Cyrene™ as a green alternative to N,N′-dimethylformamide (DMF) in the synthesis of MLCT-emissive ruthenium(ii) polypyridyl complexes for biological applications

Abstract

Ruthenium(II) polypyridyl complexes (RPCs) that emit from triplet metal-to-ligand charge transfer (MLCT) states find a wide variety of uses ranging from luminophores to potential anti-cancer or anti-bacterial therapeutics. Herein we describe a greener, microwave-assisted synthetic pathway for the preparation of homoleptic [Ru(N^N)₃]²⁺ and bis-heteroleptic [Ru(N^N)₂(N'^N')]²⁺ type complexes. This employs the bio-renewable solvent Cyrene™, dihydrolevoglucosenone, as a green alternative to N,N′-dimethylformamide (DMF) in the synthesis of Ru(N^N)₂Cl₂ intermediate complexes, obtaining comparable yields for N^N = 2,2′-bipyridine, 1,10-phenanthroline and methylated derivatives. Employing these intermediates, a range of RPCs were prepared and we verify that the ubiquitous luminophore [Ru(bpy)₃]²⁺ (bpy = 2,2′-bipyridine) can be prepared by this two-step green pathway where it is virtually indistinguishable from a commercial reference. Furthermore, the novel complexes [Ru(bpy)₂(10,11-dmdppz)]²⁺ (10,11-dmdppz = 10,11-dimethyl-dipyridophenazine) and [Ru(5,5′-dmbpy)₂(10,11-dmdppz)]²⁺ (5,5′-dmbpy = 5,5′-dimethyl-bpy) intercalate duplex DNA with high affinity (DNA binding constants, K_b = 5.7 × 10⁷ and 1.0 × 10⁷ M⁻¹, respectively) and function as plasma membrane and nuclear DNA dyes for confocal and STED microscopies courtesy of their long-lived MLCT luminescence.