Comparison of hydration reactions for “piano-stool” RAPTA-B and [Ru(η6− arene)(en)Cl]+ complexes: Density functional theory computational study

Abstract

The hydration process for two Ru(II) representative half-sandwich complexes: Ru(arene)(pta)Cl(2) (from the RAPTA family) and [Ru(arene)(en)Cl](+) (further labeled as Ru_en) were compared with analogous reaction of cisplatin. In the study, quantum chemical methods were employed. All the complexes were optimized at the B3LYP/6-31G(d) level using Conductor Polarizable Continuum Model (CPCM) solvent continuum model and single-point (SP) energy calculations and determination of electronic properties were performed at the B3LYP∕6-311++G(2df,2pd)/CPCM level. It was found that the hydration model works fairly well for the replacement of the first chloride by water where an acceptable agreement for both Gibbs free energies and rate constants was obtained. However, in the second hydration step worse agreement of the experimental and calculated values was achieved. In agreement with experimental values, the rate constants for the first step can be ordered as RAPTA-B > Ru_en > cisplatin. The rate constants correlate well with binding energies (BEs) of the Pt∕Ru-Cl bond in the reactant complexes. Substitution reactions on Ru_en and cisplatin complexes proceed only via pseudoassociative (associative interchange) mechanism. On the other hand in the case of RAPTA there is also possible a competitive dissociation mechanism with metastable pentacoordinated intermediate. The first hydration step is slightly endothermic for all three complexes by 3-5 kcal∕mol. Estimated BEs confirm that the benzene ligand is relatively weakly bonded assuming the fact that it occupies three coordination positions of the Ru(II) cation.

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

“…Stable stationary geometries were obtained for the four complexes which are characterized with zero imaginary number. The bond orders, ( ), and ∇ 2 ( ) of the Ru-Cl bonds increase in the hydrated complexes 2 and 4 which suggests that the possibility of displacing the last Cl atom with aqua ligand will be difficult [42]. The results from the NBO and NEDA analyses with the features HOMO and LUMO show that complexes 1 and 4 are predominantly characterised with LMCT while complexes 2 and 3 are predominately characterised with MLCT.…”

“…to the second optimization (−6307.84, −5925.61, −6464.26, and −6082.04 A.U.). The bond orders of the Ru-Cl bonds increase in the hydrated complexes 2 and 4 which suggest that the possibility of displacing the second Cl atom with aqua ligand will be difficult [42]. But on the other hand, the Ru-P bond order decreases upon hydration of the complexes.…”

Interactions of the “piano‐stool” [ruthenium(II)(η6‐arene)(quinolone)Cl]+complexes with water; DFT computational study

“…The size of the arene ligand has only marginal influence on the hydration reaction. In the first part of the study, two possible reaction mechanisms: associative and dissociative were compared and contrary to the hydration of the [Ru(η 6 −p‐cymene)(en)Cl] + complex studied previously, it was found that the examined process occurs with a higher probability via the dissociative mechanism in the Ru(II)‐quinolone complexes. This mechanism is linked with two transition states and one intermediate structure.…”

Tuning the Optical Properties of Novel Antitumoral Drugs Based on Cyclometalated Iridium(III) Complexes

“…Density functional theory (DFT) approaches are now widely used to characterize the structure of novel antitumoral complexes. − However, computational simulations are also able to assist the design of new molecules at an earlier stage, even prior to the design of the synthetic route . Indeed, one can easily find in the literature excellent theoretical works to anticipate the structures, optical properties, and/or biochemical activities of novel drugs. − We have contributed to this field by using theoretical approaches to predict the cytotoxicity of drugs containing transition metals in their structures. − …”