Cleavage of Phosphodiesters and of DNA by a Bis(guanidinium)naphthol Acting as a Metal‐Free Anion Receptor

Abstract

Phosphoric acid diesters form anions at neutral pH. As a result of charge repulsion they are notoriously resistant to hydrolysis. Nucleophilic attack, however, can be promoted by different types of electrophilic catalysts that bind to the anions and reduce their negative charge density. Although in most cases phosphodiester-cleaving enzymes and synthetic catalysts rely on Lewis acidic metal ions, some exploit the guanidinium residues of arginine as metal-free electrophiles. Here we report that a combination of two guanidines and a hydroxy group yields highly reactive receptor molecules that can attack a broad range of phosphodiester substrates by nucleophilic displacement at phosphorus in a single-turnover mode. Some stable O-phosphates were isolated and characterized further by NMR spectroscopy. The bis(guanidinium)naphthols also cleave plasmid DNA, presumably by a transphosphorylation mechanism.

Recent Advances in Guanidine-Based Organocatalysts in Stereoselective Organic Transformation Reactions

“…Useful chemical functionalities are shown by guanidine and their corresponding salts. Free guanidine displays dual behavior, Brønsted basicity, as well as hydrogen bond donating and accepting abilities [21]. While guanidinium salts show weak Brønsted acidity, cationic hydrogen bond donating capability and the possibility of delocalizing guanidinium cationic π-Lewis acids are shown in Figure 3.…”

The Guanidinium Unit in the Catalysis of Phosphoryl Transfer Reactions: From Molecular Spacers to Nanostructured Supports

“…More recently the same group reported compound 17 , resulting from a long‐term attempt to optimize these enzyme mimics 45. The reaction with 17 and BNPP in deuterated DMF at 30 °C was followed by 31 P NMR spectroscopy, which showed new peaks that were attributed to the phosphorylated catalysts.…”

Synthesis and DNA Cleavage Properties of Triazacrown Derivatives

“…5,43.1,43.9,47.5,49.5,50.5,52.0,54.6,57.4 (NCH 2 1-(2-Aminoethyl)-4-(2-hydroxyethyl)-1,4,7-triazacrown (2) A stirred solution of compound 5 (346 mg, 1.0 mmol) and hydrazine hydrate (80%, 1 mL) in etha-nol (30 mL) was heated at 80 ℃ for 8 h. The resulting solution was cooled to room temperature and then added 30% hydrochloric acid to adjust to pH 1-2. The filtrate was evaporated to dryness under reduced pressure.…”

“…[1] Among them, DNA cleavages promoted by transition metal complexes [2] especially their dinuclear complexes [3] have been widely investigated in the last decade and are found to be quite efficient, but the clinical pharmic use of some metal complexes is hampered by concerns over the lability and toxicity in treatment of cancer due to the free radical generation via the redox pathway. [5] Especially, Yu and co-workers [6] described a metal-free peptide nucleic acid (PNA)-cyclen conjugate as DNA-cutting agent with efficient and site-selective DNA hydrolysis activity. Recently, metal-free cleaving reagents have been developed by some research groups.…”