π-Stacking between Casiopeinas® and DNA bases

Abstract

Casiopeínas® are copper complexes with the general formula [Cu(N-N)(N-O)]NO(3) and [Cu(N-N)(O-O)]NO(3) where N-N denotes a substituted bipyridine or phenanthroline, N-O indicates α-aminoacidate or peptide and O-O represents acetylacetonate or salicylaldehyde. This family of compounds has been evaluated in vitro and in vivo showing cytotoxic, genotoxic, and antineoplastic activity. The action mechanism is still not completely elucidated, but the possibility exists that these compounds interact with DNA by intercalation due to the aromatic moiety. In this work we found, using the properties of the electron density of a π-complex model base-Casiopeína®-base, that the stacking mechanism between Casiopeínas® and DNA bases is due to an electron density deficiency of the ligand of the Casiopeína® which is compensated for by an electron transfer from adenines by a π-π interaction.

The π‐Back‐Bonding Modulation and Its Impact in the Electronic Properties of CuII Antineoplastic Compounds: An Experimental and Theoretical Study

“…In the case of the Casiopeínas, the dipole moment of copper atom (μ(Cu)) is directed toward the aromatic ligand, opposing to the ligand–metal charge‐transfer (Figure 9 a). 12a μ(Cu) can be related with the σ donation from the ligand to the metal, like a σ‐donation pathway. Parallel ( Q || (Cu)) and perpendicular ( Q ⊥ (Cu)) terms of the quadrupole moment of the copper atom can be related with σ and π components of copper density (Figure 9 b and 9c).…”

A Range of Nitrato Coordination Modes in NiIIComplexes with the Versatile Ligand 1,8‐Bis(2‐pyridyl)‐3,6‐dithiaoctane: Structural, Spectroscopic, Electrochemical, and Theoretical Studies

“…Theoretical Calculations: Full geometry optimization with the structures obtained from the X‐ray experiments with C1 , C2 , and C3 , was performed by use of the hybrid meta ‐GGA functional m06‐2x47–51 with a 6–31 g (d,p) basis set in the gas phase. This functional has proved suitable for representing the structures, energetics, and stabilities of first‐row transition metal complexes as we have previously shown 52–54. Charge and multiplicity values for C1 were +1/1, for C2 +2/1, and for C3 , +1/1, respectively.…”

Modeling biophysical and biological properties from the characteristics of the molecular electron density, electron localization and delocalization matrices, and the electrostatic potential

“…These workers use BCP properties to predict NMR and UV spectroscopic transitions, while others use bond properties in the empirical prediction of π‐stacking interaction energies . Cortés‐Guzmán and coworkers use the net group charge transfer as a predictor of the strength of π‐stacking between anticancer Casiopeinas ® and adenine to support their hypothesis for the antineoplastic activity of this class of drugs through DNA intercalation.…”

“…Galindo‐Murillo et al have recently suggested that these complexes can intercalate between DNA base pairs through their aromatic moiety and that the π‐stacking interaction is driven by an electron depletion of the planar ligand (the substituted bipyridine or phenanthroline ring) due to the transfer of charge to the metal center which, in turn, drives charge transfer from the flanking DNA bases to the intercalating ligand. Using the integrated QTAIM charges summed over entire molecular fragments, these workers found a simple but strong statistical correlation between the complex stabilization energy of the adenine–Casiopeinas ® complex and the net electron population transferred from adenine to the aromatic ligand: which lends numerical support to the charge‐transfer assisted π‐stacking hypothesis advanced by these workers and, simultaneously, enhance the plausibility of their proposed mechanism of action initiated by stacking intercalation of Casiopeinas ® between DNA base pairs. What is desirable for a future study is, perhaps, to correlate energies of stacking interaction with a direct measure of biological antineoplastic activity.…”