Synthesis, characterization and computational investigation of the phosphatase activity of a dinuclear Zinc(II) complex containing a new heptadentate asymmetric ligand

• Published in: Journal of inorganic biochemistry 2023-02, Vol.239, p.112064-112064, Article 112064
• Main Authors: Costa, Luel M.O., Reis, Iago S., Fernandes, Christiane, Marques, Marcelo M., Resende, Jackson A.L.C., Krenske, Elizabeth H., Schenk, Gerhard, Gahan, Lawrence R., Horn, Adolfo
• Format: Article
• Language: English
• Subjects: 1,3-diaminopropan-2-ol; 15N NMR; Asymmetric amide ligand; Biomimetics; Crystallography, X-Ray; Hydrolysis; Kinetics; Ligands; Metallohydrolases; Phosphatases; Phosphoric Monoester Hydrolases - chemistry; Zinc - chemistry
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2022.112064

We report the synthesis of a new asymmetric heptadentate ligand based on the 1,3-diaminopropan-2-ol backbone. The ligand 3-[[3-(bis-pyridin-2-ylmethyl-amino)-2-hydroxy-propyl]-(2-carbamoyl-ethyl)-amino]-propionamide (HL1) contains two amide and two pyridine groups attached to the 1,3-diaminopropan-2-ol core. Reaction between HL1 and Zn(ClO4)2.6H2O resulted in the formation of the dinuclear [Zn2(L1)(μ-OAc)](ClO4)2 complex, characterized by single crystal X-ray diffraction, 1H, 13C and 15N NMR, ESI-(+)-MS, CHN elemental analysis as well as infrared spectroscopy. The phosphatase activity of the complex was studied in the pH range 6–11 employing pyridinium bis(2,4-dinitrophenyl)phosphate (py(BDNPP)) as substrate. The complex exhibited activity dependent on the pH, presenting an asymmetric bell shape profile with the highest activity at pH 9; at high pH ligand exchange is rate-limiting. The hydrolysis of BDNPP− at pH 9 displayed behavior characteristic of Michaelis-Menten kinetics, with kcat = 5.06 × 10−3 min−1 and Km = 5.7 ± 1.0 mM. DFT calculations map out plausible reaction pathways and identify a terminal, Zn(II)-bound hydroxide as likely nucleophile. The synthesis of a new asymmetric ligand and its dizinc complex is described, together with their characterization, including 1H, 13C, 15NMR, ESI-(+)-MS, x-ray diffraction and DFT calculation. The dizinc compound shows phosphatase activity with maximum activity at pH 9.0. [Display omitted] •A new asymmetric ligand built on the 1,3-diaminopropane-2-ol unit is described.•15N NMR shows that the signals associated with N are split after coordination.•The complex displays pH-dependent phosphatase activity.•At high pH ligand exchange is rate-limiting.•DFT calculations map out the most plausible reaction mechanism.