C02 • Synthesis and Evaluation of Functionalized Boron Clusters for Bioconjugation and Cellular Delivery

This project aims at the synthesis of boron-cluster-modified biomolecules with enhanced specific bioavailability and bioactivity. Recently, anionic perhalogenated boron clusters were reported as carriers for biomolecules based on their chaotropic properties. The interaction of different types of boron clusters with biomolecules has revealed unprecedented advantages for various applications. However, their use in the field of nucleic acids has remained underexplored. We will explore selected halogenated neutral and anionic boron clusters with site-specifically attached functional groups for covalent connection to biomolecular cargo, including nucleosides and oligonucleotides. The synthesis of per- and polyhalogenated boron clusters with one or more functional substituents that enable a covalent connection to biomolecules will be developed. The boron clusters will be adjusted in cage size, charge, and the substitution pattern. Furthermore, the functional group will ensure a selective and high yield coupling reaction to small and large biomolecules. The biomolecules include antivira nucleosides and functional oligonucleotides. Thus, the project will develop boron clusters as functional substituents leading to novel nucleotide prodrugs. The understanding of the influence of the covalently bonded boron cluster on the intrinsic properties of the biomolecules and their interaction with membranes and proteins will be in the focus.
The project combines the expertise of the Finze group on the selective functionalization of halogenated and non-halogenated boron clusters with the focus of the Höbartner group on synthesis and analysis of modified nucleosides and functional oligonucleotides. On the long term this collaborative project will enable the advancement of boron cluster chemistry into the area of therapeutic nucleotide delivery.