Effect of an audience on learning a novel motor skill.

The purpose of this study was to assess effects of an audience on learning a novel motor skill. Subjects (N=64) were randomly assigned to one of four experimental conditions and administered 15 30-sec. trials with 30 sec. intertrial periods on a pursuit rotor task on two different days. Comparison of Time-on Target performance between conditions indicated that the No Audience condition had significantly higher performance than the Audience condition in Session 1. Comparison of Absolute Retention and Final Retention scores among the four experimental conditions in Session 2 after 48 hr. yielded no significant differences attributable to the presence of an audience, thus supporting the hypothesis that an audience would have no effect on learning.

The iron(II)/reductant (DH2)-induced activation of dioxygen for the demethylation of N-methylanilines: reaction mimic for the cytochrome P-450/reductase system.

Several iron(II) complexes [FeIIL+; FeII(DPAH)2 (DPAH2 = 2,6-dicarboxyl pyridine), FeII(PA)2 (PAH = picolinic acid) and FeII(bpy)2(2+)(bpy = 2,2'-bipyridine)] in combination with a reductant [DH2; PhNHNHPh (mimic of dihydroflavin)] catalytically activate O2 (1 atm) for the demethylation of N-methylanilines [PhN(CH3)2, PhNH(CH3)]. This chemistry, which appears to involve a Fenton-like intermediate [LxFeIVOOH(DH) (1c)], mimics that of the cytochrome P-450 monooxygenase/reductase proteins.

Aromatic hydroxylation by Fenton reagents (reactive intermediate [Lx+FeIIOOH(BH+)], not free hydroxyl radical (HO.)).

Several iron complexes [FeII(bpy)2(2+), FeII(OPPh3)4(2+), and FeII(PA)2] in combination with hydrogen peroxide (HOOH) catalytically hydroxylate aromatic substrates (ArH). The base-induced nucleophilic addition of HOOH to the electrophilic iron center yields the reactive intermediate of Fenton reagents [FeIILx2+ + HOOH<-->Lx+FeIIOOH(BH+)(1)]. The latter includes a 'stabilized' hydroxyl radical that is able to replace an aromatic hydrogen (H) with a hydroxyl group (HO) via an initial addition reaction. With PhCH3 and PhCH2CH3 as substrates free HO. (from the radiolysis of H2O) reacts via aryl addition (97 and 85%, respectively) to give Ar-Ar as the predominant product, whereas 1 favors H-atom abstraction from the alkyl group (50 and 80%, respectively) and the only detectable products from aryl addition are the respective substituted phenols (o:p-ArOH). Other substituted benzenes (PhX) undergo addition by free HO at the ortho and para aryl carbons (o:p ratio, 2), followed by dimerization and elimination of two H2O molecules to yield substituted biphenyls. In contrast, 1 reacts with PhX to yield substituted phenol (ArOH; o:p ratio, 0.5-1.1). With phenol (PhOH) as the substrate, reaction with 1 yields mainly catechol (o-Ar(OH)2; o:p ratio, 20). In a solvent matrix of MeCN:H2O (3:1 mol:mol ratio) the reaction efficiencies with FeII(bpy)2(2+) and FeII(OPPh3)4(2+) for the hydroxylation of benzene to phenol are 36 and 42%, respectively (product per HOOH).

Prognostic significance of ST-segment depression during adenosine perfusion imaging.

To determine the significance of ST-segment depression during adenosine perfusion imaging for predicting future cardiac events, 188 patients with interpretable electrocardiograms were assessed 1 to 3 years (mean 21.5 +/- 6.6 months) after adenosine testing. At least 1 mm of ST-segment depression was observed in 32 (17%) patients, with > or = 2 mm of ST-segment depression in 10 (5.3%). Thirty-seven cardiac events occurred during the study period: 2 cardiac deaths, 5 nonfatal myocardial infarctions, 6 admissions for unstable angina, and 24 revascularizations. Univariate predictors of events were a history of congestive heart failure, previous non-Q-wave myocardial infarction, previous coronary angioplasty, use of antianginal medication, ST-segment depression during adenosine infusion (particularly > or = 2 mm), any reversible perfusion defect, transient left ventricular cavity dilation, and the severity of perfusion defects. Multivariate analysis identified > or = 2 mm ST-segment depression as the most significant predictor of cardiac events (relative risk [RR] = 6.5; p = 0.0001). Other independent predictors of events were left ventricular dilation (RR = 3.8; p = 0.002), previous coronary angioplasty (RR = 3.3; p = 0.001), a history of non-Q-wave myocardial infarction (RR = 2.3; p = 0.01), and the presence of any reversible defect (RR = 2.0; p = 0.05). We conclude that ST-segment depression occurs uncommonly during adenosine infusion, but the presence of > or = 2 mm of ST-segment depression is an independent predictor of future cardiac events and provides information in addition to that obtained from clinical variables and the results of adenosine perfusion imaging.

Iron(II)/reductant(DH2)-induced activation of dioxygen for the hydroxylation and ketonization of hydrocarbons; mimics for the cytochrome P-450 hydroxylase/reductase system.

Several metal complexes [(FeII(DPAH)2 (DPAH2 = 2,6-dicarboxyl pyridine), FeII(PA)2 (PAH = picolinic acid), FeII(bpy)2(2+), FeII(OPPh3)4(2+), (Cl8TPP)FeIIIX (X = Cl, OH, SCH2Ph) [Cl8TPP = tetrakis (2,6-dichlorophenyl)porphyrin], (TPP) FeIIICl (TPP = tetraphenylporphyrin), and CuI(tpy)2+ (typ = 2,2'-6,2"-terpyridine)] in combination with one of several reductants [DH2; PhNHNHPh (mimic of dihydroflavin), PhNHNH2, ascorbic acid (H2asc), and PhCH2SH (model ligand for cysteine residue)] catalytically activate O2 (1 atm) for the hydroxylation of saturated hydrocarbons (e.g. c-C6H12-->c-C6H11OH). This chemistry closely parallels that of cytochrome P-450 proteins, and both appear to involve a Fenton-like reactive intermediate), [LxFeOOH(DH)]. With cyclohexane as the substrate the dominant product is its ketone (as well as significant amounts of its hydroperoxide). 1,4-Cyclohexadiene (with two double-allylic carbon centers) undergoes dehydrogenation to give benzene, but also yields substantial amounts of phenol via ketonization of an allylic carbon. The 1:1 FeII(bpy)2(2+)/(PhNHNH2 or H2asc), FeII(PA)2/H2asc, and (Cl8TPP)FeIIICl/PhNHNH2 combinations initiate the autoxidation of 1,4-cyclohexadiene with turnover numbers (moles of product per mole of reductant) from 71 to 26, respectively (alpha-tocophenol reduces the turnover numbers by 20-80%). With respect to aerobic biology, the present results indicate that dysfunctional transition metals (degradation products of metalloproteins) in combination with biological reductants activate O2 for reaction with organic substrates. The level of activation is similar to that for Fenton reagents and cytochrome P-450 hydroxylases. Hence, dysfunctional transition metals, reductants, and O2 are a hazardous combination within a biological matrix.

Iron(II)/hydroperoxide (Fenton reagent)-induced activation of dioxygen for (A) the direct ketonization of methylenic carbon and (B) the dioxygenation of cis-stilbene.

Several iron complexes [FeII(PA)2 (PA = picolinate), FeII(bpy)2(2+), FeII(OPPh3)4(2+), FeII(MeCN)4(2+), (Cl8TPP)FeII(py)2 (Cl8TPP = tetrakis(2,6-dichlorophenyl)porphyrin), and FeIIICl3] in combination with R'OOH (R' = H, t-Bu) catalytically activate O2 to oxygenate hydrocarbons [e.g., c-C6H12-->c-C6H10(O) [9 O2 turnovers per FeII(PA)2 or FeII(bpy)2(2+), and 13 per (Cl8TPP)-FeII(py)2]; PhCH2CH3-->PhC(O)CH3 (up to 25 O2 turnovers per FeIILx); c-C6H10-->c-C6H8(O) (up to 9 O2 turnovers per FeIILx); PhCH(Me)2-->PhC(O)Me, Ph(Me)2COH, and Ph(Me)C = CH2 (up to 5 O2 turnovers per FeIILx); and cis-PhCH = CHPh-->2PhCH(O) (up to 2 O2 turnovers per FeLx)]. With large R'OOH/FeLx ratios spontaneous decomposition occurs to give free O2 that is incorporated into the substrates. The product profiles for the various FeIILx/R'OOH, O2/RH systems and their electrochemical characterization during steady-state turnover confirm that the first-formed intermediate is a one-to-one R'OOH/FeIILx adduct (e.g., [(PA)2-FeIIOOR' + pyH+] (1)) (Fenton reagent), which reacts with (a) excess FeII(PA)2 to give (PA)2FeIIIOR', (b) excess c-C6H12 to give (c-C6H11)py (kinetic isotope effect, [KIE] = kc-C6H12/kc-C6D12, 4.6 with t-BuOOH and 1.7 with HOOH), (c) excess R'OOH to give [(PA)2FeIV(OH)(OOR')] (3), then [(PA)2FeIV(O2)] (7) and O2, and (d) O2 to form an adduct, [(PA)2-FeIII(O2)(OOR') + pyH+] (5), that reacts with c-C6H12 to form c-C6H10(O), [K] = 8.2 (t-BuOOH) and 2.1 (HOOH). When PhCH2CH3 or c-C6H10 are the substrates (RH), 5 reacts to form [(PA)2FeIV(OH)(OOR)] (6), which in turn reacts with RH and O2 in a catalytic cycle to give PhC(O)Me or c-C6H8(O) [up to 7 O2 turnovers per iron with FeII(OPPh3)4(2+)]. Species 7 reacts with cis-PhCH = CHPh to give PhCH(O).

Selective dehydrogenation (oxidation) of 3,4-dimethoxybenzyl alcohol by a non-heme iron lignin-peroxidase reaction mimic.

In pyridine, bis(2,2'-bipyridine)iron(II) (Fe(bpy)2+(2)) activates hydrogen peroxide for the efficient and selective catalytic dehydrogenation (oxidation) of veratryl alcohol (model-substrate monomer for lignin; 3,4-(MeO)2PhCH2OH). Several other complexes (FeII(OPPh3)2+(4), FeII(O2bpy)2+(2), FeII(MeCN)2+(4), FeII(PA)2, FeIIICl3) are effective catalysts for the dehydrogenation of veratryl alcohol and benzyl alcohol, but their selectivity (relative reactivity with 3,4-(MeO)2PhCH2OH vs. PhCH2OH) is less than the 6.1 ratio that is observed for the optimized FeII(bpy)2+(2)/H2O2/pyridine (py) system. The reactivities have been determined for several other methoxybenzyl alcohols that are model substrates for lignin (e.g., 4-MeOPhCH2OH and (MeO)3PhCH2OH).

The interactions of superoxide ion(O2-.) with metallo-porphyrins [(C1(8)TPP)M, M = Fe,Mn,Co Zn]; models for biological systems and superoxide dismutases.

In dimethylformamide superoxide ion forms a 1:1 adduct with tetrakis (2,6-dichlorophenyl) porphinato-iron, (C1(8)TPP)FeOO-, as well as with its manganese analogue, (C1(8)TPP)MnOO-. On the basis of their electrochemical, spectroscopic, and magnetic properties these adducts have a metal-oxygen covalent bond (PorM-OO-), oxygen-centered redox chemistry, and reactivities that are similar to the hydroperoxide ion (HOO-). Addition of -OH to a solution of PorFe and O2 results in the formation of PorFe(OH)(OO-), which can be electrochemically oxidized to PorFeOH plus O2 (-0.2 V vs SCE). Addition of protons to the PorM-OO- adducts promotes their rapid decomposition to PorM, HOOH, and O2. This chemistry provides insight to the reactions of biological superoxide and superoxide dismutases.

Oxygenation by superoxide ion of halogenofluorocarbons (Freons and haloforms) in aprotic solvents.

The reactivity of chloro- and bromofluoromethanes (Freons and others) with superoxide ion (O2.-) has been evaluated by cyclic voltammetry in dimethylformamide (DMF). Substitution of fluorine atoms into chloromethanes results in a substantial decrease in their reactivity with O2.- (relative rates: CCl4 much greater than CF4, much greater than CCl4 much greater than FCCl3, CCl4 much greater than F2CCl2, CCl4 much greater than F3CCl, H3CCl much greater than F3CCl, and H2CCl2 much greater than F2CCl2). The bromo derivatives react much faster with O2.- than the corresponding chloro compounds (F3CBr much greater than F3CCl, F2CBr2 much greater than F2CCl2, and FCBr3 much greater than FCCl3). The rates of reaction for HCCl3, HCFCl2, and HCF2Cl are approximately the same, and the reactions appear to have a common path via dehydrochlorination. Reaction stoichiometries, apparent second-order rate constants, and product profiles have been determined for these fluoromethanes and related chlorofluoroethanes.

Reactivity of perhydroxyl (HOO.) with 1,4-cyclohexadiene (model for allylic groups in biomembranes).

The electron-transfer reduction of molecular oxygen yields superoxide ion (O2.-), which reacts with proton sources to form HO2.. In water the latter species disproportionates via reaction with O2.- (kbi, 10(8) M-1 s-1) and itself (kd, 10(6) M-1 s-1). The rate constants (kd) for the homolytic disproportionation process (HO2. + HO2.----H2O2 + O2), which have been determined from stopped-flow spectrophotometric decay data for HO2. at 25 degrees C, are (1.7 +/- 0.5) x 10(4) M-1 s-1 in dimethyl sulfoxide (Me2SO), (5.3 +/- 0.5) x 10(4) M-1 s-1 in dimethylformamide (DMF), and approximately 10(7) M-1 s-1 in acetonitrile. With limiting fluxes of protons to control the rate of formation of HO2. from O2.-, the rate of decay of HO2. is enhanced by reaction with the allylic hydrogens of excess 1,4-cyclohexadiene (RH). On the basis of such data the apparent second-order process (HO2. + RH----R. + H2O2) has a rate constant (kox) of (1.6 +/- 0.6) x 10(2) M-1 s-1. The reactivity of HO2. decreases as its solvation energy increases.

Ferric chloride-catalyzed activation of hydrogen peroxide for the demethylation of N,N-dimethylaniline, the epoxidation of olefins, and the oxidative cleavage of vicinal diols in acetonitrile: a reaction mimic for cytochrome P-450.

In dry acetonitrile, anhydrous Fe(III)Cl3 catalyzes the demethylation of N,N-dimethylaniline, the epoxidation of olefins, and the oxidative cleavage of 1-phenyl-1,2-ethanediol (and other 1,2-diols) by hydrogen peroxide. For each class of substrate the products closely parallel those that result from their enzymatic oxidation by cytochrome P-450. Because of the close congruence of products, the catalytic nature of the Fe(III)Cl3/H2O2 reaction mimic, and the similarity of the dipolar aprotic solvent (acetonitrile) to the proteinaceous lipid matrix of the biomembrane, the form of the reactive intermediate may be the same in each case. A mechanism is proposed in which an initial Lewis acid-base interaction of Fe(III)Cl3 with H2O2 generates a highly electrophilic Fe(III)-oxene species as the reactive intermediate. This is in contrast to the prevailing view that cytochrome P-450 acts as a redox catalyst to generate an Fe(V)-oxo species or an Fe(IV)-oxo cation radical as the reactive intermediate.

Tris(picolinato)manganese(II): a chemical model for the mechanism and function of mitochondrial superoxide dismutase.

The reaction of HO2. with the allylic groups of lipids initiates their peroxidation and auto-oxidation, and probably represents the most serious biological hazard of O2.- -derived species. The presence of tris(picolinato)manganese(II) [MnII(PA)2(PAH)(H2O)], a model complex for mitochondrial superoxide dismutase, (i) efficiently catalyzes the disproportionation of O2.-, (ii) precludes the formation HO2., and thereby (iii) prevents hydrogen abstraction from allylic and thiol groups. Such protection demonstrates that a primary function of superoxide dismutase is to block the formation of HO2., which is the obligatory intermediate for the nonenzymatic proton-induced disproportionation process. This requires that the primary step for the enzyme-O2.- reaction be kinetically favored and dominant relative to the protonation reaction (HA + O2.-).

Reactivity and activation of dioxygen-derived species in aprotic media (a model matrix for biomembranes).

In aprotic media the electrochemical reduction of dioxygen yields superoxide ion (O2-), which is an effective Brønsted base, nucleophile, one-electron reductant, and one-electron oxidant of reduced transition metal ions. With electrophilic substrates (organic halides and carbonyl carbons) O2- displaces a leaving group to form a peroxy radical (ROO.) in the primary process. Superoxide ion oxidizes the activated hydrogen atoms of ascorbic acid, catechols, hydrophenazines and hydroflavins. Combination of O2- with 1,2-diphenylhydrazine yields the anion radical of azobenzene, which reacts with O2 to give azobenzene and O2- (an example of O2--induced autoxidation). With phenylhydrazine, O2- produces phenyl radicals. The in situ formation of HO2. (O2- plus a proton source) results in H-atom abstraction from allylic and other groups with weak heteroatom--H bonds (binding energy (b.e.) less than 335 kJ). This is a competitive process with the facile second-order disproportionation of HO2. to H2O2 and O2 (kbi approximately equal to 10(4) mol-1 s-1 in Me2SO). Addition of [FeII(MeCN)4] (ClO4)2 to solutions of hydrogen peroxide in dry acetonitrile catalyses a rapid disproportionation of H2O2 via the initial formation of an adduct [FeII(H2O2)2+----Fe(O)(H2O)2+], which oxidizes a second H2O2 to oxygen. In the presence of organic substrates such as 1,4-cyclohexadiene, 1,2-diphenylhydrazine, catechols and thiols the FeII-H2O2/MeCN system yields dehydrogenated products; with alcohols, aldehydes, methylstyrene, thioethers, sulphoxides, and phosphines, the FeII(H2O2)2+ adduct promotes their monoxygenation. The product from the FeO2+-H2O2 reaction, [FeII(H2O2)22+], exhibits chemistry that is closely similar to that for singlet oxygen (1O2), which has been confirmed by the stoichiometric dioxygenation of diphenylisobenzofuran, 9,10-diphenylanthracene, rubrene and electron-rich unsaturated carbon-carbon bonds (Ph2C = CPh2, PhC = CPh and cis-PhCH = CHPh). In dry ligand-free acetonitrile (MeCN), anhydrous ferric chloride (FeIIICl3) activates hydrogen peroxide for the efficient epoxidation of alkenes. The FeIIICl3 further catalyses the dimerization of the resulting epoxides to dioxanes. These observations indicate that strong Lewis acids that are coordinatively unsaturated, [FeII(MeCN)4]2+ and [FeIIICl3], activate H2O2 to form an effective oxygenation and dehydrogenation agent.(ABSTRACT TRUNCATED AT 400 WORDS)

Photosynthetic water oxidation. A new chemical model.

A sequential four-step chemical model for the water oxidation process in photosystem II is presented, based on the observation that a peroxide-linked biquinone complex can be chemically formed as a result of hydroxide ion addition to quinone. In our model, the hydroxide ion intermediate is generated in photosystem II as a result of proton abstraction from water. In the model, the first two flashes of light raise the oxidation state of the bimanganese center, while the third and fourth flashes of light sequentially generate the peroxide-linked biquinone which is then directly oxidized by the bimanganese center to produce oxygen and regenerate quinone.