New mixed ligand cobalt(II/III) complexes based on the drug sodium valproate and bioactive nitrogen-donor ligands. Synthesis, structure and biological properties Hijazi Abu Ali *, 1 , Amani Abu Shamma 1 , Shayma Kamel 1 Department of Chemistry, Birzeit University, West Bank, Palestine article info Article history: Received 29 August 2016 Received in revised form 12 April 2017 Accepted 12 April 2017 Keywords: Cobalt valproate complexes Nitrogen donor ligands Valproate coordination modes abstract New cobalt valproate complexes with different nitrogen based ligands were synthesized and charac- terized using various techniques such as IR, UVeVis, single crystal X-ray diffraction as well as other physical properties. The general formula of the prepared complexes is [Co n (valp) m (L) z ], (n ¼ 1, 2 …; m ¼ 1, 2, …;Z ¼ 1, 2 …). The complexes [Co 2 (valp) 4 ] (1), [Co(valp) 2 (2-ampy) 2 ] (2) and [Co 2 (valp) 4 (quin) 2 ] (3) showed different carboxylate coordination modes. The crystal structures of the complexes 2 and 3 were determined using single crystal X-ray diffraction. Kinetic studies of hydrolysis reactions of BNPP [bis-(p-nitrophenyl)phosphate] with complexes 2 and 3 were performed. The hydrolysis rate of BNPP was studied at different temperatures, pH and concentrations by UVeVis spectrophotometric method. The results showed that the hydrolysis rate of BNPP was 7.70  10 2 L mol 1 s 1 for (3) and 2.60  10 1 L mol 1 s 1 for (2). © 2017 Elsevier B.V. All rights reserved. 1. Introduction Co 3þ ion can be found in different biological systems such as vitamin B12 (cobalamin) which is a cofactor for many enzymes like methyl transferases, and isomerases and it’s a key important in biological system in the formation of blood and the normal func- tioning of the nervous system and brain [1e5]. Cobalt ion has been widely used in therapeutic drugs because it has a variety of geometries, coordination numbers and oxidation states [6]. Moreover, it is less toxic than other metals like platinum [5]. Among the most common ligands which were used to prepare Co complexes as anticancer agents are phenanthroline and tri- dentate N,O-donor ligands [7]. Nitrogen based ligands can be used in the synthesis and design of compounds in biological, chemotherapy and pharmacological applications such as anti-rheumatics and anti-histamines [8,9]. The ligands 2-amino pyridine and quinoline exhibit anti-tumor, anti- bacterial, anti-viral, anti-malarial and anti-fungal activities [10e12]. Valproic acid (2-propylvaleric or n-dipropylacetic or 2- propylpentanoic acid) is a short chain fatty acid which is a car- boxylic acid [13e17]. Recently, valproic acid has a wide range clinical uses such as antibiotic drugs for treatment of many diseases such as epilepsy and bipolar disorder [13,15,17]. But it causes many side effects in human organisms such as gastrointestinal distur- bances and headache. Valproate complexation with metal may reduce these side effects and enhance the biological activity [15,17,18]. The transition metal with carboxylate complexes are used in biological systems and industrial applications such as dirheniu- m(III) dichlorotetraisobutyrate which inhibits cancer cells while dirhodium(II) tetraacetate which is used as catalyst [19]. There are many examples of metal valproate complexes such as copper, cadmium(II), cobalt(II), zinc(II) and manganese(II) [20e23]. Tabrizi and McArdle have studied cadmium (II), cobalt(II) and man- ganese(II) valproate with 1,10-phenanthroline and imidazole. These complexes were synthesized and characterized by using various techniques. The complexes were tested for their biological activities such as anti-bacterial activity by using agar diffusion method and anti-cancer cells [23]. The hydrolytic cleavage of phosphatediester bond is very diffi- cult to occur, but the hydrolysis may be enhanced by using an artificial catalyst which may be organic or inorganic compound. * Corresponding author. Department of Chemistry, Birzeit University, P.O. Box 14, West Bank, Palestine. E-mail addresses: habuali@birzeit.edu, habuali1@yahoo.com (H. Abu Ali). 1 These authors have contributed equally to this work. Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: http://www.elsevier.com/locate/molstruc http://dx.doi.org/10.1016/j.molstruc.2017.04.048 0022-2860/© 2017 Elsevier B.V. All rights reserved. Journal of Molecular Structure 1142 (2017) 40e47