre Toxizität und unspezifischen Wechselwirkungen mit Biomolekülen verhindern jedoch eine klinische Anwendung. Der Schwerpunkt bei biologisch aktiven POMs liegt gegenwärtig auf organisch funktionalisierten POMs und POM‐basierten Nanokomposit‐Strukturen, da diese Hybride eine erhöhte Aktivität gegen Tumoren aufweisen, bei einer gleichzeitig deutlich verringerten Toxizität gegen normale Zellen. Während die Antitumoraktivität von POMs ausreichend beschrieben ist, sind ihre Wirkungsmechanismen noch weitgehend unbekannt. Dieser Aufsatz gibt einen Überblick über die zytotoxischen Effekte von POMs, wobei der Schwerpunkt auf POM‐basierten Hybriden und Nanokomposit‐Strukturen liegen soll. Postulierte Wirkungsmechanismen werden vorgestellt und molekulare Targets identifiziert. POMs könnten sich zur nächsten Generation metallhaltiger Krebsmedikamente entwickeln, die selektiv nur Krebszellen angreifen und gesunde Zellen verschonen.

Protein crystallography is the most widely used method for determining the molecular structure of proteins and obtaining structural information on protein–ligand 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. However, protein crystallography suffers from some major drawbacks, whereby the unpredictability of the crystallization process represents the main bottleneck. Crystallization is still more or less a ‘trial and error’ based procedure, and therefore, very time and resource consuming. Many strategies have been developed in the past decades to improve or enable the crystallization of proteins, whereby the use of so-called additives, which are mostly small molecules that make proteins more amenable to crystallization, is one of the most convenient and successful methods. Most of the commonly used additives are, however, restricted to particular crystallization conditions or groups of proteins. Therefore, a more universal additive addressing a wider range of proteins and being applicable to a broad spectrum of crystallization conditions would represent a significant advance in the field of protein crystallography. In recent years, polyoxometalates (POMs) emerged as a promising group of crystallization additives due to their unique structures and properties. In this regard, the tellurium-centered Anderson–Evans polyoxotungstate [TeW₆O₂₄]⁶⁻ (TEW) showed its high potential as crystallization additive. In this lecture text, the development of POMs as tools in protein crystallography are discussed with a special focus on the so far most successful cluster TEW.

Polyoxometalates (POMs) are transition metal complexes that exhibit a broad diversity of structures and properties rendering them promising for biological purposes.