A promising structural zinc enzyme model for CO 2 fixation and calcification Mohamed M. Ibrahim a, * , Shaban Y. Shaban a , Kazuhiko Ichikawa b, * a Chemistry Department, Faculty of Education, Kafrelsheikh University, Kafrelsheikh 33516, Egypt b Division of Material Science, Graduate School of Environmental Earth Science, Hokkaido University, Sapporo 060-0810, Japan article info Article history: Received 1 July 2008 Revised 2 October 2008 Accepted 8 October 2008 Available online 14 October 2008 abstract A new ligand, namely, N-{tris([2-[(1-methylbenzimidazol-2-yl)ethyl]methyl]amino)-2-oxoethyl}imino- diacetic acid is synthesized and characterized and used to prepare a zinc complex as a promising model for the active site of the nacreous protein in mollusc shells. Preliminary investigation of CO 2 fixation and calcification is studied with regard to the influence of the pK a value of the coordinated water molecule and the carboxylate groups. Ó 2008 Elsevier Ltd. All rights reserved. A great deal of interest has been focused on the role of metal ions in the active centers of hydrolytic metalloenzymes. 1 In Car- bonic anhydrase CA, the active site of the enzyme consists of a zinc center coordinated to three histidine imidazole groups and a water molecule in a distorted tetrahedral environment. 2 The arrange- ment of the donors, together with an adjacent imidazole and a hydrophobic environment around the Zn(II) ion, determines the considerably high acidity of the metal-coordinated water molecule (pK a , ca. 7). Mollusc shells are generally composed of CaCO 3 crys- tals enclosed in calcitic shell layers. Analysis of the deduced amino acid residue sequence 3 revealed that the nacrein protein contains two functional domains; one is a Carbonic anhydrase active site that catalyzes HCO 3 À formation from CO 2 (Scheme 1), while the other is a Gly-Xaa-Asn (Xaa = Asp, Asn, or Glu) repeated domain which binds Ca 2+ . These domains may function as a template upon which calcification occurs. As one of the approaches adopted to resolve the nature of the active site in CA, a variety of Zn(II) complexes with synthetic recep- tors have been used as model systems for the enzyme. 5–7 Recently, we have reported simulation of CO 2 hydration and phosphoester hydrolysis using structural zinc enzyme model complexes. 8–17 As a measure to cope with the possible global warming due to the greenhouse effect of CO 2 , our aim is to clarify how to fix and calcify CO 2 as CaCO 3 by synthesizing a zinc complex, which func- tionally mimics the active site of the nacrein protein in molluscs (Scheme 2). We have synthesized and characterized a new ligand, namely, N-{tris([2-[(1-methylbenzimidazol-2-yl)ethyl]-methyl]amino)-2- oxoethyl}iminodiacetic acid L (Scheme 3). The ligand was used to prepare a complex in which a Zn(II) ion is coordinated to three benzimidazole nitrogens. In addition, a water molecule is bound to complete the distorted tetrahedral coordination sphere around Zn(II), and Ca(II) is bound to the carboxylate groups. These two functional domains may provide a model mimicking the active site of the nacrein protein in mollusc shells. 0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2008.10.033 * Corresponding author. Tel.: +20 47 3223291; fax: +20 47 3223415 (M.M.I.). E-mail address: ibrahim652001@yahoo.com (M. M. Ibrahim). Scheme 1. A proposed mechanism for the action of the Carbonic anhydrase active site toward the hydration of CO 2 . 4 Scheme 2. A model for the nacreous layer formation by nacrein. 3 Tetrahedron Letters 49 (2008) 7303–7306 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet