Weak values of a quantum observable and the cross-Wigner distribution

We study the weak values of a quantum observable from the point of view of the Wigner formalism. The main actor is here the cross-Wigner transform of two functions, which is in disguise the cross-ambiguity function familiar from radar theory and time-frequency analysis. It allows us to express weak values using a complex probability distribution. We suggest that our approach seems to confirm that the weak value of an observable is, as conjectured by several authors, due to the interference of two wavefunctions, one coming from the past, and the other from the future.Comment: Submitted for publicatio

Towards an Understanding of the Mode of Action of Human Aromatase Activity for Azoles through Quantum Chemical Descriptors-Based Regression and Structure Activity Relationship Modeling Analysis

Aromatase is an enzyme member of the cytochrome P450 superfamily coded by the CYP19A1 gene. Its main action is the conversion of androgens into estrogens, transforming androstenedione into estrone and testosterone into estradiol. This enzyme is present in several tissues and it has a key role in the maintenance of the balance of androgens and estrogens, and therefore in the regulation of the endocrine system. With regard to chemical safety and human health, azoles, which are used as agrochemicals and pharmaceuticals, are potential endocrine disruptors due to their agonist or antagonist interactions with the human aromatase enzyme. This theoretical study investigated the active agonist and antagonist properties of “chemical classes of azoles” to determine the relationships of azole interaction with CYP19A1, using stereochemical and electronic properties of the molecules through classification and multilinear regression (MLR) modeling. The antagonist activities for the same substituent on diazoles and triazoles vary with its chemical composition and its position and both heterocyclic systems require aromatic substituents. The triazoles require the spherical shape and diazoles have to be in proper proportion of the branching index and the number of ring systems for the inhibition. Considering the electronic aspects, triazole antagonist activity depends on the electrophilicity index that originates from interelectronic exchange interaction (ωHF) and the LUMO energy ( E LUMO PM 7 ), and the diazole antagonist activity originates from the penultimate orbital ( E HOMONL PM 7 ) of diazoles. The regression models for agonist activity show that it is opposed by the static charges but favored by the delocalized charges on the diazoles and thiazoles. This study proposes that the electron penetration of azoles toward heme group decides the binding behavior and stereochemistry requirement for antagonist activity against CYP19A1 enzyme

A KNIME Workflow to Assist the Analogue Identification for Read-Across, Applied to Aromatase Activity

The reduction and replacement of in vivo tests have become crucial in terms of resources and animal benefits. The read-across approach reduces the number of substances to be tested, exploiting existing experimental data to predict the properties of untested substances. Currently, several tools have been developed to perform read-across, but other approaches, such as computational workflows, can offer a more flexible and less prescriptive approach. In this paper, we are introducing a workflow to support analogue identification for read-across. The implementation of the workflow was performed using a database of azole chemicals with in vitro toxicity data for human aromatase enzymes. The workflow identified analogues based on three similarities: structural similarity (StrS), metabolic similarity (MtS), and mechanistic similarity (McS). Our results showed how multiple similarity metrics can be combined within a read-across assessment. The use of the similarity based on metabolism and toxicological mechanism improved the predictions in particular for sensitivity. Beyond the results predicting a large population of substances, practical examples illustrate the advantages of the proposed approach

Skin sensitization quantitative QSAR models based on mechanistic structural alerts.

peer reviewedAllergic contact dermatitis is increasingly of interest for the hazard characterization of chemicals. in vivo animal testing is usually adopted but in silico approaches are becoming the new frontier due to their swiftness and economic efficiency. Indeed, in silico models can rationalise the experimental outcomes besides having predictive ability. The aim of the present work was to explore the electrophilic chemical behaviour responsible for allergic contact dermatitis using quantitative QSAR regression models. Eight models were proposed, using an experimental LLNA dataset of 366 chemicals. Each model is unique to encode a type of electrophilic reactivity domain. The models were obtained using autocorrelation, electro-topological and atom centered fragment based on two-dimensional descriptors, which incorporated the electronic and stereochemical features of substances interacting with skin proteins to induce skin cell proliferation. Finally, simple steps were proposed to integrate the eight models for the application on the test chemicals