Open Journal of Inorganic Chemistry, 2013, 3, 7-13 OJIC http://dx.doi.org/10.4236/ojic.2013.31002 Published Online January 2013 (http://www.scirp.org/journal/ojic/ ) Synthesis, characterization, and stability of iron (III) complex ions possessing phenanthroline-based ligands Shawnt Tosonian * , Charles J. Ruiz * , Andrew Rios, Elma Frias, Jack F. Eichler # Department of Chemistry, University of California, Riverside, Riverside, USA Email: # eichler@ucr.edu Received 3 November 2012; revised 2 December 2012; accepted 14 December 2012 ABSTRACT It has previously been demonstrated that phenan- throline-based ligands used to make gold metallo- therapuetics have the ability to exhibit cytotoxicity when not coordinated to the metal center. In an effort to help assess the mechanism by which these ligands may cause tumor cell death, iron binding and removal experiments have been considered. The close linkage between cell proliferation and intracellular iron con- centrations suggest that iron deprivation strategies may be a mechanism involved in inhibiting tumor cell growth. With the creation of iron (III) phen com- plexes, the iron binding abilities of three polypyridal ligands [1,10-phenanthroline (phen), 2,9-dimethyl-1, 10-phenanthroline ( methyl phen), and 2,9-di-sec-butyl-1, 10-phenanthroline ( sec-butyl phen)] can be tested via a competition reaction with a known iron chelator. Therefore, iron (III) complexes possessing all three ligands were synthesized. Initial mass spectrometric and infrared absorption data indicate that iron (III) tetrachloride complex ions with protonated phen ligands ( R phenH + ) were formed: [phenH][FeCl 4 ], [ methyl phenH][FeCl 4 ], [ sec-butyl phenH][FeCl 4 ]. UV-Vis spectroscopy was used to monitor the stability of the complex ions, and it was found that the sec-butyl phen- iron complex was more stable than the phen and methyl phen analogues. This was based on the observa- tion that free ligand was observed immediately upon the addition of EDTA to the [phenH][FeCl 4 ] and [ methyl phenH] [FeCl 4 ] complex ions. Keywords: Polypyridyl Ligands; Phenanthroline; Iron (III); Complex Ions 1. INTRODUCTION Cancer is the 2nd leading cause of death in the United States. Though a wide variety of organic-based molecu- lar compounds have been used to treat tumors, the met- allotherapy cisplatin is one of the most successful anti- cancer drugs. Despite its success, cisplatin therapy has several drawbacks, including the development of resis- tance to the drug by tumors and the occurrence of severe side-effects during treatment [1]. It is well known that gold (III) complexes are potential alternatives to the platinum (II) based drugs [2]. Even though gold (III) complexes with polypyridyl based ligands [e.g., 1,10- phenanthroline (phen), 2,2’-bipyri-dine (bipy), and 2,2’- 6’,2’’-terpyridine (terpy)] have shown promise as anti- cancer agents, it has also been shown that the polyp- yridyl ligands can have antitumor activity on their own; therefore the antiproliferative properties of the ligands must be considered when evaluating the antitumor ac- tivity of the corresponding metal-based complexes [1,3,4]. We have previously reported the synthesis of a gold (III) complex bearing a 2,9-di-sec-butyl-1,10-phenant- hroline ( sec-butyl phen) ligand {[( sec-butyl phen) AuCl 3 ]} [5]. The anti-tumor activity of this gold complex compound is currently being studied, therefore it is desired to de- termine the potential activity of the sec-butyl phen ligand. It has been previously hypothesized that chelating ligands can impact tumor cell death via iron depletion [6]. Addi- tionally, Satterfield and Brodbelt reported that alkyl sub- stituents on phenanthroline ligands have an impact on metal binding [7], and this data predicts that sec-butyl phen should exhibit stronger metal binding than unsubstituted phen. To test whether alkyl substituted phenanthroline based ligands have different iron binding abilities, we synthesized and characterized iron complex ions with a series of phenanthroline-based ligands [phen, sec-butyl phen, and 2,9-dimethyl-1,10-phenanthroline ( methyl phen)], and evaluated the relative stability of these three complex ions. 2. MATERIALS AND METHODS 2.1. General Experimental Procedures sec-butyl phen was synthesized according to a previously published protocol [8]; phen and methyl phen were pur- chased from Sigma-Aldrich and used without purifica- tion, as were all other reagents and solvents used in the * These authors contributed equally to this work. # Corresponding author. OPEN ACCESS