pH-tuned metal coordination and peroxidase activity of a peptide dendrimer enzyme model with a Fe(II)bipyridine at its core

Peptide dendrimer BP1 was obtained by double thioether bond formation between 5,5'-bis(bromomethyl)-2,2'-bipyridine and two equivalents of peptide dendrimer N1 (Ac-Glu-Ser)(8)(Dap-Glu-Ala)(4)(Dap-Amb-Tyr)(2)Dap-Cys-Asp-NH2 (Dap = branching 2,3-diaminopropanoic acid, Amb = 4-aminomethyl-benzoic acid). At pH 4.0 BP1 bound Fe(II) to form the expected tris-coordinated complex [Fe-II(BP1)(3)] (K-f = 2.1 x 10(15) M-3). At pH 6.5 a monocoordinated complex [Fe-II(BP1)] was formed instead (K-f = 2.1 x 10(5) M-1) due to electrostatic repulsion between the polyanionic dendrimer branches, as confirmed by the behavior of three analogues where glutamates were partially or completely replaced by neutral glutamines or positive lysines. [Fe-II(BP1)] catalyzed the oxidation of o-phenylenediamine with H2O2 with enzyme-like kinetics (k(cat) = 1.0 min(-1), K-M = 1.5 mM, k(cat)/k(uncat) = 90 000) and multiple turnover, while Fe2+ or [Fe(bipy)(3)](2+) were inactive. The labile coordination positions allowing coordination to H2O2 and to the substrate are likely responsible for the enhanced peroxidase activity of the metallopeptide dendrimer.