Donor Atom Preference of Organoruthenium and Organorhodium Cations on the Interaction with Novel Ambidentate (N,N) and (O,O) Chelating Ligands in Aqueous Solution

Abstract

Two novel, pyridinone-based chelating ligands containing separated (O,O) and (Namino,Nhet) chelating sets (Namino = secondary amine; Nhet = pyrrole N for H(L3) (1-(3-(((1H-pyrrole-2-yl)methyl)amino)propyl)-3-hydroxy-2-methylpyridin-4(1H)-one) or pyridine N for H(L5) (3-hydroxy-2-methyl-1-(3-((pyridin-2-ylmethyl)amino)propyl)pyridin-4(1H)-one)) were synthesized via reduction of the appropriate imines. Their proton dissociation processes were explored, and the molecular structures of two synthons were assessed by X-ray crystallography. These ambidentate chelating ligands are intended to develop Co(III)/PGM (PGM = platinum group metal) heterobimetallic multitargeted complexes with anticancer potential. To explore their metal ion binding ability, the interaction with Pd(II), [(η6-p-cym)Ru]2+ and [(η5-Cp*)Rh]2+ (p-cym = 1-methyl-4-isopropylbenzene, Cp* = pentamethyl-cyclopentadienyl anion) cations was studied in aqueous solution with the combined use of pH-potentiometry, NMR and HR ESI-MS. In general, organorhodium was found to form more labile complexes over ruthenium, while complexation of the (N,N) chelating set was slower than the processes of the pyridinone unit with (O,O) coordination. Formation of the organoruthenium complexes starts at lower pH (higher thermodynamic stabilities of the corresponding complexes) than for [(η5-Cp*)Rh]2+ but, due to the higher affinity of [η6-p-cym)Ru]2+ towards hydrolysis, the complexed ligands are capable of competing with hydroxide ion in a lesser extent than for the rhodium systems. As a result, under biologically relevant conditions, the rhodium binding effectivity of the ligands becomes comparable or even slightly higher than their effectivity towards ruthenium. Our results indicate that H(L3) is a less efficient (N,N) chelator for these metal ions than H(L5). Similarly, due to the relative effectivity of the (O,O) and (N,N) chelates at a 1:1 metal-ion-to-ligand ratio, H(L5) coordinates in a (N,N) manner to both cations in the whole pH range studied while, for H(L3), the complexation starts with (O,O) coordination. At a 2:1 metal-ion-to-ligand ratio, H(L3) cannot hinder the intensive hydrolysis of the second metal ion, although a small amount of 2:1 complex with [(η5-Cp*)Rh]2+ can also be detected.

Azo naringenin‐based copper (II) complex as DNA binder: Synthesis, spectroscopic characterization, and diverse biological potentials

“…[12][13][14] Metal complexes containing aromatic planar ligands extracted from a plant source have demonstrated a high ability to bind to DNA in various patterns and thus have been considered promising therapeutic agents. 12 Natural flavonoids have structural properties that allow them to bind efficiently to DNA through noncovalent, intercalation, or groove binding modes. 15,16 One such flavonoid family is naringenin, which has a planar aromatic system structure and is expected to have a good ability to bind to DNA, giving it promising pharmacological capabilities.…”

“…In this context, DNA is the primary target of most drugs used in the treatment of tumors and many diseases that arise because of microbial infection. Several Cu (II) complexes have been implicated as DNA binders and have shown promising anticancer and antimicrobial activity 12–14 . Metal complexes containing aromatic planar ligands extracted from a plant source have demonstrated a high ability to bind to DNA in various patterns and thus have been considered promising therapeutic agents 12 .…”

Interaction between [(η6-p-cym)M(H2O)3]2+ (MII = Ru, Os) or [(η5-Cp*)M(H2O)3]2+ (MIII = Rh, Ir) and Phosphonate Derivatives of Iminodiacetic Acid: A Solution Equilibrium and DFT Study

“…In order to explore the fate of these compounds, and to obtain reliable speciation in an aqueous medium, solution equilibrium studies may provide us with help exploring the stoichiometry, the stability, and likely the binding mode of the species that are present in a solution. In this context, in the last decade, the complexation processes of several systems containing either [(η 6 - p -cym)Ru(H 2 O) 3 ] 2+ ( p -cym = 1-methyl-4-isopropylbenzene) or [(η 5 -Cp*)Rh(H 2 O) 3 ] 2+ cations were explored [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. With this type of metal ion, however, only a single publication can be found relating to any direct interaction with phosphonates.…”

Pd(II) Binding Strength of a Novel Ambidentate Dipeptide-Hydroxypyridinonate Ligand: A Solution Equilibrium Study

“…Besides the (NH 2 ,N amide ) coordinated platinum group metals (PGM; Pt(II), Pd(II) as a Pt(II) model exhibiting, however, faster ligand exchange processes, half-sandwich type organo-Ru(II), -Os(II) or -Rh(III) and -Ir(III)), all with proven anticancer activity, a separated (O,O) chelating unit of the ligand with a distinct biological function (e.g., enzyme inhibition, strong iron sequestering capability to disturb the Fe(III) homeostasis of the fast proliferating cancer cells, etc.) can bind a [Co(4N)] 3+ (4N = tren, tpa) (tpa = tris(2-pyridylmethyl)amine) unit [ 4 , 5 , 6 , 7 ]. Various types of Pd(II) complexes themselves exhibit remarkable anticancer potential sometimes via a different mechanism of action compared to the platinum(II) analogues [ 8 , 9 , 10 , 11 ].…”

“…Recently we have shown that the [Co(4N)] 3+ cation exhibits a preference toward the (O,O) chelates (e.g., hydroxamate or hydroxypyridinonate (HP)) during the reaction with similar types of ambidentate chelators. On the contrary, PGMs were found to bind preferably via the (NH 2 ,N amide ) chelating set of these ligands; although with HPs at an excess of metal ion (O,O), coordination was also revealed [ 4 , 5 , 7 ]. Notably, for peptide hydroxamates Pd(II)-assisted hydrolysis of the hydroxamate group followed by a redox reaction between Pd(II) and the hydroxylammonium ion formed under acidic conditions was detected, resulting in the formation of Pd(0) [ 7 ].…”