First-Principles Simulations of C-S Bond Cleavage in Rhenium Thioether Complexes Alessandra Magistrato,* ,²,§ Patrick Maurer, ² Thomas Fa 1 ssler, ‡ and Ursula Rothlisberger, ², | Laboratory of Inorganic Chemistry, ETH Hoenggerberg, CH-8093, Zu ¨rich, Switzerland, and Eduard Zintl Insitute, D-64289 Darmstadt, Germany ReceiVed: December 19, 2003 We present first-principles molecular dynamics studies of the reductive C-S bond cleavage reaction in hexathioether complexes of the form [Re(9S3) 2 ] m+ (with 9S3 ) 1,4,7 trithiacyclononane and m ) 1,2). Our calculations show that electron transfer and bond dissociation take place as two distinct consecutive reaction steps. For the reduced complex, C-S bond fission and subsequent release of ethene can be observed directly at only slightly elevated temperatures. Car-Parrinello molecular dynamics of the reactive process demonstrate that for the dissociation to occur two carbon-sulfur bonds have to be broken quasi simultaneously. For the oxidized form on the other hand, no release of ethene takes place at the same temperature within the limited time scale of our simulations. The activation energies of the dissociation process calculated at the gradient- corrected density functional (BP) level are 21 and 10 kcal/mol for the oxidized and the reduced form, respectively. A detailed analysis of the electronic structure in the transition states confirms the presence of a strong π-back-donation from rhenium d-orbitals into antibonding σ*-orbitals of the C-S bonds that is responsible for the pronounced weakening of the carbon-sulfur bond upon reduction. 1. Introduction Metal complexes with radioactive nuclei find multiple ap- plications in medicine as tumor, organ, and tissue imaging agents. 1,2 Radioisotopes such as the -emitting 186 Re and 188 Re have also found recent use for the in-situ treatment of cancerous tissues. 3,4 A central issue in the development of radiopharma- ceuticals with improved imaging and therapeutic properties is the search for compounds with enhanced selectivity. Unfortu- nately, a rational design of highly selective agents is hampered by the limited knowledge of the factors determining their biodistribution and their targeting abilities on the molecular level. In practice, upon injection in the human body, these molecules encounter a variety of different chemical environ- ments and their pathways and final destinations are crucially determined by their chemical transformations under these varying external conditions. A characterization of the detailed physicochemical behavior of these compounds is therefore important to assist the efforts in the development of new radiopharmaceuticals with improved features. Rhenium complexes of the form [Re(9S3) 2 ] m+ are potential radiopharmaceutical agents, and a detailed understanding of their properties is thus of direct practical interest. Moreover, these compounds exhibit also interesting chemical characteristics. In the presence of reducing agents such as ascorbic acid, Zn, Cr, or SnCl 2 , they undergo instantaneous C-S bond cleavage to yield ethene and [Re(9S3)L] + (where L ) SCH 2 CH 2 SCH 2 CH 2 S) (Figure 1). 5 This cleavage occurs under mild conditions, in aqueous solution, and at room temperature. Experimental and semiempirical calculations at the Extended Huckel level 6 suggest a possible π-back-donation from donor t 2g -metal-orbitals into antibonding C-S σ*-orbitals of the thioether ligands as possible cause for the occurrence of reductive bond fission. The ease in which the C-S bond cleavage can be induced suggests that these simple systems could also serve as homo- geneous model compounds for the complex processes involved in the industrial hydrodesulfurization (HDS) of crude oils. 7 HDS requires the use of heterogeneous catalysts, which contain molybdenum and other transition metals oxides and sulfides. The great practical importance of this reaction has stimulated many coordination studies of thiophene to transition metal compounds designed with the goal of activating C-S bonds for cleavage. 8 In this article, we present a detailed characterization of the structural, electronic, and dynamic properties of rhenium thioether compounds with first-principles molecular dynamics simulations. Our study provides a detailed understanding of the mechanism of the reductive C-S bond cleavage in these systems and thus contributes to a comprehensive characterization of the chemical behavior of these radioactive agents in redox active environments. * Author to whom correspondence should be addressed. E-mail: alema@ sissa.it. ² Laboratory of Inorganic Chemistry, ETH Zentrum. ‡ Eduard Zintl Insitute. § Current Address: INFM-Democritos Center and International School of Advanced Studies (SISSA/ISAS), Via Beirut 2-4, I-34014 Trieste, Italy. | Current Address: Institute of Molecular and Biological Chemistry, Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland. Figure 1. Schematic representation of the reductive C-S bond cleavage in [Re(9S3)2] 2+ . The reaction occurs at room temperature, in aqueous solution and in the presence of reducing agents such as ascorbic acid, Zn, Cr, and SnCl 2. 5a 2008 J. Phys. Chem. A 2004, 108, 2008-2013 10.1021/jp037932k CCC: $27.50 © 2004 American Chemical Society Published on Web 02/11/2004