Structure and properties of the 5a,6-anhydrotetracycline–platinum(II) dichloride complex: A theoretical ab initio study

Ab initio structural parameters, relative energies and spectroscopic properties are reported for the 5a,6-anhydrotetracycline–platinum(II) dichloride complex. Distinct coordination modes were analyzed in gas phase and aqueous medium indicating the tricarbonylmethane moiety (O3–Oam–O1) as the most probable Pt(II) complexation sites, supporting experimental proposals. The theoretical 1H NMR analysis in conjunction with the observed data suggests that the Pt(II) might be bound to the O3–Oam preferentially, even though this site was found slightly unfavorable, based on energetic grounds, relative to O1–Oam. The aquation reaction, which is an important activation step in the action mechanism of cisplatin like molecules, was also investigated showing rate constants (0.5–1 × 10−5 M−1 s−1) of the same order of magnitude as those for the parent cisplatin compound. This is an important result stressing the importance of tetracyclines–Pt(II) complexes as lead compounds for the development of new platinum based antitumor drugs.