Investigation of the Hydroxylation Mechanism of Noncoupled Copper Oxygenases by Ab Initio Molecular Dynamics Simulations

In Nature, the family of copper monooxygenases comprised of peptidylglycine α‐hydroxylating monooxygenase (PHM), dopamine β‐monooxygenase (DβM), and tyramine β‐monooxygenase (TβM) is known to perform dioxygen‐dependent hydroxylation of aliphatic C? H bonds by using two uncoupled metal sites. In spite of many investigations, including biochemical, chemical, and computational, details of the C? H bond oxygenation mechanism remain elusive. Herein we report an investigation of the mechanism of hydroxylation by PHM by using hybrid quantum/classical potentials (i.e., QM/MM). Although previous investigations using hybrid QM/MM techniques were restricted to geometry optimizations, we have carried out ab initio molecular dynamics simulations in order to include the intrinsic flexibility of the active sites in the modeling protocol. The major finding of this study is an extremely fast rebound step after the initial hydrogen‐abstraction step promoted by the cupric–superoxide adduct. The hydrogen‐abstraction/rebound sequence leads to the formation of an alkyl hydroperoxide intermediate. Long‐range electron transfer from the remote copper site subsequently triggers its reduction to the hydroxylated substrate. We finally show two reactivity consequences inherent in the new mechanistic proposal, the investigation of which would provide a means to check its validity by experimental means.     

Mapping C−H⋅⋅⋅M Interactions in Confined Spaces: (α-ICyDMe)Au,Ag, Cu Complexes Reveal “Contra-electrostatic H Bonds” Masquerading as Anagostic Interactions**

What happens when a C−H bond is forced to interact with unpaired pairs of electrons at a positively charged metal? Such interactions can be considered as “contra-electrostatic” H-bonds, which combine the familiar orbital interaction pattern characteristic for the covalent contribution to the conventional H-bonding with an unusual contra-electrostatic component. While electrostatics is strongly stabilizing component in the conventional C−H⋅⋅⋅X bonds where X is an electronegative main group element, it is destabilizing in the C−H⋅⋅⋅M contacts when M is Au(I), Ag(I), or Cu(I) of NHC−M−Cl systems. Such remarkable C−H⋅⋅⋅M interaction became experimentally accessible within (α-ICyD^Me)MCl, NHC-Metal complexes embedded into cyclodextrins. Computational analysis of the model systems suggests that the overall interaction energies are relatively insensitive to moderate variations in the directionality of interaction between a C−H bond and the metal center, indicating stereoelectronic promiscuity of fully filled set of d-orbitals. A combination of experimental and computational data demonstrates that metal encapsulation inside the cyclodextrin cavity forces the C−H bond to point toward the metal, and reveals a still attractive “contra-electrostatic” H-bonding interaction.     

Abraham Model Correlations for Triethylene Glycol Solvent Derived from Infinite Dilution Activity Coefficient,Partition Coefficient and Solubility Data Measured at 298.15 K

A gas chromatographic headspace analysis method was used to experimentally determine gas-to-liquid partition coefficients and infinite dilution activity coefficients for 29 liquid organic solutes dissolved in triethylene glycol at 298.15 K. Solubilities were also determined at 298.15 K for 23 crystalline nonelectrolyte organic compounds in triethylene glycol based on spectroscopic absorbance measurements. The experimental results of the headspace chromatographic and spectroscopic solubility measurements were converted to gas-to-triethylene glycol and water-to-triethylene glycol partition coefficients, and molar solubility ratios using standard thermodynamic relationships. Expressions were derived for solute transfer into triethylene glycol by combining our measured experimental values with published literature data. Mathematical correlations based on the Abraham model describe the observed partition coefficient and solubility data to within 0.16 log₁₀ units (or less).     

Intramolecular Carbonyl–Carbonyl Interaction as the Directing Motif of the Opposed Conformational Preferences Among [4?+?2] Cycloadducts of 3-Ethoxycarbonyl- and 3-Acetyl-Coumarins with 2,3-Dimethyl-1,3-Butadiene

Abstract  

In this work, the molecular structures of the Diels–Alder adducts: ethyl (6aR/S,10aR/S)-6a,7,10,10a-tetrahydro-8,9-dimethyl-6-oxodibenzo[b,d]pyran-6a-carboxylate C₁₈H₂₀O₄ 1 and (6aR/S,10aR/S)-6a-acetyl-6a,7,10,10a-tetrahydro-8,9-dimethyl-6-oxodibenzo[b,d]pyran C₁₇H₁₈O₃ 2; and the epoxide of this last (6aR/S,7aR/S,8aS/R,9aR/S)-6a-acetyl-6a,7,7a,8a,9,9a-hexahydro-7a,8a-dimethyl-6-oxo-6H-5,8-dioxacyclopropa[b]phenanthrene C₁₇H₁₈O₄ 3, are comparatively analyzed. Compound 1 is triclinic, space group P-1 with a = 7.7529(6) ?, b = 9.8625(8) ?, c = 11.3103(9) ?, α = 109.387(9)°, β = 95.484(1)°, γ = 99.753(1)°, Z = 2. Compound 2 is monoclinic, space group Cc, a = 7.7285(7) ?, b = 16.6813(15) ?, c = 11.3213(10) ?, β = 92.470(2)°, Z = 4. Compound 3 is monoclinic, space group P2 ₁ /c a = 11.2036(10), b = 15.8326(14), c = 8.3182(7), β = 90.600(2)°, Z = 4. The molecular structures of compounds 1–3 show conformational differences between lactone and 6a-acyl carbonyls. CO···CO dipolar interactions stabilize the less favoured syn conformation in 2–3, conclusions are supported on theoretical calculations. The molecular structure of compound 3 demonstrates that epoxidation of 2 leads to the stereo-selective addition of the oxygen atom.     

Temperature and pressure dependences of volumetric properties of two poly(propylene glycol) dimethyl ether lubricants

The densities at high pressures of two dimethoxy end-capped poly(propylene glycols), CH₃–O–[CH₂–CH(CH₃)–O]_m–CH₃, with average molar masses higher than 1300 g · mol^?1, were measured in the range (0.1 to 60) MPa at five different temperatures from (298.15 to 398.15) K. The measurements were performed in a high-pressure vibrating tube densimeter. A correction factor, due to the viscosity of the sample, was applied to the experimental density values. The pressure–volume–temperature behavior of these lubricants was evaluated accurately over wide temperature and pressure ranges and correlated successfully with the empirical Tammann–Tait equation. The experimental data and the correlations were used to study the behavior and the influence of temperature and pressure on the isothermal compressibility, the isobaric thermal expansivity, and the internal pressure, as well as the effect of the polyether molecular structure on these properties.     

Electronic and optical properties of Si and Ge nanocrystals: An ab initio study

First-principles calculations within density functional theory and many-body perturbation theory have been carried out in order to investigate the structural, electronic and optical properties of undoped and doped silicon nanostructures. We consider Si nanoclusters co-doped with B and P. We find that the electronic band gap is reduced with respect to that of the undoped crystals, suggesting the possibility of impurity based engineering of electronic and optical properties of Si nanocrystals. Finally, motivated by recent suggestions concerning the chance of exploiting Ge dots for photovoltaic nanodevices, we present calculations of the electronic and optical properties of a Ge₃₅H₃₆ nanocrystal, and compare the results with those for the corresponding Si₃₅H₃₆ nanocrystals and the co-doped Si₃₃BPH₃₆.     

Method optimization by solid-phase microextraction in combination with gas chromatography with mass spectrometry for analysis of beer volatile fraction

A simple and sensitive method for the analysis of beer volatile compounds was optimised using headspace solid-phase microextraction (SPME) and gas chromatography with mass detection. Headspace SPME using a 75 microm Carboxen-polydimethylsiloxane (CAR-PDMS) fiber provided effective sample enrichment and enabled extraction of a wide variety of compounds. The reproducibility depended on the compounds, with a mean value of 1.4% for alcohols, 3.3% for ethers, 6.7% for aldehydes, 3.4% for acids, 1.7% for aromatic compounds, 2.4% for esters, 7.4% for hydrocarbons, 1.8% for alicyclic compounds, and 3.4% for heterocyclic compounds. The optimised methodology can be used to compare volatile profile from different types of beers and eventually to study the evolution of a particular beer during aging.     

Why local air pollution is more than daily peaks: modelling policies in a city in order to avoid premature deaths

We use a predator–prey representation of an urban system to analyse how policy interventions can prevent the adverse effects of air pollution on people’s health. The number of residents is treated as prey variable, and particulate matter that consists of particles with a diameter of up to 10 micrometres (PM10) as predator variable. This representation allows integration of population trends and the effects of environmental interventions on the average level of PM10 concentration (which establishes a baseline for the potential health burden for residents). For the case of Graz, Austria, we illustrate the insights generated regarding the interdependency of market-based and technological pollution controls, and propose an indicator that assesses the cost of delayed interventions by counting additional premature deaths caused by polluted environments.

     

Managing contribution and capital market risk in a funded public defined benefit plan: Impact of CVaR cost constraints

Using a Monte Carlo framework, we analyze the risks and rewards of moving from an unfunded defined benefit pension system to a funded plan for German civil servants, allowing for alternative strategic contribution and investment patterns. In the process we integrate a Conditional Value at Risk (CVaR) restriction on overall plan costs into the pension manager’s objective of controlling contribution rate volatility. After estimating the contribution rate that would fully fund future benefit promises for current and prospective employees, we identify the optimal contribution and investment strategy that minimizes contribution rate volatility while restricting worst-case plan costs. Finally, we analyze the time path of expected and worst-case contribution rates to assess the chances of reduced contribution rates for current and future generations. Our results show that moving toward a funded public pension system can be beneficial for both civil servants and taxpayers.