Research Article: Interactions of Isophorone Derivatives with DNA: Spectroscopic Studies

Date Published: June 12, 2015

Publisher: Public Library of Science

Author(s): Marco Deiana, Katarzyna Matczyszyn, Julien Massin, Joanna Olesiak-Banska, Chantal Andraud, Marek Samoc, Heidar-Ali Tajmir-Riahi.


Interactions of three new isophorone derivatives, Isoa Isob and Isoc with salmon testes DNA have been investigated using UV-Vis, fluorescence and circular dichroism spectroscopic methods. All the studied compounds interact with DNA through intercalative binding mode. The stoichiometry of the isophorone/DNA adducts was found to be 1:1. The fluorescence quenching data revealed a binding interaction with the base pairs of DNA. The CD data indicate that all the investigated isophorones induce DNA modifications.

Partial Text

A number of studies have indicated that deoxyribonucleic acid (DNA) can be an interesting material not only for biological aspects but also for applications in photonics and electronics [1], [2]. With this in mind, our group has investigated the nonlinear optical properties of well-known intercalators and minor groove binders, such as ethidium bromide and Hoechst 33258 by Z-scan and two-photon fluorescence light microscopy techniques [3–7] gaining expertise in the field of DNA studies. The binding mechanism of small molecules to biomolecules such as ds-DNA, ss-DNA and proteins has attracted the attention of many research groups and is an active area in the field of biochemistry and medicinal chemistry [8–12]. DNA, being a biodegradable material can have advantages over synthetic polymers which usually are characterized by a very long degradation time [13]. DNA can act as a host for luminescent chromophores: as an example, the DNA-CTMA complex (CTMA:cetyltrimethylammonium chloride) has been shown to be a good matrix for photonic applications [1]. A DNA chain presents sites suitable for various modes of interaction with small molecules, such as intercalation, groove and external binding [14], [15]. Intercalating agents, containing planar heterocyclic groups which stack between adjacent DNA base pairs, can inhibit DNA replication in rapidly growing cancer cells [16], [17]. The complex formed by intercalation is thought to be stabilized, among other factors, by π-π stacking interactions between the drug (the intercalator) and DNA bases [15]. Intercalators introduce strong structural perturbations to DNA. On the other hand, groove binding molecules complement the shape of the groove via van der Waals interactions [18], [19]. The third mentioned type of interaction, the external binding, refers to electrostatic association between molecules that are charged positively and the DNA phosphate sugar backbone, e.g. cations as Mg2+ and Ru(II) complexes that are positively charged, interact electrostatically with the DNA phosphate that is negatively charged [20], [21].

The data obtained from spectrophotometric measurements indicate that all the studied isophorones interact with DNA, the affinity of Isoc to DNA being the highest. The UV-Vis spectra, recorded by keeping constant the concentration of isophorones and increasing the DNA concentration, suggest that the isophorones interact with DNA mainly through a stacking interaction between the aromatic chromophore and the base pair of DNA with a 1:1 stoichiometry.