In Silico Prediction of Physicochemical Properties

This report provides a critical review of computational models, and in particular(quantitative) structure-property relationship (QSPR) models, that are available for the prediction of physicochemical properties. The emphasis of the review is on the usefulness of the models for the regulatory assessment of chemicals, particularly for the purposes of the new European legislation for the Registration, Evaluation, Authorisation and Restriction of CHemicals (REACH), which entered into force in the European Union (EU) on 1 June 2007. It is estimated that some 30,000 chemicals will need to be further assessed under REACH. Clearly, the cost of determining the toxicological and ecotoxicological effects, the distribution and fate of 30,000 chemicals would be enormous. However, the legislation makes it clear that testing need not be carried out if adequate data can be obtained through information exchange between manufacturers, from in vitro testing, and from in silico predictions. The effects of a chemical on a living organism or on its distribution in the environment is controlled by the physicochemical properties of the chemical. Important physicochemical properties in this respect are, for example, partition coefficient, aqueous solubility, vapour pressure and dissociation constant. Whilst all of these properties can be measured, it is much quicker and cheaper, and in many cases just as accurate, to calculate them by using dedicated software packages or by using (QSPRs). These in silico approaches are critically reviewed in this report.JRC.I.3-Toxicology and chemical substance

Prediction of physico-chemical properties for REACH based on QSPR models

International audienceQuantitative Structure Property Relationship models have been developed for the prediction of flash points of two families of organic compounds selected in the PREDIMOL French Project: amines and organic peroxides. If the model dedicated to amines respected all OECD validation principles with excellent performances in predictivity, the one dedicated to organic peroxides was not validated on an external validation set, due to the low number of available data, but already presented high performances in fitting and robustness. This work highlighted the need of gathering experimental data, as in progress in the PREDIMOL project, to achieve validated reliable models that could be used in a regulatory framework, like REACH. Such models are expected to be submitted to the European Joint Research Comity (JRC) and to existing tools (like the OECD ECHA QSAR Toolbox) to be available for use by industrials and regulatory instances

Predicting Skin Permeability by means of Computational Approaches : Reliability and Caveats in Pharmaceutical Studies

© 2019 American Chemical Society.The skin is the main barrier between the internal body environment and the external one. The characteristics of this barrier and its properties are able to modify and affect drug delivery and chemical toxicity parameters. Therefore, it is not surprising that permeability of many different compounds has been measured through several in vitro and in vivo techniques. Moreover, many different in silico approaches have been used to identify the correlation between the structure of the permeants and their permeability, to reproduce the skin behavior, and to predict the ability of specific chemicals to permeate this barrier. A significant number of issues, like interlaboratory variability, experimental conditions, data set building rationales, and skin site of origin and hydration, still prevent us from obtaining a definitive predictive skin permeability model. This review wants to show the main advances and the principal approaches in computational methods used to predict this property, to enlighten the main issues that have arisen, and to address the challenges to develop in future research.Peer reviewedFinal Accepted Versio

QSPR calculation of normal boiling points of organic molecules based on the use of correlation weighting of atomic orbitals with extended connectivity of zero- and first-order graphs of atomic orbitals

We report the results of a calculation of the normal boiling points of a representative set of 200 organic molecules through the application of QSPR theory. For this purpose we have used a particular set of flexible molecular descriptors, the so called Correlation Weighting of Atomic Orbitals with Extended Connectivity of Zero- and First-Order Graphs of Atomic Orbitals. Although in general the results show suitable behavior to predict this physical chemistry property, the existence of some deviant behaviors points to a need to complement this index with some other sort of molecular descriptors. Some possible extensions of this study are discussed.SCOPU

Develop a Hazard Index Using Machine Learning Approach for the Hazard Identification of Chemical Logistic Warehouses

PresentationWith the rapid development of chemical process plants, the safe storage of hazardous chemicals become an essential topic. Several chemical warehouse incidents related to fire and explosion have been reported recently. Therefore, an accurate hazard identification method for the logistic warehouse is needed not only for the facility to develop a proper emergency response plan but also for the residents who live near the facility to have an effective hazard communication. Furthermore, the government can better allocate the resources for first responders to make fire protection strategies, and the stakeholders can lead to improved risk management. Hazard index is a helpful tool to identify and quantify the hazard in a facility or a process unit. The challenge for this research is to improve the current method with the novel technique to implement our purpose. The first objective of this research is to develop a “Storage Hazard Factor” (SHF) to evaluate and rank the inherent hazards of chemicals stored in logistic warehouses. In the factor calculation, the inherent hazard of chemicals is determined by various parameters (e.g., the NFPA rating, the flammability limit, and the protective action criteria values, etc.) and validated by the comparison with other indices. The current criteria for flammable hazard ratings are based on flash point, which is proved to be insufficient. Two machine learning based methods will be used for the classification of liquid flammability considering aerosolization based on DIPPR 801 database. Subsequently, SHF and other warehouse safety penalty factors (e.g., the quantity of the chemicals, the distance to the nearest fire department, etc.) are utilized to identify the Logistic Warehouse Hazard Index (LWHI) of the facilities. In the last chapter, this method is applied to real-time data from Houston Chronicle, and several statistical analyses are used to prove the hazard index is helpful for hazard identification to emergency responders and hazard communication to the public

Development of a QSPR model for predicting thermal stabilities of nitroaromatic compounds taking into account their decomposition mechanisms

International audienceThe molecular structures of 77 nitroaromatic compounds have been correlated to their thermal stabilities by combining the quantitative structure-property relationship (QSPR) method with density functional theory (DFT). More than 300 descriptors (constitutional, topological, geometrical and quantum chemical) have been calculated, and multilinear regressions have been performed to find accurate quantitative relationships with experimental heats of decomposition (deltaH). In particular, this work demonstrates the importance of accounting for chemical mechanisms during the selection of an adequate experimental data set. A reliable QSPR model that presents a strong correlation with experimental data for both the training and the validation molecular sets (R 2 = 0.90 and 0.84, respectively) was developed for non-ortho-substituted nitroaromatic compounds. Moreover, its applicability domain was determined, and the model's predictivity reached 0.86 within this applicability domain. To our knowledge, this work has produced the first QSPR model, developed according to the OECD principles of regulatory acceptability, for predicting the thermal stabilities of energetic compounds

Machine Learning Prediction of Glass Transition Temperature of Conjugated Polymers From Chemical Structure

Predicting the glass transition temperature (Tg) is of critical importance as it governs the thermomechanical performance of conjugated polymers (CPs). Here, we report a predictive modeling framework to predict Tg of CPs through the integration of machine learning (ML), molecular dynamics (MD) simulations, and experiments. With 154 Tg data collected, an ML model is developed by taking simplified “geometry” of six chemical building blocks as molecular features, where side-chain fraction, isolated rings, fused rings, and bridged rings features are identified as the dominant ones for Tg. MD simulations further unravel the fundamental roles of those chemical building blocks in dynamical heterogeneity and local mobility of CPs at a molecular level. The developed ML model is demonstrated for its capability of predicting Tg of several new high-performance solar cell materials to a good approximation. The established predictive framework facilitates the design and prediction of Tg of complex CPs, paving the way for addressing device stability issues that have hampered the field from developing stable organic electronics

Machine learning based adaptive soft sensor for flash point inference in a refinery realtime process

In industrial control processes, certain characteristics are sometimes difficult to measure by a physical sensor due to technical and/or economic limitations. This fact is especially true in the petrochemical industry. Some of those quantities are especially crucial for operators and process safety. This is the case for the automotive diesel Flash Point Temperature (FT). Traditional methods for FT estimation are based on the study of the empirical inference between flammability properties and the denoted target magnitude. The necessary measures are taken indirectly by samples from the process and analyzing them in the laboratory, this process implies time (can take hours from collection to flash temperature measurement) and thus make it very difficult for real-time monitorization, which in fact results in security and economical losses. This study defines a procedure based on Machine Learning modules that demonstrate the power of real-time monitorization over real data from an important international refinery. As input, easily measured values provided in real-time, such as temperature, pressure, and hydraulic flow are used and a benchmark of different regressive algorithms for FT estimation is presented. The study highlights the importance of sequencing preprocessing techniques for the correct inference of values. The implementation of adaptive learning strategies achieves considerable economic benefits in the productization of this soft sensor. The validity of the method is tested in the reality of a refinery. In addition, real-world industrial data sets tend to be unstable and volatile, and the data is often affected by noise, outliers, irrelevant or unnecessary features, and missing data. This contribution demonstrates with the inclusion of a new concept, called an adaptive soft sensor, the importance of the dynamic adaptation of the conformed schemes based on Machine Learning through their combination with feature selection, dimensional reduction, and signal processing techniques. The economic benefits of applying this soft sensor in the refinery's production plant and presented as potential semi-annual savings.This work has received funding support from the SPRI-Basque Gov- ernment through the ELKARTEK program (OILTWIN project, ref. KK- 2020/00052)