Dye-containing macrocycles for recognition and detection of nucleotides

• Applicant: Privatdozent Dr. Evgeny Kataev
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 523997105

The project aims to investigate principles of nucleotide recognition and sensing in an aqueous solution. Several parts of the project deal with new concepts for nucleobase- and sequences selective recognition, while in other parts, we develop approaches to visualize the binding with unprecedented fluorescence response. The results of both directions will enable in an exploration of new receptors as fluorescence markers and as biologically active compounds against viral infections and cancer. Our recent experiments have revealed the importance of spacers in the structure of cyclophanes for the selective recognition of nucleotides. Now, we propose to study a new generation of cyclophanes bearing a) chiral spacers, b) amide binding sites c) conjugation with nucleobases. A dimerization approach is proposed to reach high affinity of our cytosine-selective receptors. The design, synthesis, and analysis of host-guest structures using spectroscopic methods with cytosine-rich oligos and DNA i-motif will be carried out. High-affinity binding will enable us to investigate our systems as site-specific binders and as fluorescent indicators in enzymatic assays. A new family of pyridinium-naphthalimide receptors is proposed with a record fluorescence enhancement in the presence of nucleotides and oligos. The fluorescence signal generation is based on hindering two efficient intramolecular PET processes by supramolecular complexation. Detailed studies of the receptor's properties and nucleotide binding are planned to get insights into the binding and sensing mechanisms.

• DFG Programme: Research Grants