DOSY NMR and MALDI-TOF evidence of covalent binding the DNA duplex by trimethylammonium salts of topotecan upon near UV irradiation

Abstract

Using DOSY NMR and MALDI-TOF MS techniques, we present evidence that quaternary trimethylammonium salts of topotecan, [TPT-NMe3 ](+) X(-) (X = CF3SO3, HCOO), bind covalently the natural DNA oligomer upon near UV irradiation in water under physiological conditions. It is shown that formate salt is very reactive at pH 7 and requires short irradiation time. This weak irradiation at 365 nm paves the way for a new application of TPT derivatives in clinical use, which can dramatically increase the therapeutic effects of a medicine.

Keywords: DNA duplex; MALDI-TOF MS; NMR; UV irradiation; covalent binding; topotecan.