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

Abstract

AbstractNucleoside 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 π‐π 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.