Amphiphilic dendrimers with heteroleptic bis([2,2':6',2"]terpyridine)-ruthenium(II) cores

A new series of dendrimers was assembled through formation of homo- and heteroleptic Ru-II complexes with [2,2':6',2"]terpyridine ligands bearing hydrophilic and hydrophobic dendrons, with the aim to develop amphiphilic vectors for potential use in gene delivery (Scheme 1). The synthesis started with the preparation of the 4'-(3,5-dihalo-4-methoxyphenyl)-[2,2':6',2"]terpyridine ligands 1a,b via the Krohnke pyridine synthesis (Scheme 2), followed by attachment of dendrons 10a-10f (Fig. 2) by Sonogashira cross-coupling to give the dendritic ligands 11 - 16 (Schemes 3 and 4). Ligands were subsequently introduced into the coordination sphere of Ru-III to give the stable intermediates [Ru(11)Cl-3] (24; Scheme 7) and [Ru(14)Cl-3] (27; Scheme 8). These were transformed under reductive conditions into the heteroleptic complexes [Ru(11)(13)](PF6)(2) (25) and [Ru(13)(14)](PF6)(2) (29). Removal of the (tert-butoxy)carbonyl (Boc) protecting groups in 25 and 29 then gave the desired amphiphilic dendrimers 26 (Scheme 7) and 30 (Scheme 8) with branchings of generations 0 and 1. Complex formation was analyzed by high-resolution matrix-assisted laser-desorption-ionization Fourier-transform ion-cyclotron-resonance mass spectrometry (HR-MALDI-FT-ICR-MS), which provided spectra featuring unique fragment-ion series and perfectly resolved isotope distribution patterns (Figs. 4 and 5). The preparation of homo- and heteroleptic complexes with terpyridine ligands bearing generation-2 dendrons failed due to steric hindrance by the bulky wedges.