New tetracyclic heteroaromatic compounds based on dehydroamino acids : photophysical and electrochemical studies of interaction with DNA

Abstract

A benzothienoindole (BTIN) and a benzofuroindole (BFIN) were synthesized in high yields, as potential new target DNA compounds, using a metal-assisted intramolecular C-N cyclization, developed by us, of the methyl esters of N-(t-butoxycarbonyl)-b,b-bis(dibenzothien-4-yl or dibenzofuro-4-yl)dehydroalanines. The latter were obtained by a bis-Suzuki coupling of a b,b-dibromodehydroalanine with the corresponding heteroarylboronic acids. The absorption and fluorescence properties of the novel tetracyclic heteroaromatic compounds were studied in different solvents and in the presence of natural double-stranded (ds) salmon sperm DNA. The results in several solvents show that either BTIN or BFIN can be used as fluorescence solvent sensitive probes. Spectroscopic studies of the interaction of both compounds with dsDNA allowed to determine binding constant (Ki) values and binding site sizes (n). Fluorescence quenching experiments using iodide ion allowed the determination of the accessibilities to the quencher, showing that intercalation is the preferred mode of binding of these molecules to DNA. From the results obtained BTIN is the more intercalative compound and has a higher affinity to DNA. The interaction of this more promising compound with DNA was also studied electrochemically, by using differential pulse voltammetry (DPV) in connection with disposable pencil graphite electrode (PGE). These studies are based on the differences in the BTIN and adenine oxidation signals. After the interaction of BTIN with DNA, the oxidation signals of BTIN and adenine strongly decreased. The latter was attributed to the binding of the BTIN to DNA and the former points to a possible damage of the oxidizable groups of the compound after intercalation into DNA. Several concentrations of BTIN were tested and 50 μg/mL was found to be the optimum concentration in order to detect its interaction with DNA. In addition, the detection limit and the reproducibility were determined by using a disposable electrochemical transducer. The results of spectroscopic and electrochemical detection of BTIN interaction with DNA are in good agreement.