A Strongly Bound High-Spin Iron(II) Coordinates Cysteine and Homocysteine in Cysteine Dioxygenase

The first experimental evidence of a tight binding iron­(II)–CDO complex is presented. These data enabled the relationship between iron bound and activity to be explicitly proven. Cysteine dioxygenase (CDO) from <i>Rattus norvegicus</i> has been expressed and purified with ∼0.17 Fe/polypeptide chain. Following addition of exogenous iron, iron determination using the ferrozine assay supported a very tight stoichiometric binding of iron with an extremely slow rate of dissociation, <i>k</i>_off ∼ 1.7 × 10^–6 s^–1. Dioxygenase activity was directly proportional to the concentration of iron. A rate of cysteine binding to iron­(III)–CDO was also measured. Mössbauer spectra show that in its resting state CDO binds the iron as high-spin iron­(II). This iron­(II) active site binds cysteine with a dissociation constant of ∼10 mM but is also able to bind homocysteine, which has previously been shown to inhibit the enzyme

Targeted structural modification of spin crossover complexes: pyridine vs pyrazine

<p>2-(Aminomethyl)pyrazine has been prepared in five steps from 2-pyrazine carboxylic acid. From this key amine, two new bis-terdentate triazole-based ligands which feature pendant <i>pyrazine</i> groups, <b>P</b>_<b>Z</b><b>MAT</b> and <b>P</b>_<b>Z</b><b>MPT</b> (4-amino- and 4-pyrrolyl-3,5-bis{[(2-pyrazylmethyl)amino]methyl}-4H-1,2,4-triazole, respectively), and two dinuclear complexes of them, [Fe^II₂(<b>P</b>_<b>Z</b><b>MAT</b>)₂](BF₄)₄∙MeOH∙2H₂O (<b>1</b>∙MeOH∙2H₂O) and [Fe^II₂(<b>P</b>_<b>Z</b><b>MPT</b>)₂](BF₄)₄∙3H₂O (<b>2</b>∙3H₂O), have been prepared. A structure determination at 100 K on <b>2</b>∙3.5MeCN confirmed that the ligands adopt the expected binding mode, providing all twelve donors to the two iron(II) centres and two <i>N</i>¹,<i>N</i>²-triazole bridges between them. Both undergo gradual incomplete spin transitions: at room temperature <b>1</b>∙MeOH∙2H₂O and <b>2</b>∙3H₂O are approximately two-thirds to three-quarters [HS-HS], dropping to mostly ‘[HS-LS]’ at 50 K. The structure determination and Mössbauer spectroscopy of <b>2</b> qualitatively support this. These findings are consistent with the pendant pyrazines providing a somewhat higher field strength than the pendant pyridines do in the analogous <b>PMRT</b> complexes.</p

Nine Diiron(II) Complexes of Three Bis-tetradentate Pyrimidine Based Ligands with NCE (E = S, Se, BH₃) Coligands

Three bis-<i>tetra</i>dentate acyclic amine ligands differing only in the arm length of the pyridine pendant arms attached to the 4,6-positions of the pyrimidine ring, namely, 4,6-bis­[<i>N</i>,<i>N</i>-bis­(2′-pyridylethyl)­aminomethyl]-2-phenylpyrimidine (<b>L</b>^<b>Et</b>), 4,6-bis­[<i>N</i>,<i>N</i>-bis­(2′-pyridylmethyl)­aminomethyl]-2-phenylpyrimidine (<b>L</b>^<b>Me</b>), and 4,6-[(2′-pyridylmethyl)-2′-pyridylethyl)­aminomethyl]-2-phenylpyrimidine (<b>L</b>^<b>Mix</b>) have been used to synthesize nine air-sensitive diiron­(II) complexes: [Fe^II₂<b>L</b>^<b>Et</b>(NCS)₄]·MeOH·³/₄H₂O (<b>1</b>·MeOH·³/₄H₂O), [Fe^II₂<b>L</b>^<b>Et</b>(NCSe)₄]·H₂O (<b>2</b>·H₂O), [Fe^II₂<b>L</b>^<b>Et</b>(NCBH₃)₄]·⁵/₂H₂O (<b>3</b>·⁵/₂H₂O), [Fe^II₂<b>L</b>^<b>Me</b>(NCS)₄]·¹/₂H₂O (<b>4</b>·¹/₂H₂O), [Fe^II₂<b>L</b>^<b>Me</b>(NCSe)₄] (<b>5</b>), [Fe^II₂<b>L</b>^<b>Me</b>(NCBH₃)₄]·³/₂H₂O (<b>6</b>·³/₂H₂O), [Fe^II₂<b>L</b>^<b>Mix</b>(NCS)₄]·¹/₂H₂O (<b>7</b>·¹/₂H₂O), [Fe^II₂<b>L</b>^<b>Mix</b>(NCSe)₄]·³/₂H₂O (<b>8</b>·³/₂H₂O), and [Fe^II₂<b>L</b>^<b>Mix</b>(NCBH₃)₄]·³/₂H₂O (<b>9</b>·³/₂H₂O). Complexes <b>3</b>·⁵/₂H₂O, <b>4</b>·¹/₂H₂O, <b>5</b>, <b>6</b>·³/₂H₂O, and <b>8</b>·³/₂H₂O were structurally characterized by X-ray crystallography, revealing, in all cases, both of the iron­(II) centers in an octahedral environment with two NCE (E = S, Se, or BH₃) anions in a cis-position relative to one another. Variable temperature magnetic susceptibility measurements showed that all nine diiron­(II) complexes are stabilized in the [HS-HS] state from 300 K to 4 K, and exhibit weak antiferromagnetic coupling. Mössbauer spectroscopy confirmed the spin and oxidation states of eight of the nine complexes (the synthesis of air-sensitive complex <b>3</b> was not readily reproduced)

Nine Diiron(II) Complexes of Three Bis-tetradentate Pyrimidine Based Ligands with NCE (E = S, Se, BH₃) Coligands

Three bis-<i>tetra</i>dentate acyclic amine ligands differing only in the arm length of the pyridine pendant arms attached to the 4,6-positions of the pyrimidine ring, namely, 4,6-bis­[<i>N</i>,<i>N</i>-bis­(2′-pyridylethyl)­aminomethyl]-2-phenylpyrimidine (<b>L</b>^<b>Et</b>), 4,6-bis­[<i>N</i>,<i>N</i>-bis­(2′-pyridylmethyl)­aminomethyl]-2-phenylpyrimidine (<b>L</b>^<b>Me</b>), and 4,6-[(2′-pyridylmethyl)-2′-pyridylethyl)­aminomethyl]-2-phenylpyrimidine (<b>L</b>^<b>Mix</b>) have been used to synthesize nine air-sensitive diiron­(II) complexes: [Fe^II₂<b>L</b>^<b>Et</b>(NCS)₄]·MeOH·³/₄H₂O (<b>1</b>·MeOH·³/₄H₂O), [Fe^II₂<b>L</b>^<b>Et</b>(NCSe)₄]·H₂O (<b>2</b>·H₂O), [Fe^II₂<b>L</b>^<b>Et</b>(NCBH₃)₄]·⁵/₂H₂O (<b>3</b>·⁵/₂H₂O), [Fe^II₂<b>L</b>^<b>Me</b>(NCS)₄]·¹/₂H₂O (<b>4</b>·¹/₂H₂O), [Fe^II₂<b>L</b>^<b>Me</b>(NCSe)₄] (<b>5</b>), [Fe^II₂<b>L</b>^<b>Me</b>(NCBH₃)₄]·³/₂H₂O (<b>6</b>·³/₂H₂O), [Fe^II₂<b>L</b>^<b>Mix</b>(NCS)₄]·¹/₂H₂O (<b>7</b>·¹/₂H₂O), [Fe^II₂<b>L</b>^<b>Mix</b>(NCSe)₄]·³/₂H₂O (<b>8</b>·³/₂H₂O), and [Fe^II₂<b>L</b>^<b>Mix</b>(NCBH₃)₄]·³/₂H₂O (<b>9</b>·³/₂H₂O). Complexes <b>3</b>·⁵/₂H₂O, <b>4</b>·¹/₂H₂O, <b>5</b>, <b>6</b>·³/₂H₂O, and <b>8</b>·³/₂H₂O were structurally characterized by X-ray crystallography, revealing, in all cases, both of the iron­(II) centers in an octahedral environment with two NCE (E = S, Se, or BH₃) anions in a cis-position relative to one another. Variable temperature magnetic susceptibility measurements showed that all nine diiron­(II) complexes are stabilized in the [HS-HS] state from 300 K to 4 K, and exhibit weak antiferromagnetic coupling. Mössbauer spectroscopy confirmed the spin and oxidation states of eight of the nine complexes (the synthesis of air-sensitive complex <b>3</b> was not readily reproduced)

Mechanistic Implications of Persulfenate and Persulfide Binding in the Active Site of Cysteine Dioxygenase

Describing the organization of substrates and substrate analogues in the active site of cysteine dioxygenase identifies potential intermediates in this critical yet poorly understood reaction, the oxidation of cysteine to cysteine sulfinic acid. The fortuitous formation of persulfides under crystallization conditions has allowed their binding in the active site of cysteine dioxygenase to be studied. The crystal structures of cysteine persulfide and 3-mercaptopropionic acid persulfide bound to iron­(II) in the active site show that binding of the persulfide occurs via the distal sulfide and, in the case of the cysteine persulfide, the amine also binds. Persulfide was detected by mass spectrometry in both the crystal and the drop, suggesting its origin is chemical rather than enzymatic. A mechanism involving the formation of the relevant disulfide from sulfide produced by hydrolysis of dithionite is proposed. In comparison, persulfenate {observed bound to cysteine dioxygenase [Simmons, C. R., et al. (2008) <i>Biochemistry 47</i>, 11390]} is shown through mass spectrometry to occur only in the crystal and not in the surrounding drop, suggesting that in the crystalline state the persulfenate does not lie on the reaction pathway. Stabilization of both the persulfenate and the persulfides does, however, suggest the position in which dioxygen binds during catalysis

Noticiero de Vigo : diario independiente de la mañana: Ano XXVIII Número 11530 - 1913 setembro 21

The generation of a new high-valent iron terminal imido complex prepared with a corrolazine macrocycle is reported. The reaction of [Fe^III(TBP₈Cz)] (TBP₈Cz = octakis­(4<i>-tert</i>-butylphenyl)­corrolazinato) with the commercially available chloramine-T (Na⁺TsNCl^–) leads to oxidative N-tosyl transfer to afford [Fe^IV(TBP₈Cz^+•)­(NTs)] in dichloromethane/acetonitrile at room temperature. This complex was characterized by UV–vis, Mössbauer (δ = −0.05 mm s^–1, Δ<i>E</i>_Q = 2.94 mm s^–1), and EPR (X-band (15 K), <i>g</i> = 2.10, 2.00) spectroscopies, and together with reactivity patterns and DFT calculations has been established as an iron­(IV) species antiferromagnetically coupled with a Cz-π-cation-radical (<i>S</i>_total = ¹/₂ ground state). Reactivity studies with triphenylphosphine as substrate show that [Fe^IV(TBP₈Cz^+•)­(NTs)] is an efficient NTs transfer agent, affording the phospharane product Ph₃PNTs under both stoichiometric and catalytic conditions. Kinetic analysis of this reaction supports a bimolecular NTs transfer mechanism with rate constant of 70(15) M^–1 s^–1. These data indicate that [Fe^IV(TBP₈Cz^+•)­(NTs)] reacts about 100 times faster than analogous Mn terminal arylimido corrole analogues. It was found that two products crystallize from the same reaction mixture of Fe^III(TBP₈Cz) + chloramine-T + PPh₃, [Fe^IV(TBP₈Cz)­(NPPh₃)] and [Fe^III(TBP₈Cz)­(OPPh₃)], which were definitively characterized by X-ray crystallography. The sequential production of Ph₃PNTs, Ph₃PNH, and Ph₃PO was observed by ³¹P NMR spectroscopy and led to a proposed mechanism that accounts for all of the observed products. The latter Fe^III complex was then rationally synthesized and structurally characterized from Fe^III(TBP₈Cz) and OPPh₃, providing an important benchmark compound for spectroscopic studies. A combination of Mössbauer and EPR spectroscopies led to the characterization of both intermediate spin (<i>S</i> = ³/₂) and low spin (<i>S</i> = ¹/₂) Fe^III corrolazines, as well as a formally Fe^IV corrolazine which may also be described by its valence tautomer Fe^III(Cz^+•)

Generation of a High-Valent Iron Imido Corrolazine Complex and NR Group Transfer Reactivity

The generation of a new high-valent iron terminal imido complex prepared with a corrolazine macrocycle is reported. The reaction of [Fe^III(TBP₈Cz)] (TBP₈Cz = octakis­(4<i>-tert</i>-butylphenyl)­corrolazinato) with the commercially available chloramine-T (Na⁺TsNCl^–) leads to oxidative N-tosyl transfer to afford [Fe^IV(TBP₈Cz^+•)­(NTs)] in dichloromethane/acetonitrile at room temperature. This complex was characterized by UV–vis, Mössbauer (δ = −0.05 mm s^–1, Δ<i>E</i>_Q = 2.94 mm s^–1), and EPR (X-band (15 K), <i>g</i> = 2.10, 2.00) spectroscopies, and together with reactivity patterns and DFT calculations has been established as an iron­(IV) species antiferromagnetically coupled with a Cz-π-cation-radical (<i>S</i>_total = ¹/₂ ground state). Reactivity studies with triphenylphosphine as substrate show that [Fe^IV(TBP₈Cz^+•)­(NTs)] is an efficient NTs transfer agent, affording the phospharane product Ph₃PNTs under both stoichiometric and catalytic conditions. Kinetic analysis of this reaction supports a bimolecular NTs transfer mechanism with rate constant of 70(15) M^–1 s^–1. These data indicate that [Fe^IV(TBP₈Cz^+•)­(NTs)] reacts about 100 times faster than analogous Mn terminal arylimido corrole analogues. It was found that two products crystallize from the same reaction mixture of Fe^III(TBP₈Cz) + chloramine-T + PPh₃, [Fe^IV(TBP₈Cz)­(NPPh₃)] and [Fe^III(TBP₈Cz)­(OPPh₃)], which were definitively characterized by X-ray crystallography. The sequential production of Ph₃PNTs, Ph₃PNH, and Ph₃PO was observed by ³¹P NMR spectroscopy and led to a proposed mechanism that accounts for all of the observed products. The latter Fe^III complex was then rationally synthesized and structurally characterized from Fe^III(TBP₈Cz) and OPPh₃, providing an important benchmark compound for spectroscopic studies. A combination of Mössbauer and EPR spectroscopies led to the characterization of both intermediate spin (<i>S</i> = ³/₂) and low spin (<i>S</i> = ¹/₂) Fe^III corrolazines, as well as a formally Fe^IV corrolazine which may also be described by its valence tautomer Fe^III(Cz^+•)

Remarkable Scan Rate Dependence for a Highly Constrained Dinuclear Iron(II) Spin Crossover Complex with a Wide Thermal Hysteresis Loop

The abrupt [HS-HS] ↔ localized [HS-LS] spin crossovers of a new triazole-based diiron­(II) complex result in a record-equaling thermal hysteresis loop width for a dinuclear complex (Δ<i>T</i> = 22 K by SQUID magnetometer in “settle” mode) and show a remarkable scan rate dependence of only the cooling branch, as revealed by detailed magnetic, DSC, and Mössbauer studies

Generation of a High-Valent Iron Imido Corrolazine Complex and NR Group Transfer Reactivity

The generation of a new high-valent iron terminal imido complex prepared with a corrolazine macrocycle is reported. The reaction of [Fe^III(TBP₈Cz)] (TBP₈Cz = octakis­(4<i>-tert</i>-butylphenyl)­corrolazinato) with the commercially available chloramine-T (Na⁺TsNCl^–) leads to oxidative N-tosyl transfer to afford [Fe^IV(TBP₈Cz^+•)­(NTs)] in dichloromethane/acetonitrile at room temperature. This complex was characterized by UV–vis, Mössbauer (δ = −0.05 mm s^–1, Δ<i>E</i>_Q = 2.94 mm s^–1), and EPR (X-band (15 K), <i>g</i> = 2.10, 2.00) spectroscopies, and together with reactivity patterns and DFT calculations has been established as an iron­(IV) species antiferromagnetically coupled with a Cz-π-cation-radical (<i>S</i>_total = ¹/₂ ground state). Reactivity studies with triphenylphosphine as substrate show that [Fe^IV(TBP₈Cz^+•)­(NTs)] is an efficient NTs transfer agent, affording the phospharane product Ph₃PNTs under both stoichiometric and catalytic conditions. Kinetic analysis of this reaction supports a bimolecular NTs transfer mechanism with rate constant of 70(15) M^–1 s^–1. These data indicate that [Fe^IV(TBP₈Cz^+•)­(NTs)] reacts about 100 times faster than analogous Mn terminal arylimido corrole analogues. It was found that two products crystallize from the same reaction mixture of Fe^III(TBP₈Cz) + chloramine-T + PPh₃, [Fe^IV(TBP₈Cz)­(NPPh₃)] and [Fe^III(TBP₈Cz)­(OPPh₃)], which were definitively characterized by X-ray crystallography. The sequential production of Ph₃PNTs, Ph₃PNH, and Ph₃PO was observed by ³¹P NMR spectroscopy and led to a proposed mechanism that accounts for all of the observed products. The latter Fe^III complex was then rationally synthesized and structurally characterized from Fe^III(TBP₈Cz) and OPPh₃, providing an important benchmark compound for spectroscopic studies. A combination of Mössbauer and EPR spectroscopies led to the characterization of both intermediate spin (<i>S</i> = ³/₂) and low spin (<i>S</i> = ¹/₂) Fe^III corrolazines, as well as a formally Fe^IV corrolazine which may also be described by its valence tautomer Fe^III(Cz^+•)

Effect of <i>N</i>⁴‑Substituent Choice on Spin Crossover in Dinuclear Iron(II) Complexes of Bis-Terdentate 1,2,4-Triazole-Based Ligands

Seven new dinuclear iron­(II) complexes of the general formula [Fe^II₂(<b>PMRT</b>)₂]­(BF₄)₄·solvent, where <b>PMRT</b> is a 4-substituted-3,5-bis­{[(2-pyridylmethyl)-amino]­methyl}-4<i>H</i>-1,2,4-triazole, have been prepared in order to investigate the substituent effect on the spin crossover event. Variable temperature magnetic susceptibility and ⁵⁷Fe Mössbauer spectroscopy studies show that two of the complexes, [Fe^II₂(<b>PMPT</b>)₂]­(BF₄)₄·H₂O (<i>N</i>⁴ substituent is pyrrolyl) and [Fe^II₂(<b>PM</b>^<b>Ph</b><b>AT</b>)₂]­(BF₄)₄ (<i>N</i>⁴ is <i>N</i>,<i>N</i>-diphenylamine), are stabilized in the [HS–HS] state between 300 and 2 K with weak antiferromagnetic interactions between the iron­(II) centers. Five of the complexes showed gradual half spin crossover, from [HS–HS] to [HS–LS], with the following <i>T</i>_1/2 (K) values: 234 for [Fe^II₂(<b>PMibT</b>)₂]­(BF₄)₄·3H₂O (<i>N</i>⁴ is isobutyl), 147 for [Fe^II₂(<b>PMBzT</b>)₂]­(BF₄)₄ (<i>N</i>⁴ is benzyl), 133 for [Fe^II₂(<b>PM</b>^<b>CF3</b><b>PhT</b>)₂]­(BF₄)₄·DMF·H₂O (<i>N</i>⁴ is 3,5-bis­(trifluoromethyl)­phenyl), 187 for [Fe^II₂(<b>PMPhT</b>)₂]­(BF₄)₄ (<i>N</i>⁴ is phenyl), and 224 for [Fe^II₂(<b>PMC</b>_<b>16</b><b>T</b>)₂]­(BF₄)₄ (<i>N</i>⁴ is hexadecyl). Structure determinations carried out for three complexes, [Fe^II₂(<b>PMPT</b>)₂]­(BF₄)₄·4DMF, [Fe^II₂(<b>PMBzT</b>)₂]­(BF₄)₄·CH₃CN, and [Fe^II₂(<b>PM</b>^<b>Ph</b><b>AT</b>)₂]­(BF₄)₄·solvent, revealed that in all three complexes both iron­(II) centers are stabilized in the high spin state at 90 K. A general and reliable 4-step route to <b>PMRT</b> ligands is also detailed