Anharmonic Molecular Mechanics: Ab Initio Based Morse Parametrizations for the Popular MM3 Force Field.

Methodologies for creating reactive potential energy surfaces from molecular mechanics force-fields are becoming increasingly popular. To date, molecular mechanics force-fields in biochemistry and small molecule organic chemistry tend to use harmonic expressions to treat bonding stretches, which is a poor approximation in reactive and nonequilibirum molecular dynamics simulations since bonds are often displaced significantly from their equilibrium positions. For such applications there is need for a better treatment of anharmonicity. In this contribution, Morse bonding potentials have been extensively parametrized for the atom types in the MM3 force field of Allinger and co-workers using high level CCSD(T)(F12*) energies. To our knowledge this is among the first instances of a comprehensive parametrization of Morse potentials in a popular organic chemistry force field. In the context of molecular dynamics simulations, these data will: (1) facilitate the fitting of reactive potential energy surfaces using empirical valence bond approaches and (2) enable more accurate treatments of energy transfer.

Comment on "Methanol dimer formation drastically enhances hydrogen abstraction from methanol by OH at low temperature" by W. Siebrand, Z. Smedarchina, E. Martínez-Núñez and A. Fernández-Ramos, Phys. Chem. Chem. Phys., 2016, 18, 22712.

The article "Methanol dimer formation drastically enhances hydrogen abstraction from methanol by OH at low temperature" proposes a dimer mediated mechanism in order to explain the large low temperature rate coefficients for the OH + methanol reaction measured by several groups. It is demonstrated here theoretically that under the conditions of these low temperature experiments, there are insufficient dimers formed for the proposed new mechanism to apply. Experimental evidence is also presented to show that dimerization of the methanol reagent does not influence the rate coefficients reported under the conditions of methanol concentration used for the kinetics studies. It is also emphasised that the low temperature experiments have been performed using both the Laval nozzle expansion and flow-tube methods, with good agreement found for the rate coefficients measured using these two distinct techniques.

Reanalysis of Rate Data for the Reaction CH3 + CH3 → C2H6 Using Revised Cross Sections and a Linearized Second-Order Master Equation.

Rate coefficients for the CH3 + CH3 reaction, over the temperature range 300-900 K, have been corrected for errors in the absorption coefficients used in the original publication ( Slagle et al., J. Phys. Chem. 1988 , 92 , 2455 - 2462 ). These corrections necessitated the development of a detailed model of the B̃(2)A1' (3s)-X̃(2)A2″ transition in CH3 and its validation against both low temperature and high temperature experimental absorption cross sections. A master equation (ME) model was developed, using a local linearization of the second-order decay, which allows the use of standard matrix diagonalization methods for the determination of the rate coefficients for CH3 + CH3. The ME model utilized inverse Laplace transformation to link the microcanonical rate constants for dissociation of C2H6 to the limiting high pressure rate coefficient for association, k∞(T); it was used to fit the experimental rate coefficients using the Levenberg-Marquardt algorithm to minimize χ(2) calculated from the differences between experimental and calculated rate coefficients. Parameters for both k∞(T) and for energy transfer ⟨ΔE⟩down(T) were varied and optimized in the fitting procedure. A wide range of experimental data were fitted, covering the temperature range 300-2000 K. A high pressure limit of k∞(T) = 5.76 × 10(-11)(T/298 K)(-0.34) cm(3) molecule(-1) s(-1) was obtained, which agrees well with the best available theoretical expression.

Global Uncertainty Propagation and Sensitivity Analysis in the CH3OCH2 + O2 System: Combining Experiment and Theory To Constrain Key Rate Coefficients in DME Combustion.

Statistical rate theory calculations, in particular formulations of the chemical master equation, are widely used to calculate rate coefficients of interest in combustion environments as a function of temperature and pressure. However, despite the increasing accuracy of electronic structure calculations, small uncertainties in the input parameters for these master equation models can lead to relatively large uncertainties in the calculated rate coefficients. Master equation input parameters may be constrained further by using experimental data and the relationship between experiment and theory warrants further investigation. In this work, the CH3OCH2 + O2 system, of relevance to the combustion of dimethyl ether (DME), is used as an example and the input parameters for master equation calculations on this system are refined through fitting to experimental data. Complementing these fitting calculations, global sensitivity analysis is used to explore which input parameters are constrained by which experimental conditions, and which parameters need to be further constrained to accurately predict key elementary rate coefficients. Finally, uncertainties in the calculated rate coefficients are obtained using both correlated and uncorrelated distributions of input parameters.

Analysis of the kinetics and yields of OH radical production from the CH3OCH2 + O2 reaction in the temperature range 195-650 K: an experimental and computational study.

The methoxymethyl radical, CH3OCH2, is an important intermediate in the low temperature combustion of dimethyl ether. The kinetics and yields of OH from the reaction of the methoxymethyl radical with O2 have been measured over the temperature and pressure ranges of 195-650 K and 5-500 Torr by detecting the hydroxyl radical using laser-induced fluorescence following the excimer laser photolysis (248 nm) of CH3OCH2Br. The reaction proceeds via the formation of an energized CH3OCH2O2 adduct, which either dissociates to OH + 2 H2CO or is collisionally stabilized by the buffer gas. At temperatures above 550 K, a secondary source of OH was observed consistent with thermal decomposition of stabilized CH3OCH2O2 radicals. In order to quantify OH production from the CH3OCH2 + O2 reaction, extensive relative and absolute OH yield measurements were performed over the same (T, P) conditions as the kinetic experiments. The reaction was studied at sufficiently low radical concentrations (∼10(11) cm(-3)) that secondary (radical + radical) reactions were unimportant and the rate coefficients could be extracted from simple bi- or triexponential analysis. Ab initio (CBS-GB3)/master equation calculations (using the program MESMER) of the CH3OCH2 + O2 system were also performed to better understand this combustion-related reaction as well as be able to extrapolate experimental results to higher temperatures and pressures. To obtain agreement with experimental results (both kinetics and yield data), energies of the key transition states were substantially reduced (by 20-40 kJ mol(-1)) from their ab initio values and the effect of hindered rotations in the CH3OCH2 and CH3OCH2OO intermediates were taken into account. The optimized master equation model was used to generate a set of pressure and temperature dependent rate coefficients for the component nine phenomenological reactions that describe the CH3OCH2 + O2 system, including four well-skipping reactions. The rate coefficients were fitted to Chebyshev polynomials over the temperature and density ranges 200 to 1000 K and 1 × 10(17) to 1 × 10(23) molecules cm(-3) respectively for both N2 and He bath gases. Comparisons with an existing autoignition mechanism show that the well-skipping reactions are important at a pressure of 1 bar but are not significant at 10 bar. The main differences derive from the calculated rate coefficient for the CH3OCH2OO → CH2OCH2OOH reaction, which leads to a faster rate of formation of O2CH2OCH2OOH.

A combined experimental and theoretical study of reactions between the hydroxyl radical and oxygenated hydrocarbons relevant to astrochemical environments.

The kinetics of the reactions of the hydroxyl radical (OH) with acetone and dimethyl ether (DME) have been studied between 63-148 K and at a range of pressures using laser-flash photolysis coupled with laser induced fluorescence detection of OH in a pulsed Laval nozzle apparatus. For acetone, a large negative temperature dependence was observed, with the rate coefficient increasing from k1 = (1.6 ± 0.8) × 10(-12) cm(3) molecule(-1) s(-1) at 148 K to (1.0 ± 0.1) × 10(-10) cm(3) molecule(-1) s(-1) at 79 K, and also increasing with pressure. For DME, a similar behaviour was found, with the rate coefficient increasing from k2 = (3.1 ± 0.5) × 10(-12) cm(3) molecule(-1) s(-1) at 138 K to (1.7 ± 0.1) × 10(-11) cm(3) molecule(-1) s(-1) at 63 K, and also increasing with pressure. The temperature and pressure dependence of the experimental rate coefficients are rationalised for both reactions by the formation and subsequent stabilisation of a hydrogen bonded complex, with a non-zero rate coefficient extrapolated to zero pressure supportive of quantum mechanical tunnelling on the timescale of the experiments leading to products. In the case of DME, experiments performed in the presence of O2 provide additional evidence that the yield of the CH3OCH2 abstraction product, which can recycle OH in the presence of O2, is ≥50%. The experimental data are modelled using the MESMER (Master Equation Solver for Multi Energy Well Reactions) code which includes a treatment of quantum mechanical tunnelling, and uses energies and structures of transition states and complexes calculated by ab initio methods. Good agreement is seen between experiment and theory, with MESMER being able to reproduce for both reactions the temperature behaviour between ~70-800 K and the pressure dependence observed at ~80 K. At the limit of zero pressure, the model predicts a rate coefficient of ~10(-11) cm(3) molecule(-1) s(-1) for the reaction of OH with acetone at 20 K, providing evidence that the reaction can proceed quickly in those regions of space where both species have been observed. The results and modelling build considerably on our previous experimental study performed under a much more limited range of conditions (Shannon et al., Phys. Chem. Chem. Phys., 2010, 12, 13511-13514).

Experimental and theoretical study of the kinetics and mechanism of the reaction of OH radicals with dimethyl ether.

The reaction of OH with dimethyl ether (CH3OCH3) has been studied from 195 to 850 K using laser flash photolysis coupled to laser induced fluorescence detection of OH radicals. The rate coefficient from this work can be parametrized by the modified Arrhenius expression k = (1.23 ± 0.46) × 10(-12) (T/298)(2.05±0.23) exp((257 ± 107)/T) cm(3) molecule(-1) s(-1). Including other recent literature data (923-1423 K) gives a modified Arrhenius expression of k1 = (1.54 ± 0.48) × 10(-12) (T/298 K)(1.89±0.16) exp((184 ± 112)/T) cm(3) molecule(-1) s(-1) over the range 195-1423 K. Various isotopomeric combinations of the reaction have also been investigated with deuteration of dimethyl ether leading to a normal isotope effect. Deuteration of the hydroxyl group leads to a small inverse isotope effect. To gain insight into the reaction mechanisms and to support the experimental work, theoretical studies have also been undertaken calculating the energies and structures of the transition states and complexes using high level ab initio methods. The calculations also identify pre- and post-reaction complexes. The calculations show that the pre-reaction complex has a binding energy of ~22 kJ mol(-1). Stabilization into the complex could influence the kinetics of the reaction, especially at low temperatures (<300 K), but there is no direct evidence of this occurring under the experimental conditions of this study. The experimental data have been modeled using the recently developed MESMER (master equation solver for multi energy well reactions) code; the calculated rate coefficients lie within 16% of the experimental values over the temperature range 200-1400 K with a model based on a single transition state. This model also qualitatively reproduces the observed isotope effects, agreeing closely above ~600 K but overestimating them at low temperatures. The low temperature differences may derive from an inadequate treatment of tunnelling and/or from an enhanced role of an outer transition state leading to the pre-reaction complex.

GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I).

The sequences of 42 subunits of NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria have been described previously. Seven are encoded by mitochondrial DNA, whereas the remaining 35 are nuclear gene products imported into the organelle from the cytoplasm. An additional protein, which does not correspond to any previously known subunit of the complex I assembly, has now been detected. Denaturing gels of subcomplex Ilambda, the hydrophilic arm of complex I, clearly show a hitherto unidentified band, which was digested with trypsin and subjected to mass-spectrometric analysis to provide several peptide sequences, used in cDNA cloning and sequencing. Measurement of the intact protein mass indicated that the N terminus is acetylated. The new complex I subunit (B16.6) is the bovine homolog of GRIM-19, the product of a cell death regulatory gene induced by interferon-beta and retinoic acid, thus providing a new link between the mitochondrion and its electron-transport chain and apoptotic cell death.

Hyalinizing spindle cell tumor with giant rosettes: a distinctive tumor closely resembling low-grade fibromyxoid sarcoma.

We report the findings of 19 cases of a previously undescribed spindle cell tumor of soft tissues that resembles a low-grade fibromyxoid sarcoma but contains distinctive rosettelike structures. The tumors occurred principally as a painless, slowly growing, deeply situated mass of the proximal extremities in young to middle-aged adults (age range 14-65 years; mean 38). Although grossly circumscribed, the tumors had infiltrative borders microscopically and were composed of bland spindled cells situated in a hyalinized to myxoid stroma. The most characteristic feature of the tumor was scattered large rosettelike structures that often merged with serpinginous areas of dense hyalinization. The rosettes consisted of a central collagen core surrounded by a rim of rounded cells morphologically and immunophenotypically different from the cells of the spindled stroma. These cells expressed a number of antigens, including S-100 protein, neuron-specific enolase, and leu 22, in contrast to the stroma, which usually lacked these antigens. Of the 12 patients with available follow-up information, one patient treated with simple excision clinically developed local recurrence of the tumor 20 months after initial biopsy. No other recurrences were reported during the limited follow-up period, and no patient developed metastatic disease. However, the favorable prognosis of the patients in our series to date may relate to the limited follow-up period (approximately 3 years), as well as initial treatment by wide excision in nearly half of the patients. We regard the hyalinizing spindle cell tumor with giant rosettes as a distinctive type of low-grade fibroblastic tumor that with time may prove to behave similar to a low-grade fibromyxoid sarcoma and, hence, to represent an unusual variant thereof.

Effect of calcium alginate dressings on partial-thickness wounds in swine.

The epithelization of partial-thickness wounds (PTW) has been shown to be enhanced with the use of moisture-retentive dressings (MRD), and not with nonmoisture-retentive dressings (NMRD) like gauze. This study was designed to explore this effect using two different alginate products with and without MRDs. We evaluated these alginate dressings under a polyurethane film dressing (FMRD) and under an NMRD gauze. They were compared to hydrocolloid moisture-retentive dressings (HMRD). Twelve PTW measuring 22 x 22 x 0.5 mm were made on the dorsum of six swine with a Castroviejo dermatome. Return of the epithelial barrier function was measured with an EP1 ServoMed evaporimeter. On postoperative day 4, the first alginate product under the NMRD and under the FMRD had a significantly slower healing rate than the HMRDs. By postoperative day 7, the second alginate product under the NMRD had a poorer rate of epidermal wound healing than the HMRD. Our results indicate that these alginate products have a satisfactory partial-thickness wound healing capability when used under MRDs. When used under MRDs, the return of the epithelial barrier function is delayed, indicating that these dressings should not be used on dry wounds or under gauze dressings.

Symptomatic bacterial urinary tract infections in men: limitations of quantitative urine cultures.

Occasionally, physicians have discarded the diagnosis of acute symptomatic bacterial urinary tract infection when the urine coutn failed to approach or exceed 100,000 organisms per ml. Previous studies done in women have established the fact that sole reliance cannot be placed on this value to exclude the diagnosis of symptomatic bacterial urinary tract infection. A retrospective analysis of the charts of male patients, with an unequivocal diagnosis of symptomatic bacterial urinary tract infection, demonstrates the limitations of the urine colony count as a diagnostic test in men.