Organoditelluride-mediated catalytic S-nitrosothiol decomposition{ Sangyeul Hwang and Mark E. Meyerhoff* Received 10th January 2007, Accepted 22nd February 2007 First published as an Advance Article on the web 6th March 2007 DOI: 10.1039/b700375g An organoditelluride (5,59 -ditelluro-2,29 -dithiophenecarboxylic acid) and a polymeric derivative thereof are shown to exhibit catalytic decomposition of S-nitrosothiols such as S-nitro- soglutathione (GSNO) and S-nitrosocysteine (CySNO). Physiological S-nitrosothiols (RSNOs) such as S-nitrosogluta- thione (GSNO), S-nitrosocysteine (CySNO), and S-nitrosoalbu- min (AlbSNO) are known to serve as storage and transfer agents of physiologically active nitric oxide (NO). 1 Because of the many biological functions of NO, including smooth muscle relaxation, anti-platelet activity, anti-inflammatory activity, and involvement in wound healing, 2 the decomposition of RSNOs to NO is of great interest. 3 Known methods for the decomposition of RSNOs to NO include catalytic reactions by metal ions (Cu + , Fe 2+ , Hg 2+ , and Ag + ) 4 and organodiselenides (RSeSeR) 5 as well as air, photo- and thermal-induced decomposition pathways. 6 Some enzymes such as glutathione peroxidase (GPx), 5 thioredoxin (Trxn), 7 and protein disulfide isomerase (PDI), 8 are also known for their ability to generate NO from RSNOs. Although a few groups have proposed a mechanism for selenium-mediated RSNO decom- position, 5,9,10 the exact catalytic mechanism is not yet clear. Considering the similar chemical properties of selenium and tellurium, including the well known GPx activities of organo- dichalcogenides, 11–13 it is plausible that organotellurium com- pounds could also liberate NO from RSNOs. Indeed, we now report that certain organoditelluride species (RTeTeR), specifi- cally, 5,59-ditelluro-2,29-dithiophenecarboxylic acid 1 and its polymeric derivative 3 (see Scheme 1), can catalyze RSNO decomposition to NO in the presence of endogenous reducing agents such as glutathione (GSH) or cysteine (CySH) at physiological pH. Organoditelluride 1 was synthesized by modifying a previously reported procedure (see Scheme 1). 14 The 5,59-positioned regio- isomer was isolated as the major product, as identified by NMR through the substitution of a deuterium on the Te site using NaOD (see Fig. 1s in ESI{). Further, organoditelluride 1 was tethered to an amine modified hydrophilic polyurethane (HPU: Tecophilic, SP-93A-100), resulting in 10.5 mg cm 23 density of organo- ditelluride 1 in the polymer based on the Te analysis via ICP-MS (see Scheme 1 and synthetic details in ESI{). This polymer is useful for studying both the mechanism and the potential biomedical applications of the new organotellurium chemistry. Organoditelluride 1 is fairly stable (first order decomposition, k = 9.0 6 10 25 min 21 ; see Fig. 7s in ESI{) and soluble in 10 mM phosphate-buffered saline (PBS) buffer, pH 7.4, containing 0.5 mM EDTA (added to prevent any metal ion-induced RSNO decom- position by impurities). The NO generated from a reaction solution containing RSNO, free thiol (RSH), and the catalytic amount of organoditelluride 1 can be continuously monitored using a chemiluminescence NO analyzer (NOA). As shown in Fig. 1(A), a relatively large signal appears quickly upon adding organoditelluride 1 (2.5 mM) into a solution containing GSNO (25 mM) and GSH (100 mM) in deoxygenated PBS buffer. However, the rate of NO generation slowly decreases with time to reach a steady-state that lasts until all of the GSNO is consumed. It was found that organoditelluride 1 also decomposes GSNO to NO without adding GSH to the reaction mixture (see Fig. 1(B)). For example, upon the addition of organoditelluride 1 (2.5 mM) into a solution of GSNO (50 mM) in deoxygenated PBS buffer without GSH, approximately 1.5 equivalents (after baseline correction) of NO relative to the catalyst are quickly evolved. The NO generation then returns to baseline. The exact number of Department of Chemistry, University of Michigan, 930 N. University Ave, Ann Arbor, MI, 48109, USA. E-mail: mmeyerho@umich.edu; Fax: +1-734-6474865; Tel: +1-734-7642169 { Electronic supplementary information (ESI) available: all synthetic preparations and characterization data, including NMR and IR spectra, NOA experiments, UV measurements, and mass spectrometry data. See DOI: 10.1039/b700375g Scheme 1 The synthesis of 5,59-ditelluro-2,29-dithiophenecarboxylic acid, 1, and ditelluride derivatized polymer, 3. See synthetic experimental section in ESI{ for details. COMMUNICATION www.rsc.org/materials | Journal of Materials Chemistry 1462 | J. Mater. Chem., 2007, 17, 1462–1465 This journal is ß The Royal Society of Chemistry 2007 Downloaded on 14 November 2011 Published on 06 March 2007 on http://pubs.rsc.org | doi:10.1039/B700375G View Online / Journal Homepage / Table of Contents for this issue