Novel bifunctional viologen-linked pyrene conjugates: synthesis and study of their interactions with nucleosides and DNA

Abstract

With the objective of developing efficient DNA oxidizing agents, a new series of viologen-linked pyrene conjugates with the general formula PYLnV²⁺, having a different number of methylene spacer units (Ln) was synthesized, and their interactions with nucleosides and DNA have been investigated through photophysical and biophysical techniques. The viologen-linked pyrene derivatives PYL1V²⁺ (n = 1), PYL7V²⁺ (n = 7), and PYL12V²⁺ (n = 12) exhibited characteristic fluorescence emission of the pyrene chromophore centered around 380 nm but with significantly reduced yields when compared to those of the model compound PYL1Et₃⁺. The fluorescence quenching observed in these systems is explained through an electron-transfer mechanism based on a calculated favorable change in free energy (ΔG^ET=−1.59 eV), and the redox species characterized through laser flash photolysis studies. Intramolecular electron-transfer rate constants (k_ET) were calculated from the observed fluorescence yields, and the singlet lifetimes of the model compound and are found to decrease with increasing spacer length. The DNA binding studies of these systems through photophysical, chiroptical, and viscometric techniques demonstrated that these systems effectively undergo DNA intercalation with association constants (K_DNA) in the range of 1.1-2.6 × 10⁴ M⁻¹ and exhibit 2:1 sequence selectivity for poly(dG).poly(dC) over poly(dA).poly(dT). Photoactivation of these systems initiates electron transfer from the singlet excited state of the pyrene chromophore to the viologen moiety followed by an electron transfer from DNA to the oxidized pyrene. This results in the formation of stable charge-separated species such as radical cations of both DNA and reduced viologen as characterized by laser flash photolysis studies and subsequently the oxidized DNA modifications. These novel systems are soluble in buffer media, stable under irradiation conditions, and oxidize DNA efficiently and selectively through a cosensitization mechanism and hence can be useful as photoactivated DNA cleaving agents.