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Biomedical subjects

M Newcomb

Publications and source records attributed to M Newcomb.

At least 19 recordsLinked to original sources
PubMed2001

Product studies and laser flash photolysis on alkyl radicals containing two different beta-leaving groups are consonant with the formation of an olefin cation radical.

1-Bromo-2-methoxy-1-phenylpropan-2-yl (3) and 2-methoxy-1-phenyl-1-diphenylphosphatopropan-2-yl (4) were generated under continual photolysis from the respective PTOC precursors in a mixture of acetonitrile and methanol. The radicals undergo heterolytic fragmentation of the substituent in the beta-position to generate the olefin cation radical (5). Z-2-Methoxy-1-phenylpropene (15) is the major product formed in the presence of 1,4-cyclohexadiene, and is believed to result from hydrogen atom transfer to the oxygen of the olefin cation radical, followed by deprotonation. Laser flash photolysis experiments indicate that reaction between 5 and 1,4-cyclohexadiene occurs with a rate constant of approximately 6 x 10(5) M(-1) s(-1). 2,2-Dimethoxy-1-phenylpropane (18) is observed as a minor product. Laser flash photolysis experiments place an upper limit on methanol trapping of 5 at k <1 x 10(3) M(-1) s(-1) and do not provide any evidence for the formation of reactive intermediates other than 5. The use of two PTOC precursors containing different leaving groups to generate a common olefin cation radical enables one to utilize product analysis to probe for the intermediacy of other reactive intermediates. The ratio of 15:18 is dependent upon hydrogen atom donor concentration, but is independent of the PTOC precursor. These observations are consistent with the proposal that both products result from trapping of 5 that is formed via heterolysis of 3 and 4.

Alkenes↗
PubMed2000

Laser flash photolysis studies of alkoxyl radical kinetics using 4-nitrobenzenesulfenate esters as radical precursors

4-Nitrobenzenesulfenate esters were used as precursors for the generation of alkoxyl radicals under laser flash photolysis conditions. The esters were efficiently cleaved using the Nd:YAG third harmonic (355 nm) to produce alkoxyl radicals and the 4-nitrobenzenethiyl radical. Rate constants for beta-scission and 1, 5-hydrogen abstraction reactions of alkoxyl radicals were measured.

Journal Article↗
PubMed2000

Inter- and intramolecular pathways for the formation of tetrahydrofurans from beta-(Phosphatoxy)alkyl radicals. Evidence for a dissociative mechanism

beta-(Phosphatoxy)alkyl radicals generated by photolysis of Barton PTOC esters in the presence of allyl alcohol and tert-butyl mercaptan undergo nucleophilic substitution followed by 5-exo-trig radical ring closure leading to tetrahydrofurans in good yield and with high trans selectivity. beta-(Phosphatoxy)alkyl radicals obtained by intramolecular hydrogen 1,5-abstraction with an alkoxyl radical undergo nucleophilic displacement providing tetrahydrofurans. The ensemble of results, including the effects of leaving groups and substituents, strongly support a dissociative mechanism for these radical nucleophilic displacement reactions.

Journal Article↗
PubMed2000

Hypersensitive radical probes and the mechanisms of cytochrome P450-catalyzed hydroxylation reactions.

The title probes are precursors to kinetically calibrated, aryl-substituted cyclopropylcarbinyl radicals that rearrange with picosecond lifetimes. Applications in studies of cytochrome P450-catalyzed hydroxylation reactions are reviewed. Initially confusing results regarding lifetimes of radicals in the hydroxylation reactions were resolved when second-generation probes that distinguish between radicals and cations were employed. The results indicate that two electrophilic oxidizing species are involved in P450-catalyzed hydroxylations, an iron-oxo species that inserts oxygen and a hydroperoxo-iron species that inserts OH(+). The cationic rearrangement products are ascribed to reactions of the protonated alcohol products formed from the latter.

Biochemistry↗
PubMed2000

Adolescent substance abuse treatment outcome: the role of substance abuse problem severity, psychosocial, and treatment factors.

A structural equation model incorporating substance abuse problem severity, psychosocial risk and protection, and treatment variables examined adolescent drug abuse treatment outcome pathways across 6- and 12-month follow-up points. Findings on resiliency factors and an empirical method adapted from previous research were used to select and assign 10 psychosocial factors to either a multiple protective factor index or a risk factor index. Gender, substance abuse problem severity, treatment modality, treatment length, and aftercare participation were also examined as outcome predictors. The findings suggest that treatment intensity decisions may be better informed by pretreatment psychosocial risk level rather than by substance abuse problem severity. The present study also suggests that drug-abusing adolescents who receive sufficiently long treatment, participate in aftercare, and possess at least 1 individual or interpersonal protective factor during their recovery process have the best chance to maintain gains made during treatment.

Adolescent↗
PubMed1999

Heterolytic cleavage of a beta-phosphatoxyalkyl radical resulting in phosphate migration or radical cation formation as a function of solvent polarity.

[formula: see text] The 2-(diethylphosphatoxy)-2-(p-methoxyphenyl)-1,1-dimethylethyl radical (1) reacted to give the benzylic radical product from phosphate migration or a radical cation (or a mixture of the two) as a function of solvent. Smooth acceleration in rates of reactions of 1 in solvents of increasing polarity and consistent entropies of activation indicate that radical 1 reacts by common mechanism irrespective of the final products formed, specifically by initial heterolysis to a radical cation-phosphate anion pair.

Cations↗
PubMed1999

Oxidation of ultrafast radical clock substrate probes by the soluble methane monooxygenase from Methylococcus capsulatus (Bath).

Radical clock substrate probes were used to assess the viability of a discrete substrate radical species in the mechanism of hydrocarbon oxidation by the soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath). New substituted cyclopropane probes were used with very fast ring-opening rate constants and other desirable attributes, such as the ability to discriminate between radical and cationic intermediates. Oxidation of these substrates by a reconstituted sMMO system resulted in no rearranged products, allowing an upper limit of 150 fs to be placed on the lifetime of a putative radical species. This limit strongly suggests that there is no such substrate radical intermediate. The two enantiomers of trans-1-methyl-2-phenyl-cyclopropane were prepared, and the regioselectivity of their oxidation to the corresponding cyclopropylmethanol and cyclopropylphenol products was determined. The results are consistent with selective orientation of the two enantiomeric substrates in the hydrophobic cavity at the active site of sMMO, specific models for which were examined by molecular modeling.

Binding Sites↗
PubMed1998

Hypersensitive radical probe studies of chloroperoxidase-catalyzed hydroxylation reactions.

The oxidation of hypersensitive radical probes by chloroperoxidase from Caldariomyces fumago (CPO) was studied in an attempt to "time" a putative radical intermediate. Oxidation of (trans-2-phenylcyclopropyl)methane, previously studied by Zaks and Dodds [Zaks, A., and Dodds, D. R. (1995) J. Am. Chem. Soc. 115, 10419-10424] was reinvestigated. Unrearranged oxidation products were found as previously reported, and control experiments demonstrated that the cyclic alcohol from oxidation at the cyclopropylcarbinyl position, while subject to further oxidation, survives CPO oxidation as detectable species. However, in contrast to the report by Zaks and Dodds, the rearranged alcohol product expected from ring opening of a cyclopropylcarbinyl radical intermediate was shown to be unstable toward the enzyme oxidation reaction. Because of this instability, two new hypersensitive radical probes, (trans-2-phenylcyclopropyl)ethane and 2-(trans-2-phenylcyclopropyl)propane, and their potential cyclic and acyclic products from oxidation at the cyclopropylcarbinyl position were synthesized and tested. Oxidation of both of these probes at the cyclopropylcarbinyl position by CPO gave unrearranged alcohol products only, but control experiments again demonstrated that the rearranged alcohol products were unstable toward CPO oxidation conditions. From the combination of the probe and control studies, the lifetime of a putative radical intermediate must be less than 3 ps. Whereas the results are consistent with an insertion mechanism for production of alcohol product, they do not exclude a very short-lived intermediate.

Catalysis↗
PubMed1997

Fear of fat, disregulated-restrained eating, and body-esteem: prevalence and gender differences among eight- to ten-year-old children.

Examined whether: (a) societal directives to be thin are perceived among children, (b) discontent with body and attitudes and behaviors associated with eating disorders begin before adolescence, and (c) these differ by sex. These issues were assessed in 239 Grade 3 students. Scales of eating and weight attitudes and behaviors for this under-studied population were either created or modified from existing instruments. These 8- to 10-year-old children expressed weight, dieting, and physique concerns that reflect Western sociocultural values and preoccupation with body weight and dieting. Sex differences were examined and revealed several but not very reliable distinctions at this young age. These findings appear to be consistent with research on adolescents. The components that may lead to the development of an eating disorder or disregulated-restrained eating in a vulnerable adolescent may be both internalized and expressed at a very early age.

Attitude to Health↗
PubMed1994

Cytochrome P450-catalyzed hydroxylation of hydrocarbons: kinetic deuterium isotope effects for the hydroxylation of an ultrafast radical clock.

The ultrafast radical clock probe trans-1-methyl-2-phenylcyclopropane (1CH3) and its mono-, di-, and trideuteriomethyl analogues were oxidized by phenobarbital-induced rat liver microsomal enzymes. This cytochrome P450-catalyzed hydroxylation of 1CH3 gave three products: the alcohol trans-(2-phenylcyclopropyl)methanol (2), the rearranged alcohol 1-phenylbut-3-en-1-ol (3), and the phenol trans-2-(p-hydroxyphenyl)-1-methylcyclopropane (4). The identification of both the unrearranged and rearranged products of oxidation, 2 and 3, is consistent with the formation of a radical intermediate via a hydrogen atom abstraction from the methyl group by the catalytically active iron-oxo center. Hydroxylation of three deuteriomethyl forms of 1CH3 produced the analogous deuterated products, although in different amounts of each. Perdeuteration of the methyl group (1CD3) disfavored oxidation at the methyl group and caused an increase in the oxidation of the phenyl ring (metabolic switching). By comparing the amounts of alcohols and phenol formed from the individual, noncompetitive oxidation of 1CH3 and 1CD3 the overall (i.e., combined primary and secondary) deuterium kinetic isotope effect (DKIE) was found to be 12.5. Intramolecular DKIEs for 1CHD2 and 1CH2D were 2.9 and 13.2, respectively. From these results, the primary and secondary DKIEs were calculated to be 7.87 and 1.26, respectively, values that indicate that there is extensive C--H bond stretching in the transition state for the rate-controlling step in P450-catalyzed hydroxylation of 1CH3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Internal and external mediators of women's sexual abuse in childhood.

A community sample of 111 women's retrospective reports of childhood sexual abuse was examined in an effort to understand the circumstances and coping strategies that mediated the immediate and lasting effects of those stressful experiences. Aspects of single or multiple abuse incidents were captured in 11 variables, each reflecting 1 of 3 domains: circumstances of abuse, mediators, and outcomes (the negative effects of abuse). Observed variable simultaneous path analysis models revealed several direct and mediated influences on the outcomes. Long-term negative outcomes of abuse were directly affected by a close relationship to the perpetrator and severity of abuse from the circumstance of abuse domain, and immediate negative responses, self-blame, and nondisclosure regarding the incident from the mediational domain. The importance of examining factors that mediate the negative effects of child sexual abuse is discussed.

Adaptation, Psychological↗
PubMed1987

Hepatic intra-arterial adriamycin in metastatic leiomyosarcoma: exploiting the steep dose-response curve.

We report a case of extensive leiomyosarcoma of the liver that failed on systemic Adriamycin. Hepatic intra-arterial chemotherapy with Adriamycin has resulted in a lasting clinical remission. This report illustrates the importance of the dose-response curve of drug to tumor in regional chemotherapy as with Adriamycin used in sarcoma, and the need to further explore such therapy in moderately chemosensitive tumors that are surgically unresectable for anatomic reasons.

Adult↗
PubMed1980

Cyclic AMP-dependent protein kinases in the rat myocardial cytosol.

The optimal assay conditions for rat myocardial cytosol protein kinases have been determined. The assay medium contained in 0.25 ml: 40 mM Tris/HCl pH 7.4, 5 mM MgCl2, 600 micrograms histone f1, 10--30 micrograms enzyme protein, 32 microM [gamma-32P]-ATP, with or without additions of 1 microM cAMP. The incubation time at 37 degrees C was 5 minutes. The protein kinase activity in the absence of cAMP decreased with development, while the activity in the presence of cAMP remained unchanged. The protein kinase activity of the left ventricle was higher than that in the right ventricle.

Aging↗