Contents lists available at ScienceDirect Journal of Inorganic Biochemistry journal homepage: www.elsevier.com/locate/jinorgbio Carboxyl groups of citric acid in the process of complex formation with bivalent and trivalent metal ions in biological systems Michał Zabiszak, Martyna Nowak, Katarzyna Taras-Goslinska, Małgorzata T. Kaczmarek, Zbigniew Hnatejko, Renata Jastrzab ⁎ Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland ARTICLE INFO Keywords: d-Electron complexes f-Electron complexes Citric acid Potentiometric measurements Spectroscopic studies ABSTRACT Binary complexes of citric acid (H 3 L – protonated form, H 2 L and HL – partly protonated forms, L – fully de- protonated) with d- and f-electron metal ions were investigated. The studies have been performed in aqueous solution using the potentiometric method with computer analysis of the data, electron paramagnetic resonance, infrared, visible as well as luminescence spectroscopies. The overall stability constants of the complexes were determined. Analysis of the equilibrium constants of the reactions and spectroscopic data has allowed de- termination of the type of coordination and effectiveness of the carboxyl groups in the process of complex formation. On the basis of potentiometric titration for d-electron were found dimeric and monomeric type of complexes and for f-electron four type of complexes: MHL, ML, ML(OH) and ML(OH) 2 . 1. Introduction There is no doubt that metal ions play significant role in biological processes as well as human metabolism e.g. for transport of oxygen, functions of enzymes, functioning of the central nervous system. These metal ions in trace amounts are important to sustain life but their ac- cumulation can contribute to some serious diseases (e.g. Huntington's, Alzheimer's, Parkinson, Wilson and Merkes diseases) [1–3]. Moreover complexes of d-electron metal ions such as copper, cobalt or nickel are interesting as model compounds of active sites of biological enzymes [4–9], essential for folate and fatty acid metabolism and are associated with the active part of hydrogenase and are involved in hydrogen oxidation [10–17]. The lanthanide(III) compounds do not naturally occur in living or- ganisms but are useful as a radiopharmaceuticals and magnetic re- sonance imaging (MRI) contrast agents. In particular, gadolinium complexes are applied as contrasting agents in MRI, one of the most accurate imaging techniques for diagnostic purposes or for monitoring of therapy effects, usually applied for patients with cancers, diseases of heart and central nervous system and other maladies. The wide variety of structural types of rare-earth carboxylates depend on high and variable coordination numbers available to the 4f-block elements and their unique f-f electronic transition [9,18–21]. Moreover the lantha- nide(III) complexes show antibacterial and antifungal properties, and the activity of the complexes is higher than that of free ligands [22,23]. On the other hand, the lanthanide(III) compounds can be used as a very effective catalysts with high site selectivity for the hydrolytic cleavage or transesterification of RNA and as a substance promoting DNA clea- vage [24]. The unique properties of lanthanide complexes make them applicable as magnetic materials e.g. lanthanide ions have been proven to be particularly suitable for the synthesis of 4f Single Molecule Magnets (SMM) [25–29]. Citric acid belongs to the strongest fruit acid and is commonly found in human organisms and plays a crucial role in the Krebs cycle also called the citric acid cycle. It is an essential compound in a number of metalloenzyme active sites such as aconitase iron‑sulfur cluster and nitrogen fixation homocitrate synthase (NifV − ). Salts of citric acid occur in bones where they are responsible for the regulation of size of apatite crystals. Citric acid molecule comprises one α-position hydroxyl group, one α-position carboxyl group and two β-position carboxyl groups, and contains at least seven potential donor sites capable of coordinating metal ions. This type of structure permits formation of coordination complexes of novel structure types [30–34]. Citric acid with the seven potentially O–donor atoms is an asym- metric ligand which can be assembled around metal ions in diverse arrangements as a chelating and bridging spacer. These properties permit formation of coordination complexes of novel structure types. Therefore citric acid is a very attractive agent in design of potentially useful compound as a monomeric, binuclear and polymeric complexes with both d- and f-electron metal ions [35–39]. https://doi.org/10.1016/j.jinorgbio.2018.01.017 Received 14 September 2017; Received in revised form 19 January 2018; Accepted 22 January 2018 ⁎ Corresponding author. E-mail address: renatad@amu.edu.pl (R. Jastrzab). Journal of Inorganic Biochemistry 182 (2018) 37–47 0162-0134/ © 2018 Elsevier Inc. All rights reserved. T