Physical Nature of Ethidium and Proflavine Interactions with Nucleic Acid Bases in the Intercalation Plane

Abstract

On the basis of the crystallographic structures of three nucleic acid intercalation complexes involving ethidium and proflavine, we have analyzed the interaction energies between intercalator chromophores and their four nearest bases, using a hybrid variation-perturbation method at the second-order Møller-Plesset theory level (MP2) with a 6-31G(d,p) basis set. A total MP2 interaction energy minimum precisely reproduces the crystallographic position of the ethidium chromophore in the intercalation plane between UA/AU bases. The electrostatic component constitutes the same fraction of the total energy for all three studied structures. The multipole electrostatic interaction energy, calculated from cumulative atomic multipole moments (CAMMs), was found to converge only after including components above the fifth order. CAMM interaction surfaces, calculated on grids in the intercalation planes of these structures, reasonably reproduce the alignment of intercalators in crystal structures; they exhibit additional minima in the direction of the DNA grooves, however, which also need to be examined at higher theory levels if no crystallographic data are given.

Novel bis-phenanthridine derivatives with easily tunable linkers, study of their interactions with DNA and screening of antiproliferative activity

“…[1][2][3] In addition, it was shown that the chemical modulation of the ethidium substituents is a profitable option to tune the nucleic acid recognition properties of phenanthridine dyes. [4] Very recent reports about numerous applications point toward versatility of the phenanthridine core, [5][6][7][8][9] including even intriguing biological activity.…”

Electrochemical Study of the Interaction Mechanism of Proflavine (PF) with DNA Using Carbon Paste (CPE) and Hanging Mercury Drop (HMDE) Electrode

“…Among the first known intercalators was 3-6-diamino-acridine (proflavine, PF), which is a heterotricyclic dye of the family of aminoacridines. The interaction of PF with DNA has been studied by viscometry, relaxation techniques (Ramstein, Dourlent, and Leng 1972), spectrophotometry (Biver et al 2003;Dasgupta, Misra, and Dasgupta 1973;Dourlent and Hélène 1971), and techniques based on crystallographic structures of complexes containing proflavine (Langner et al 2006;Westhof, Rao, and Sundaralingam 1980). Lately, the interaction of proflavine with DNA has been investigated by cyclic voltammetry and a Pt disk working electrode (Aslanoglu 2006) and by differential pulse voltammetry and a modified CPE working electrode, in which DNA was mixed in the paste (Vaníckov a a et al 2000).…”

PT-ACRAMTU, A Platinum–Acridine Anticancer Agent, Lengthens and Aggregates, but does not Stiffen or Soften DNA

“…In the same study, netropsin, a dicationic minor groove binder (not an intercalator), did not cause a significant change in contour length, but also decreased the persistence length by a factor of ~3. The decrease in the persistence length may be attributed to the positive charges on ethidium bromide and doxorubicin (44), and netropsin (dicationic) (45), which reduce the intramolecular electrostatic repulsion within the DNA molecule. Using laser tweezers, Baumann et al showed reduced stiffness in DNA due to interaction with monovalent and multivalent cations (46).…”