Interactions of Aromatic Radicals with Water

The interactions of the benzyl radical (1), the anilinyl radical (2), and the phenoxyl radical (3) with water are investigated using density functional theory (DFT). In addition, we report dispersion-corrected DFT-D molecular dynamics simulations on these three systems and a matrix isolation study on 1–water. The radicals 1–3 form an interesting series with the number of lone pairs increasing from none to two. The anilinyl and benzyl radicals can act as Lewis base through their unpaired electrons, the lone pairs of the heteroatoms, or the doubly occupied π orbitals of the aromatic system. Matrix isolation experiments provide evidence for the formation of a π complex between 1 and water. By combining computational and experimental techniques we identify the possible interactions between the aromatic radicals 1–3 and water, predict the structure and vibrational spectra of the resulting complexes, and analyze the effects of substitution and temperature

Coupling and uncoupling mechanisms in the methoxythreonine mutant of cytochrome P450cam: a quantum mechanical/molecular mechanical study

The Thr252 residue plays a vital role in the catalytic cycle of cytochrome P450cam during the formation of the active species (Compound I) from its precursor (Compound 0). We investigate the effect of replacing Thr252 by methoxythreonine (MeO-Thr) on this protonation reaction (coupling) and on the competing formation of the ferric resting state and H2O2 (uncoupling) by combined quantum mechanical/molecular mechanical (QM/MM) methods. For each reaction, two possible mechanisms are studied, and for each of these the residues Asp251 and Glu366 are considered as proton sources. The computed QM/MM barriers indicate that uncoupling is unfavorable in the case of the Thr252MeO-Thr mutant, whereas there are two energetically feasible proton transfer pathways for coupling. The corresponding rate-limiting barriers for the formation of Compound I are higher in the mutant than in the wild-type enzyme. These findings are consistent with the experimental observations that the Thr252MeO-Thr mutant forms the alcohol product exclusively (via Compound I), but at lower reaction rates compared with the wild-type enzyme

Mental models in nuclear emergency management

This paper reports on the research of mental models of uncertainties management in an emergency situation which was carried out in the framework of the European CONFIDENCE (COping with uNcertainties For Improved modelling and DEcision making in Nuclear emergenCiEs) Project. The methodology included the mapping of mental models among several emergency preparedness and response experts and then performing interviews based on structured protocol with lay people in five countries: Germany, Greece, Slovak Republic, Slovenia and Spain. The aim of these investigations was to trace the concepts and understandings of emergency preparedness and response and to identify possible gaps between experts and lay people. The article presents the main results of this research and suggestions for the improvement of EP & R planning

Guidance on communicating about uncertainties in nuclear emergency management

Within the European project CONFIDENCE, an extensive research programme has been conducted on a range of different tools, including Apps, SMS, numerical, narrative or mixed news messages and videos linked to uncertainty communication following potential nuclear or radiological emergencies. For this purpose, qualitative and quantitative research methods were applied in different European countries. Based on the results of these studies, we have formulated guidelines for efficient and effective communication about uncertainties that can be used in nuclear or radiological emergencies

Quantum mechanics/molecular mechanics dual Hamiltonian free energy perturbation

The dual Hamiltonian free energy perturbation (DH-FEP) method is designed for accurate and efficient evaluation of the free energy profile of chemical reactions in quantum mechanical/molecular mechanical (QM/MM) calculations. In contrast to existing QM/MM FEP variants, the QM region is not kept frozen during sampling, but all degrees of freedom except for the reaction coordinate are sampled. In the DH-FEP scheme, the sampling is done by semiempirical QM/MM molecular dynamics (MD), while the perturbation energy differences are evaluated from high-level QM/MM single-point calculations at regular intervals, skipping a pre-defined number of MD sampling steps. After validating our method using an analytic model potential with an exactly known solution, we report a QM/MM DH-FEP study of the enzymatic reaction catalyzed by chorismate mutase. We suggest guidelines for QM/MM DH-FEP calculations and default values for the required computational parameters. In the case of chorismate mutase, we apply the DH-FEP approach in combination with a single one-dimensional reaction coordinate and with a two-dimensional collective coordinate (two individual distances), with superior results for the latter choice