- Penicillamine and captopril: mechanistic exploration of defensive actions of thiol drugs against a metal bound-superoxo complex
-
In acid-media ([H+]?=?0.01–0.06?M), each of the thiol compounds, D-penicillamine (PEN, LPH2) and captopril (CAP, LCH2) exist in several proton-dependent forms which can reduce the superoxo complex [(en)(dien)CoIII(O2)CoIII(en)(dien)]5+ (1) to the corresponding peroxo [(en)(dien)CoIII(O2)CoIII(en)(dien)]4+ (2) or the hydroperoxo complex [(en)(dien)CoIII(OOH)CoIII(en)(dien)]5+ (3). The observed first-order rate constants, k o,P and k o,C for PEN and CAP increase with the increase in [TPEN] and [TCAP] (which are the analytical concentrations of the respective thiols) but decrease with the increase in the media-acidity ([H+]) and the media ionic strength (I). The protolytic equilibria in aqueous solution allow several potentially reducing forms to coexist for both PEN (LPH3 +, LPH2, LPH?, and LP 2?) and CAP (LCH2, LCH?, LC 2?) but the kinetic analyses reveal that the order of reactivity for the species are LPH3 + ~ LPH2?PH? and LCH2?CH??C 2?, respectively. The predominance and higher reactivities of the anionic species, LPH? and LC 2? are supported by the negative slopes of the plots of k o,P or k o,C versus I. Moreover, a large value of k H/k D for PEN suggests an inner-sphere electroprotic reaction pathway while the absence of such effect for CAP strongly supports an outer-sphere electron transfer reaction. These propositions are supported by the structural features of LPH? and LC 2?.
- Mandal, Arabinda,Das, Ranendu Sekhar,Singh, Bula,Banerjee, Rupendranath,Mukhopadhyay, Subrata
-
-
Read Online
- The species- and site-specific acid-base properties of penicillamine and its homodisulfide
-
Penicillamine, penicillamine disulfide and 4 related compounds were studied by 1H NMR-pH titrations and case-tailored evaluation methods. The resulting acid-base properties are quantified in terms of 14 macroscopic and 28 microscopic protonation constants and the concomitant 7 interactivity parameters. The species- and site-specific basicities are interpreted by means of inductive and shielding effects through various intra- and intermolecular comparisons. The thiolate basicities determined this way are key parameters and exclusive means for the prediction of thiolate oxidizabilities and chelate forming properties in order to understand and influence chelation therapy and oxidative stress at the molecular level.
- Mirzahosseini, Arash,Szilvay, András,Noszál, Béla
-
-
Read Online
- Mechanistic scrutiny of the oxidations of thiol-containing drugs cysteamine and d-penicillamine by cis-diamminetetrachloroplatinum(IV)
-
Cysteamine (CA) and d-penicillamine (Pen) are the thiol-containing drugs and good antioxidants. Their reactions with a cisplatin Pt(IV) prodrug cis-diamminetetrachloroplatinum(IV) (cis-[Pt(NH3)2Cl4]) were investigated by use of rapid scan, stopped-flow, and mass spectral techniques. The kinetic traces are biphasic in nature, encompassing a faster reduction of cis-[Pt(NH3)2Cl4] to cisplatin followed by slow substitutions on cisplatin. The reduction reactions were demonstrated to follow overall second-order kinetics over a wide pH range. The observed second-order rate constants versus pH profiles were established at 25.0°C and 1.0?M ionic strength, indicating a huge increase of reaction rate with the increase of pH. However, the oxidations of CA and Pen by cis-[Pt(NH3)2Cl4] displayed different reaction stoichiometric ratios as revealed by the spectrophotometric titration experiments. Accordingly, CA was oxidized to CA-disulfide while Pen-sulfinic acid and Pen-disulfide were identified as the major products in the case of Pen via mass spectral analysis. The above similarities and differences are rationalized in terms of the proposed reaction mechanisms, which encompass similar rate-determining reactions for both CA and Pen, but involve disparate and faster followed-up reactions. Rate constants of the rate determining were derived at 25.0°C and 1.0?M ionic strength. A consequent species reactivity analysis revealed that the species -SCH2CH2NH3+ of CA and the species +H3NCH(COO?)CMe2S? of Pen played a predominant role toward the reduction of cis-[Pt(NH3)2Cl4] from pH 5 to 8, which also is a critical pH region for most of drugs.
- Zhou, Li,Li, Tiejian,Sun, Ying,Tian, Hongwu,Gao, Cunxiu,Liu, Chunli,Kong, Lingli,Zhang, Guimin,Shi, Tiesheng
-
-
Read Online
- The species- and site-specific acid-base properties of penicillamine and its homodisulfide
-
Penicillamine, penicillamine disulfide and 4 related compounds were studied by 1H NMR-pH titrations and case-tailored evaluation methods. The resulting acid-base properties are quantified in terms of 14 macroscopic and 28 microscopic protonation constants and the concomitant 7 interactivity parameters. The species- and site-specific basicities are interpreted by means of inductive and shielding effects through various intra- and intermolecular comparisons. The thiolate basicities determined this way are key parameters and exclusive means for the prediction of thiolate oxidizabilities and chelate forming properties in order to understand and influence chelation therapy and oxidative stress at the molecular level.
- Mirzahosseini, Arash,Szilvay, András,Noszál, Béla
-
-
- The trans opening of ethylene diamine tetra acetic acid bis anhydride (EDTAA) with cystine-di-OMe: One-step synthesis of bihelical systems Respectfully dedicated to Professor M.V. George on the occasion of his 85th birthday
-
The generation of a bihelical (figure of 8) motif has been illustrated by trans opening of EDTAA with l-cystine-di-OMe and d-penicillamine disulfide-di-OMe. In the former case the open cyclic system, arising by cis addition, was secured as a minor product.
- Naini, Santhosh Reddy,Ranganathan, Subramania,Yadav, Jhillu Singh,Sarma,Ramakrishna,Nagaraj, Ramakrishnan,Premkumar, J. Richard,Sastry, G. Narahari
-
p. 1132 - 1135
(2014/02/14)
-
- Metal-free air oxidation of thiols in recyclable ionic liquid: A simple and efficient method for the synthesis of disulfides
-
An efficient procedure for the oxidative coupling of alkyl, aryl and heteroaryl thiols with atmospheric oxygen is reported. The methodology utilizes BMIM-BF4 as a recyclable solvent and does not require support materials or metal salts. Symmetric disulfides are obtained in excellent yields.
- Singh, Devender,Galetto, Fabio Z.,Soares, Letiere C.,Rodrigues, Oscar E. Dorneles,Braga, Antonio Luiz
-
experimental part
p. 2661 - 2665
(2010/07/18)
-
- Production of polyselenodipenicillamines, unique selenium compounds
-
Selenite (H2SeO3) reacts with thiol compounds (RSH) under acidic conditions to form selenotrisulfides (RSSeSR, i.e. monoselenodithiols). The stoichiometry of the reaction is proposed as 4RSH+H2SeO3→RSSeSR+ RSSR+
- Nishida, Hiroyuki,Ando, Motozumi,Itoh, Kazuo,Ueda, Koji,Nishida, Yujiro,Okamoto, Yoshinori,Toda, Chitose,Kojima, Nakao
-
experimental part
p. 957 - 960
(2010/09/04)
-
- Keactions of cysteine sulfenyl thiocyanate with thiols to give unsymmetrical disulfides
-
Cysteine sulfenyl thiocyanate (CSSCN) reacts with thiols at pH 0 to cleanly yield disulfides. 2-Mercaptoethanol (2-MESH), 3-mercaptopropionic acid (3-MPASH), penicillamine (PENSH), and glutathione (GSH) react with CSSCN to give the corresponding mixed disulfides: 2-MESSC, 3-MPASSC, PENSSC, and GSSC. These compounds are stable at pH 0 and have been characterized by 1H and 13C NMR spectroscopy.
- Alguindigue Nimmo, Susan L.,Lemma, Kelemu,Ashby, Michael T.
-
p. 467 - 471
(2008/02/08)
-
- A study of the glutathione metaboloma peptides by energy-resolved mass spectrometry as a tool to investigate into the interference of toxic heavy metals with their metabolic processes
-
To better understand the fragmentation processes of the metal-biothiol conjugates and their possible significance in biological terms, an energy-resolved mass spectrometric study of the glutathione conjugates of heavy metals, of several thiols and disulfides of the glutathione metaboloma has been carried out. The main fragmentation process of γ-glutamyl compounds, whether in the thiol, disulfide, thioether or metal-bis-thiolate form, is the loss of the γ-glutamyl residue, a process which ERMS data showed to be hardly influenced by the sulfur substitution. However, loss of the γ-glutamyl residue from the mono-S-glutathionyl-mercury (II) cation is a much more energetic process, possibly pointing at a strong coordination of the carboxylic group to the metal. Moreover, loss of neutral mercury from ions containing the γ-glutamyl residue to yield a sulfenium cation was a much more energetic process than those not containing them, suggesting that the redox potential of the thiol/disulfide system plays a role in the formal reduction of the mercury dication in the gas phase. Occurrence of complementary sulfenium and protonated thiol fragments in the spectra of protonated disulfides of the glutathione metaboloma mirrors the thiol/disulfide redox process of biological importance. The intensity ratio of the fragments is proportional to the reduction potential in solution of the corresponding redox pairs. This finding has allowed the calculation of the previously unreported reduction potentials for the disulfide/thiol pair of cysteinylglycine, thereby confirming the decomposition scheme of bis- and mono-S-glutathionyl-mercury (II) ions. Finally, on the sole basis of the mass spectrometric fragmentation of the glutathione-mercury conjugates, and supported by independent literature evidence, an unprecedented mechanism for mercury ion-induced cellular oxidative stress could be proposed, based on the depletion of the glutathione pool by a catalytic mechanism acting on the metal (II)-thiol conjugates and involving as a necessary step the enzymatic removal of the glutamic acid residue to yield a mercury (II)-cysteinyl-glycine conjugate capable of regenerating neutral mercury through the oxidation of glutathione thiols to the corresponding disulfides. Copyright
- Rubino, Federico Maria,Pitton, Marco,Brambilla, Gabri,Colombi, Antonio
-
p. 1578 - 1593
(2007/10/03)
-
