Ab Initio Study on the Mechanism of Cycloaddition Reaction between Silylene Carbene （H_2Si=C：） and Acetone

The mechanism of cycloaddition reaction between singlet silylene carbene and acetone has been investigated with CCSD(T)//MP2/6-31G method. From the potential energy profile, it can be predicted that the reaction has two competitive dominant reaction pathways. One consists of two steps: (1) the two reactants (R1, R2) firstly form a four-membered ring intermediate (INT4) through a barrier-free exothermic reaction of 585.9 kJ/mol; (2) Then intermediate (INT4) isomerizes to CH3-transfer product (P4.1) via a transition state (TS4.1) with energy barrier of 5.3 kJ/mol. The other is as follows: on the basis of intermediate (INT4) created between R1 and R2, intermediate (INT4) further reacts with acetone (R2) to form the intermediate (INT5) through a barrier-free exothermic reaction of 166.3 kJ/mol; Then, intermediate (INT5) isomerizes to a silicic bis-heterocyclic product (P5) via a transition state (TS5), for which the barrier is 54.9 kJ/mol. The presented rule of this reaction: the [2+2] cycloaddition effect between the π orbital of silylene carbene and the π orbital of π-bonded compounds leads to the formation of a four-membered ring intermediate (INT4); The unsaturated property of C atom from carbene in the four-membered ring intermediate (INT4) results in the generation of CH3-transfer product (P4.1) and silicic bis-heterocyclic compound (P5).     

Ab initio Study of Mechanism of Forming a Germanic Hetero-Polycyclic Compound between Germylidene (H2C=Ge:) and Acetone

The mechanism of the cycloaddition reaction of forming a germanic hetero‐polycyclic compound between singlet germylidene (R1) and acetone (R2) has been investigated with CCSD(T)//MP2/6‐31G* method. From the surface energy profile, it can be predicted that the dominant reaction pathway for this reaction consists of three steps: (1) the two reactants (R1, R2) firstly form a twisted four‐membered ring intermediate (INT2); (2) the intermediate (INT2) reacts further with acetone (R2) to give another intermediate (INT4); (3) intermediate (INT4) isomerizes to a hetero‐polycyclic germanic compound (P4) via a transition state TS4. The presented rule of this reaction: the [2+2] cycloaddition effect between the π orbital of germylidene and the π orbital of π‐bonded compounds leads to the formation of four‐membered ring intermediate (INT2). The 4p unoccupied orbital and the lone‐pair sp electrons of Ge in the four‐membered ring intermediate (INT2) react with the π orbital and the antibonding π* orbital of π‐bonded compounds, respectively, forming the π→p and sp→ π* cyclic donor‐acceptor bonds, resulting in the generation of a stable germanic hetero‐polycyclic compound (P4).     

Mechanism of the etherification of 2-alkylamino-1-phenylethanol derivatives

Derivatives of 2-alkylamino-1-(4-hydroxyphenyl)-1-ethanol have been converted to the β-methylethers in good yield. Etherification of 2-alkylamino-1-(4-methoxyphenyl)-1-ethanol could not be accomplished. Based on this unreactivity, a mechanism is proposed whereby the etherification proceeds via a quinoidal intermediate and not via a carbonium ion intermediate. It is concluded that the acid catalyzed racemization of catecholamines may occur via a quinoidal intermediate.     

Hydrogen peroxide and dioxygen activation by dinuclear copper complexes in aqueous solution: hydroxyl radical production initiated by internal electron transfer

Dinuclear Cu(II) complexes, CuII2Nn (n = 4 or 5), were recently found to specifically cleave DNA in the presence of a reducing thiol and O2 or in the presence of H2O2 alone. However, CuII2N3 and a closely related mononuclear Cu(II) complex exhibited no selective reaction under either condition. Spectroscopic studies indicate an intermediate is generated from CuII2Nn (n = 4 or 5) and mononuclear Cu(II) solutions in the presence of H2O2 or from CuI2Nn (n = 4 or 5) in the presence of O2. This intermediate decays to generate OH radicals and ligand degradation products at room temperature. The lack of reactivity of the intermediate with a series of added electron donors suggests the intermediate discharges through a rate-limiting intramolecular electron transfer from the ligand to the metal peroxo center to produce an OH radical and a ligand-based radical. These results imply that DNA cleavage does not result from direct reaction with a metal-peroxo intermediate but instead arises from reaction with either OH radicals or ligand-based radicals.     

Theoretical study of mechanism of cycloaddition reaction between singlet dichlorosilylene carbene (Cl<Subscript>2</Subscript>Si=C:) and formaldehyde

The mechanism of the cycloaddition reaction between singlet dichlorosilylene carbene (Cl₂Si=C:) and formaldehyde has been investigated with MP2/6-31G* method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. The energies of the different conformations are calculated by Zero-point energy and CCSD (T)//MP2/6-31G* method. From the potential energy profile, it can be predicted that the reaction has two competitive dominant reaction pathways. The first dominant reaction pathway consists of two steps: (1) the two reactants (R1, R2) firstly form a four-membered ring intermediate (INT4) through a barrier-free exothermic reaction of 387.9 kJ/mol; (2) intermediate (INT4) then isomerizes to H-transfer product (P4.2) via a transition state (TS4.2) with energy barrier of 4.7 kJ/mol. The second dominant reaction pathway as follows: on the basis of intermediate (INT4) created between R1 and R2, intermediate (INT4) further reacts with formaldehyde (R2) to form the intermediate (INT5) through a barrier-free exothermic reaction of 158.3 kJ/mol. Then, intermediate (INT5) isomerizes to a silicic bis-heterocyclic product (P5) via a transition state (TS5), for which the barrier is 40.1 kJ/mol.     

Multistate reactivity in styrene epoxidation by compound I of cytochrome p450: mechanisms of products and side products formation

Density functional theoretical calculations are used to elucidate the epoxidation mechanism of styrene with a cytochrome P450 model Compound I, and the formation of side products. The reaction features multistate reactivity (MSR) with different spin states (doublet and quartet) and different electromeric situations having carbon radicals and cations, as well as iron(III) and iron(IV) oxidation states. The mechanisms involve state-specific product formation, as follows: a) The low-spin pathways lead to epoxide formation in effectively concerted mechanisms. b) The high-spin pathways have finite barriers for ring-closure and may have a sufficiently long lifetime to undergo rearrangement and lead to side products. c) The high-spin radical intermediate, (4)2(rad)-IV, has a ring closure barrier as small as the C--C rotation barrier. This intermediate will therefore lose stereochemistry and lead to a mixture of cis and trans epoxides. The barriers for the production of aldehyde and suicidal complexes are too high for this intermediate. d) The high-spin radical intermediate, (4)2(rad)-III, has a substantial ring closure barrier and may survive long enough time to lead to suicidal, phenacetaldehyde and 2-hydroxostyrene side products. e) The phenacetaldehyde and 2-hydroxostyrene products both originate from crossover from the (4)2(rad)-III radical intermediate to the cationic state, (4)2(cat,z(2) ). The process involves an N-protonated porphyrin intermediate that re-shuttles the proton back to the substrate to form either phenacetaldehyde or 2-hydroxostyrene products. This resembles the internally mediated NIH-shift observed during benzene hydroxylation.     

Direct studies on 5-coordinate intermediates formed during substitution at tetrahedral Fe sites: role of bound nucleophile in labilisation of leaving group

The substitution reactions of the tetrahedral Fe sites in [FeCl(4)](-), [Fe(2)S(2)Cl(4)](2-), [Fe(4)S(4)Cl(4)](2-) and [{MoFe(3)S(4)Cl(3)}(2)(micro-SEt)(3)](3-) with 4-RC(6)H(4)S(-) (R = MeO, Me, H, Cl or NO(2)) all involve rapid binding of the thiolate to a Fe site and formation of a kinetically and spectroscopically detectable intermediate. Kinetic studies allow calculation of the rate of Fe-Cl dissociation from the 5-coordinate site of the intermediate (k(2)(R)). The rate of Fe-Cl dissociation from the intermediate exhibits a marked dependence on the nature of the bound thiolate with log(10)(k(2)(R)) increasing in a linear manner with the calculated NBO charge on the sulfur atom of the coordinated thiolate. This behaviour indicates that Fe-Cl bond dissociation at the 5-coordinate intermediate involves a process in which Fe-thiolate bond shortening occurs prior to movement of the Fe-Cl bond.     

Studies into the mechanism of CO-induced N2 cleavage promoted by an ansa-hafnocene complex and C-C bond formation from an observed intermediate

Carbonylation of the hafnocene dinitrogen complex, [Me(2)Si(η(5)-C(5)Me(4))(η(5)-C(5)H(3)-(t)Bu)Hf](2)(μ(2), η(2), η(2)-N(2)), yields the corresponding hafnocene oxamidide compound, arising from N(2) cleavage with concomitant C-C and C-N bond formation. Monitoring the addition of 4 atm of CO by NMR spectroscopy allowed observation of an intermediate hafnocene complex with terminal and bridging isocyanates and a terminal carbonyl. (13)C labeling studies revealed that the carbonyl is the most substitutionally labile ligand in the intermediate and that N-C bond formation in the bridging isocyanate is reversible. No exchange was observed with the terminal isocyanate. Kinetic data established that the conversion of the intermediate to the hafnocene oxamidide was not appreciably inhibited by carbon monoxide and support a pathway involving rate-determining C-C coupling of the isocyanate ligands. Addition of methyl iodide to the intermediate hafnocene resulted in additional carbon-carbon bond formation arising from CO homologation following nitrogen methylation. Similar reactivity with (t)BuNCO was observed where C-C coupling occurred upon cycloaddition of the heterocumulene. By contrast, treatment of the intermediate hafnocene with CO(2) resulted in formation of a μ-oxo hafnocene with two terminal isocyanate ligands.     

Reaction of the 4-biphenylnitrenium ion with 4-biphenyl azide to produce a 4,4'-azobisbiphenyl stable product: a time-resolved resonance Raman and density functional theory study

A time-resolved resonance Raman (TR(3)) and density functional theory (DFT) study of the reaction of the 4-biphenylnitrenium ion with 4-biphenyl azide in a mixed aqueous solution is reported. The reaction of the 4-biphenylnitrenium ion with its unphotolyzed precursor 4-biphenyl azide in a mixed aqueous solution generates a 4,4'-azobisbiphenyl stable product via an intermediate species. With the aid of DFT calculations for likely transient species, this intermediate was tentatively assigned to a 4,4'-azobisbiphenyl cation. The DFT calculations predict this reaction can take place via two pathways that compete with one another to produce the trans and cis 4,4'-azobisbiphenyl product. The observation of the 4,4'-azobisbiphenyl cation intermediate demonstrates that the reaction of the arylnitrenium ion with its aryl azide to produce a stable azo product occurs via a stepwise mechanism.     

Theoretical study of mechanism of forming a silapolycyclic compound between methylenesilylene and acetone

The mechanism of the cycloaddition reaction of forming a silapolycyclic compound between singlet methylenesilylene and acetone has been investigated with MP2/6‐31G* method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. The energies of the different conformations are calculated by CCSD(T)//MP2/6‐31G* method. From the potential energy profile, we predict that the cycloaddition reaction of forming a silapolycyclic compound between singlet methylenesilylene and acetone has two competitive dominant reaction pathways. First dominant reaction pathway consists of four steps: (I) the two reactants (R1, R2) first form an intermediate (INT1) through a barrier‐free exothermic reaction of 46.2 kJ/mol; (II) intermediate (INT1) then isomerizes to a planar four‐membered ring product (P3) via transition state (TS3) with an energy barrier of 47.1 kJ/mol; (III) planar four‐membered ring product (P3) further reacts with acetone (R2) to form an intermediate (INT4), which is also a barrier‐free exothermic reaction of 40.0 kJ/mol; (IV) intermediate (INT4) isomerizes to a silapolycyclic compound (P4) via transition state (TS4) with an energy barrier of 57.0 kJ/mol. Second dominant reaction pathway consists of three steps: (I) the two reactants (R1, R2) first form a four‐membered ring intermediate (INT2) through a barrier‐free exothermic reaction of 0.5 kJ/mol; (II) INT2 further reacts with acetone (R2) to form an intermediate (INT5), which is also a barrier‐free exothermic reaction of 45.4 kJ/mol; (III) intermediate (INT5) isomerizes to a silapolycyclic compound (P5) via transition state (TS5) with an energy barrier of 49.3 kJ/mol. P4 and P5 are isomeric compounds. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Copper(II)-mediated oxidative transformation of vic-dioxime to furoxan: evidence for a copper(II)-dinitrosoalkene intermediate

The mononuclear copper(II) complex [Cu(H(2)L(1))(2)(H(2)O)](ClO(4))(2) (1) (where H(2)L(1) = 1,10-phenanthroline-5,6-dioxime) reacts with copper(II) perchlorate in acetonitrile at ambient conditions in the presence of triethylamine to afford a copper(II) complex, [Cu(L(3))(2)(H(2)O)](ClO(4))(2) (2a), of 1,10-phenanthroline furoxan. A similar complex [Cu(L(3))(2)Cl](ClO(4)) (2) is isolated from the reaction of H(2)L(1) with copper(II) chloride, triethylamine, and sodium perchlorate in acetonitrile. The two-electron oxidation of the vic-dioxime to furoxan is confirmed from the X-ray single crystal structure of 2. An intermediate species, showing an absorption band at 608 nm, is observed at -20 °C during the conversion of 1 to 2a. A similar blue intermediate is formed during the reaction of [Cu(HDMG)(2)] (H(2)DMG = dimethylglyoxime) with ceric ammonium nitrate, but H(2)DMG treated with ceric ammonium nitrate does not form any intermediate. This suggests the involvement of a copper(II) complex in the intermediate step. The intermediate species is also observed during the two-electron oxidation of other vic-dioximes. On the basis of the spectroscopic evidence and the nature of the final products, the intermediate is proposed to be a mononuclear copper(II) complex ligated by a vic-dioxime and a dinitrosoalkene. The dinitrosoalkene is generated upon two-electron oxidation of the dioxime. The transient blue color of the dioxime-copper(II)-dinitrosoalkene complex may be attributed to the ligand-to-ligand charge transfer transition. The intermediate species slowly decays to the corresponding two-electron oxidized form of vic-dioxime, i.e. furoxan and [Cu(CH(3)CN)(4)](ClO(4)). The formation of two isomeric furoxans derived from the reaction of an asymmetric vic-dioxime, hexane-2,3-dioxime, and copper(II) perchlorate supports the involvement of a dinitrosoalkene species in the intermediate step. In addition, the oxidation of 2,9-dimethyl-1,10-phenanthroline-5,6-dioxime (H(2)L(2)) to the corresponding furoxan and subsequent formation of a copper(I) complex [Cu(L(4))(2)](ClO(4)) (3) (where L(4) = 2,9-dimethyl-1,10-phenanthroline furoxan) are discussed.     

ISOLATION AND IDENTIFICATION OF TRYPTOPHAN PHOTOPRODUCTS FROM AQUEOUS SOLUTIONS OF TRYPTOPHAN EXPOSED TO NEAR-UV LIGHT*

Abstract—One of the previously unidentified photoproducts isolated from the photolysate of aqueous tryptophan solutions was identified as 2-carboxy-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo(2,3b)-indole by direct comparison with the authentic reference compound synthesized using the established procedure. This pyrroloindole alcohol has been shown to be the reduction product of the 3a-hydroperoxy intermediate (structure 4 in Fig. 1) by Nakagawa et al . (1977). The isolation and identification of this derivative and the detection of the peroxy intermediate 3a-hydroperoxypyrrolidinoindole ( 4 ). from irradiated aqueous tryptophan solutions suggests that the direct photooxidation of l -tryptophan to fromylkynurenine may follow a pathway via a tricyclic intermediate instead of the energetically unfavorable dioxotane intermediate. This scheme is similar to the mechanistic model proposed by Nakagawa et al . (1977) for the rose bengal sensitized photooxidation of tryptophan.     

An ENDOR and HYSCORE investigation of a reaction intermediate in IspG (GcpE) catalysis

IspG is a 4Fe-4S protein that carries out an essential reduction step in isoprenoid biosynthesis. Using electron-nuclear double resonance (ENDOR) and hyperfine sublevel correlation (HYSCORE) spectroscopies on labeled samples, we have specifically assigned the hyperfine interactions in a reaction intermediate. These results help clarify the nature of the reaction intermediate, supporting a direct interaction between the unique fourth Fe in the cluster and C2 and O3 of the ligand.     

Three homeotropically aligned nematic liquid crystals: comparison of ultrafast to slow time-scale dynamics

The dynamics of two nematic liquid crystals, 4-(trans-4(')-n-octylcyclohexyl)isothiocyanatobenzene and 4-(4-pentyl-cyclohexyl)-benzonitrile, are investigated as a function of temperature both in the homeotropically aligned nematic phase and in the isotropic phase using optical heterodyne-detected optical Kerr effect experiments, which measures the time derivative of the polarizability-polarizability-correlation function (orientational relaxation). Data are presented over a time range of 500 fs-70 micros for the nematic phase and 500 fs to a few hundred nanoseconds for the isotropic phase. The nematic dynamics are compared with a previously studied liquid crystal in the nematic phase. All three liquid crystals have very similar dynamics in the nematic phase that are very different from the isotropic phase. On the slowest time scale (20 ns-70 micros), a temperature-independent power law, the final power law, t(-f) with f approximately 0.5, is observed. On short time scales (approximately 3 ps to approximately 1 ns), a temperature-dependent intermediate power law is observed with an exponent that displays a linear dependence on the nematic order parameter. Between the intermediate power law and the final power law, there is a crossover region that has an inflection point. For times that are short compared to the intermediate power law (approximately <2 ps), the data decay much faster, and can be described as a third power law, although this functional form is not definitive. The isotopic phase data have the same features as found in previous studies of nematogens in the isotropic phase, i.e., the temperature-independent intermediate power law and von Schweidler power law at short to intermediate times, and a highly temperature-dependent long time exponential decay that is well described by the Landau-de Gennes theory. The results show that liquid-crystal dynamics in the nematic phase exhibit universal behavior.     

Bacteriorhodopsin photocycle kinetics analyzed by the maximum entropy method

A maximum entropy method (MEM) was developed for the study of the bacteriorhodopsin photocycle kinetics. The method can be applied directly to experimental kinetic absorption data without any assumption for the number of the intermediate states taking part in the photocycle. Though this method does not give a specific kinetics, its result is very useful for selection between possible photocycle kinetics. Using simulated data, it is shown that MEM gives correct results for the number of the intermediate states and the amplitude distributions around the characteristic lifetimes. Analyzing experimental absorption data at five different wavelengths, MEM gives seven or eight characteristic lifetimes, which means that at least so many distinct intermediate states exist during the photocycle. Many possible photocycle kinetic models were studied and compared with the MEM result. The best agreement was found with a branching photocycle model of eight intermediate states (K, L, M(1), M(2), M(3), M(4), N, O). The branching occurs at the L intermediate state (M(1) and M(2) being in one branch and M(3) and M(4) in the other branch), but at high pH it occurs already at the K state.     

Single-molecule resolution of an organometallic intermediate in a surface-supported Ullmann coupling reaction

We have studied the organometallic intermediate of a surface-supported Ullmann coupling reaction from 4, 4″-dibromo-p-terphenyl to poly(para-phenylene) by scanning tunneling microscopy/spectroscopy and density functional theory calculations. Our study reveals at a single-molecular level that the intermediate consists of biradical terphenyl (ph)(3) units that are connected by single Cu atoms through C-Cu-C bridges. Upon further increasing the temperature, the neighboring biradical (ph)(3) units are coupled by C-C bonds forming poly(para-phenylene) oligomers while the Cu atoms are released.     

Theoretical studies of mechanism of cycloaddition reaction between germylidene and formaldehyde

Mechanism of the cycloadditional reaction between singlet germylidene (R1) and formaldehyde (R2) has been investigated with MP2/6‐31G* method, including geometry optimization, and vibrational analysis for the involved stationary points on the potential energy surface. The energies of the different conformations are calculated by CCSD(T)//MP2/6‐31G* method. From the potential energy profile, it can be predicted that the dominant reaction pathway of the cycloadditional reaction between singlet germylidene and formaldehyde is reaction (4) , which consists of three steps: the two reactants (R1, R2) first form an intermediate INT1b through a barrier‐free exothermic reaction of 28.1 kJ/mol; this intermediate reacts further with formaldehyde (R2) to give an intermediate INT4, which is also a barrier‐free exothermic reaction of 37.2 kJ/mol; subsequently, the intermediate INT4 isomerizes to a heteropolycyclic germanic compound P4 via a transition state TS4, for which the barrier is 18.6 kJ/mol. The dominant reaction has an excellent selectivity and differs considerably from its competitive reactions in thermodynamic property and reaction rate. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008     

A three-step synthesis of 4-(4-iodo-1H-pyrazol-1-yl)piperidine, a key intermediate in the synthesis of Crizotinib

4-(4-Iodo-1H-pyrazol-1-yl)piperidine is a key intermediate in the synthesis of Crizotinib. We report a robust three-step synthesis that has successfully delivered multi-kilogram quantities of the key intermediate. The process includes nucleophilic aromatic substitution of 4-chloropyridine with pyrazole, followed by hydrogenation of the pyridine moiety and subsequent iodination of the pyrazole which all required optimization to ensure successful scale-up.     

钛基氧化物电极的性能及电化学行为

本文研究了某些氧化物中间层对Ti/PbO_2、Ti/MnO_2、Ti/Co_3O_4和Ti/CuCo_2O_4电极性能及电化学行为的影响。结果表明,Ti/MnO_2或Ti/PbO_2电极在加入Co_3O_4、PdO_x、SnO_2或Sb_2O_3中间层后,界面电阻大大降低。在低于出现电阻极化电流密度时,极化曲线符合Tafel规律(无论对于O_2或Cl_2,低极化区的Tafel斜率为厶b_1=2.303RT/(1+β)F;高极化区为b_2=2,303RT/βF,其中β=0.5)这时主要为电化学极化。对有中间层Sb_2O_3+PdO_x的Ti/PbO_2电极和具有中间层SnO_2+PdO_x的Ti/Co_3O_4电极,其阳极析Cl_2的反应活性与工业用的Ti/RuO_2+TiO_2电极相近,而氧的过电位则高于Ti/RuO_2+TiO_2电极。     

A point mutation converts dihydroneopterin aldolase to a cofactor-independent oxygenase

Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7,8-dihydroneopterin (1) to 6-hydroxymethyl-7,8-dihydropterin (4) in the folate biosynthetic pathway. Substitution of a conserved tyrosine residue at the active site of DHNA by phenylalanine converts the enzyme to a cofactor-independent oxygenase, which generates mainly 7,8-dihydroxanthopterin (6) rather than 4. 6 is generated via the same enol intermediate as in the wild-type enzyme-catalyzed reaction, but this species undergoes an oxygenation reaction to form 6. The conserved tyrosine residue plays only a minor role in the formation of the enol reaction intermediate but a critical role in the protonation of the enol intermediate to form 4.