Insights into the Intramolecular Properties of η6-Arene-Ru-Based Anticancer Complexes Using Quantum Calculations

Hindawi Publishing Corporation Journal of Chemistry Volume 2013, Article ID 892052, 14 pages http://dx.doi.org/10.1155/2013/892052 Research Article Insights into the Intramolecular Properties of 𝜂6-Arene-Ru-Based Anticancer Complexes Using Quantum Calculations Adebayo A. Adeniyi and Peter A. Ajibade Department of Chemistry, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa Correspondence should be addressed to Peter A. Ajibade; Received 21 May 2013; Revised 23 July 2013; Accepted 23 July 2013 Academic Editor: James W. Gauld Copyright © 2013 A. A. Adeniyi and P. A. Ajibade. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The factors that determine the stability and the effects of noncovalent interaction on the 𝜂6-arene ruthenium anticancer complexes are determined using DFT method. The intramolecular and intra-atomic properties were computed for two models of these half-sandwich ruthenium anticancer complexes and their respective hydrated forms. The results showed that the stability of these complexes depends largely on the network of hydrogen bonds (HB), strong nature of charge transfer, polarizability, and electrostatic energies that exist within the complexes. The hydrogen bonds strength was found to be related to the reported anticancer activities and the activation of the complexes by hydration. The metal–ligand bonds were found to be closed shell systems that are characterised by high positive Laplacian values of electron density. Two of the complexes are found to be predominantly characterised by LMCT while the other two are predominately characterised by MLCT. 1. Introduction There have been several research efforts to synthesize Rubased anticancer complexes as alternative to cis-platin in cancer therapy [1–3]. Among the most studied compounds are the half-sandwich complexes of ruthenium due to their unique properties [4–6]. Among the most studied complexes are the half-sandwich complexes of ruthenium. Several of these half-sandwich ruthenium complexes have found numerous applications as catalysts for organic transformations, in the supramolecular field and in medicinal chemistry [7]. The applications of these complexes as anticancer agent have been reported [3, 8–12]. Some of the properties of interest are the existing noncovalent interactions and the effect of hydration on the interatomic interactions in the complexes. The noncovalent interactions such as hydrogen bonding, anion-𝜋, cation-𝜋, and 𝜋-𝜋 interactions and other weak forces are important in chemical reactions, molecular recognition, and regulation of biochemical processes [13, 14]. Deep understanding of these interactions has been pointed out to be of great importance in rationalizing their effects [14]. Using Bader’s quantum theory of atoms in molecules (QTAIM) [15], the atomic properties such as electronic population, energies, and (de)localization are evaluated over the atomic basins. Computer simulation is known to be helpful in giving detailed atomic structural properties and in interpreting experimental data at atomic level of interaction to show the mechanisms of biomolecular function [16]. Also, the quantum calculation plays significant roles in determination of force fields [17, 18] necessary for the in silico drug designs which is known to be pivotal in discovering new drugs and designing more efficient ones [19, 20]. In this research work, we have selected two of the models compounds (Figure 1) which are [Ru(𝜂6-p-benzene) Cl2 (pta)] (RAPTA-H named as complexes 1 and 2) and [Ru(𝜂6-p-cymene)Cl2 (pta)] (RAPTA-C named as complexes 3 and 4) reported by Chatterjee et al. as anticancer agents [21]. The hydrated form of these complexes which are [Ru(𝜂6p-benzene)Cl(H2 O)(pta)] named complex 2 and [Ru(𝜂6p-cymene)Cl(H2 O)(pta)] named complex 4 (Figure 1) is considered since activation of Ru complexes is known to 2 Journal of Chemistry CH3 H3 C Cl Ru N P N N Cl Complex 1 (a) Cl Ru N P N N H2 O Complex 2 (b) CH3 Cl Ru N P N N Cl CH3 H3 C CH3 Cl Ru N P N N H2 O Complex 3 Complex 4 (c) (d) Figure 1: The schematic structures of complexes 1, 2, 3, and 4. occur through hydration [10, 22–24]. Complexes with PTA ligand have in recent years received attention because of their water solubility and applications as catalyst [25]. The only difference between complexes 1 and 3 is the use of cymene as arene unit in 3 while benzene is used in complex 1. This little change in ligand has been reported to enhance the anticancer activities of complex 3 compare to 1 [21]. The choice of ligand is important because a too strongly bound ligand could render the drug inactive, while a labile ligand could be easily hydrolysed or replaced [26]. Many of these ruthenium-arene complexes are known to have complicated and unstable ligand exchange [2]. In order to improve their anticancer activities and obtain a better lead compounds, their stability must be improved [2]. In this study, we have used the quantum theory of atoms in molecules (QTAIM) to understand the effects of noncovalent interactions on the stability and hydration of these complexes. 2. Computational Method In this work, the geometries of the complexes were first optimized with PBE0 [27] functional and mixed basis sets SBKJC VDZ with effective core potential (ESP) [28] for Ru, P, and Cl while basis set 6-31G∗ was applied on other atoms in each of the complexes (this will subsequently be referred to as ECP (Ru,P,Cl)|6-31G∗ ). In the second optimization, the SBKJC VDZ is limited to only the ruthenium atom while the scaled-up basis set 6-31+G(d,p) was applied on other atoms in the complexes which shall subsequently be referred to as ECP(Ru)|6-31+G(d,p). The external basis sets were obtained from EMSL basis set library [29, 30] and were incorporated into the input files in a format that each FIREFLY and Gaussian 09 (G09) can read. SBKJC VDZ ECP basis set with PBE0 functional has been shown to be effective in treating complexes with large number of electrons and has been applied in computing properties of many metal clusters [31, 32]. Other properties of the complexes are computed at B3LYP hybrid functional level of theories [33] using basis set DGDVZP applied on Ru atom while others are treated with 6-31+G(d,p) which will be referred to as DGDVZP(Ru)|631+G(d,p) subsequently. Also lower basis set 3-21G [34] was applied on all atoms of the complexes in order to compare its values with DGDVZP(Ru)|6-31+G(d,p) systems. The Bader quantum theory of atoms in molecules (QTAIM) analysis was done mainly using the wavefunction obtained from both DGDVZP(Ru)|6-31+G(d,p) and 3-21G basis sets treated systems. A topological analysis was performed in order to calculate the charge density (𝜌) and its second Laplacian derivative of charge density (∇2 𝜌) for the bond cri (...truncated)