Proton and charge transfer in the intercalating antitumour drug pazelliptine

Abstract

The photophysical properties of the synthetic drug pazelliptine (PZE) have been investigated in order to characterize the geometric and electronic structure of the molecule bound to DNA. Whatever the pH of the solution, a proton tranfer reaction occurs in the excited state: this leads to the excited 9-N monoprotonated form of PZE. Deexcitation of this excited species is mainly non-radiative. A study of the fluorescence properties of sterically hindered derivatives allows us to propose the existence of a twisted internal charge transfer state to explain this non-radiative deexcitation. The formation of this state occurs on the picosecond timescale (τ∼ 200 ps) when PZE is fully protonated ring nitrogens (i.e. in acidic aqueous solutions).

The acido-basic properties of PZE and five related amino and amino-substituted derivatives have been previously studied by spectroscopic measurements. The absorption, fluorescence spectra and the fluorescence quantum yields as a function of pH (range 2–12) and buffer concentration (50 mmol dm^–3 to 1 mol dm^–3) have been measured. Three pK_a values have been determined, at 5.5, 6.5 and 9.2. This is good evidence for PZE having an appropriate pK_a when bound to a hydrophobic and/or a hydrophilic structure.