Bioinorganic studies on beryllium and related metals

• Applicant: Dr. Magnus Richard Buchner
• Subject Area: Inorganic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 298748096

Beryllium counts as the most toxic non-radioactive element and is classified, together with its compounds, as highly toxic and carcinogenic. However this toxicity has been doubted in recent medical investigations. In fact it seems to be an autoimmune reaction, however the mechanism of action is hitherto unknown. Due to the widely spread resentments towards the handling of beryllium there is a lack of studies dealing with the interaction of beryllium (and its compounds) with bio-relevant ligands. Generally, beryllium-chemistry is underdeveloped when being compared to its neighboring elements in the periodic table. Therefore the coordination chemistry of beryllium compounds shall be investigated from a bio-inorganic point of view. First, the reactivity with amino acids and sugars shall be investigated in aqueous media, in organic, and in protic, oxygen-donor-atom-free (liquid anhydrous ammonia as well as anhydrous hydrogen-fluoride) solvents. Furthermore, hydrolysis experiments shall be performed with the obtained compounds. These will be followed by the investigation of reactions of beryllium compounds with oligopeptides and nucleotides and finally small serum-proteins. Additionally, it shall be studied which beryllium species are present at physiological conditions. So the interaction of beryllium ions with anions present in the blood-serum (hydrogen-carbonate, phosphate, etc.) and other small serum-solutes (urea, lipids, etc.) shall be investigated. A focus will be placed on the solubility at physiological pH-values as well as on the bonding-affinity to berylliumcations (e.g. via competition reactions). Based on these findings, attempts to synthesize highly beryllium-specific ligand-systems shall be conducted. Here the development of novel ligand-types for beryllium with hard donor-atoms shall be tackled. In order to achieve this, the suitability of phosphineoxides/-imines and borato-phosphinooxides/-imines as polydentate ligands will be studied. Additionally, the similar structure of the anticipated uncharged and anionic ligands allows the examination of isoelectronic beryllium-, zinc- and aluminium complexes. This will hopefully allow new insights into the commonalities and especially into the differences of the reactivity of these three related metals. For several selected substances the related aluminium- and zinc-derivatives shall be synthesized, since Be- and Al-cations (diagonal relationship) and Be- and Zn-cations (electronegativity, preferred charge, coordination behavior) exhibit similar properties. From these experiments, insights into the different mechanisms of action in the human body of highly toxic beryllium-cation, non essential aluminium-cation, which is suspected to cause Alzheimer's disease and breast cancer, and essential zinc-cation shall be gained. Utilizing the gained knowledge a highly beryllium-specific ligand shall be finally synthesized which can be applied in chelate-therapy, since none is available to date.

• DFG Programme: Research Grants