Related Experiment Video
Updated: May 22, 2026
07:38
A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
Published on: September 25, 2017
Reactivity of nitroxyl-derived sulfinamides
1Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.
Biochemistry
|May 11, 2012
Summary
Sulfinamide formation from cysteine modification by nitroxyl is reversible. Excess thiols can reduce sulfinamides back to thiols in peptides and proteins.
Area of Science:
- Biochemistry
- Chemical Biology
Background:
- Nitroxyl (HNO) reacts with cysteine residues to form sulfinamides.
- Sulfinamide formation can alter protein structure and function.
- HNO is being investigated as a potential therapeutic for heart failure.
Purpose of the Study:
- To investigate the reactivity and reversibility of the sulfinamide modification.
- To explore the mechanisms of sulfinamide reduction in various chemical environments.
- To assess the viability of sulfinamide reduction in a protein context.
Main Methods:
- Studied sulfinamide reactivity in a small organic molecule, peptides, and the protein papain.
- Examined the effect of excess thiol on sulfinamide reduction at physiological conditions.
- Investigated reaction mechanisms including direct thiolysis and cyclic intermediate formation.
Main Results:
- Sulfinamides are reducible back to free thiols in the presence of excess thiol at physiological pH and temperature.
- Sulfinamide reduction occurs via direct thiolysis in small molecules and can involve a cyclic intermediate in peptides.
- The contribution of the cyclic intermediate is more significant in lower dielectric constant environments.
- Sulfinamide reduction dominates over sulfinic acid formation in the presence of thiols.
- Sulfinamide reduction is demonstrated to be viable in the cysteine protease papain.
Conclusions:
- The thiol to sulfinamide modification is reversible under physiological conditions.
- Understanding sulfinamide reduction is crucial for evaluating nitroxyl-based therapeutics.
- Sulfinamide reduction is a viable process in biological systems, including proteins.
Related Concept Videos
01:202° Amines to N-Nitrosamines: Reaction with NaNO2
Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
01:23Amines to Sulfonamides: The Hinsberg Test
The Hinsberg test is a method to identify primary, secondary and tertiary amines, named after its pioneer, Oscar Hinsberg. Here, amines are treated with benzenesulfonyl chloride, also known as the Hinsberg reagent, in the presence of an excess of aqueous base, followed by acidification. Based on the nature of the amines, different changes are observed.
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing sulfonyl...
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing sulfonyl...
01:261° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Overview
Nitrous acid and nitric acids are two types of acids containing nitrogen, among which nitrous acid is weaker than nitric acid. Nitrous acid with a pKa value of 3.37 ionizes in water to give a nitrite ion and the hydronium ion.
The nitrous acid is unstable. Hence, it is formed in situ from a solution of sodium nitrite and cold aqueous acids such as hydrochloric or sulfuric acid. In an acidic solution, the –OH group of nitrous acid undergoes protonation to give oxonium ion, followed by water loss...
The nitrous acid is unstable. Hence, it is formed in situ from a solution of sodium nitrite and cold aqueous acids such as hydrochloric or sulfuric acid. In an acidic solution, the –OH group of nitrous acid undergoes protonation to give oxonium ion, followed by water loss...
01:29Preparation of Amines: Reduction of Oximes and Nitro Compounds
Oximes can be reduced to primary amines using catalytic hydrogenation, hydride reduction, or sodium metal reduction. The reduction of aliphatic and aromatic nitro compounds to primary amines takes place by either catalytic hydrogenation or by using active metals like Fe, Zn, and Sn in the presence of an acid.
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
01:27Phase I Reactions: Reductive Reactions
Phase I biotransformation reductive reactions are chemical processes that modify drugs by introducing or revealing polar functional groups via reduction. Enzymes called reductases catalyze these reactions, playing a pivotal role in drug metabolism by transforming lipophilic drugs into more polar, water-soluble metabolites for easy excretion. An essential type of reductive reaction is the carbonyl group reduction, where aldehydes and ketones are reduced to alcohols. An example is the...
02:26Preparation and Reactions of Sulfides
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.