# Efficient Cleavage of pUC19 DNA by Tetraaminonaphthols

## TL;DR

Researchers developed a new compound that efficiently cleaves DNA by modifying naphthol structures with ethylene diamine and azo groups.

## Contribution

Replacing guanidines with ethylene diamine and adding azo groups significantly improves DNA cleavage efficiency in naphthol compounds.

## Key findings

- Compound 13 with ethylene diamine cleaves plasmid DNA with a half-life of 22 hours.
- Azo naphthol 17 nicks and linearizes pUC19 DNA with a half-life of about 1 hour.
- Azo naphthol 17 reacts four times faster than naphthol 13 and follows first-order kinetics in the presence of EDTA.

## Abstract

In an attempt to create models of phosphodiesterases, we previously investigated bis(guanidinium) naphthols. Such metal‐free anion receptors cleaved aryl phosphates and also plasmid DNA. Observed reaction rates, however, could not compete with those of highly reactive metal complexes. In the present study, we have replaced the guanidines by ethylene diamine side chains which accelerates the plasmid cleavage by compound 13 significantly (1 mM 13: t1/2=22 h). Further gains in reactivity are achieved by azo coupling of the naphthol unit. The electron accepting azo group decreases the pK
a of the hydroxy group. It can also serve as a dye label and a handle for attaching DNA binding moieties. The resulting azo naphthol 17 not only nicks (1 mM 17: t1/2~1 h) but also linearizes pUC19 DNA. Although the high reactivity of 17 seems to result in part from aggregation, in the presence of EDTA azo naphthol 17 obeys first order kinetics (1 mM 17: t1/2=4.8 h), reacts four times faster than naphthol 13 and surpasses by far the former bis(guanidinium) naphthols 4 and 5.

Anion receptor 4 was shown previously to cleave phosphodiesters by nucleophilic substitution. It also nicks plasmid DNA to some extent. We have now replaced the guanidines by ethylene diamine side chains. By this modification, the resulting tetraamine 13 becomes an effective DNA cleaver (R=H). Azo coupling of 13 further boosts the reactivity of the resulting naphthols 16 and 17 (16: R=4‐carboxyphenylazo; 17: R=4‐methoxyphenylazo).