Controlling the Reactivity of Ruthenium(II) Arene Complexes by Tether Ring-Opening

Abstract

The closed- and open-tethered Ru(II) eta(6)-arene complexes [Ru(II)(eta(6):eta(1)-C(6)H(5)(C(6)H(4))NH(2))(en)]Cl(2) (2) and [Ru(II)(eta(6)-C(6)H(5)(C(6)H(4))NH(2))Cl(en)]Cl (3), where en is ethylenediamine, have been synthesized and their X-ray structures determined. Interconversion between 2 and 3, that is, tethered-arene ring-closure and ring-opening, in different solvents has been investigated. Complex 2 opens in dimethylsulfoxide (DMSO) by solvent-induced dissociation of the NH(2) group of the pendant arm. In methanol, however, equilibrium between 2 and 3 is reached after 12 h when both species coexist in solution in a ratio of 2:1 (open/closed). In water (pH 7), complete ring closure of 3 to 2 at 298 K occurs in less than 2 h. The tether ring of complex 2 opens at basic pH and closes at neutral pH. Complex 2 opens over time (18 h) in concentrated HCl. The opening-closing process is fully reversible in the pH range 2-12. Density Functional Theory calculations have been used to obtain insights into the electronic structure of complexes 2 and 3, their UV-vis properties, and their stability compared to their aqua derivatives. Control of tether-ring-opening can contribute toward a strategy for activation and for achieving cytotoxic selectivity of ruthenium arene anticancer drugs.

Organometallic cis‐Dichlorido Ruthenium(II) Ammine Complexes

“…The Ru–Cl bonds in complexes 1a [2.421(2)/2.427(2) Å] and 2 [2.4246(9)/2.4284(8) Å] as well as the corresponding Ru–N bonds [2.116(8) for 1a and 2.135(3) Å for 2 ] do not vary with a change in arene. The Ru–Cl bond lengths are within the range found for other Ru–N(sp 3 ) arene complexes29 such as [(η 6 :η 1 -C 6 H 5 (CH 2 ) 3 NH 2 )RuCl 2 ]7 and longer than those found in related structures where the N atom belongs to an aromatic pyridine ring 30,13. The Ru–N distances are not significantly affected by a change of arene from p -cym ( 1a ) to bip ( 2 ) and are within the range found in similar complexes such as [(η 6 - p -cym)Ru(NH 3 ) 2 Cl] + [2.1504(15) and 2.1425(15) Å] 11.…”

Solution equilibrium studies of anticancer ruthenium(II)-η6-p-cymene complexes of pyridinecarboxylic acids

“…These comprise picolinic acid, thiomaltol, thioallomaltol, etc. [26,[29][30][31][32][33][34][35]. The type of chelating ligands does not only have an influence on the biological properties but also impacts the stability of the complex formed by preventing hydrolysis of the Ru(II)( 6 -p-cymene) organometallic fragment.…”

Solution equilibria of anticancer ruthenium(II)-(η6-p-cymene)-hydroxy(thio)pyr(id)one complexes: Impact of sulfur vs. oxygen donor systems on the speciation and bioactivity

“…In the last decade, numerous organometallic ruthenium(II)- 6 -arene complexes mainly with piano-stool structure were synthesized and tested in in vitro assays regarding their bioactivity. In these Ru II [5][6][7][8][9][10][11][12]. The chloride ligand acts a leaving group and its replacement by a water molecule facilitates the reaction with biological targets.…”