Phase Transition Detection in Accumulation of a Potential Anticancer Drug Cl-IPBD with DNA: Supercoiled and Linear pUC19 Plasmids

Abstract The electrochemical investigation of the plasmid DNA (pUC19) interactions with Cl-IPBD (4-chloro-6-(1 H -imidazo[4,5-b]phenasine-2-yl)benzene-1,3-diol), a prospective anticancer drug, have revealed the presence of a phase transition between two orientations of the compound in the DNA layer adsorbed on a glassy carbon (GC) electrode. Except for the needed sufficient incorporation of the compound into the plasmid, these Orientations, I and II, depend significantly on the superhelicity of the plasmid, used either in a superhelical circular (sc) or linear (lin) form. Different architecture of compact layers produced by these sc and lin plasmids has been confirmed by AFM measurements. The incorporation of Cl-IPBD into the DNA layers is tested here using a dual approach: (a) Differential Pulse (DP) or Square Wave (SW), as well as Alternating Current (AC) and impedance spectroscopy is used to monitor the redox activity of Cl-IPBD and (b) Alternating Current (AC) is used to detect the Cl-IPBD condensation via capacitative/resistive (C/R) mode. Since the initial accumulation of the pUC19 plasmid in the electrode layer has been detected in a ‘label-free’ procedure, i.e. without the addition of the redox probe, then the electroactive compound under investigation, accumulated in the DNA layer, can be, in fact, regarded as an actual redox probe and tested. The condensation of such a probe, in the case of a prospective anticancer drug, depends significantly on the superhelicity of the plasmid, thus showing, additionally, the role of the three-dimensional DNA structure on the formation of the DNA-compound complex. The correlations between redox and C/R properties of a vitamin (riboflavin) and an antioxidant (rutin), different from Cl-IPBD compound, confirm the role of the condensation of the compounds in realizing their interactions with DNA, important for a possible future use of Cl-IPBD as a drug.