| Abstract
| - With the objective of developing efficient DNA oxidizing agents, a new series of viologen-linked pyreneconjugates 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 photophysicaland 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 centeredaround 380 nm but with significantly reduced yields when compared to those of the model compoundPYL1Et3+. The fluorescence quenching observed in these systems is explained through an electron-transfermechanism based on a calculated favorable change in free energy (ΔGET = −1.59 eV), and the redox speciescharacterized through laser flash photolysis studies. Intramolecular electron-transfer rate constants (kET) werecalculated from the observed fluorescence yields, and the singlet lifetimes of the model compound and arefound to decrease with increasing spacer length. The DNA binding studies of these systems throughphotophysical, chiroptical, and viscometric techniques demonstrated that these systems effectively undergoDNA intercalation with association constants (KDNA) in the range of 1.1−2.6 × 104 M-1 and exhibit 2:1sequence selectivity for poly(dG)·poly(dC) over poly(dA)·poly(dT). Photoactivation of these systems initiateselectron transfer from the singlet excited state of the pyrene chromophore to the viologen moiety followed byan electron transfer from DNA to the oxidized pyrene. This results in the formation of stable charge-separatedspecies such as radical cations of both DNA and reduced viologen as characterized by laser flash photolysisstudies 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 cosensitizationmechanism and hence can be useful as photoactivated DNA cleaving agents.
|
