Non-Heme Mononitrosyldiiron Complexes: Importance of Iron Oxidation State in Controlling the Nature of the Nitrosylated Products

Mononitrosyldiiron complexes having either an [Fe^II·{FeNO}⁷] or an [Fe^III·{FeNO}⁷] core formulation have been synthesized by methods that rely on redox-state-induced differentiation of the diiron starting materials in an otherwise symmetrical dinucleating ligand environment. The synthesis, X-ray structures, Mössbauer spectroscopy, cyclic voltammetry, and dioxygen reactivity of [Fe^III·{FeNO}⁷] are described

Variable Nitric Oxide Reactivity of Tropocoronand Cobalt(III) Nitrite Complexes as a Function of the Polymethylene Linker Chain Length

The size-dependent reactivity of cobalt tropocoronands [TC-<i>n</i>,<i>n</i>]^2– is manifest in the NO chemistry of the cobalt­(III) nitrite complexes [Co­(η²-NO₂)­(TC-<i>n</i>,<i>n</i>)] (<i>n</i> = 4–6), the synthesis and characterization of which are reported for the first time. Complete conversion of [Co­(η²-NO₂)­(TC-4,4)] to the cobalt mononitrosyl [Co­(NO)­(TC-4,4)] occurs upon exposure to NO­(g). In contrast, addition of NO­(g) to [Co­(η²-NO₂)­(TC-5,5)] generates both cobalt mono- and dinitrosyl adducts, and addition of nitric oxide to [Co­(η²-NO₂)­(TC-6,6)] converts this complex to the dicobalt tetranitrosyl species [Co₂(NO)₄(TC-6,6)]. In the latter complex, two tetrahedral cobalt dinitrosyl units are bound to the aminotroponeiminate poles of the [TC-6,6]^2– ligand. These results significantly broaden the chemistry of cobalt tropocoronands with nitric oxide and the nitrite anion

Diiron Oxidation State Control of Substrate Access to the Active Site of Soluble Methane Monooxygenase Mediated by the Regulatory Component

The regulatory component (MMOB) of soluble methane monooxygenase (sMMO) has a unique N-terminal tail not found in regulatory proteins of other bacterial multicomponent monooxygenases. This N-terminal tail is indispensable for proper function, yet its solution structure and role in catalysis remain elusive. Here, by using double electron–electron resonance (DEER) spectroscopy, we show that the oxidation state of the hydroxylase component, MMOH, modulates the conformation of the N-terminal tail in the MMOH–2MMOB complex, which in turn facilitates catalysis. The results reveal that the N-terminal tail switches from a relaxed, flexible conformational state to an ordered state upon MMOH reduction from the diiron­(III) to the diiron­(II) state. This observation suggests that some of the crystallographically observed allosteric effects that result in the connection of substrate ingress cavities in the MMOH–2MMOB complex may not occur in solution in the diiron­(III) state. Thus, O₂ may not have easy access to the active site until after reduction of the diiron center. The observed conformational change is also consistent with a higher binding affinity of MMOB to MMOH in the diiron­(II) state, which may allow MMOB to displace more readily the reductase component (MMOR) from MMOH following reduction

Influence of Tetraazamacrocyclic Ligands on the Nitric Oxide Reactivity of their Cobalt(II) Complexes

The reactions of cobalt­(II) complexes of tetraazamacrocyclic tropocoronand (TC) ligands with nitric oxide (NO) were investigated. When [Co­(TC-5,5)] was allowed to react with NO­(g), the {CoNO}⁸ mononitrosyl [Co­(NO)­(TC-5,5)] was isolated and structurally characterized. In contrast, a {Co­(NO)₂}¹⁰ species formed when [Co­(TC-6,6)] was exposed to NO­(g), and the nitrito [Co­(NO₂)­(TC-6,6)] complex was structurally and spectroscopically characterized from the reaction mixture. The {Co­(NO)₂}¹⁰ species was assigned as the bis­(cobalt dinitrosyl) complex [Co₂(NO)₄(TC-6,6)] by spectroscopic comparison with independently synthesized and characterized material. These results provide the first evidence for the influence of tropocoronand ring size on the nitric oxide reactivity of the cobalt­(II) complexes

Variable Nitric Oxide Reactivity of Tropocoronand Cobalt(III) Nitrite Complexes as a Function of the Polymethylene Linker Chain Length

The size-dependent reactivity of cobalt tropocoronands [TC-<i>n</i>,<i>n</i>]^2– is manifest in the NO chemistry of the cobalt­(III) nitrite complexes [Co­(η²-NO₂)­(TC-<i>n</i>,<i>n</i>)] (<i>n</i> = 4–6), the synthesis and characterization of which are reported for the first time. Complete conversion of [Co­(η²-NO₂)­(TC-4,4)] to the cobalt mononitrosyl [Co­(NO)­(TC-4,4)] occurs upon exposure to NO­(g). In contrast, addition of NO­(g) to [Co­(η²-NO₂)­(TC-5,5)] generates both cobalt mono- and dinitrosyl adducts, and addition of nitric oxide to [Co­(η²-NO₂)­(TC-6,6)] converts this complex to the dicobalt tetranitrosyl species [Co₂(NO)₄(TC-6,6)]. In the latter complex, two tetrahedral cobalt dinitrosyl units are bound to the aminotroponeiminate poles of the [TC-6,6]^2– ligand. These results significantly broaden the chemistry of cobalt tropocoronands with nitric oxide and the nitrite anion

Non-Heme Mononitrosyldiiron Complexes: Importance of Iron Oxidation State in Controlling the Nature of the Nitrosylated Products

Mononitrosyldiiron complexes having either an [Fe^II·{FeNO}⁷] or an [Fe^III·{FeNO}⁷] core formulation have been synthesized by methods that rely on redox-state-induced differentiation of the diiron starting materials in an otherwise symmetrical dinucleating ligand environment. The synthesis, X-ray structures, Mössbauer spectroscopy, cyclic voltammetry, and dioxygen reactivity of [Fe^III·{FeNO}⁷] are described

Acetate-Bridged Platinum(III) Complexes Derived from Cisplatin

Oxidation of the acetate-bridged half-lantern platinum­(II) complex <i>cis</i>-[Pt^II(NH₃)₂(μ-OAc)₂Pt^II(NH₃)₂]­(NO₃)₂, [<b>1</b>]­(NO₃)₂, with iodobenzene dichloride or bromine generates the halide-capped platinum­(III) species <i>cis</i>-[XPt^III(NH₃)₂(μ-OAc)₂Pt^III(NH₃)₂X]­(NO₃)₂, where X is Cl in [<b>2</b>]­(NO₃)₂ or Br in [<b>3</b>]­(NO₃)₂, respectively. These three complexes, characterized structurally by X-ray crystallography, feature short (≈2.6 Å) Pt–Pt separations, consistent with formation of a formal metal–metal bond upon oxidation. Elongated axial Pt–X distances occur, reflecting the strong trans influence of the metal–metal bond. The three structures are compared to those of other known dinuclear platinum complexes. A combination of ¹H, ¹³C, ¹⁴N, and ¹⁹⁵Pt NMR spectroscopy was used to characterize [<b>1</b>]²⁺–[<b>3</b>]²⁺ in solution. All resonances shift downfield upon oxidation of [<b>1</b>]²⁺ to [<b>2</b>]²⁺ and [<b>3</b>]²⁺. For the platinum­(III) complexes, the ¹⁴N and ¹⁹⁵Pt resonances exhibit decreased line widths by comparison to those of [<b>1</b>]²⁺. Density functional theory calculations suggest that the decrease in the ¹⁴N line width arises from a diminished electric field gradient at the ¹⁴N nuclei in the higher valent compounds. The oxidation of [<b>1</b>]­(NO₃)₂ with the alternative oxidizing agent bis­(trifluoroacetoxy)­iodobenzene affords the novel tetranuclear complex <i>cis</i>-[(O₂CCF₃)­Pt^III(NH₃)₂(μ-OAc)₂Pt^III(NH₃)­(μ-NH₂)]₂(NO₃)₄, [<b>4</b>]­(NO₃)₄, also characterized structurally by X-ray crystallography. In solution, this complex exists as a mixture of species, the identities of which are proposed

In Vitro Anticancer Activity of <i>cis</i>-Diammineplatinum(II) Complexes with β-Diketonate Leaving Group Ligands

Five cationic platinum­(II) complexes of general formula, [Pt­(NH₃)₂(β-diketonate)]­X are reported, where X is a noncoordinating anion and β-diketonate = acetylacetonate (acac), 1,1,1,-trifluoroacetylacetonate (tfac), benzoylacetonate (bzac), 4,4,4-trifluorobenzoylacetonate (tfbz), or dibenzoylmethide (dbm), corresponding, respectively, to complexes <b>1</b>–<b>5</b>. The log <i>P</i> values and the stabilities of <b>1</b>–<b>5</b> in aqueous solution were evaluated. The phenyl ring substituents of <b>3</b>–<b>5</b> increase the lipophilicity of the resulting complexes, whereas the trifluoromethyl groups of <b>2</b> and <b>4</b> decrease the stability of the complexes in aqueous solution. The uptake of <b>1</b>–<b>5</b> in HeLa cells increases as the lipophilicity of the investigated complex increases. Cancer cell cytotoxicity studies indicate that <b>1</b> and <b>3</b> are the least active complexes whereas <b>2</b>, <b>4</b>, and <b>5</b> are comparable in activity to cisplatin

Influence of Tetraazamacrocyclic Ligands on the Nitric Oxide Reactivity of their Cobalt(II) Complexes

The reactions of cobalt­(II) complexes of tetraazamacrocyclic tropocoronand (TC) ligands with nitric oxide (NO) were investigated. When [Co­(TC-5,5)] was allowed to react with NO­(g), the {CoNO}⁸ mononitrosyl [Co­(NO)­(TC-5,5)] was isolated and structurally characterized. In contrast, a {Co­(NO)₂}¹⁰ species formed when [Co­(TC-6,6)] was exposed to NO­(g), and the nitrito [Co­(NO₂)­(TC-6,6)] complex was structurally and spectroscopically characterized from the reaction mixture. The {Co­(NO)₂}¹⁰ species was assigned as the bis­(cobalt dinitrosyl) complex [Co₂(NO)₄(TC-6,6)] by spectroscopic comparison with independently synthesized and characterized material. These results provide the first evidence for the influence of tropocoronand ring size on the nitric oxide reactivity of the cobalt­(II) complexes

Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn²⁺ with <i>S</i>-Nitrosothiols and Implications for Nitric Oxide Synthase

Zinc thiolate complexes containing N₂S tridentate ligands were prepared to investigate their reactivity toward reactive nitrogen species, chemistry proposed to occur at the zinc tetracysteine thiolate site of nitric oxide synthase (NOS). The complexes are unreactive toward nitric oxide (NO) in the absence of dioxygen, strongly indicating that NO cannot be the species directly responsible for <i>S</i>-nitrosothiol formation and loss of Zn²⁺ at the NOS dimer interface in vivo. <i>S</i>-Nitrosothiol formation does occur upon exposure of zinc thiolate solutions to NO in the presence of air, however, or to NO₂ or NOBF₄, indicating that these reactive nitrogen/oxygen species are capable of liberating zinc from the enzyme, possibly through generation of the <i>S</i>-nitrosothiol. Interaction between simple Zn²⁺ salts and preformed <i>S</i>-nitrosothiols leads to decomposition of the −SNO moiety, resulting in release of gaseous NO and N₂O. The potential biological relevance of this chemistry is discussed