Phosphatase models: Synthesis, structure and catalytic activity of zinc complexes derived from a phenolic Mannich-base ligand Ria Sanyal a , Prateeti Chakraborty a , Ennio Zangrando b,⇑ , Debasis Das a,⇑ a Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata 700009, India b Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy article info Article history: Received 20 December 2014 Accepted 10 May 2015 Available online 19 May 2015 Keywords: Mannich-base Zinc(II) Phosphatase Mechanistic pathway Halide abstract A series of dinuclear [Zn 2 (L1) 2 X 2 ](1–3) and mononuclear [Zn(HL2)X 2 ] complexes (4–6), (X = Cl, Br, I) were synthesised from two Mannich-base compartmental ligands, namely [bis(2-methoxyethyl)amino- methyl]-4-chlorophenol (HL1) and 2,6-bis[bis(2-methoxyethyl)aminomethyl]-4-chlorophenol (HL2), respectively. They were characterised by routine physicochemical techniques (CHN, UV, IR, ESI-MS and NMR) and complex 2–5 was further structurally characterised by single crystal X-ray analysis where the Zn...Zn bond-distance is 3.10–3.12 Å. All the quintessential complexes exhibit excellent phosphatase activity and the experimental first order rate constant values (k cat ) for the hydrolysis of 4-nitrophenyl phosphate ester (PNPP) reaction in methanol are in the range from 1.05 to 214 s 1 at 25 °C evaluated by monitoring spectrophotometrically the gradual release of p-nitrophenolate (k max = 427 nm, e = 18 500 M 1 cm 1 ). The coordinated X halides affect the phosphatase activity in the order Br > Cl > I (in dinuclear complexes) and Cl > Br > I (in mononuclear) and the trend in the two cases has been well recognised to be due to a different rate determining step. Moreover the influence of chloro atom in para-position of the phenol ring and the role of solvent have been rationalised by comparing the kinetic parameters with those obtained for the corresponding methyl analogues having reasonably close struc- tural resemblance as reported by Sanyal et al. (2014). Ó 2015 Published by Elsevier Ltd. 1. Introduction Among the model metalloenzymes studied till date, those con- taining zinc(II) constitute by far the widest category [1,2]. Indeed, there has been a remarkable success in the identification of zinc- dependent enzymes attributing to emerging crystallographic and spectroscopic techniques [3]. As a matter of fact, each of the funda- mental enzyme class, namely, oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases, is a benchmark of a zinc(II) active site [4–6]. Undoubtedly, phosphatase activity is one of the outstanding functions among the versatile range of enzymatic behaviour of divalent zinc ion [7–10] paving the path for an extensive study of various functional mimics of phospho- esterases. Over the years, synthetic Zn(II) (and also other transition metal) complexes have been judiciously studied as phosphate ester models taking into account their extraordinary Lewis acidity, redox rigidity, nucleophile generation, leaving group stabilization and physiological relevancy [11,12]. However, among the numerous catalytically promiscuous Zn(II) derivatives [13–29] some com- plexes show low activity, others require rigorous synthetic condi- tions or have high toxicity. Therefore the development of new efficient metallocatalysts is still a tough challenge in the field of biocatalysis. The aim of this work is neatly directed to expand the compre- hension of the structure–function relationship of zinc-based model systems showing phosphatase activity (Scheme 1). Recently we have reported that mono- and dinuclear Zn(II) complexes derived from two novel synthesised Mannich-base ligands are not only capable of promoting the hydrolysis of activated phosphate monoesters, but likewise were found to possess promising cat- alytic activity [30]. In this context, here we report the synthesis and characterisation of a series of similar methoxyamine based mono- and dinuclear Zn II complexes, where the ligands differ from those previously reported for the presence in para position of the phenol ring of a chloro instead of a methyl group (Scheme 2). The electronic effects of the substituent in para-position and of the solvent in which the hydrolysis is carried out have been eval- uated. More importantly, a possible mechanism for the PNPP cleav- age promoted by Zn 2 L and the concomitant halide role is proposed on the basis of kinetic and spectral analysis. http://dx.doi.org/10.1016/j.poly.2015.05.013 0277-5387/Ó 2015 Published by Elsevier Ltd. ⇑ Corresponding authors. E-mail addresses: zangrando@units.it (E. Zangrando), dasdebasis2001@yahoo. com (D. Das). Polyhedron 97 (2015) 55–65 Contents lists available at ScienceDirect Polyhedron journal homepage: www.elsevier.com/locate/poly