Quantum mechanical investigation of aqueous desferrioxamine B metal complexes: Trends in structure, binding, and infrared spectroscopy Bonnie I. Kruft a , James M. Harrington b , Owen W. Duckworth b , Andrzej A. Jarzęcki a, ⁎ a Brooklyn College Chemistry Department, The Brooklyn College and the Graduate School of the City University of New York, Brooklyn, NY 11210, United States b Department of Soil Science, North Carolina State University, Raleigh, NC 27695-7619, United States abstract article info Article history: Received 9 May 2013 Received in revised form 23 August 2013 Accepted 26 August 2013 Available online 31 August 2013 Keywords: Desferrioxamine B metal complexes DFT calculations EXAFS spectra Vibrational spectra Binding constants A systematic density functional theory study supported by extended X-ray absorption fine structure (EXAFS) and infrared spectroscopic data was conducted to elucidate how structure and vibrational spectra of aqueous desferrioxamine B (DFOB) metal complexes vary with the metal ion identity. Structural parameters derived from EXAFS analyses and trends in metal binding constants are well reproduced and validated by the applied computational model. Vibrational mode analysis guides determination and recognition of crucial structure- and metal-sensitive infrared marker bands. The key marker bands, CO and CN stretching modes, dominate the infrared spectra in the 1400–1650 cm −1 region. The modes are sensitive to the stability and size of the metal core (first coordination shell) and indicative of its deformation from the octahedral symmetry. The results shed light on the fundamental structural and electronic factors that control metal binding by siderophores, and drive their potentially rich and largely unexplored interactions with trace metals. Published by Elsevier Inc. 1. Introduction A wide variety of transition metals are required for organisms to maintain normal metabolic function. Iron, the most abundant transition metal in the Earth's crust, typically has both the highest concentration in soils and sediments, and the highest intracellular quota of the transition metals [1]. However, in most aerobic aqueous environments, the bio- availability of iron is limited by the low solubility of iron (hydr)oxide minerals [2]. Similarly, in most mammalian biological fluids, the con- centration of free iron is tightly regulated to avoid unwanted chemical reactions and opportunistic infections [3–5]. To facilitate acquisition of iron, organisms including bacteria, fungi, and plants, have developed specific strategies that increase its availability to cells [6,7]. The exuda- tion of siderophores, generally tetra- or hexa-dentate chelating agents that form exceptionally strong complexes (log K N 20) with trivalent iron via hard Lewis base-bearing functional groups, is a biological re- sponse to low iron availability that is widely distributed throughout the microbial tree of life [8–10]. The most widely studied microbial siderophore is desferrioxamine B (DFOB) [11], which is often used as a convenient model to represent the properties of a common class of siderophores, the trishydroxamates [12]. Recent work has suggested that siderophores, once solely thought of as iron transport agents, may be involved in the solubilization [13–16], binding [13,17–26], and biological uptake [27–31] of metals other than iron, and that the presence of high concentrations of these metals (e.g., Mn) may interfere with siderophore-mediated iron transport [32]. Although biologically relevant metal–hydroxamate complexes have been extensively studied [33–38], there are fewer detailed structural characterizations of siderophore complexes with metals other than iron. Investigating the structure and stability of the resulting metal– siderophore complexes is critical to understanding how metals interact with siderophores. Additionally, structural factors play key roles in regulating the recognition and uptake of the metal at cell membranes [7,39–41]. In contrast to crystallography approaches that probe the structure of solid-phase Fe–siderophore complexes [42–46], modern spectroscopic approaches allow for the study of the molecular and electronic structure of aqueous complexes in solution. In particular, extended X-ray absorp- tion fine structure (EXAFS) spectroscopy is well suited to understanding the molecular structure of complexes because it probes the local coordi- nation environment of a specific element [47]. X-ray spectroscopic approaches have previously been used to study the speciation and structure of siderophore–metal complexes [20,25,26,48–54]. Similarly, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy provides information about bond energies that are espe- cially complementary to EXAFS observations [20,55]. These approaches, when used in conjunction with computational techniques, have provid- ed specific insights into the structural factors that control metal– siderophore complex speciation and stability [20,25,48,49,55,56]. We have conducted a systematic quantum-mechanical study to predict and complement the experimental data for aqueous DFOB complexes with environmentally and biologically important metals (Scheme 1). A primary motivation of the present work is to assess structural, binding, and vibrational properties that can be reproduced, revealed, and established for these complexes by using modern density Journal of Inorganic Biochemistry 129 (2013) 150–161 ⁎ Corresponding author. E-mail address: jarzecki@brooklyn.cuny.edu (A.A. Jarzęcki). 0162-0134/$ – see front matter. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jinorgbio.2013.08.008 Contents lists available at ScienceDirect Journal of Inorganic Biochemistry journal homepage: www.elsevier.com/locate/jinorgbio