Synthesis, characterization, and reactivity of coordinated sulfenic acids

Adzamli, I. Kofi; Libson, Karen; Lydon, J. D.; Elder, R. C.; Deutsch, Edward

doi:10.1021/ic50192a019

Cited by 89 publications

(64 citation statements)

References 12 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…27,39,68,[70][71][72][73][74] DFT calculations described earlier indicated that the S-O bond of 5 is single and significantly polarized. This is supported by the X-ray structure.…”

Section: Structural and Reactivity Properties Of The Metal-bound Sulfmentioning

confidence: 90%

How Does Single Oxygen Atom Addition Affect the Properties of an Fe−Nitrile Hydratase Analogue? The Compensatory Role of the Unmodified Thiolate

et al. 2006

View full text Add to dashboard Cite

Nitrile hydratase (NHase) is one of a growing number of enzymes shown to contain posttranslationally modified cysteine sulfenic acids (Cys-SOH). Cysteine sulfenic acids have been shown to play diverse roles in cellular processes, including transcriptional regulation, signal transduction, and the regulation of oxygen metabolism and oxidative stress responses. The function of the cysteine sulfenic acid coordinated to the iron active site of NHase is unknown. Herein we report the first example of a sulfenate-ligated iron complex, [Fe III (ADIT)(ADIT-O)] + (5), and compare its electronic and magnetic properties with those of structurally related complexes in which the sulfur oxidation state and protonation state have been systematically altered. Oxygen atom addition was found to decrease the unmodified thiolate Fe-S bond length and blue-shift the ligand-to-metal charge-transfer band (without loss of intensity). S K-edge X-ray absorption spectroscopy and density functional theory calculations show that, although the modified RS-O − fragment is incapable of forming a π bond with the Fe III center, the unmodified thiolate compensates for this loss of π bonding by increasing its covalent bond strength. The redox potential shifts only slightly (75 mV), and the magnetic properties are not affected (the S = ½ spin state is maintained). The coordinated sulfenate S-O bond is activated and fairly polarized (S + -O − ). Addition of strong acids at low temperatures results in the reversible protonation of sulfenateligated 5. An X-ray structure demonstrates that Zn 2+ binds to the sulfenate oxygen to afford [Fe III HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript unmodified NHase thiolate, involving its ability to "tune" the electronics in response to protonation of the sulfenate (RS-O − ) oxygen and/or substrate binding, is discussed.Nitrile hydratases (NHases) are non-heme iron enzymes that convert nitriles to less toxic amides cleanly, and rapidly, under mild conditions. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] It is unusual for a hydrolytic metalloenzyme to incorporate iron, as opposed to zinc, 17,18 presumably because, unlike other metal ions, Zn 2+ is not complicated by redox chemistry. Iron, on the other hand, can promote unwanted side reactions with dioxygen (i.e., Fenton chemistry involving OH · radicals) upon reduction to the Fe 2+ oxidation state. 19,20 The NHase iron site is, however, redox inactive and stabilized in the 3+ oxidation state. The stabilization of Fe 3+ is accomplished by placing the iron in an electron-rich environment consisting of five anionic ligands-two deprotonated peptide amides and three cysteinates (Figure 1). Two of the three coordinated cysteinate sulfurs are oxidized (post-translationally modified) in NHase -one to a sulfenic acid ( 114 Cys-S-(OH)) and the other to a sulfinate 112 CysSO 2 −.3,21 The third cysteinate sulfur, which is trans to the inhibitor/substrate binding site and less accessible to solvent, remains unmodifie...

show abstract

“…27,39,68,[70][71][72][73][74] DFT calculations described earlier indicated that the S-O bond of 5 is single and significantly polarized. This is supported by the X-ray structure.…”

Section: Structural and Reactivity Properties Of The Metal-bound Sulfmentioning

confidence: 90%

How Does Single Oxygen Atom Addition Affect the Properties of an Fe−Nitrile Hydratase Analogue? The Compensatory Role of the Unmodified Thiolate

et al. 2006

View full text Add to dashboard Cite

show abstract

“…These signals are within the range expected for S-bonded sulfone. [35][36][37] The SdO stretching vibration of diphenyl sulfone, Ph-SO 2 - Ph, is present at 1165 cm -1 . 35 These results confirm both the sulfonation of PEEK and the cross-linking.…”

Section: Atr/ftir Study Of Membranesmentioning

confidence: 99%

A Simple New Route to Covalent Organic/Inorganic Hybrid Proton Exchange Polymeric Membranes

et al. 2005

View full text Add to dashboard Cite

The development of proton exchange membranes as electrolytes for polymer electrolyte fuel cells operating at intermediate temperatures has been achieved combining two approaches: the preparation of a cross-linked polymer and the formation of covalent organic/inorganic hybrids. A covalently crosslinked sulfonated polyetheretherketone with elevated degree of sulfonation (DS ) 0.8) was prepared by reaction with HSO 3 Cl (SOPEEK). No degradation of PEEK was detected upon sulfonation, but only cross-linking via sulfonic groups with formation of SO 2 moieties was observed. The extent of ramification was calculated by analyzing the 1 H nuclear magnetic resonance (NMR) spectra of the products and resulted in 20% of the total amount of -SO 3 H groups present in the polymer. The solubility of the -SO 2 Cl precursor in organic solvents allowed easy carrying out of functionalization reactions in homogeneous conditions by lithiation and subsequent reaction with SiCl 4 , thus introducing covalenly linked silicon moieties (SOSiPEEK) at the ratios 1:0.25 and 1:0.50 per monomeric unit. The products were characterized by 1 H and 13 C NMR, attenuated total reflectance Fourier transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry.

show abstract

“…Early studies on sulfenato ligands in cobalt complexes demonstrated the nucleophilicity of the sulfenato oxygen (9,10), and recently, this same characteristic was observed in NHases wherein the sulfenato oxygen reacted with electrophilic boronic acids (11). Quite tellingly, the activities of NHase, the related thiocyanate hydrolase, and NHase mimics were found to depend on the presence of these sulfenato ligands where oxidation to the sulfinate abrogated activity (12)(13)(14).…”

Section: Nitrile Hydratases (Nhases)mentioning

confidence: 79%

A Protein-derived Oxygen Is the Source of the Amide Oxygen of Nitrile Hydratases

Nelp

Song

Wysocki

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Nitrile hydratase metalloenzymes are unique and important biocatalysts that are used industrially to produce high value amides from their corresponding nitriles. After more than three decades since their discovery, the mechanism of this class of enzymes is becoming clear with evidence from multiple recent studies that the cysteine-derived sulfenato ligand of the active site metal serves as the nucleophile that initially attacks the nitrile. Herein we describe the first direct evidence from solution phase catalysis that the source of the product carboxamido oxygen is the protein. Using 18 O-labeled water under single turnover conditions and native high resolution protein mass spectrometry, we show that the incorporation of labeled oxygen into both product and protein is turnover-dependent and that only a single oxygen is exchanged into the protein even under multiple turnover conditions, lending significant support to proposals that the post-translationally modified sulfenato group serves as the nucleophile to initiate hydration of nitriles. Nitrile hydratases (NHases)2 catalyze the formation of amides from nitriles in aqueous, pH-neutral environments without any carboxylic acid byproducts (1, 2). These bacterial enzymes utilize trivalent iron or cobalt metal cations in this non-redox reaction, and uniquely, these metal ions are ligated directly to the protein backbone through amidate ligands and three cysteine sulfur ligands, of which two are post-translationally modified to the sulfinic and sulfenic acid ( Fig. 1A) (3). The mechanism of hydration is slowly emerging through multiple studies and appears to involve the sulfenic acid oxygen as the nucleophile. This sulfenate oxygen is proposed to initially attack the metal-bound nitrile carbon atom, creating a cyclic intermediate that is then resolved through attack at the sulfenic sulfur either directly by water or from the neighboring axial thiolato sulfur (Fig. 1B) (4 -6). Alternative mechanisms have also found support from time-resolved crystallographic and kinetic studies that involve an activated water molecule attacking the metal-bound nitrile (Fig. 1C) (7, 8).Early studies on sulfenato ligands in cobalt complexes demonstrated the nucleophilicity of the sulfenato oxygen (9, 10), and recently, this same characteristic was observed in NHases wherein the sulfenato oxygen reacted with electrophilic boronic acids (11). Quite tellingly, the activities of NHase, the related thiocyanate hydrolase, and NHase mimics were found to depend on the presence of these sulfenato ligands where oxidation to the sulfinate abrogated activity (12-14).To find direct evidence of either a protein-based or a solventbased nucleophile, we became interested in the observations made by Heinrich et al. (14) with an iron NHase mimic bearing two sulfenato ligands that is capable of hydrating nitriles with up to 50 turnovers. They discovered that labeled oxygen from solvent water was exchanged into one of these sulfenato groups only if the nitrile hydration reaction occurred. This provides a...

show abstract

Synthesis, characterization, and reactivity of coordinated sulfenic acids

Cited by 89 publications

References 12 publications

How Does Single Oxygen Atom Addition Affect the Properties of an Fe−Nitrile Hydratase Analogue? The Compensatory Role of the Unmodified Thiolate

How Does Single Oxygen Atom Addition Affect the Properties of an Fe−Nitrile Hydratase Analogue? The Compensatory Role of the Unmodified Thiolate

A Simple New Route to Covalent Organic/Inorganic Hybrid Proton Exchange Polymeric Membranes

A Protein-derived Oxygen Is the Source of the Amide Oxygen of Nitrile Hydratases

Contact Info

Product

Resources

About