Thermodynamic of metal complexation of the macrocylic antibiotic rifampicin

The acid-base and complexation equilibria of rifampicin with H⁺, Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Hg²⁺, and Pb²⁺ were studied by means of potentiometry. The stoichiometric equilibrium constants were determined in 50% (v/v) methanol-water medium at different temperatures and constant ionic strength (0.05 M KCl). It was established that rifampicin has two proton-binding sites. The distribution diagram of the corresponding ionic species as a function of pH is given and indicated that rifampicin exists predominantly in the zwitterionic form at pH ≤ 5. The thermodynamic parameters of protonation and complexation were derived and discussed. The formation of the complexes is spontaneous, more favourable at lower temperatures, entropically unfavourable, and an enthalpy-driven process. The order of the changes in Gibbs energy and enthalpy accompanying the complexation was found to be Mn²⁺ < Co²⁺ < Ni²⁺ < Cu²⁺ > Pb²⁺ > Zn²⁺ > Cd²⁺ > Hg²⁺ in accordance with the well-known sequence of Irving and Williams. The transition series contraction energy (E_r(Mn-Zn)), and the ligand field stabilization energy (δH) were calculated from the enthalpy changes.