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

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 [Cu 2 (µ-NO 3 ) 2 L 2 ] ( 2a - b ) and [Cu 2 (µ-Cl) 2 Cl 2 (HL) 2 ] ( 3a - b ), containing impurities of EPR-active mono-species [Cu(NO 3 )L] ( 2a' - b' ) and [CuCl 2 (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.