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

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 by31P NMR spectroscopy and by stacking between its acridine derivative and the nucleic base of nucleotides as observed by both1H 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. © 1990, American Chemical Society. All rights reserved.