Products from the Oxidation of n-Butane from 298 to 735 K Using Either Cl Atom or Thermal Initiation: Formation of Acetone and Acetic Acid-Possible Roaming Reactions?

The oxidation of 2-butyl radicals (and to a lesser extent 1-butyl radicals) has been studied over the temperature range of 298-735 K. The reaction of Cl atoms (formed by 360 nm irradiation of Cl2) with n-butane generated the 2-butyl radicals in mixtures of n-C4H10, O2, and Cl2 at temperatures below 600 K. Above 600 K, 2-butyl radicals were produced by thermal combustion reactions in the absence of chlorine. The yields of the products were measured by gas chromatography using a flame ionization detector. Major products quantified include acetone, acetic acid, acetaldehyde, butanone, 2-butanol, butanal, 1- and 2- chlorobutane, 1-butene, trans-2-butene, and cis-2-butene. At 298 K, the major oxygenated products are those expected from bimolecular reactions of 2-butylperoxy radicals (butanone, 2-butanol, and acetaldehyde). As the temperature rises to 390 K, the butanone decreases while acetaldehyde increases because of the increased rate of 2-butoxy radical decomposition. Acetone and acetic acid first appear in significant yield near 400 K, and these species rise slowly at first and then sharply, peaking near 525 K at yields of ∼25 and ∼20 mol %, respectively. In the same temperature range (400-525 K), butanone, acetaldehyde, and 2-butanol decrease rapidly. This suggests that acetone and acetic acid may be formed by previously unknown reaction channels of the 2-butylperoxy radical, which are in competition with those that lead to butanone, acetaldehyde, and 2-butanol. Above 570 K, the yields of acetone and acetic acid fall rapidly as the yields of the butenes rise. Experiments varying the Cl atom density, which in turn controls the entire radical pool density, were performed in the temperature range of 410-440 K. Decreasing the Cl atom density increased the yields of acetone and acetic acid while the yields of butanone, acetaldehyde, and 2-butanol decreased. This is consistent with the formation of acetone and acetic acid by unimolecular decomposition channels of the 2-butylperoxy radical, which are in competition with the bimolecular channels that form butanone, acetaldehyde, and 2-butanol. Such unimolecular decomposition channels would be unlikely to proceed through conventional transition states because those states would be very constrained. Therefore, the possibility that these decomposition channels proceed via roaming should be considered. In addition, we investigated and were unable to fit our data trends by a simplified ketohydroperoxide mechanism.

Study of the Reaction Cl + Ethyl Formate at 700-950 Torr and 297 to 435 K: Product Distribution and the Kinetics of the Reaction C2H5OC(═O) → CO2 + C2H5.

The kinetics and mechanism of the reaction of atomic chlorine with ethyl formate [Cl + CH3CH2O(C═O)H, reaction 1] have been examined. These experiments were performed at pressures of 760-950 Torr and temperatures from 297 to 435 K. Reactants and products were quantified by gas chromatography-flame ionization detector (GC/FID) analysis. The initial mixture contained ethyl formate, Cl2, and N2. Cl atoms were generated by UV photolysis of this initial mixture at 360 nm, which dissociates Cl2. The rate constant of reaction 1 was measured at 297 K relative to that of the reaction Cl + C2H5Cl (reaction 2), yielding the rate constant ratio k1/k2 = 1.09 ± 0.05. The final products formed from reaction 1 are ethyl chloroformate, 1-chloroethyl formate, and 2-chloroethyl formate. These products result from the reactions with Cl2 of the three free radicals formed by H atom abstraction from ethylformate in reaction 1. Based on the molar yields of these three chlorinated products, the yields of the three radicals formed from reaction 1 at 297 K are (25 ± 3) mole percent of CH3CH2O(C═O); (67 ± 5) mole percent of CH3CHO(C═O)H; and (8 ± 2) mole percent of CH2CH2O(C═O)H. A second phase of this experiment measured the rate constant of the decarboxylation of the ethoxy carbonyl radical [CH3CH2O(C═O) → CO2 + C2H5, reaction 4] relative to the rate constant of its reaction with Cl2 [CH3CH2O(C═O) + Cl2 → CH3CH2O(C═O)Cl + Cl, reaction 3a]. Over the temperature range 297 to 404 K at 1 atm total pressure, this ratio can be expressed by k4/k3a = 10(23.56±0.22) e(-(12700±375)/RT) molecules cm(-3). Estimating the value of k3a (which has not been measured) based on similar reactions, the expression k4 = 5.8 × 10(12) e(-(12700)/RT) s(-1) is obtained. The estimated error of this rate constant is ± a factor of 2 over the experimental temperature range. This rate expression is compared with recent ab initio calculations of the decarboxylation of the analogous methoxy carbonyl radical.

Study of the Thermodynamics (Thermal and Cl Catalyzed) and Kinetics of the Cis and Trans Isomerizations of CF3CF═CHF, CF3CH═CHCF3, and CH3CH═CHCH3 in 100-950 Torr of N2 Diluent at 296-875 K: Effect of F and CF3 Substitution on the Isomerization Process Including the Fluorine "Cis Effect".

The equilibrium constants for the Z to E isomerizations of CF3CF═CHF (K1) and CF3CH═CHCF3 (K2) have been measured using GC/FID analysis over the temperature ranges 360­850 and 297­850 K, respectively. At lower temperature, K was determined using Cl atom catalysis. At higher temperature, K was measured without a catalyst. The temperature-dependent expressions are K1 (Z to E) = 1.45(±0.15)e(­[2845(±100)/RT]) and K2 (Z to E) = 1.9(±0.22)e(+[4330(±120)/RT]) (where the gas constant R ≡ 1.986 cal mol(­1) K(­1)). For isomerization 1, the Z (fluorine cis) isomer is 2.85 kcal mol(­1) lower in energy than the E (fluorine trans) isomer, providing another example of the fluorine "cis effect" in olefins. For isomerization 2, the E(trans) isomer is 4.3 kcal mol(­1) lower in energy than the corresponding Z(cis) isomer as is normal for olefins. The isomerization rate constant in a single direction was also measured for each fluorinated compound: k­1(E to Z) = 10(13.87±0.24)e(­59530(±887)/RT) s(­1); and k2(Z to E) = 10(13.89±0.23)e(­58845(±675)/RT) s(­1). To verify the experimental method, cis to trans (k3) and trans to cis (k­3) isomerization rate constants were also measured for cis- and trans-2-butene for comparison to several previous studies. The rate constants determined herein are k3 (cis to trans) = 10(13.95±0.23)e(­63245(±815)/RT) s(­1); and k­3 (trans to cis) = 10(14.32±0.28)e(­64993(±1132)/RT) s(­1). k3 agrees well with four previous measurements and represents the best available rate constant for 2-butene. All errors quoted here are 2σ. The typical total pressure for these experiments was 760 ± 100 Torr. Limited experiments performed at 100 Torr showed no pressure dependence for any of the compounds above 100 Torr. Thus, all isomerization rate constants represent high-pressure limits. The rates of the addition reactions of Cl to the double bonds of CF3CF═CHF (k4) and CF3CH═CHCF3 (k7) (used in Cl catalysis) were also measured in pure N2 and in pure O2. In O2, the rate constants expressions are k4 = 1.56 (±0.22) × 10(­11) e(+(643/RT)) cm3 molecule(­1) s(­1); and k7 = 1.05 × 10(­12) e(+(1874/RT)) cm(3) molecule(­1) s(­1). In N2, k4 and k7 decrease several orders of magnitude as the temperature increases because of the increasing reversibility of the Cl addition reaction, which produces the catalytic effect.

Consumer exposure modelling under REACH: Assessing the defaults.

Consumer exposure to chemicals from products and articles is rarely monitored. Since an assessment of consumer exposure has become particularly important under the European REACH Regulation, dedicated modelling approaches with exposure assessment tools are applied. The results of these tools are critically dependent on the default input values embedded in the tools. These inputs were therefore compiled for three lower tier tools (ECETOC TRA (version 3.0), EGRET and REACT)) and benchmarked against a higher tier tool (ConsExpo (version 4.1)). Mostly, conservative input values are used in the lower tier tools. Some cases were identified where the lower tier tools used less conservative values than ConsExpo. However, these deviations only rarely resulted in less conservative exposure estimates compared to ConsExpo, when tested in reference scenarios. This finding is mainly due to the conservatism of (a) the default value for the thickness of the product layer (with complete release of the substance) used for the prediction of dermal exposure and (b) the complete release assumed for volatile substances (i.e. substances with a vapour pressure ⩾10Pa) for inhalation exposure estimates. The examples demonstrate that care must be taken when changing critical defaults in order to retain conservative estimates of consumer exposure to chemicals.

Rate constant and mechanism of the reaction Cl + CFCl2H → CFCl2 + HCl over the temperature range 298-670 K in N2 or N2/O2 diluent.

The rate constant of the reaction Cl + CFCl2H (k1) has been measured relative to the established rate constant for the reaction Cl + CH4 (k2) at 760 Torr. The measurements were carried out in Pyrex reactors using a mixture of CFCl2H, CH4, and Cl2 in either N2 or N2/O2 diluent. Reactants and products were quantified by GC/FID analysis. Cl atoms were generated by irradiation of the mixture with 360 nm light to dissociate the Cl2 for temperatures up to ~550 K. At higher temperature, the Cl2 dissociated thermally, and no irradiation was used. Over the temperature range 298-670 K, k1 is consistently a factor of ~5 smaller than that of k2 with a nearly identical temperature dependence. The optimum non-Arrhenius rate constant is represented by the expression k1 = 1.14 × 10(-22) T(3.49) e(-241/T) cm(3) molecule(-1) s(-1) with an estimated uncertainty of ±15% including uncertainty in the reference reaction. CFCl3 formed from the reaction CFCl2 + Cl2 (k3) is the sole product in N2 diluent. In ~20% O2 at 298 K, the CFCl3 product is suppressed. The rate constant of reaction 3 was measured relative to that of reaction 4 [CFCl2 + O2 (k4)] giving the result k3/k4 = 0.0031 ± 0.0005 at 298 K. An earlier experiment by others observed C(O)FCl to be the major product of reaction channel 4 [formed via the sequence, CFCl2(O2) → CFCl2O → C(O)FCl + Cl]. Our current experiments verified that there is a Cl atom chain reaction in the presence of O2 as required by this mechanism.

Relative rate study of the kinetics, mechanism, and thermodynamics of the reaction of chlorine atoms with CF3CF═CH2 (HFO-1234yf) in 650-950 Torr of N2 or N2/O2 diluent at 296-462 K.

The rate constant of the reaction Cl + CF(3)CF═CH(2) (k(1)) has been measured relative to several reference species using the relative rate technique with either gas chromatographic analysis with flame-ionization detection (GC/FID) or Fourier transform infrared (FTIR) analysis. Cl atoms were generated by UV irradiation of Cl(2)/CF(3)CF═CH(2)/reference/N(2)/O(2) mixtures. At 300-400 K in the presence of >20 Torr O(2), k(1) = 1.2 × 10(-11) e((+1100/RT)) cm(3) molecule(-1) s(-1). In N(2) diluent, k(1) has a sharp negative temperature coefficient resulting from the relatively small exothermicity of the following reactions: (1a) Cl + CF(3)CF═CH(2) ↔ CF(3)CFClCH(2)(•); (1b) Cl + CF(3)CF═CH(2) ↔ CF(3)CF(•)CH(2)Cl (reaction 1), which were determined in these experiments to be ∼16.5 (±2.0) kcal mol(-1). This low exothermicity causes reaction 1 to become significantly reversible even at ambient temperature. The rate constant ratio for the reaction of the chloroalkyl radicals formed in reaction 1 with Cl(2) (k(2)) or O(2) (k(3)) was measured to be k(2)/k(3) = 0.4 e(-(3000/RT)) for 300-400 K. At 300 K, k(2)/k(3) = 0.0026. The reversibility of reaction 1 combined with the small value of k(2)/k(3) leads to a sensitive dependence of k(1) on the O(2) concentration. Products measured by GC/FID as a function of temperature are CF(3)CFClCH(2)Cl, CF(3)COF, and CH(2)Cl(2). The mechanism leading to these products is discussed. The rate constant for the reaction Cl + CF(3)CFClCH(2)Cl (k(11)) was measured as a function of temperature (300-462 K) at 760 Torr to be k(11) = 8.2 × 10(-12) e(-(4065/RT)) cm(3) molecule(-1) s(-1). Rate constants relative to CH(4) for the reactions of Cl with the reference compounds CH(3)Cl, CH(2)Cl(2), and CHCl(3) were measured at 470 K to resolve a literature discrepancy. (R = 1.986 cal K(-1) mol(-1)).

Aliskiren for the treatment of essential hypertension under real-life practice conditions: design and baseline data of the prospective 3A registry.

BACKGROUND: The renin-angiotensin system (RAS) is a key target for blood pressure control and for cardiovascular and renal protection. Aliskiren is the first-in-class direct oral inhibitor of renin that controls the rate-limiting step in the RAS cascade. So far little is known about the use and efficacy of aliskiren in the treatment of essential hypertension under clinical practice conditions. METHODS: The 3A registry was an open, prospective cohort study (observational registry) of 14,988 patients in 899 offices throughout Germany. Consecutive patients were eligible for inclusion if their physician had decided to modify their antihypertensive therapy. This included treatment with aliskiren or an angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB) or agents not blocking the RAS, alone or on top of an existing drug regimen. RESULTS: Mean age of patients was 65 years, their mean body mass index was 28.2 kg/m(2) 53.5% were men, 36% working, 90% in statutory health insurance and 26% in any disease management programme. Patients in the aliskiren and the RAS groups compared with the non-RAS group were older, more often men, had a longer history of hypertension, and had a higher prevalence of comorbidities (diabetes, chronic heart failure, ischaemic heart disease, renal disease). Mean systolic, but not diastolic blood pressure was substantially higher in the aliskiren group (158/91 mmHg vs. 154/89 mmHg in ACE-I/ARB vs. 152/89 mmHg in non-RAS). Mean number of antihypertensive drugs was higher in the aliskiren group compared with the other groups (3.0 drugs vs. 2.5 in ACE-I/ARB vs. 1.6 in non-RAS; p < 0.0001). CONCLUSIONS: In this large cohort of outpatients with hypertension, aliskiren was used mainly in patients with more severe stages of hypertension and those with concomitant diseases such as diabetes mellitus and impaired renal function. The 3A registry will provide important information about the use and efficacy of aliskiren in a real-life setting.

[Medication safety in the home care setting: error-prone process steps]. / Medikationssicherheit im Home-Care-Bereich: Identifikation von kritischen Prozessschritten.

So far, little is known about drug-related problems in the homecare setting. It is estimated that up to 30% of homecare patients experience a potential medication error, most frequently happening during preparation and administration of drugs. In order to identify error-prone process steps in a Swiss homecare organisation caring for 1854 patients per year, direct observation of the medication use process, including the analysis of 10% of all prescriptions, was executed. Three complimentary methods were combined for the assessment of qualitative aspects of the medication use process: the analysis of a critical incident reporting system, a survey among homecare nurses, and a failure, mode and effects analysis. The medication use process is complex, consisting of 20 individual steps. Patients are prescribed an average of 7.5 ± 3.5 drugs per day, including 1 to 9 doses not suitable for deblistering into weekly dispensing systems. Of 84 reported errors, 74% happened during drug preparation. Communication with physicians, patients interrupting drug preparation and not transmitted changes of the drug regimen were considered the most critical process steps.

Decompressive craniectomy guided by cerebral microdialysis and brain tissue oxygenation in a patient with meningitis.

Bacterial meningitis remains a life-threatening disease mainly due to intracranial hypertension. However, decompressive craniectomy (DC) and the use of cerebral microdialysis (MD) and brain tissue oxygen pressure measurement (pTiO(2) ) are poorly described in this disease. We report a case of a 56-year-old woman admitted for severe bacterial meningitis complicating mastoiditis. Despite maximal medical treatment, intracranial pressure increased above 30 mmHg, with a decline in pTiO(2) and MD results indicating cerebral ischaemia. A bilateral DC was performed. Neurological outcome was favourable, and on discharge, the patient was able to live independently. This is the first report of DC in meningitis guided by cerebral MD and pTiO(2) . Invasive multimodal neuromonitoring should be used in severe meningitis and DC could be considered in the case of refractory intracranial hypertension.

[Rare cause of heart failure in an elderly woman in Djibouti: left ventricular non compaction]. / Une cause rare d'insuffisance cardiaque chez une djiboutienne. Non compaction ventricule guache (NCVG).

The purpose of this report is to describe the first case of left ventricular non compaction diagnosed in Djibouti. The patient was a 74-year-old Djiboutian woman with symptomatic heart failure. Echocardiography is the key tool for assessment of left ventricular non compaction. This rare cardiomyopathy is probably underdiagnosed in Africa.

[Upper airway management during anesthesia for reconstructive surgery in patients with noma]. / Gestion des voies aériennes supérieures pour l'anesthésie du noma.

Noma causes tissue degeneration of the face resulting in impaired mouth opening with secondary malnutrition and metabolic disorders. Reconstructive plastic surgery for noma can be lifesaving but requires special airway and ventilation techniques because of limited mouth opening. In addition, the African context imposes logistic and budgetary constraints. The purpose of this article is to describe an upper airway management strategy that takes into account disease factors and available resources.

Current status and future challenges in implementing and upscaling vertical farming systems.

Vertical farming can produce food in a climate-resilient manner, potentially emitting zero pesticides and fertilizers, and with lower land and water use than conventional agriculture. Vertical farming systems (VFS) can meet daily consumer demands for nutritious fresh products, forming a part of resilient food systems-particularly in and around densely populated areas. VFS currently produce a limited range of crops including fruits, vegetables and herbs, but successful implementation of vertical farming as part of mainstream agriculture will require improvements in profitability, energy efficiency, public policy and consumer acceptance. Here we discuss VFS as multi-layer indoor crop cultivation systems, exploring state-of-the-art vertical farming and future challenges in the fields of plant growth, product quality, automation, robotics, system control and environmental sustainability and how research and development, socio-economic and policy-related institutions must work together to ensure successful upscaling of VFS to future food systems.

Products and mechanism of the reaction of chlorine atoms with 3-pentanone in 700-950 torr of N(2)/O(2) diluent at 297-515 K.

The products, kinetics, and mechanism of the reaction Cl + 3-pentanone have been measured by UV irradiation of Cl(2)/3-pentanone/N(2) (O(2)) mixtures using primarily GC analysis with selected cross checks by FTIR. In the absence of O(2), the products are 1- and 2-chloro-3-pentanone with yields of 21 and 78%, respectively. As the temperature is increased, the yield of 1-chloro-3-pentanone increases modestly relative to the 2-chloro-3-pentanone yield. On the basis of this increase, the activation energy for hydrogen abstraction at the 1 position is determined to be 500 (+/-500) cal mole(-1) relative to abstraction at the 2 position. In the presence of 500 ppm of O(2) with 900-1000 ppm of Cl(2) at 297 K, the yield of 2-chloro-3-pentanone decreases dramatically from 78 to 2.5%, while the 1-chloro-3-pentanone decreases only modestly from 21 to 17%. The observed oxygenated species are acetaldehyde (59%), 2,3-pentanedione (9%), and propionyl chloride (56%). Increasing the temperature to 420 K (O(2) = 500 ppm) suppresses these oxygenated products, and 2-chloro-3-pentanone again becomes the primary product, indicating that the O(2) addition reaction to the 2-pentanonyl radical has become reversible. At 500 K and 10 000 ppm O(2), a new product channel opens which forms a small yield ( approximately 4%) of ethylvinylketone. Computer modeling of the product yields has been performed to gain an understanding of the overall reaction mechanism in the presence and absence of O(2). The reaction of chlorine atoms with 3-pentanone proceeds with a rate constant of 8.1 (+/-0.8) x 10(-11) cm(3) molecule(-1) s(-1) independent of temperature over the range of 297-490 K (E(a) = 0 +/- 200 cal mole(-1)). Rate constant ratios of k(C(2)H(5)C(O)CHCH(3) + Cl(2))/k(C(2)H(5)C(O)CHCH(3) + O(2)) = 0.0185 +/- 0.0037 and k(C(2)H(5)C(O)CH(2)CH(2) + Cl(2))/k(C(2)H(5)CH(2)C(O)CH(2)CH(2) + O(2)) = 2.7 +/- 0.4 were determined at 297 K in 800-950 Torr of N(2)/O(2) diluent. In 800-950 Torr of N(2)/O(2) diluent, the major fate of the alkoxy radical CH(3)CH(O)C(O)C(2)H(5) is decomposition to give C(2)H(5)C(O) radicals and CH(3)CHO. These results show that the chemical mechanisms of the 3-pentanone reactions are very similar to those observed for butanone. In addition, the rate constants of the reactions of chlorine atoms with 1-chloro-3-pentanone [3 (+/-0.6) x 10(-11) over the range of 297-460 K], 2,3-pentanedione [1.4 (+/-0.3) x 10(-11) at 297 K], and ethylvinylketone [1.9 (+/-0.4) x 10(-10) over the range of 297-400 K, decreasing rapidly above 400 K] were measured at ambient pressure.

Kinetics and mechanism of the reaction of methacrolein with chlorine atoms in 1-950 Torr of N2 or N2/O2 diluent at 297 K.

The rate constant of the reaction of Cl atoms with methacrolein (k(1)) has been measured relative to that of Cl with propane (k(2)) or cyclohexane (k(6)) at ambient temperature and pressures varying from 1-950 Torr. The experiments were carried out by irradiation (350 nm) of Cl(2)/methacrolein/propane or cyclohexane mixtures in N(2) or N(2)/O(2) diluent at ambient temperature in a spherical (500 cm(3)) Pyrex reactor (GC/FID analyses) or a 140 L FTIR smog chamber. The measured relative rate constant ratios in the GC/FID experiments were k(1)/k(2) = 1.464 +/- 0.015(2sigma) in N(2) and k(1)/k(2) = 1.68 +/- 0.03(2sigma) in N(2)/O(2) diluent (O(2) > 20,000 ppm). No pressure dependence was observed over the range studied in N(2) (120-950 Torr) using the GC/FID. In the FTIR/smog chamber experiments values of k(1)/k(6) = 0.645 +/- 0.032, 0.626 +/- 0.037, 0.586 +/- 0.026, and 0.479 +/- 0.024 were measured in 700, 100, 10, and 1 Torr, respectively, of N(2) diluent. Using k(2) = (1.4 +/- 0.2) x 10(-10) and k(6) = (3.3 +/- 0.5) x 10(-10) high pressure limiting rate constants of k(1) = (2.05 +/- 0.3) x 10(-10) [GC/FID] and (2.13 +/- 0.34) x 10(-10) [FTIR] cm(3) molecule(-1) s(-1) were determined. In experiments using the GC/FID reactor with N(2) diluent the following products (molar yields) were observed: 2,3-dichloro-2-methylpropanal [(47.2 +/- 8)% excluding error in calibration]; methacryloyl chloride [(22.9 +/- 2)%]; and 2-chloromethylacrolein [(2.3 +/- 0.8)%]. Addition of 200 ppm O(2) (with Cl(2) = 5000 ppm) resulted in a sharp reduction of the 2,3-dichloro-2-methylpropanal yield (to approximately 2%) with an accompanying appearance of chloroacetone [yield = (55 +/- 7)% decreasing to (44 +/- 7)% in air diluent]. The methacryloyl chloride yield was 23% for [O(2)]/[Cl(2)] ratios from 0 to 0.2 but decreased to near zero as the O(2)/Cl(2) ratio was increased to approximately 400. The variation in methacryloyl chloride yield with the O(2)/Cl(2) ratio in the initial mixture allowed an approximate measurement of the rate constant for the reaction of the methacryloyl radical with O(2) relative to that with Cl(2) (k(O(2))/k(Cl(2)) = 0.066 +/- 0.02). In experiments using the FTIR reactor in 700 Torr of N(2) diluent, methacryloyl chloride [(26 +/- 3)%] and HCl [(27 +/- 3)%] were observed as products. In 700 Torr of air diluent, the observed products were: chloroacetone [(44 +/- 5)%], CO(2) [(27 +/- 3)%], HCl [(21 +/- 3)%], and HCHO [(14 +/- 2)%], and CH(3)C(O)CH(2)OH (3-4%). The observation of CH(3)C(O)CH(2)OH indicates the presence of OH radicals in the system. At atmospheric pressure and 297 K, the title reaction proceeds [(24.5 +/- 5)%] via abstraction of the aldehydic hydrogen atom, [(2.3 +/- 0.8)%] via abstraction from the -CH(3) group, and approximately [(47 +/- 8) %] via addition to the CH(2)=C < double bond with most of the addition occurring at the terminal carbon atom (uncertainties represent statistical 2sigma). The results are discussed with respect to the literature data.

A chemically synthesized Antennapedia homeo domain binds to a specific DNA sequence.

A peptide 60 residues in length that corresponds to the homeo domain of Antennapedia (Antp), a protein governing development in Drosophila, was synthesized by segment condensation with protected peptide segments prepared on an oxime resin. A footprinting assay showed that the homeo domain binds specifically to a TAA repeat DNA sequence in the Antp gene. Thus the Antp homeo domain has a sequence-specific DNA binding property. The circular dichroism spectra of the homeo domain peptide showed the presence of a significant amount of alpha-helical structure in aqueous solution and in 50 percent trifluoroethanol. The alpha helicity measured in water appears to depend on the peptide concentration, which suggests that the peptide aggregates. These results support the hypothesis that the homeo domain binds to DNA through a helix-turn-helix motif.

Chemical mutation of enzyme active sites.

New active sites can be introduced into naturally occurring enzymes by the chemical modification of specific amino acid residues with the use of appropriately designed coenzyme analogs. The resultant semisynthetic enzymes can have catalytic activities very different from those of the corresponding native enzymes. For example, papain has been converted into a highly effective oxidoreductase by covalent modification of the sulfhydryl group of the active site cysteine residue (Cys25) with flavins such as 8-bromoacetyl-10-methylisoalloxazine. Thus, it is now possible to enhance the catalytic versatility of existing enzymes through the process of "chemical mutation" of the active site.

Amphiphilic secondary structure: design of peptide hormones.

Peptide synthesis can be used for elucidating the roles of secondary structures in the specificity of hormones, antigens, and toxins. Intermediate sized peptides with these activities assume amphiphilic secondary structures in the presence of membranes. When models are designed to optimize the amphiphilicity of the secondary structure, stronger interactions can be observed with the synthetic peptides than with the naturally occurring analogs.

Modification of the active site of alkaline phosphatase by site-directed mutagenesis.

The catalytically essential amino acid in the active site of bacterial alkaline phosphatase (Ser-102) has been replaced with a cysteine by site-directed mutagenesis. The resulting thiol enzyme catalyzes the hydrolysis of a variety of phosphate monoesters. The rate-determining step of hydrolysis, however, is no longer the same for catalysis when the active protein nucleophile is changed from the hydroxyl of serine to the thiol of cysteine. Unlike the steady-state kinetics of native alkaline phosphatase, those of the mutant show sensitivity to the leaving group of the phosphate ester.

Peptide and protein synthesis by segment synthesis-condensation.

The chemical synthesis of biologically active peptides and polypeptides can be achieved by using a convergent strategy of condensing protected peptide segments to form the desired molecule. An oxime support increases the ease with which intermediate protected peptides can be synthesized and makes this approach useful for the synthesis of peptides in which secondary structural elements have been redesigned. The extension of these methods to large peptides and proteins, for which folding of secondary structures into functional tertiary structures is critical, is discussed. Models of apolipoproteins, the homeo domain from the developmental protein encoded by the Antennapedia gene of Drosophila, a part of the Cro repressor, and the enzyme ribonuclease T1 and a structural analog have been synthesized with this method.

Products and mechanism of the reaction of Cl with butanone in N2/O2 diluent at 297-526 K.

The products, kinetics, and mechanism of the reaction Cl + butanone have been measured by UV irradiation of Cl(2)/butanone/N(2) (O(2)) mixtures using either GC or FTIR analysis. In the absence of O(2), the products are 1-, 3-, and 4-chlorobutanone with yields of 3.1%, 76%, and 22.5%, respectively. As the temperature is increased, the yields of 1- and 4-chlorobutanone increase relative to the 3-chlorobutanone yield. On the basis of these increases, the activation energies for hydrogen abstraction at the 1 and 4 positions are determined to be 1800 (+/-300) and 470 (+300, -150) cal mol(-1) relative to abstraction at the 3 position. In the presence of 400 ppm of O(2) with 700-900 ppm of Cl(2) at 297 K, the yields of 1- and 3-chlorobutanone decrease dramatically from 3.1% to 0.25% and from 76% to 2%, respectively, while the 4-chlorobutanone decreases only slightly from 22.5% to 18.5%. The observed oxygenated species are acetaldehyde (52%), butanedione (11%), and propionyl chloride (2.5%). Increasing the temperature to 400 K (O(2) = 500 ppm) suppresses these oxygenated products and 1- and 3-chlorobutanone again become the primary products, indicating that the O(2) addition reaction to the 1- and 3-butanonyl radicals is becoming reversible. At 500 K and very high O(2) mole fraction (170,000 ppm), a new product channel opens which forms a substantial yield (approximately 20%) of methylvinylketone. Computer modeling of the product yields has been performed to gain an understanding of the overall reaction mechanism in the presence and absence of O(2). The reaction of chlorine atoms with butanone proceeds with a rate constant of 4.0 (+/-0.4) x 10(-11) cm(3) molecule(-1) s(-1) independent of temperature over the range 297-475 K (E(a) = 0 +/- 200 cal mol(-1)). Rate constant ratios of k(CH(2)C(O)C(2)H(5) + Cl(2))/k(CH(2)C(O)C(2)H(5) + O(2)) = 0.027 +/- 0.008, k(CH(3)C(O)CHCH(3) + Cl(2))/ k(CH(3)C(O)CHCH(3) + O(2)) = 0.0113 +/- 0.0011, and k(CH(3)C(O)CH(2)CH(2) + Cl(2))/k(CH(3)C(O)CH(2)CH(2) + O(2)) = 1.52 +/- 0.32 were determined at 297 K in 800-950 Torr of N(2) diluent. In 700-900 Torr of N(2)/O(2) diluent, the major fate of the alkoxy radicals CH(3)C(O)CH(O)CH(3) and OCH(2)C(O)C(2)H(5) is decomposition to give CH(3)C(O) radicals and CH(3)CHO and HCHO and C(O)C(2)H(5) radicals, respectively.