A combined solid state, solution and DFT study of a dimethyl-cyclen-Pd(II) complex

A new palladium(ii) complex containing the previously synthesized 4,10-bis[(3-hydroxy-4-pyron-2-yl)methyl]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane ligand maltonis was prepared and characterized both in solution and in the solid state. Hirshfeld surface and energy framework analyses were also performed. Because maltonis already showed antineoplastic activity, the complexation of Pd(ii), chosen as an alternative to Pt(II), was investigated to study its possible biological activity. UV-vis and NMR studies confirmed the formation and stability of the complex in aqueous solution at physiological pH. X-ray diffraction data revealed a structure where the Pd(II) ion is lodged in the dimethyl-cyclen cavity, with maltol rings facing each other (closed shape) even if they are not involved in the coordination. DFT analysis was performed in order to understand the most stable shape of the complex. In view of evaluating its possible bioactive conformation, the DFT study suggested a slight energetic preference for the closed one. The resulting closed complex was stabilized in the X-ray structure by intermolecular interactions that replace the intramolecular interactions present in the optimized complex. According to the DFT calculated formation energies, notwithstanding its rarity, the Pd(II) complex of maltonis is the thermodynamically preferred one among analogous complexes containing different metal ions (Pt(II), Co(II), and Cu(II)). Finally, to study its possible biological activity, the interaction between the Pd(II) complex of maltonis and nucleosides was evaluated through NMR and DFT calculations, revealing a possible interaction with purines via the maltol moieties.