Cytosine-Functionalized Macrocyclic Receptor for Nucleotides: Combining Three Recognition Motifs

Nucleoside monophosphates perform various essential functions and serve as second messengers in living systems. Despite the success of nucleotide-selective probes based on proteins, the creation of synthetic receptors for nucleoside monophosphates remains a challenging task. In this paper, we explore the design of synthetic receptors based on a combination of three recognition motifs. We show that each binding motif contributes to the formation of the host-guest complexes. The core macrocycle provides recognition of the phosphate residue of the nucleotide, while naphthalimide and the attached cytosine residue participate in the coordination of the nucleobase via pi-pi and hydrogen bonding interactions. The presence of cytosine in the receptor structure substantially increases the overall affinity of receptors for nucleotides. A considerable increase (100-fold) in binding affinities is observed for the tetranucleotide DNA sequences 5 '-GGGG -3 ' and 5 '-CCCC-3 ', as compared to the previously reported system without the attached cytosine. The macrocyclic receptor for nucleotides that combines motifs for electrostatic, pi-pi stacking, and hydrogen bonding interactions was designed and investigated. The presence of cytosine in the structure of the receptor increases the affinity and selectivity for guanine-containing nucleotides and cyclic di-GMP.image