International Journal of Mass Spectrometry 313 (2012) 47–57 Contents lists available at SciVerse ScienceDirect International Journal of Mass Spectrometry j our na l ho me page: www.elsevier.com/locate/ijms A theoretical elucidation of coordination properties of histidine and lysine to Mn 2+ M. Hassan Khodabandeh, Hamid Reisi, Karim Zare, Mansour Zahedi ∗ Department of Chemistry, Faculty of Sciences, Shahid Beheshti University, G.C., Evin, 19839-63113 Tehran, Iran a r t i c l e i n f o Article history: Received 12 November 2011 Received in revised form 29 December 2011 Accepted 30 December 2011 Available online 8 January 2012 Keywords: Histidine Lysine Mn 2+ Complexation Gas phase metal ion chemistry Ab initio calculations Density functional theory a b s t r a c t Present account is an elucidation of interaction between histidine and lysine with Mn 2+ in the gas phase by quantum chemical calculations. In addition, side chain effects of these amino acids on relative stability of different coordination modes have been considered by theoretical methods. Three types of complexation mode have been considered: (i) three dentate chelation of neutral amino acids; (ii) two dentate chelation of neutral amino acids; (iii) chelation of amino acids to metal ion in zwitterionic forms. Structure and vibrational frequencies have been determined by B3LYP method. Energy calculations are carried out in CCSD(T) level. For both Mn 2+ –Histidine and Mn 2+ –Lysine systems, the most stable structure resulted from interaction of neutral amino acids with metal cation via two amino groups and carbonyl oxygen while the complexes ground electronic state is determined as 6 A. This is in contrast to Mn 2+ –Glycine system in which the most stable structure resulted from interaction of zwitterionic amino acid with metal ion. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Metallic cations are involved in a wide range of basic pro- cesses in living organisms such as their wide presence in some protein structures, generally known as metaloproteins. Most of these metals are transition elements that due to their catalytic and structural properties are very important [1–3]. Accumulation of different transition metal cations such as manganese, cobalt, zinc and/or nickel in cells and tissues has been shown to be toxic [4–10]. Such toxicity will diminish if ions concentration is moder- ated. One way to achieve the latter goal in plants and mammals is intracellular complexation of toxic metal ions by peptides and amino acid residues [11–13]. Although, metal ions compete in the complexation process, sometimes metals exposure occurs with little or no competition. As an important case of metal ions com- petition in complexation with a protein, copper and manganese cations interaction with prion protein (PrP) which leads to prion disease have been investigated [5,14]. It has been reported that one of the most important residues, namely histidine is the interac- tion site for complexation competition [15]. Cylation of manganese ions with histdine in PrP by replacing copper ions has been pro- posed as the cause of protein abnormal isoform formation leading ∗ Corresponding author. Tel.: +98 21 22431667; fax: +98 21 22431663. E-mail addresses: m-zahedi@sbu.ac.ir, mansourzahedi@yahoo.com (M. Zahedi). to prion disease [5]. In a recent investigation on the interac- tion of manganese ions with a section of the PrP sequence in mouse, GGGTHNQWNKPSKPKTNLKHVAGAAAAGA [15], although the major complexation sites are revealed to be G and A, still the disease causing interaction site has been determined as histidine. Interactions of amino acid residues with some metal cations, that are often electrostatic and noncovalent in nature, determine the structure of these species. Primary step in understanding the coordination properties of such peptides appear to be dependent upon the exact consideration of the interaction type and deter- mining the relative contribution of each kind in the gas phase. Moreover, the gas phase results are complementary to the mass spectrometry data in analyzing the metal complexes mass spectra generated in an experimental work. Theoretical methods are very useful tools for investigation of intrinsic properties of metal cation-biomolecules. In particular numerous works have been done to investigate the effect of transition metal cations on stability of various amino acids as well as small peptides [4,16–73]. Even though, the interaction of transition metal cations such as copper [17–19,23,24,26–28,34,35,38,39,41–45,48,51–54,56,58,62,64,68– 71], zinc [16,19,20,25,27,30–35,50,53,60,62,68,73], cobalt [4,25,34, 35,37,39,44,47,53,62,67], nickel [25–27,29,34,35,39,42,44,46,53,59, 62,67], with histidine and some other amino acids have been exten- sively studied, but reports on manganese interaction with amino acids are rare except those with glycine [25,49] and a few more with some small molecules [74–78]. 1387-3806/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.ijms.2011.12.019