Structure and properties of the new complexes of platinum (II) with the chemically modified tetracycline CMT-3: A theoretical DFT study

The present paper reports DFT calculations of structure and spectroscopic properties for new complexes of platinum (II) with the most important chemically modified tetracycline, named CMT-3 or Col-3. A detailed analysis is carried out for the free ligand at distinct ionization states as well as for 18 structures with Pt(II) coordinated at potential sites on CMT-3. From the calculated thermodynamic properties the main coordination sites could be assigned according to the pH of the medium. At acid conditions the [Pt(LH2)Cl2] complex should be formed with Pt(II) bound to either O12-O1 or O1-Nam site, which are equally probable. Increasing the pH, the first ionization occurs at O3 and the complex [Pt(LH)Cl2]− should present the metal bound to site O3-Oam. This is the common Pt(II) coordination site for parent tetracyclines. At high pH the O3-Oam is also predicted as the most favorable coordination site followed by site O11-O12. The results reported in the present paper suggest that different Pt(II)-CMT-3 complexes might be obtained controlling the pH of the medium. In addition to the structures for all molecules studied, UV/Vis and 13C NMR data are provided in order to assist the experimentalists in the characterization of the Pt(II)-CMT-3 coordination mode.