Dinuclear vs. Mononuclear Copper(II) Coordination Species of Tylosin and Tilmicosin in Non-Aqueous Solutions

Abstract

The veterinary 16-membered macrolide antibiotics tylosin (HTyl, 1a) and tilmicosin (HTilm, 1b) react with copper(II) ions in acetone at metal-to-ligand molar ratio of 1:2 to form blue (2) or green (3) metal(II) coordination species, containing nitrate or chloride anions, respectively. The complexation processes and the properties of 2–3 were studied by an assortment of physicochemical techniques (UV-Vis, EPR, NMR, FTIR, elemental analysis). The experimental data revealed that the main portion of copper(II) ions are bound as neutral EPR-silent dinuclear complexes of composition [Cu2(µ-NO3)2L2] (2a–b) and [Cu2(µ-Cl)2Cl2(HL)2] (3a–b), containing impurities of EPR-active mono-species [Cu(NO3)L] (2a’–b’) and [CuCl2(HL)] (3a’–b’). The possible structural variants of the dinuclear- and mono-complexes were modeled by the DFT method, and the computed spectroscopic parameters of the optimized constructs were compared to those measured experimentally. Using such a combined approach, the main coordination unit of the macrolides, involved in the complex formation, was defined to be their mycaminosyl substituent, which acts as a terminal ligand in a bidentate mode through the tertiary nitrogen atom and the oxygen from a deprotonated (2) or non-dissociated (3) hydroxyl group, respectively.