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Content archived on 2024-05-29

Multidisciplinary approach to polyoxometalate-protein interactions: mechanisms and biological applications

Final Activity Report Summary - NANOCLUSTERPROTEIN (Multidisciplinary approach to polyoxometalate-protein interactions: mechanisms and biological applications)

Firstly, molecular recognition or molecular interaction, in a broad sense, is largely admitted to constitute a prerequisite for the action of drugs on biomolecules. Secondly, polyoxometalates (POMs for short) are early transition metal-oxygen anionic molecular nanoclusters that simultaneously exhibit many properties that make them attractive for applications in catalysis, separations, imaging, materials science, and medicine. Specifically, some POMs exhibit anti-bacterial, anti-viral, anti-tumour, anti-cancer activities or are observed to reduce the symptoms of diabetes. However, the detailed mechanisms of these phenomena at the molecular level are still to be elucidated. In this context, the project was aimed at shedding some light on the interactions between polyoxometalates and biomelecular systems, including proteins in order to open the way for a rational application of POMs in the medical domain.

We have demonstrated that POMs efficiently interact with human serum albumin (HSA) and that the structure of the POM plays a key role in this interaction. Three main POM structures were studied: the Keggin-type structure, the Dawson-type structure and a wheel -shaped POM primarily derived from the Dawson structure. Transition metal ion substituted POMs were also studied.

In short, we found that a Keggin-type structure POM specifically binds on the protein with a 1:1 stoichimetry. More complicated assemblies were found for other structures. For example, the wheel shaped POM showed complicated binding behaviour with more than 5 binding sites. In addition, the atomic composition of the POMs also has an important influence on the interaction.

We have also prepared POM-covered metal nanoparticles, with the plan to study the interactions of this new material with proteins, as a further step toward a rational application of POMs in the medical domain. As a matter of fact, metal nanoparticles are useful in protein detection, biomedicines, etc. The first issue is the preparation of POM-modified nanoparticles and we have accomplished a successful step in this direction. We observed charge transfer to occur between partially reduced POMs and some noble metal cations, thus inducing the reduction of these cations and formation of noble metal nanoparticles. In this process, POMs serve both as reductants and capping agents of the metal nanoparticles. Both 0D and 1D metal nanoparticles are obtained. By changing the metal cation initial concentration and the metallic salt to POM molar ratio, the morphology control of the nanoparticles can be achieved.