Supramolecular recognition and sensing of nucleotides, RNA, and DNA by synthetic receptors
In this project, we design synthetic receptors targeting single nucleotides and longer sequences. In most systems, we incorporate fluorescent dyes to detect host-guest complexes in biological medium. We mainly explore non-covalent interactions between nucleobases and designed artificial receptors to understand the binding strength, geometry of complexes, and selectivity of the generated fluorometric response. Fluorescent receptors for recognizing unusual secondary nucleic acid structures are also our focus. The ultimate goal is to achieve high-affinity receptors to control replication and DNA-protein interactions (Angew. Chem. Int. Ed. 2023). For instance, we developed a new bellows-type sensing mechanism for nucleotide detection in an aqueous solution based on the pyrene-containing cyclophane for ratiometric detection of ATP (Chem. Eur. J. 2020, JACS 2024). Another series of cyclophanes can bind to RNA sequences, specifically those containing C-rich subunits. Our naphthalimide-containing cyclophanes can selectively encapsulate free cytosine and cytidine phosphates in an aqueous solution with up to 60-fold fluorescence enhancement (JACS au 2023). These receptors are effective against breast cancer cells.
Functional fluorescent dyes
In many projects, we synthesize and functionalize fluorescent dyes to conjugate them with supramolecular recognition subunits. These functionalized dyes are used to detect and visualize biologically important anions (Chem. Eur. J. 2018), cations (Sensor. Actuat. B-Chem, 2020), gases (Chem. Comm. 2022), and biomembranes (Sensor. Actuat. B-Chem. 2023). Our strategy for the design of anion-selective fluorescent probes is based on the supramolecular pKa shift of amino-groups placed in proximity to dyes (Chem. Comm. 2023). We developed probes for many anions, such as chloride, fluoride, phosphate, oxalate and pyrophosphate.
Molecular switches and artificial signal transduction
Molecular switches are important topics for signal-processing at molecular level. We are looking at the molecular transformations in an unconventional way by combining molecular recognition events in one assembly to achieve such properties as reading, writing, memory, switching, logic operations and etc. We have developed a first cation molecular exchanger based on the cyclohexane ring. We have demostrated that binding of the zinc(II) cation to the bipyridine subunit induces the conformational switching of the crown ether subunits, which subsequently results in a release of the potassium cation. The release of the potassium cation can be detected by a cation sensor. (Org. Lett. 2018, 20 (19), 6211–6214)
Design of fluorescent sensors for analyte detection in water
It is still a challenge to rationally design cheap and selective sensors for certain analytes functioning in a competitive aqueous medium. Though the problem is partially solved using substrate-selective proteins which are modified with fluorescent labels, less expensive sensors with novel selectivities are required. In this project we develop a new approach for the design of fluorescence sensors for a series of substrates (phosphates, carboxylates, amino acids and amines) that are operating in aqueous solution. Our approach is based on the screening of dynamic combinatorial libraries consisting of metal cations and newly designed ligands bearing fluorophores, and a consecutive evaluation of the components that are responsible for a selective detection of a particular guest (Chem. Eur. J. 2018, 24(7), 1500-1504)