Dissecting the hindered rotation of ethane

The existence of a rotational barrier of ca. 3 kcal mol À1 around the CÀC single bond in ethane has been known The steric repulsion still remains the most popular explanation of the hindered rotation of ethane. This effect is often understood as the increase in energy that accompanies the antisymmetrization of a wave function originally formed by strictly localized descriptions of two methyl groups brought up to the final ethane geometry where they overlap. This so-called Pauli repulsion is considered to be more important for the eclipsed conformation, The hyperconjugation [21] The electron delocalization effect can easily be assessed in valence bond (VB) theory calculations Previous energy decomposition analyses relied, in one way or another, on the definition of two methyl fragments. However, in the last years there have been a growing interest in other kinds of energy partitioning schemes, The diatomic terms naturally reflect the attractive or repulsive interactions between the atoms in the molecule. The onecenter terms correspond to the effective energy of each atom in the molecule; its value relative to that of the corresponding free atom accounts for the promotion that occurs upon bond formation. In this sense, it is important to recall that the oneand two-center contributions are static parameters. [26] They measure to which extent the energy of a given atom or atomic pair contributes to the total molecular energy at that geometry and with the wave function used at that point. Thus, the diatomic values cannot be put into direct correspondence with the dissociation energies, as dissociation involves changes in both geometry and wave function. The main advantage of this methodology for the present case is that one can decompose all energetic interactions within the molecule on the basis of a single ab initio calculation, without recurring to an arbitrar

Grouping of nanomaterials to read-across hazard endpoints: a review

The use of non-testing strategies like read-across in the hazard assessment of chemicals and nanomaterials (NMs) is deemed essential to perform the safety assessment of all NMs in due time and at lower costs. The identification of physicochemical (PC) properties affecting the hazard potential of NMs is crucial, as it could enable to predict impacts from similar NMs and outcomes of similar assays, reducing the need for experimental (and in particular animal) testing. This manuscript presents a review of approaches and available case studies on the grouping of NMs to read-across hazard endpoints. We include in this review grouping frameworks aimed at identifying hazard classes depending on PC properties, hazard classification modules in control banding (CB) approaches, and computational methods that can be used for grouping for read-across. The existing frameworks and case studies are systematically reported. Relevant nanospecific PC properties taken into account in the reviewed frameworks to support grouping are shape and surface properties (surface chemistry or reactivity) and hazard classes are identified on the basis of biopersistence, morphology, reactivity, and solubility.JRC.F.3-Chemicals Safety and Alternative Method

Grouping of nanomaterials to read-across hazard endpoints: from data collection to assessment of the grouping hypothesis by application of chemoinformatic techniques

An increasing number of manufactured nanomaterials (NMs) are being used in industrial products and need to be registered under the REACH legislation. The hazard characterisation of all these forms is not only technically challenging but resource and time demanding. The use of non-testing strategies like read-across is deemed essential to assure the assessment of all NMs in due time and at lower cost. The fact that read-across is based on the structural similarity of substances represents an additional difficulty for NMs as in general their structure is not unequivocally defined. In such a scenario, the identification of physicochemical properties affecting the hazard potential of NMs is crucial to define a grouping hypothesis and predict the toxicological hazards of similar NMs. In order to promote the read-across of NMs, ECHA has recently published “Recommendations for nanomaterials applicable to the guidance on QSARs and Grouping”, but no practical examples were provided in the document. Due to the lack of publicly available data and the inherent difficulties of reading-across NMs, only a few examples of read-across of NMs can be found in the literature. This manuscript presents the first case study of the practical process of grouping and read-across of NMs following the workflow proposed by ECHA. The workflow proposed by ECHA was used and slightly modified to present the read-across case study. The Read-Across Assessment Framework (RAAF) was used to evaluate the uncertainties of a read-across within NMs. Chemoinformatic techniques were used to support the grouping hypothesis and identify key physicochemical properties. A dataset of 6 nanoforms of TiO2 with more than 100 physicochemical properties each was collected. In vitro comet assay result was selected as the endpoint to read-across due to data availability. A correlation between the presence of coating or large amounts of impurities and negative comet assay results was observed. The workflow proposed by ECHA to read-across NMs was applied successfully. Chemoinformatic techniques were shown to provide key evidence for the assessment of the grouping hypothesis and the definition of similar NMs. The RAAF was found to be applicable to NMs

Electronic states of porphycene-O₂ complex and photoinduced singlet O₂ production

Porphycene (PC), a structural isomer of porphine, is a promising photosensitizer for photodynamic therapy. Its excited states can be quenched by molecular oxygen, generating singlet O2. The electronic structures of PC and of the PC· · ·O2 complex were investigated using complete active space perturbation theory. It is shown that singlet oxygen generation involves 12 electronic states of the complex, with singlet, triplet, and quintet multiplicities. Two scenarios for singlet-O2 yield are analyzed: (I) quenching of triplet states of PC and (II) quenching of singlet states of PC. In the first scenario, which is favored under low O2 concentration, singlet-O2 yield is limited by the relatively low triplet quantum yield of PC. We discuss how the singlet-O2 yield would be busted if conditions for occurrence of the second scenario could be achieved

Exploring the sloped-to-peaked S-2/S-1 seam of intersection of thymine with electronic structure and direct quantum dynamics calculations

The role of the seam of intersection between the lowest (pi,pi*) and (n,pi*) excited states in the decay of electronically excited singlet thymine has been investigated with ab initio complete active space self-consistent field (CASSCF) calculations and direct dynamics variational multiconfiguration Gaussian (DD-vMCG) quantum dynamics on the full-dimensional CASSCF surface, with 39 degrees of freedom. The seam has a sloped-to-peaked topography, and the dynamics at the different segments of the seam have been studied by varying the initial conditions of the propagation. When the wave packet is directed to the peaked segments, part of it traverses the seam, stays on the (pi,pi*) state and heads towards decay to the ground state. In contrast to this, when the wave packet is driven to sloped seam segments it bounces back to the minimum of the (pi,pi*) state. Significant population transfer to the (n,pi*) state is observed in both cases. The results suggest that a sloped-to-peaked topography can be used to control photochemical reactivity, by driving the wave packet to different regions of the seam where a different outcome of the propagation can be expected

Computational models for the assessment of manufactured nanomaterials: development of model reporting standards and mapping of the model landscape

Different types of computational models have been developed for the prediction of biokinetics, environmental fate, and the estimation of exposure levels and toxicological effects of chemicals and manufactured nanomaterials (MNs). However, these models are not described in a consistent manner in the scientific literature, which is one of the barriers to their broader use and acceptance, especially for regulatory purposes. Quantitative structure-activity relationships (QSARs) are in silico models based on the assumption that the activity of a substance is related to its chemical structure. These models can be used to provide information of (eco)toxicological effects in hazard assessment. In the context of an environmental risk assessment, environmental exposure models can be used to estimate the predicted environmental concentration (PEC). In addition, physiologically based kinetic (PBK) models can be used in various ways to support a human health risk assessment. In this paper, we propose model reporting templates for systematically and transparently describing models that could potentially be used to support regulatory risk assessments of MNs, for example under the REACH regulation. The model reporting templates include (a) the adaptation of the QSAR Model Reporting Format (QMRF) to report models for MNs, and (b) the development of a model reporting template for PBK and environmental exposure models applicable to MNs. Second, we show the usefulness of these templates to report different models, resulting in an overview of the landscape of available computational models for MNs

Physiologically based mathematical models of nanomaterials for regulatory toxicology: A review

The development of physiologically based (PB) models to support safety assessments in the field of nanotechnology has grown steadily during the last decade. This review reports on the availability of PB models for toxicokinetic (TK) and toxicodynamic (TD) processes, including in vitro and in vivo dosimetry models applied to manufactured nanomaterials (MNs). In addition to reporting on the state-of-the-art in the scientific literature concerning the availability of physiologically based kinetic (PBK) models, we evaluate their relevance for regulatory applications, mainly considering the EU REACH regulation. First, we performed a literature search to identify all available PBK models. Then, we systematically reported the content of the identified papers in a tailored template to build a consistent inventory, thereby supporting model comparison. We also described model availability for physiologically based dynamic (PBD) and in vitro and in vivo dosimetry models according to the same template. For completeness, a number of classical toxicokinetic (CTK) models were also included in the inventory. The review describes the PBK model landscape applied to MNs on the basis of the type of MNs covered by the models, their stated applicability domain, the type of (nano-specific) inputs required, and the type of outputs generated. We identify the main assumptions made during model development that may influence the uncertainty in the final assessment, and we assess the REACH relevance of the available models within each model category. Finally, we compare the state of PB model acceptance for chemicals and for MNs. In general, PB model acceptance is limited by the absence of standardised reporting formats, psychological factors such as the complexity of the models, and technical considerations such as lack of blood:tissue partitioning data for model calibration/validation

Can currently available non-animal methods detect pre and pro-haptens?

Presented at QSAR 201