Mossbauer evidence for an exchange-coupled {[Fe4S4]1+ Nip1+} A-cluster in isolated alpha subunits of acetyl-coenzyme A synthase/carbon monoxide dehydrogenase

The active site A-cluster in the alpha subunit of the title enzyme consists of an Fe4S4 cluster coordinated to a [Nip Nid] subcomponent. The cluster must be activated for catalysis using low-potential reductants such as Ti(III) citrate. Relative to the inactive {[Fe4S4]2+ Nip2+ Nid2+} state, the activated state appears to be 2-electrons more reduced, but the location of these electrons within the A-cluster is uncertain, with {[Fe4S4]2+ Nip0 Nid2+} and {[Fe4S4]1+ Nip1+ Nid2+} configurations proposed. Recombinant apo-alpha subunits oligomerize after activation with NiCl2. The dimer fraction, upon reduction with excess Ti(III)citrate, exhibited M?ssbauer spectra consisting of two quadrupole doublets representing 51% and 21% of the Fe, with parameters indicating [Fe4S4]1+ states. Spectra recorded in strong magnetic fields were typical of diamagnetic systems, indicating an exchange-coupled S = 0 {[Fe4S4]1+ Nip1+} state. Additional treatment with CO altered the doublet M?ssbauer parameters, suggesting an interaction with CO, but maintaining the cluster in the {[Fe4S4]1+ Nip1+} state. Reduction with substoichiometric equivalents of Ti(III) citrate afforded an EPR signal typical of Ni1+ ions, with g parallel = 2.10 and g perpendicular = 2.02. Addition of more Ti caused the signal intensity to decline, suggesting that it arises from the semireduced {[Fe4S4]2+ Nip1+} state.     

Double exchange in polynuclear mixed-valence clusters. 2. Iron-sulfur proteins [Fe4S4]+ and [Fe4S4]3+

The energy states of tetrameric iron clusters with d⁶-d⁶-d⁶-d⁵ and d⁵-d⁵-d⁵-d⁶ electronic configurations, which form the metal frameworks of the [Fe₄S₄]⁺ and [Fe₄S₄]³⁺ iron-sulfur proteins, are calculated using a general approach. It is revealed that the structural distortions of these systems significantly affect the composition of the magnetic states. The effect of the isotropic Heisenberg exchange is considered. Valencia University, Spain. Bordeaux University, France. Moldova State University. Institute of Chemistry, Academy of Sciences, Moldova Republic. Translated fromZhurnal Strukturnoi Khimii, Vol. 37, No. 5, pp. 816–825, September–October, 1996. Translated by I. Izvekova     

Reactivity of [Fe4S4(SR)4]2-,3- clusters with sulfonium cations: analogue reaction systems for the initial step in biotin synthase catalysis

The first step in catalysis by a class of iron-sulfur enzymes that includes biotin synthase is the one-electron reductive cleavage of the obligatory cofactor S-adenosylmethionine by an [Fe(4)S(4)](+) cluster to afford methionine and the deoxyadenosyl radical (DOA*). To provide detailed information about the reactions of sulfonium ions with [Fe(4)S(4)](2+,+) clusters, the analogue reaction systems [Fe(4)S(4)(SR')(4)](2)(-)(,3)(-)/[PhMeSCH(2)R](+) (R' = Et (4, 6), Ph (5, 7); R = H (8), COPh (9), p-C(6)H(4)CN (10)) were examined by (1)H NMR spectroscopy. Sulfonium ions 8-10 react completely with oxidized clusters 4 and 5 to afford PhSMe and R'SCH(2)R in equimolar amounts as a result of electrophilic attack by the sulfonium ion on cluster thiolate ligands. Reactions are also complete with reduced clusters 6 and 7 but afford, depending on the substrate, the additional products RCH(3) (R = PhCO, p-C(6)H(4)CN) and the ylid PhMeS=CHR or (p-NCC(6)H(4)CH(2))(2). Redox potentials of 9 and 10 allow electron transfer from 6 or 7. The reaction systems 6/9,10 and 7/9,10 exhibit two reaction pathways, reductive cleavage and electrophilic attack, in an ca. 4:1 ratio inferred from product distribution. Cleavage is a two-electron process and, for example in the system 6/9, is described by the overall reaction 2[Fe(4)S(4)(SR')(4)](3)(-) + 2[PhMeSCH(2)R](+) --> 2[Fe(4)S(4)(SR')(4)](2)(-) + PhSMe + RCH(3) + PhMeS=CHR. This and other reactions may be summarized as [PhMeSCH(2)R](+) + 2e(-) + H(+) --> PhSMe + RCH(3); proposed reaction sequences parallel those for electrochemical reduction of sulfonium ions. This work demonstrates the intrinsic ability of [Fe(4)S(4)](+) clusters with appropriate redox potentials to reductively cleave sulfonium substrates in overall two-electron reactions. The analogue systems differ from the enzymes in that DOA* is generated in a one-electron reduction and is sufficiently stabilized within the protein matrix to abstract a hydrogen atom from substrate or an amino acid residue in a succeeding step. In the present systems, the radical produced in the initial step of the reaction sequence, [Fe(4)S(4)(SR')(4)](3)(-) + [PhMeSCH(2)R](+) --> [Fe(4)S(4)(SR')(4)](2)(-) + PhSMe + RCH(2)*, is not stabilized and is quenched by reduction and protonation.     

Fe2S2(SH)4[2-,3-]的从头计算

正确的能级次序应与分子的活性位置一致.实验证实,铁硫蛋白或模型化合物Fe_2S_2(SR)~(2-)及Fe_4S_4(SR)_4~(2-)的活性位置在端基,易于发生多种取代反应,而Fe_2S_2和Fe_4S_4实一般是稳定的.但是,经过电化学还原生成的Fe_2S_2(SR)_4~(3-),却不可逆地二聚化,生成Fe_4S_4(SR)_4~(2-)     

Formal [4 + 1]- and [5 + 1]-annulation by an S(N)2-conjugate addition sequence: stereoselective synthesis of highly substituted carbocycles

K(2)CO(3)-mediated reactions of 6-bromo-2-hexenoates and 7-bromo-2-heptenoate with active methylene compounds deliver highly substituted cyclopentane and cyclohexane derivatives, respectively via a sequence of S(N)2-conjugate addition reactions (formal [4 + 1]- and [5 + 1]-annulation) in a diastereoselective manner.     

Probing the role of the bridging C509 between the [Fe4S4] cubane and the [Ni(p)Ni(d)] centre in the A-cluster of acetyl-coenzyme A synthase

The A-cluster of acetyl-coenzyme A synthase consists of an [Fe(4)S(4)] cubane bridged to a [Ni(p)Ni(d)] centre via C509 cysteinate. The bridging cysteinate, which could be substituted by histidine imidazole, mediates "communication" between the [Fe(4)S(4)] cubane and the [Ni(p)Ni(d)] centre during the synthesis of acetyl-coenzyme A.     

Total synthesis of (+/-)-strychnine via a [4 + 2]-cycloaddition/rearrangement cascade

A new strategy for the synthesis of the Strychnos alkaloid (+/-)-strychnine has been developed and is based on an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium-catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide. [reaction: see text].     

Cluster oxalate complexes [M3(mu3-Q)(mu2-Q2)3(C2O4)3]2- and [Mo3(mu3-Q)(mu2-Q)3(C2O4)3(H2O)3]2- (M = Mo, W; Q = S, Se): mechanochemical synthesis and crystal structure

Mechanochemical reaction of cluster coordination polymers 1infinity[M3Q7Br4] (M = Mo, W; Q = S, Se) with solid K2C2O4 leads to cluster core excision with the formation of anionic complexes [M3Q7(C2O4)3]2-. Extraction of the reaction mixture with water followed by crystallization gives crystalline K2[M3Q7(C2O4)3].0.5KBr.nH2O (M = Mo, Q = S, n = 3 (1); M = Mo, Q = Se, n = 4 (2); M = W, Q = S, n = 5 (3)). Cs2[Mo3S7(C2O4)3].0.5CsCl.3.5H2O (4) and (Et4N)1.5H0.5K{[Mo3S7(C2O4)3]Br}.2H2O (5) were also prepared. Close Q...Br contacts result in the formation of ionic triples {[M3Q7(C2O4)3](2)Br}5- in 1-4 and the 1:1 adduct {[Mo3S7(C2O4)3]Br}3- in 5. Treatment of 1 or 2 with PPh(3) leads to chalcogen abstraction with the formation of [Mo3(mu3-Q)(mu2-Q)3(C2O4)3(H2O)3]2-, isolated as (Ph4P)2[Mo3(mu3-S)(mu2-S)3(C2O4)3(H2O)3].11H2O (6) and (Ph4P2[Mo3(mu3-Se)(mu2-Se)3(C2O4)3(H2O)3].8.5H2O.0.5C2H5OH (7). All compounds were characterized by X-ray structure analysis. IR, Raman, electronic, and 77Se NMR spectra are also reported. Thermal decomposition of 1-3 was studied by thermogravimetry.     

Novel non-peptide GPIIb/IIIa antagonists: synthesis and biological activities of 2-[4-[2-(4-amidinobenzoylamino)-2-(substituted)acetyl]-3-(2-methoxy-2-oxoethyl)-2-oxopiperazinyl] acetic acids

To improve the in vitro and in vivo potency of our first low molecular weight GPIIb/IIIa antagonist 1 (TAK-029), a series of 2-[4-[2-(4-amidinobenzoylamino)-2-(substituted)acetyl]-3-(2-methoxy-2-oxoethyl)-2-oxopiper-azinyllacetic acids were synthesized through modification of the glycine moiety of 1 and evaluated for their ability to inhibit in vitro adenosine 5'-diphosphate (ADP)-induced platelet aggregation of guinea pig platelet rich plasma (PRP). Among the compounds examined, the (3S,2S)-4-methoxyphenylalanine derivative 4h showed the most potent antagonistic activity with an IC50 value of 13 nM. Dose-dependent inhibition of ex vivo platelet aggregation was achieved with oral administration of 4h (0.3-1.0 mg/kg) to guinea pigs. Complete inhibition was observed for up to 8 h, and 43% inhibition could still be observed 24 h after oral administration of 1.0 mg/kg. The long-lasting antiplatelet effect of 4h suggests that 4h would be suitable for once-a-day dosing. Structure-activity relationships (SAR) were examined in the series of the phenylalanine derivatives. An increase in the electron density around the 4-position of the phenyl ring of the phenylalanine moiety led to an increase in the antiplatelet activity, suggesting the existence of a hydrophobic and electrostatic interaction site in addition to the ionic binding sites in the GPIIb/IIIa.     

Octanuclearity and tetradecanuclearity in manganese chemistry: an octanuclear manganese(II)/(III) complex featuring the novel [Mn8(mu4-O)2(mu3-OH)2]14+ core and [Mn10(II)Mn4(III)O4(O2CMe)20[(2-py)2C(OH)O]4] (2-py = 2-pyridyl)

Reactions of Mn sources with di-2-pyridyl ketone, (2-py)2CO, and phenyl 2-pyridyl ketone oxime, (ph)(2-py)CNOH, give the novel clusters [Mn10(II)Mn4(III)O4(O2CMe)20[(2-py)2C(OH)O]4] 1 and [Mn4(II)Mn4(III)O2(OH)2(O2CPh)10[(ph)(2-py)CNO]4] 2, respectively, which possess low-spin ground states; the observed tetradecanuclearity in 1 is extremely rare in 3d-metal chemistry, while the core of 2 has a unique topology consisting of two linked [Mn2(II)Mn2(III)O(OH)] units.     

Ligand movement modulates the rate of proton transfer in reactions of [Fe4S4Cl4]2-

Substitution of the first chloro-ligand in [Fe4S4Cl4]2- by 4-RC6H4S- (R = CF3, Cl, H, Me or MeO), in the presence of [H2N(CH2)3CH2]+, involves initial binding of thiolate, followed by protonation and finally chloride dissociation; the rate of protonation is facilitated by electron-withdrawing R-substituents indicating that Fe-thiolate bond length changes modulate proton transfer.     

The formal total synthesis of (+/-)-strychnine via a cobalt-mediated [2 + 2 + 2]cycloaddition

A short, highly convergent total synthesis of racemic isostrychnine, and thus strychnine, has been completed. The route involves 14 steps in the longest linear sequence and is highlighted by a cobalt-mediated [2 + 2 + 2]cycloaddition of an alkynylindole nucleus to acetylene.     

High-spin [2 x 2] [Fe(III)2Ni(II)2] heterometallic square grid with an S = 3 ground state

A [2 x 2] heterometallic [Fe(III)2Ni(II)2] ferrimagnetic, square-grid complex has been synthesized by the self-assembly reaction of a mononuclear Fe(III) precursor with Ni(NO3)2. Intramolecular antiferromagnetic exchange through the resulting hydrazone O-bridging framework (M-O-M 133.3-136.4 degrees) leads to an S = 3 ground state. Structural and magnetic properties are discussed.     

A novel [Cu II 4] cluster from the assembly of two [Cu II 2L]+ units by a central mu4-1,1,2,2 perchlorate ligand

A perchlorate ligand in the rare mu4-1,1,2,2 binding mode is seen for the first time as the sole support for the assembly of two cationic [Cu II 2L]+ fragments (H3L = a dinucleating ligand) in the formation of a magnetically-exchanged tetranuclear cluster.