cis-Locked Ru(II)-DMSO Precursors for the Microwave-Assisted Synthesis of Bis-Heteroleptic Polypyridyl Compounds

Abstract

We describe a synthetic strategy for the preparation of bis-heteroleptic polypyridyl Ru(II) complexes of the type [Ru(L1) 2 (L2)] 2+ (L1 and L2 = diimine ligands) from well-defined Ru(II) precursors. For this purpose, a series of six neutral, anionic, and cationic cis -locked Ru(II)-DMSO complexes ( 2 – 7 ) of the general formula [Y] fac -[RuX(DMSO–S) 3 (O–O)] n (where O–O is a symmetrical chelating anion: oxalate (ox), malonate (mal), acetylacetonate (acac); X = DMSO–O or Cl – ; n = −1/0/+1 depending on the nature and charge of X and O–O; when present, Y = K + or PF 6 – ) were efficiently prepared from the well-known cis -[RuCl 2 (DMSO) 4 ] ( 1 ). When treated with diimine chelating ligands (L1 = bpy, phen, dpphen), the compounds 2 – 7 afforded the target [Ru(L1) 2 (O–O)] 0/+ complex together with the undesired (and unexpected) [Ru(L1) 3 ] 2+ species. Nevertheless, we found that the formation of [Ru(L1) 3 ] 2+ can be minimized by carefully adjusting the reaction conditions: in particular, high selectivity toward [Ru(L1) 2 (O–O)] 0/+ and almost complete conversion of the precursor was obtained within minutes, also on a 100–200 mg scale, when the reactions were performed in absolute ethanol at 150 °C in a microwave reactor. Depending on the nature of L1 and concentration, with the oxalate and malonate precursors, the neutral product [Ru(L1) 2 (O–O)] can precipitate spontaneously from the final mixture, in pure form and acceptable-to-good yields. When spontaneous precipitation of the disubstituted product does not occur, purification from [Ru(L1) 3 ] 2+ can be rather easily accomplished by column chromatography or solvent extraction. By comparison, under the same conditions, compound 1 is much less selective, thus demonstrating that locking the geometry of the precursor through the introduction of O–O in the coordination sphere of Ru is a valid strategic approach. By virtue of its proton-sensitive nature, facile and quantitative replacement of O–O in [Ru(L1) 2 (O–O)] 0/+ by L2, selectively affording [Ru(L1) 2 (L2)] 2+ , was accomplished in refluxing ethanol in the presence of a slight excess of trifluoroacetic acid or HPF 6 .

Ruthenium(II) Polypyridyl Complexes Containing Simple Dioxo Ligands: a Structure‐Activity Relationship Study Shows the Importance of the Charge

“…Compounds 3-8 were prepared and fully characterized as described in ref. 36. Spectroscopic data were in accordance with the literature.…”

“…As mentioned above, we recently described how cis-locked Ru(II)-DMSO precursors with dioxo ligands can be exploited for ChemBioChem the efficient microwave-assisted synthesis of bis-heteroleptic polypyridyl compounds. [36] Ruthenium(II) complexes 3-8 were obtained as intermediates following this novel approach, as exemplified in Figure 3 for a neutral (6) and a cationic (7) complex. Compounds 3-8 are all soluble in DMSO, chloroform, and in aqueous media containing 1 % of DMSO.…”

“…We recently developed a synthetic strategy for the microwave-assisted efficient preparation of bis-heteroleptic Ru(II) polypyridyl compounds [Ru(L1) 2 (L2)] 2 + that involves the isolation of intermediates of the type [Ru(L1) 2 (O^O)]Cl n , where O^O is a symmetrical anionic dioxo ligand. [36] The dioxo complexes are neutral (n = 0) when O^O is oxalate (ox) or malonate (mal), mono-cationic (n = 1) when O^O is acetylacetonate (acac). Having this synthetic capability at hand, we decided to extend the studies mentioned above and investigated how the nature and charge of the dioxo ligand affected the anticancer properties of the {Ru(DIP) 2 } core.…”

“…drugs by our groups. [33][34][35] We recently developed a synthetic strategy for the microwave-assisted efficient preparation of bis-heteroleptic Ru(II) polypyridyl compounds [Ru(L1)2(L2)] 2+ that involves the isolation of intermediates of the type [Ru(L1)2(O^O)]Cln, where O^O is a symmetrical anionic dioxo ligand [36]. The dioxo complexes are neutral (n = 0) when O^O is oxalate (ox) or malonate (mal), mono-cationic (n = 1) when O^O is acetylacetonate (acac).…”

Photocytotoxic kinetically stable ruthenium(ii)-N,N-donor polypyridyl complexes of oxalate with anticancer activity against HepG2 liver cancer cells

“…Complex 1 was characterized by literature reported methods. 51 FT-IR (KBr, ν max cm −1 ): ῡ (aromatic C–H) 3009 (s) cm −1 , ῡ (CO) 1670 (s) cm −1 , ῡ (CN) 1627 (w) cm −1 , ῡ (CC) 1470 (w) cm −1 , ῡ (C–O) 1202 (w) cm −1 , ῡ (Ru–N) 460 (s) cm −1 , ῡ (Ru–O) 430 (w) cm −1 (w, weak; s, strong). 1 H NMR (400 MHz, DMSO- d 6 ): δ 7.73 (dd, 2H), 8.36 (s, 2H), 8.04 (d, 2H), 8.74 (d, 2H).…”