Organoditelluride-mediated catalytic S-nitrosothiol decomposition

Abstract

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-nitrosoglutathione (GSNO) and S-nitrosocysteine (CySNO).Physiological S-nitrosothiols (RSNOs) such as S-nitrosoglutathione (GSNO), S-nitrosocysteine (CySNO), and S-nitrosoalbumin (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, photoand 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 decomposition, 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 organodichalcogenides, [11][12][13] it is plausible that organotellurium compounds could also liberate NO from RSNOs. Indeed, we now report that certain organoditelluride species (RTeTeR), specifically, 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 regioisomer 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 organoditelluride 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.

Decomposition of S‐Nitrosothiols Induced by UV and Sunlight

“…The irradiated solutions were then analyzed using HPLC. It was found that disulfide was the major product in argon saturated solutions, in agreement with earlier reports [5][6][7][8][9]. Meanwhile, in aerated solutions, nitrite was also formed along with disulfide.…”

“…S-Nitrosothiols (RSNO) are generally believed as the bio reservoir for nitric oxide (NO) in a biological system [1] and hence their various ways of decomposition are very relevant [2][3][4][5][6][7]. The bond dissociation energy for S-N bond is between 20 and 32 kcal mol −1 [8,9].…”

Polyurethane with tethered copper(II)–cyclen complex: Preparation, characterization and catalytic generation of nitric oxide from S-nitrosothiols

“…All NO generation measurements from RSNO species by the new PU-based NOGP were carried out using an NOA via the same methodology described in several previous papers [16][17][18]. Various RSNOs (GSNO, CySNO, and macromolecular BSA-NO) were freshly prepared by methods reported previously [17,19,32].…”

“…Amine equivalents in the aminated PU (2) were determined by a conventional colorimetric titration method as a reported elsewhere [18,31]. Three different solutions were prepared as follows; i) colorimetric indicator: 0.1 N NaOH solution was slowly dropped into a solution of bromophenol blue (0.1 g) in MeOH (100 mL) until the solution color changed from pale purple to blue; ii) samples: three solutions of aminated PU (2) (73.1, 73.6, and 71.6 mg, respectively) dissolved in DMAC (5 mL), and a blank solution having only the solvent; and iii) titrating agent: 1.0 mM p-toluenesulfonic acid monohydrate dissolved in isopropanol.…”

“…NOGPs may be broadly classified into two types; those based on immobilized metal-ion complexes and those using immobilized organodichalcogenides as catalysts. For example, a Cu(II)-cyclen complex [16] or organodichalcogenides (RSeSeR [17] and RTeTeR [18]) can be tethered to polymeric materials to serve as redox catalytic sites. The oxidized form of catalytic site (Cu(II), RSeSeR, or RTeTeR) is reduced to Cu(I), RSe -, or RTe -species by common endogenous reducing agents such as free thiolates (RS -) in blood.…”