Fast and Accurate Prediction of Refractive Index of Organic Liquids with Graph Machines.

The refractive index (RI) of liquids is a key physical property of molecular compounds and materials. In addition to its ubiquitous role in physics, it is also exploited to impart specific optical properties (transparency, opacity, and gloss) to materials and various end-use products. Since few methods exist to accurately estimate this property, we have designed a graph machine model (GMM) capable of predicting the RI of liquid organic compounds containing up to 16 different types of atoms and effective in discriminating between stereoisomers. Using 8267 carefully checked RI values from the literature and the corresponding 2D organic structures, the GMM provides a training root mean square relative error of less than 0.5%, i.e., an RMSE of 0.004 for the estimation of the refractive index of the 8267 compounds. The GMM predictive ability is also compared to that obtained by several fragment-based approaches. Finally, a Docker-based tool is proposed to predict the RI of organic compounds solely from their SMILES code. The GMM developed is easy to apply, as shown by the video tutorials provided on YouTube.

Fast Prediction of the Equivalent Alkane Carbon Number Using Graph Machines and Neural Networks.

The hydrophobicity of oils is a key parameter to design surfactant/oil/water (SOW) macro-, micro-, or nano-dispersed systems with the desired features. This essential physicochemical characteristic is quantitatively expressed by the equivalent alkane carbon number (EACN) whose experimental determination is tedious since it requires knowledge of the phase behavior of the SOW systems at different temperatures and for different surfactant concentrations. In this work, two mathematical models are proposed for the rapid prediction of the EACN of oils. They have been designed using artificial intelligence (machine-learning) methods, namely, neural networks (NN) and graph machines (GM). While the GM model is implemented from the SMILES codes of a 111-molecule training set of known EACN values, the NN model is fed with some σ-moment descriptors computed with the COSMOtherm software for the 111-molecule set. In a preliminary step, the leave-one-out algorithm is used to select, given the available data, the appropriate complexity of the two models. A comparison of the EACNs of liquids of a fresh set of 10 complex cosmetic and perfumery molecules shows that the two approaches provide comparable results in terms of accuracy and reliability. Finally, the NN and GM models are applied to nine series of homologous compounds, for which the GM model results are in better agreement with the experimental EACN trends than the NN model predictions. The results obtained by the GMs and by the NN based on σ-moments can be duplicated with the demonstration tool available for download as detailed in the Supporting Information.

Bio-based alternatives to volatile silicones: Relationships between chemical structure, physicochemical properties and functional performances.

Emollient oils are ubiquitous ingredients of personal care products, especially skin care and hair care formulations. They offer excellent spreading properties and give end-use products a soft, pleasant and non-sticky after-feel. Emollients belong to various petro- or bio-based chemical families among which silicone oils, hydrocarbons and esters are the most prominent. Silicones have exceptional physicochemical and sensory properties but their high chemical stability results in very low biodegradability and a high bioaccumulation potential. Nowadays, consumers are increasingly responsive to environmental issues and demand more environmentally friendly products. This awareness strongly encourages cosmetics industries to develop bio-based alternatives to silicone oils. Finding effective silicon-free emollients requires understanding the molecular origin of emollience. This review details the relationships between the molecular structures of emollients and their physicochemical properties as well as the resulting functional performances in order to facilitate the design of alternative oils with suitable physicochemical and sensory properties. The molecular profile of an ideal emollient in terms of chemical function (alkane, ether, ester, carbonate, alcohol), optimal number of carbons and branching is established to obtain an odourless oil with good spreading on the skin. Since none of the carbon-based emollients alone can imitate the non-sticky and dry feel of silicone oils, it is judicious to blend alkanes and esters to significantly improve both the sensory properties and the solubilizing properties of the synergistic mixture towards polar ingredients (sun filters, antioxidants, fragrances). Finally, it is shown how modelling tools (QSPR, COSMO-RS and neural networks) can predict in silico the key properties of hundreds of virtual candidate molecules in order to synthesize only the most promising whose predicted properties are close to the specifications.

Eco-conception of Highly Salt-Tolerant Alkyl Ether Carboxylate Hydrotropes with a Glyceryl Spacer.

New alkyl ether carboxylates with a glyceryl spacer instead of ethylene glycol units have been synthesised using environmentally friendly methodology. A cascade synthesis of acetalisation and hydrogenolysis was developed to obtain products containing an alkyl chain linked to a glycerol unit bearing a polar carboxylate head. These products were methylated by using trimethyl phosphate to observe the influence of a free or methoxylated alcohol on the physicochemical properties. Finally, saponification gave the carboxylate anionic group of the new hydrotropes. Studying the amphiphilicity, the tolerance to sodium and calcium ions, and the solubilising power of these bio-based ionic/nonionic hydrotropes has shown that they exhibit significantly improved application properties compared to similar petro-based hydrotropes.

The Salinity-Phase-Inversion method (SPI-slope): A straightforward experimental approach to assess the hydrophilic-lipophilic-ratio and the salt-sensitivity of surfactants.

HYPOTHESIS: The salinity at which the dynamic phase inversion of the reference system C10E4/n-Octane/Water occurs in the presence of increasing amounts of a test surfactant S2 provides quantitative information on the hydrophilic/lipophilic ratio and on the sensitivity to NaClaq of S2. EXPERIENCES: The Salinities causing the Phase Inversion (SPI) of the reference system mixed with 12 ionic and 10 nonionic well-defined surfactants are determined in order to quantify the contributions of the nature of the polar head and of the alkyl chain length. FINDINGS: The SPI varies linearly upon the addition of S2. The slope of the straight variation with the molar fraction of S2 is called the "SPI-slope". It quantifies the hydrophilic/lipophilic ratio of S2 in saline environment and its salt-sensitivity with respect to the reference surfactant C10E4. The SPI-slopes of C12 surfactants bearing different polar heads are found to decrease in the following order: C12NMe3Br > C12E8 > C12E7 ≥C12SO3Na ≈ C12COONa ≥ C12SO4Na > C12E6 > C12E5 > C12E3. This classification is different from that obtained when the phase inversion is caused by a change in temperature (PIT-slope method) because the addition of NaCl in significant amounts (3 to 10 wt%) partially screens the ionic heads and diminishes their apparent hydrophilicities. A simple model, valid for all types of nonionic surfactants, is developed on the basis of the HLDN equation (Normalized Hydrophilic-Lipophilic Deviation) to express the SPI-slope as a function of the hydrophilic/lipophilic ratio (PACN2) and the salinity coefficient (δ2) of S2. All studied surfactants are positioned on a 2D map according to the values of their SPI-slope and their PIT-slope to graphically highlight their hydrophilic/lipophilic ratio and their salt-sensitivity. Finally, a linear model connecting the PIT-slope and the SPI-slope is derived for nonionics, emphasizing that the thermal partitioning of C10E4 towards n-octane is much greater in the PIT-slope than in the SPI-slope experiments.

Simultaneous Determination of the Chemical (kr ) and the Physical (kq ) Quenching Rate Constants of Singlet Oxygen in Aqueous Solution by the Chemiluminescence-quenching Method.

This work reports a novel and visual method for the simultaneous determination of the chemical (kr ) and the physical (kq ) quenching rate constants of singlet oxygen (1 O2 ,1 ∆g ) in aqueous media. It is based on the disruption, by a water-soluble substrate S, of the 1 O2 chemiluminescence (CL) generated by the H2 O2 /Na2 MoO4 catalytic system. A mathematical analysis of the CL signal at 1270 nm vs time provides separately the overall (kr + kq ) and the chemical (kr ) quenching rate constants. In ordinary water (H2 O), 1 O2 lifetime is short and the CL intensity is weak allowing solely the investigation of very reactive substrates for which (kr + kq ) > 3 × 106 m-1 s-1 while, in D2 O, 1 O2 lifetime is significantly longer lifetime and the CL signal is much stronger allowing the study of poorly reactive substrates for which (kr + kq ) > 4 × 105 m-1 s-1 . The method has been successfully tested on a series of anionic and nonionic water-soluble naphthalene derivatives commonly used as bio-compatible 1 O2 carriers. The obtained kr and kq values are in good agreement with the values determined by conventional techniques, namely, flash photolysis and competitive kinetics with a reference quencher.

Salt-tolerance of alkyl-glyceryl ether carboxylates hydrotropes and surfactants. Dramatic effect of the methylation of the glyceryl spacer.

HYPOTHESIS: The insertion of polyether spacers between the anionic head and the alkyl chain of ionic surfactants significantly improves their salt-tolerance. The aim of this work is to study whether the petro-based polyethoxy spacer can be replaced by a glyceryl ether group for high salinity applications. EXPERIMENTS: A series of amphiphilic sodium salts of alkyl glyceryl ether carboxylates are synthesized with different alkyl chain lengths from 4 to 12 and various spacers between the glyceryl and the carboxylate groups. Their aggregation behavior is studied by tensiometry and their amphiphilicities are assessed by the PIT-slope method. The dramatic effect of the methylation of the glyceryl spacer on the salt-tolerance is highlighted, and rationalized by DFT calculations and molecular dynamics. FINDINGS: In contrast to the corresponding sodium soap, n-C6H13-CO2Na, and to the non-methylated counterpart, the sodium salt of 1-pentyl-3-methyl glyceryl ether methylene carboxylate ([5.0.1]-CH2CO2Na) exhibits an excellent salt-tolerance since it remains water-soluble with NaCl or CaCl2 concentrations greater than 20 wt% at 25 °C. Amphiphiles with short alkyl chains (

A New Machine-Learning Tool for Fast Estimation of Liquid Viscosity. Application to Cosmetic Oils.

The viscosities of pure liquids are estimated at 25 °C, from their molecular structures, using three modeling approaches: group contributions, COSMO-RS σ-moment-based neural networks, and graph machines. The last two are machine-learning methods, whereby models are designed and trained from a database of viscosities of 300 molecules at 25 °C. Group contributions and graph machines make use of the 2D-structures only (the SMILES codes of the molecules), while neural networks estimations are based on a set of five descriptors: COSMO-RS σ-moments. For the first time, leave-one-out is used for graph machine selection, and it is shown that it can be replaced with the much faster virtual leave-one-out algorithm. The database covers a wide diversity of chemical structures, namely, alkanes, ethers, esters, ketones, carbonates, acids, alcohols, silanes, and siloxanes, as well as different chemical backbone, i.e., straight, branched, or cyclic chains. A comparison of the viscosities of liquids of an independent set of 22 cosmetic oils shows that the graph machine approach provides the most accurate results given the available data. The results obtained by the neural network based on sigma-moments and by the graph machines can be duplicated easily by using a demonstration tool based on the Docker technology, available for download as explained in the Supporting Information. This demonstration also allows the reader to predict, at 25 °C, the viscosity of any liquid of moderate molecular size (M < 600 Da) that contains C, H, O, or Si atoms, starting either from its SMILES code or from its σ-moments computed with the COSMOtherm software.

Use of the normalized hydrophilic-lipophilic-deviation (HLDN) equation for determining the equivalent alkane carbon number (EACN) of oils and the preferred alkane carbon number (PACN) of nonionic surfactants by the fish-tail method (FTM).

The standard HLD (Hydrophilic-Lipophilic-Deviation) equation expressing quantitatively the deviation from the "optimum formulation" of Surfactant/Oil/Water systems is normalized and simplified into a relation including only the three more meaningful formulation variables, namely (i) the "Preferred Alkane Carbon Number" PACN which expresses the amphiphilicity of the surfactant, (ii) the "Equivalent Alkane Carbon Number" EACN which accurately reflects the hydrophobicity of the oil and (iii) the temperature which has a strong influence on ethoxylated surfactants and is thus selected as an effective, continuous and reversible scanning variable. The PACN and EACN values, as well as the "temperature-sensitivity-coefficient"τ of surfactants are determined by reviewing available data in the literature for 17 nonionic n-alkyl polyglycol ether (CiEj) surfactants and 125 well-defined oils. The key information used is the so-called "fish-tail-temperature" T* which is a unique data point in true ternary CiEj/Oil/Water fish diagrams. The PACNs of CiEj surfactants are compared with other descriptors of their amphiphilicity, namely, the cloud point, the HLB number and the PIT-slope value. The EACNs of oils are rationalized by the Effective-Packing-Parameter concept and modelled thanks to the COSMO-RS theory.

Hexahydrofarnesyl as an original bio-sourced alkyl chain for the preparation of glycosides surfactants with enhanced physicochemical properties.

Five new bio-based surfactants have been synthetized by coupling hexahydrofarnesol with mono and di-saccharides. Hexahydrofarnesol (3,7,11-trimethyl-dodecan-1-ol) is a by-product of the industrial production of farnesane, a sustainable aviation fuel obtained by a fermentation process from sugar feedstocks. Using hexahydrofarnesol as the lipophilic starting material allows obtaining 100% bio-based surfactants while valorizing an industrial by-product. Moreover, the C15-branched alkyl chain brings unique properties to the surfactants. This paper presents a physicochemical characterization of these new surfactants including their behaviors in water (water solubility, critical micellar concentration and surface tension) and in oil/water systems (interfacial tension against model oil and ternary phase behavior). Their hydrophilicities have been determined thanks to the PIT-slope method and compared to the ones of standard surfactants with linear alkyl chains, in order to distinguish the contributions of the sugar polar heads and of the branched hexahydrofarnesyl lipophilic chain. This novel class of surfactants combines the properties of sugar-based surfactants (low sensitivity to temperature and salinity, ability to form Winsor III microemulsion systems over a wide range of salinity), along with specificities linked to the branched alkyl chain (lower Krafft temperature, low surface tension).

Using the dynamic Phase Inversion Temperature (PIT) as a fast and effective method to track optimum formulation for Enhanced Oil Recovery.

HYPOTHESIS: The attainment of ultralow interfacial tensions between crude oil and injected aqueous surfactant mixtures is a prerequisite for an effective chemical Enhanced Oil Recovery (EOR). The dynamic Phase Inversion Temperature (PIT) of SOW emulsified systems is very close to the "optimum temperature" currently identified with equilibrated SOW systems. Therefore, the PIT could be a tool to track the "optimum formulation" and determine EACN of crude oils. Additionally, the PIT-slope method could be used to characterize EOR surfactants. EXPERIMENTS: The PIT of 3% C10E4/crude oils/water emulsions are compared to the PIT for n-alkanes in order to estimate crude oils EACN. The "PIT-slope" method is applied to different non-ionic and ionic extended EOR surfactants to assess their amphiphilicity. The conductivity profiles of different EOR surfactants/crude oil/NaCl(aq) emulsions at fw = 0.5 are determined at different salinities. FINDINGS: Considering the PIT shifts and shapes, it is possible to infer relevant information on the crude oil such as precise EACN and relationships between optimum salinity and temperature. The "PIT-Slope method" allows ranking EOR surfactants according to their amphiphilicity. Mixing both results allows a faster determination of key parameters used in EOR compared to studies with equilibrated system.

Predicting the Surface Tension of Liquids: Comparison of Four Modeling Approaches and Application to Cosmetic Oils.

The efficiency of four modeling approaches, namely, group contributions, corresponding-states principle, σ-moment-based neural networks, and graph machines, are compared for the estimation of the surface tension (ST) of 269 pure liquid compounds at 25 °C from their molecular structure. This study focuses on liquids containing only carbon, oxygen, hydrogen, or silicon atoms since our purpose is to predict the surface tension of cosmetic oils. Neural network estimations are performed from σ-moment descriptors as defined in the COSMO-RS model, while methods based on group contributions, corresponding-states principle, and graph machines use 2D molecular information (SMILES codes). The graph machine approach provides the best results, estimating the surface tensions of 23 cosmetic oils, such as hemisqualane, isopropyl myristate, or decamethylcyclopentasiloxane (D5), with accuracy better than 1 mN·m-1. A demonstration of the graph machine model using the recent Docker technology is available for download in the Supporting Information.

Synthesis, surfactant properties and antimicrobial activities of methyl glycopyranoside ethers.

A series of amphiphilic methyl glucopyranoside ethers incorporating various alkyl chain lengths has been synthesized from commercially available methyl glucopyranosides following an acetalisation/hydrogenolysis sequence. The amphiphilic properties of ethers and acetal intermediates were evaluated. Both families exhibit excellent surfactant properties with a maximum efficiency obtained for compounds bearing a linear dodecyl chain (CMC = 0.012 mM, γsat. = 30 mN m-1). Antimicrobial activity studies revealed an efficient activity (0.03 < MIC < 0.12 mM) against Gram-positive bacteria such as Listeria monocytogenes, Enterococcus faecalis, Enterococcus faecium and Staphylococcus aureus. More importantly, these compounds were found to be active against multi-resistant strains such as vancomycin-, methicillin- and daptomycin-resistant strains. Finally, it was found that antimicrobial activities are closely related to physicochemical properties and are also influenced by the nature of the carbohydrate moiety.

Supramolecular assistance between cyclodextrins and didecyldimethylammonium chloride against enveloped viruses: Toward eco-biocidal formulations.

Nosocomial infections have emerged as important causes of morbidity and mortality in immunocompromised individuals. In this respect, biocides are widely used in hospitals leading to resistant microorganisms. We show here that cyclodextrins can remarkably boost the virucidal activity of di-n-decyldimethylammonium chloride. These oligosaccharides synergistically work with the biocide affording a noticeable reduction of the active virucide concentration between 40 and 85%. Partial replacement of a significant amount of the biocide by eco- and bio-compatible cyclodextrins whilst maintaining the same activity is of great interest as it allows the reduction of the toxicological drawbacks of classical biocide mixtures.

Theoretical and Kinetic Tools for Selecting Effective Antioxidants: Application to the Protection of Omega-3 Oils with Natural and Synthetic Phenols.

Radical-scavenging antioxidants play crucial roles in the protection of unsaturated oils against autoxidation and, especially, edible oils rich in omega-3 because of their high sensitivity to oxygen. Two complementary tools are employed to select, among a large set of natural and synthetic phenols, the most promising antioxidants. On the one hand, density functional theory (DFT) calculations provide bond dissociation enthalpies (BDEs) of 70 natural (i.e., tocopherols, hydroxybenzoic and cinnamic acids, flavonoids, stilbenes, lignans, and coumarins) and synthetic (i.e., 2,6-di-tert-butyl-4-methylphenol (BHT), 3-tert-butyl-4-hydroxyanisol (BHA), and tert-butylhydroquinone (TBHQ)) phenols. These BDEs are discussed on the basis of structure-activity relationships with regard to their potential antioxidant activities. On the other hand, the kinetic rate constants and number of hydrogen atoms released per phenol molecule are measured by monitoring the reaction of phenols with 2,2-diphenyl-1-picrylhydrazyl (DPPH(•)) radical. The comparison of the results obtained with these two complementary methods allows highlighting the most promising antioxidants. Finally, the antioxidant effectiveness of the best candidates is assessed by following the absorption of oxygen by methyl esters of linseed oil containing 0.5 mmol L(-1) of antioxidant and warmed at 90 °C under oxygen atmosphere. Under these conditions, some natural phenols namely epigallocatechin gallate, myricetin, rosmarinic and carnosic acids were found to be more effective antioxidants than α-tocopherol.

Myricetin, rosmarinic and carnosic acids as superior natural antioxidant alternatives to α-tocopherol for the preservation of omega-3 oils.

22 natural polyphenols are compared to 7 synthetic antioxidants including BHT, BHA, TBHQ and PG with regard to their ability to protect omega-3 oils from autoxidation. The antioxidant efficiency of phenols is assessed using the DPPH test and the measurement of oxygen consumption during the autoxidation of oils rich in omega-3 fatty acids. Also, the bond dissociation enthalpies (BDE) of the Ar-OH bonds are calculated and excellent correlations between thermodynamic, kinetic and oxidation data are obtained. It is shown that kinetic rates of hydrogen transfer, number of radicals scavenged per antioxidant molecule, BDE and formation of antioxidant dimers from the primary radicals play an important role regarding the antioxidant activity of phenols. Based on this, it is finally shown that myricetin, rosmarinic and carnosic acids are more efficient than α-tocopherol and synthetic antioxidants for the preservation of omega-3 oils.

Boosting effect of ortho-propenyl substituent on the antioxidant activity of natural phenols.

Seven new antioxidants derived from natural or synthetic phenols have been designed as alternatives to BHT and BHA antioxidants. Influence of various substituents at the ortho, meta and para positions of the aromatic core of phenols on the bond dissociation enthalpy of the ArO-H bond was evaluated using a DFT method B3LYP/6-311++G(2d,2p)//B3LYP/6-311G(d,p). This prediction highlighted the ortho-propenyl group as the best substituent to decrease the bond dissociation enthalpy (BDE) value. The rate constants of hydrogen transfer from these phenols to DPPH radical in a non-polar and non-protic solvent have been measured and were found to be in agreement with the BDE calculations. For o-propenyl derivatives from 2-tert-butyl-4-methylphenol, BHA, creosol, isoeugenol and di-o-propenyl p-cresol, fewer radicals were trapped by a single phenol molecule, i.e. a lower stoichiometric number. Reaction mechanisms involving the evolution of the primary phenoxyl radical ArO are proposed to rationalise these effects.

Rationalization and Prediction of the Equivalent Alkane Carbon Number (EACN) of Polar Hydrocarbon Oils with COSMO-RS σ-Moments.

The equivalent alkane carbon numbers (EACNs) of 20 polar hydrocarbon oils are determined by the fishtail method. These values supplemented by 43 already reported EACNs of other hydrocarbons are rationalized by using the COSMO-RS σ-moments as descriptors for a QSPR analysis. A reliable model, with only two meaningful physicochemical parameters, namely the surface area (M0(X)) and the overall polarity (M2(X)) of the oil X, is able to predict the EACN values of a large variety of oils including (cyclo)alkanes, (cyclo)alkenes, terpenes, aromatics, alkynes, and chloroalkanes and to rationalize structural effects on EACNs. Furthermore, the dependence of the EACN of homologous oils on the chain length provides some molecular insight into how the different oils penetrate into the interfacial film of surfactants.

Structure-interfacial properties relationship and quantification of the amphiphilicity of well-defined ionic and non-ionic surfactants using the PIT-slope method.

The Phase Inversion Temperature of a reference C10E4/n-Octane/Water system exhibits a quasi-linear variation versus the mole fraction of a second surfactant S2 added in the mixture. This variation was recently proposed as a classification tool to quantify the Hydrophilic-Lipophilic Balance (HLB) of commercial surfactants. The feasibility of the so-called PIT-slope method for a wide range of well-defined non-ionic and ionic surfactants is investigated. The comparison of various surfactants having the same dodecyl chain tail allows to rank the polar head hydrophilicity as: SO3Na⩾SO4Na⩾NMe3Br>E2SO3Na≈CO2Na⩾E1SO3Na⩾PhSO3Na>Isosorbide(exo)SO4Na≫IsosorbideendoSO4Na≫E8⩾NMe2O>E7>E6⩾Glucosyl>E5⩾Diglyceryl⩾E4>E3>E2≈Isosorbide(exo)>Glyceryl>Isosorbide(endo). The influence on the surfactant HLB of other structural parameters, i.e. hydrophobic chain length, unsaturation, replacement of Na(+) by K(+) counterion, and isomerism is also investigated. Finally, the method is successfully used to predict the optimal formulation of a new bio-based surfactant, 1-O-dodecyldiglycerol, when performing an oil scan at 25 °C.

Dramatic solvent effect on the synergy between α-tocopherol and BHT antioxidants.

During the DPPH scavenging assay carried out in non polar and non protic solvents, such as toluene, BHT regenerates α-tocopherol from tocopheryl radical, whereas in polar and protic solvents, like methanol, no regeneration is observed due to a fast electron transfer reaction from the tocopheryl radical to the reactive DPPH radical. Surprisingly, in the presence of a small amount of alcohol, the synergy is exalted and BHT regenerates twice as much α-tocopherol due to a nucleophilic addition of short alcohols on the BHT oxidation product, giving a new phenolic co-antioxidant.