Nucleotides are constituents of nucleic acids and they have a variety of functions in cellular metabolism. Synthetic receptors and sensors are required to reveal the role of nucleotides in living organisms and mechanisms of signal transduction events. In recent years, a large number of nucleotide‐selective synthetic receptors have been devised, which utilize different molecular designs and sensing mechanisms. This Minireview presents recent progress in the design of synthetic molecular receptors for selective recognition of nucleotides in aqueous solution. The binding properties of receptors and the origins of their selectivity for a particular nucleotide are discussed.
A straightforward design of receptors for binding and sensing of sulfate in aqueous medium was developed. The design involves the connection of two naphthalimide-based pH probes through a hydrogen-bonding motif. The structure of the receptor-sulfate complex, predicted by DFT calculations, was unambiguously confirmed by NMR measurements. There are three major interactions stabilizing the host-guest complex: electrostatic interactions, hydrogen bonding, and stacking interactions of the dyes. Study of two control receptors containing either one dye or methyl amide groups instead of amides, revealed that electrostatic and hydrogen bonding interactions contribute the most to affinity and selectivity of receptors. The receptors can detect sulfate in a 1:1 THF-buffer mixture in pH window 3.6-4.5 demonstrating up to 7-fold fluorescence enhancement. To the best of our knowledge, the reported PET (photoinduced electron transfer) anion probes possess the largest response for sulfate in aqueous solution yet described.
Synthesis and anion binding properties of hybrid macrocycles containing ammonium and hydrogen bond donor groups are reported. Receptor properties were studied in a 10 mM MES buffer solution at pH 6.2, at which the receptors carry two positive charges at the secondary amine groups. Receptor 1 was found to bind fluoride with the highest affinity (10 M) and selectivity among the synthesized receptors. It was the only receptor that demonstrated fluorescence increase upon addition of fluoride. Other titration experiments with halides and oxyanions led to an anion-induced aggregation and fluorescence quenching. The mechanism of the particular turn-on fluorescence for fluoride was explained by the ability of receptor 1 to encapsulate several fluoride anions. Multiple anion coordination resulted in the protonation of the tertiary amine group and subsequent hindering of the PET process. H andF NMR titrations, single-crystal X-ray structure of chloride complex, and DFT calculation suggest that 1 can perfectly accommodate two fluoride anions in the inner cavity but only one chloride, keeping the second chloride in the outer coordination sphere. Thus, the importance of size selectivity, which is reflected in a collective behavior of molecules in an aqueous solution, represents a new strategy for the design of highly selective probes for fluoride functioning in an aqueous solution.
Pyrene-based cyclophanes have been synthesized with the aim to realize ab ellows-type sensing mechanism for the ratiometric detection of nucleotide concentrations in ab uffered aqueous solution. The sensing mechanism involves the encapsulationo fan ucleobase between two pyrene rings,w hich affects the monomer-excimer equilibrium of the receptori nt he excited state. The nature of the spacer and its connection pattern to pyrene rings have been varied to achieve high selectivity for ATP. The 1,8-substituted pyrene-basedc yclophane with the 2,2'-diaminodiethylamine spacer demonstrates the best selectivity for ATPs howing a 50-fold increase in the monomer-excimer emission ratio upon saturation with the nucleotide. The receptor can detect ATPw ithin the biological concentrations range over a wide pH range. NMR and spectroscopic studies have revealed the importance of hydrogen bonding and stacking interactions for achievingarequired receptors electivity.T he probe has been successfully applied for the real-time monitoring of creatine kinase activity.
Amido-amine macrocycles with two and four naphthalimide dyes were designed to bind nucleoside monophosphates and oligonucleotides in an aqueous buffered solution. Anion-templated synthesis was used to direct the macrocyclization reaction to the [2+2] product, while high dilution conditions favored the formation of the [4+4] macrocycle with an unprecedented geometry, as revealed from the X-ray analysis. The [2+2] product was found to exhibit a remarkable binding strength and fluorescence response for cyclic guanosine monophosphate (cGMP) in an aqueous solution. To our knowledge, this is the first synthetic receptor for cGMP, which also demonstrates a high preference to bind guanine-rich sequences accomplished by a strong fluorescence quenching. The receptor conformation is very sensitive to the guest structure in an aqueous solution, thus modeling the adaptive behavior of proteins. The study of synthetic systems with a detectable conformational equilibrium represents a great potential for understanding highly specific and tightly regulated interactions in biological systems.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.