The anionic sulphonylamine mechanism in the hydrolysis of aryl sulphamates

Thea, Sergio; Cevasco, Giorgio; Guanti, Giuseppe; Williams, Andrew

doi:10.1039/c39860001582

Cited by 24 publications

(27 citation statements)

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“…However, no mechanistically orientated studies that involve amino acids or even amines reacting with sulfamate esters or sulfamoyl chlorides (precursors for N-sulfonylamines such as [HN --SO 2 ] or [RN --SO 2 ]) have been reported. Thus our recent results and those of Thea and Williams 21 are the only ones that throw light on the reaction mechanism(s) taking place.…”

Section: Resultssupporting

confidence: 59%

“…This unusual behaviour can apparently be neatly explained using the scheme (Scheme 3) proposed by Thea and Williams and coworkers 21 to explain some years ago the kinetics of hydrolysis of 10c in aqueous media. They proposed a double deprotonation leading first to the conventional N-sulfonylamine, [HN --SO 2 ] and at higher basic strength a novel anionic sulfonylamine, [ À N --SO 2 ].…”

Section: Resultsmentioning

confidence: 92%

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Kinetic and mechanistic studies on sulfamate esters: models of enzyme inhibitors

McCaw¹,

Spillane²

2006

J of Physical Organic Chem

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Many compounds containing a sulfamate moiety, such as NH 2 SO 2 O-are now known to be medicinally important. However, very little is known about their mechanisms of reaction even under non-biological conditions. In this work the various types of elimination mechanisms that may occur have been probed by studying the kinetics of the reactions of model sulfamate substrates with amines (bases) that act as models for the enzymes involved. The principal mechanistic tool employed has been Brönsted plots and both 'normal' rectilinear and two types of biphasic plots have been found for the decomposition of the esters in acetonitrile (ACN). The mechanisms operating are seen as being of the E2 and E1cB types.

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Section: Resultssupporting

confidence: 59%

Section: Resultsmentioning

confidence: 92%

Kinetic and mechanistic studies on sulfamate esters: models of enzyme inhibitors

McCaw¹,

Spillane²

2006

J of Physical Organic Chem

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“…The O―S bond cleavage occurs through an E1cB mechanism and a sulfur trioxide‐like transition state . For substituted aryl sulfamate esters, this reaction has a β lg value of −1.20 in water at 25 °C, similar to the observed reaction of substituted aryl N ‐phenylmethylsulfamates with tert ‐butylamine in CH 3 CN ( β lg = −1.25 at 25 °C) . A HNSO 2 species is proposed to be the intermediate before the nucleophilic attack that gives the final products.…”

Section: Resultsmentioning

confidence: 91%

Linear correlation between effective charge and bond length sensitivity to electronic effects in phosphoryl, sulfonyl, and sulfuryl compounds

Brandão

2013

J of Physical Organic Chem

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This work presents a linear correlation between bond length sensitivity (Δr/ΔpKlg) and effective charge by comparing a series of the following ROX compounds bearing phosphoryl (XP) and sulfonyl and sulfuryl (XS) moieties: phosphate monoester dianions and monoanions, phosphate diesters, phosphate and phosphorothioate triesters, 4‐Me, 3‐NO2 and 2‐ or 4‐NO2 substituted aryl benzene sulfonates, sulfate monoesters, and a previously determined series of sulfamate and mesylate esters. In every series for ROX compounds, the shortest C―O bond corresponds to the longest O―X bond, showing a linear correlation with the pKlg of the ROH parent compound. The chemical reasons for the extent of bond elongation are discussed, and a linear correlation is found between O―X bond length sensitivity and effective charge. These data show that bond length elongation depends on its strength regarding the equilibrium related to the full bond cleavage. Effective charges for phosphorothioate triesters and sulfonates are estimated, and the effective charge for aryl sulfamate esters is determined on the basis of the available linear free energy relationship data. It is expected that the observations of this paper will illuminate the effect of the electronic demand on the O―X bond lengths during phosphoryl, sulfonyl, and sulfuryl group transfer. Copyright © 2013 John Wiley & Sons, Ltd.

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“…Aryl sulfamates undergo spontaneous hydrolysis in aqueous solution by an ElcB mechanism: deprotonation of the nitrogen atom is followed by elimination of the conjugate base to afford HNSO 2 , which reacts to form various addition products. [31] The spontaneous rate of hydrolysis increases with increasing pH and is inversely proportional to the pK a value of the parent phenol. [31] Thus, for the maximum stability of aryl sulfamates, inactivation assays should be performed at low pH values.…”

Section: Discussionmentioning

confidence: 99%

Direct Evidence for ArOS Bond Cleavage upon Inactivation of Pseudomonas aeruginosa Arylsulfatase by Aryl Sulfamates

Bojarová¹,

Denehy²,

Walker³

et al. 2008

ChemBioChem

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Pseudomonas aeruginosa arylsulfatase catalyses the cleavage of aryl sulfates and is an excellent model for human estrone sulfatase, which is implicated in hormone-dependent breast cancer. Aryl sulfamates are inactivators of sulfatases; however, little is known about their mechanism. We studied the inactivation of Pseudomonas aeruginosa arylsulfatase A by a range of aryl sulfamates, including the clinical agent 667COUMATE (STX64) used to inactivate estrone sulfatase. Inactivation was time dependent, irreversible, and active-site directed, consistent with a covalent modification at the active site. In terms of the kinetic parameters of inactivation k(inact) and K(i), K(i) values are in the micromolar to nanomolar range, and the inactivation half-life is less than 30 s. A Brønsted plot of k(inact)/K(i) has a steep slope (beta(lg) = -1.1), which implies that the transition state for the first irreversible chemical step of inactivation involves a high degree of charge transfer and cleavage of the ArO-S bond. Detection of the released phenol and titration of the residual activity showed the stoichiometry of inactivation to be in the range 3-6, with the greatest values found for the most effective inactivators. Thus, multiple sulfamoylation events appear to occur during the inactivation process. These data provide valuable insight into the mechanism of sulfatase inactivation by sulfamates.

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The anionic sulphonylamine mechanism in the hydrolysis of aryl sulphamates

Cited by 24 publications

References 0 publications

Kinetic and mechanistic studies on sulfamate esters: models of enzyme inhibitors

Kinetic and mechanistic studies on sulfamate esters: models of enzyme inhibitors

Linear correlation between effective charge and bond length sensitivity to electronic effects in phosphoryl, sulfonyl, and sulfuryl compounds

Direct Evidence for ArOS Bond Cleavage upon Inactivation of Pseudomonas aeruginosa Arylsulfatase by Aryl Sulfamates

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