Multiple molecular recognition and catalysis. A multifunctional anion receptor bearing an anion binding site, an intercalating group, and a catalytic site for nucleotide binding and hydrolysis

Article abstract of DOI:10.1021/ja00166a025

The multifunctional receptor molecule 2 has been designed and synthesized in order to achieve higher molecular recognition and reaction selectivity via multiple interactions with bound substrates. It combines three functional subunits: two recognition sites - a macrocyclic polyammonium moiety as anion binding site and an acridine side-chain for stacking interactions - as well as a catalytic amino group in the macrocycle for facilitating hydrolytic reactions. Compound 2 binds mono- and dinucleotide polyphosphates by simultaneous interactions between its macrocyclic polycationic moiety and the polyphosphate chain as demonstrated by ³¹P NMR spectroscopy and by stacking between its acridine derivative and the nucleic base of nucleotides as observed by both ¹H NMR spectroscopy and by fluorescence spectrophotometry. Binding of nucleotides by protonated 2 induces significant upfield shifts of the polyphosphate signals and of protons of the acridine moiety of 2 as well as of the adenine and the anomeric proton of the nucleotides; at the same time the proton signals corresponding to CH₂ groups of the macrocyclic part of 2 are downfield shifted. Upon complexation of ATP and CTP, the fluorescence emission of 2 is enhanced, whereas guanosine triphosphate causes a slight quenching; thus, 2 acts as a sensitive and selective fluorescent probe for ATP. At neutral pH the hydrolytic reaction proceeds, at least in part, through a covalent intermediate, the phosphorylated macrocycle 2 indicating nucleophilic catalysis. Compound 2 shows greater selectivity between ATP and ADP than the parent compound 1 which does not contain the acridine binding site. 2 also binds strongly to DNA plasmid pBR 322 at 10^-6 M probably via a double type of interaction, involving both intercalation and electrostatic interactions with the phosphate groups.