Organic Sunscreens and Their Products of Degradation in Biotic and Abiotic Conditions-In Silico Studies of Drug-Likeness and Human Placental Transport.

A total of 16 organic sunscreens and over 160 products of their degradation in biotic and abiotic conditions were investigated in the context of their safety during pregnancy. Drug-likeness and the ability of the studied compounds to be absorbed from the gastrointestinal tract and cross the human placenta were predicted in silico using the SwissADME software (for drug-likeness and oral absorption) and multiple linear regression and "ARKA" models (for placenta permeability expressed as fetus-to-mother blood concentration in the state of equilibrium), with the latter outperforming the MLR models. It was established that most of the studied compounds can be absorbed from the gastrointestinal tract.

Immobilized Keratin HPLC Stationary Phase-A Forgotten Model of Transdermal Absorption: To What Molecular and Biological Properties Is It Relevant?

Chromatographic retention data collected on immobilized keratin (KER) or immobilized artificial membrane (IAM) stationary phases were used to predict skin permeability coefficient (log ) and bioconcentration factor (log ) of structurally unrelated compounds. Models of both properties contained, apart from chromatographic descriptors, calculated physico-chemical parameters. The log model, containing keratin-based retention factor, has slightly better statistical parameters and is in a better agreement with experimental log data than the model derived from IAM chromatography; both models are applicable primarily to non-ionized compounds.

In silico assessment of risks associated with pesticides exposure during pregnancy.

Novel Quantitative Structure-Activity Relationship (QSAR) models of compounds' placenta (PL) permeability expressed as their log FM (fetus-to-mother blood concentration) values or binary PL1/0 (crossing/non-crossing) score were generated using a number of statistical tools: Multiple Linear Regression, Boosted Trees, Principal Component Analysis and Artificial Neural Networks, on the basis of molecular descriptors calculated by Mordred software and selected using Partial Least Squares (PLS) analysis. It was established that the most important predictor of both log FM and the binary PL1/0 score is Lipinski - a binary variable reflecting the compounds' ability to satisfy the criteria of drug-likeness according to the Lipinski's "Rule of 5". The quantitative (log FM) and qualitative (PL1/0) models of PL permeability were applied to 345 pesticides from different chemical families (triazines, carbamates, pyrethroids, organochlorine, organophosphorus and miscellaneous compounds).

Affinity of Compounds for Phosphatydylcholine-Based Immobilized Artificial Membrane-A Measure of Their Bioconcentration in Aquatic Organisms.

The (bioconcentration factor) of solutes in aquatic organisms is an important parameter because many undesired chemicals enter the ecosystem and affect the wildlife. Chromatographic retention factor log obtained from immobilized artificial membrane (IAM) HPLC chromatography with buffered, aqueous mobile phases and calculated molecular descriptors obtained for a group of 120 structurally unrelated compounds were used to generate useful models of log . It was established that log obtained in the conditions described in this study is not sufficient as a sole predictor of bioconcentration.

Immobilized artificial membrane-chromatographic and computational descriptors in studies of soil-water partition of environmentally relevant compounds.

Chromatographic retention factor log k obtained from immobilized artificial membrane (IAM) HPLC with buffered, aqueous mobile phases and calculated molecular descriptors (molecular weight - log M; molar volume - V; polar surface area - PSA; total count of nitrogen and oxygen atoms -(N + O); count of freely rotable bonds - FRB; H-bond donor count - HD; H-bond acceptor count - HA; energy of the highest occupied molecular orbital - E; energy of the lowest unoccupied orbital - E; dipole moment - DM; polarizability - α) obtained for a group of 175 structurally unrelated compounds were tested in order to generate useful models of solutes' soil-water partition coefficient normalized to organic carbon log K. It was established that log k obtained in the conditions described in this study is not sufficient as a sole predictor of the soil-water partition coefficient. Simple, potentially useful models based on log k and a selection of readily available, calculated descriptors and accounting for over 88% of total variability were generated using multiple linear regression (MLR) and artificial neural networks (ANN).

IAM Chromatographic Models of Skin Permeation.

Chromatographic retention factor log obtained from IAM HPLC chromatography with buffered aqueous mobile phases and calculated molecular descriptors (surface area-; molar volume-; polar surface area-; count of freely rotable bonds-; H-bond acceptor count-; energy of the highest occupied molecular orbital-; energy of the lowest unoccupied orbital-; and polarizability-) obtained for a group of 160 structurally unrelated compounds were tested in order to generate useful models of solutes' skin permeability coefficient log . It was established that log obtained in the conditions described in this study is not sufficient as a sole predictor of the skin permeability coefficient. Simple put, potentially useful models based on log and readily available calculated descriptors, accounting for 85 to 91% of the total variability, were generated using Multiple Linear Regression (MLR).

RP-18 TLC and Computational Descriptors of Skin Permeability of Sunscreens.

The relationships between the reversed-phase thin layer chromatographic retention parameters obtained on octadecyl-modified silica (RP-18) sorbent for mobile phases containing water and one of six water-miscible organic modifiers (acetone, methanol, acetonitrile, tetrahydrofurane, N,N-dimethylformamide, 1,4-dioxane) and skin permeability coefficients were studied for a group of 21 cosmetic raw materials, mainly organic sunscreens and preservatives. The correlations between the skin permeability coefficients log Kd calculated in silico using EpiSuite software and the RP-18 thin layer chromatographic retention parameters are mostly linear, especially for compounds of lower-to-medium lipophilicity. It was established that skin permeability coefficient models based on retention parameters collected for mobile phases containing acetone or dioxane (75% v/v), proposed for structurally unrelated cosmetic raw materials are also applicable to other actives, as shown using a test set of compounds whose in vivo log Kd data are available.

Evaluation of drug-likeness and ADME properties of sunscreens and preservatives using reversed-phase thin layer chromatographic retention data and calculated descriptors.

RP-18 TLC chromatography was used to evaluate the pharmacokinetic properties (volume of distribution, V; plasma protein binding, %PPB; the ability to cross the blood-brain barrier expressed as log PS and log BB) of several cosmetic raw materials - sunscreen and preservatives. The majority of these compounds are intended for topical use on skin and their drug-likeness and the ability to cross biological barriers are undesired. The retention parameters R, S, PC and R obtained for mobile phases containing six organic modifiers (methanol, acetonitrile, THF, acetone, dioxane, DMF) were used as the sole descriptors or combined with calculated physicochemical properties (PSA, M, V) of studied compounds.

RP-18 TLC retention data and calculated physico-chemical parameters as predictors of soil-water partition and bioconcentration of organic sunscreens.

RP-18 TLC chromatography was used to evaluate the impact on the environment (mobility in soil expressed as soil-water partition coefficient, log K; bioconcentration factor in aquatic organisms, log BCF) of several cosmetic raw materials - sunscreens, preservatives and vitamins. The retention parameters R (R extrapolated to zero concentration of an organic modifier in a mobile phase), S (slope), PC (1st principal component) and R (single TLC run parameter for mobile phases containing 75% (v/v) of an organic modifier) obtained for six organic modifiers (methanol, acetonitrile, THF, acetone, dioxane, DMF) were used as the sole descriptors or combined with calculated physico-chemical properties (PSA - polar surface area; M - molecular weight; V - molar volume) of studied compounds. The chromatographic parameters considered in this study are, generally speaking, good predictors of the compounds' mobility in soil or the affinity for aquatic organisms.

Application of RP-18 TLC Retention Data to the Prediction of the Transdermal Absorption of Drugs.

Several chromatographic parameters ( and obtained from RP-18 TLC with methanol-pH 7.4 phosphate buffer mobile phases by extrapolation to zero concentration of methanol; and obtained from RP-18 TLC with acetonitrile-pH 7.4 phosphate buffer 70:30 / as a mobile phase) and calculated molecular descriptors (molecular weight-; molar volume-; polar surface area-; total count of nitrogen and oxygen atoms-(); H-bond donor count-; H-bond acceptor count-; distribution coefficient-log ; total energy-; binding energy-; hydration energy-; energy of the highest occupied molecular orbital-; energy of the lowest unoccupied orbital-; electronic energy-; surface area-; octanol-water partition coefficient-log ; dipole moment-; refractivity-, polarizability-) and their combinations (/, /, /) were tested in order to generate useful models of solutes' skin permeability coefficient log .

Emerging or Underestimated Silica-Based Stationary Phases in Liquid Chromatography.

Several newly synthesized or forgotten silica-based stationary phases proposed for liquid chromatography are described, including non-endcapped, short-chain alkyl phases; hydrophilic and polar-endcapped stationary phases; polar-embedded alkyl phases; long-chain alkyl phases. Stationary phases with aromatic, cyanopropyl, diol and aminopropyl functionalities are also reviewed. Stationary phases of particular interest are biomolecular materials - based on immobilized cholesterol, aminoacids, peptides, proteins or lipoproteins.

Quantification of Sunscreen Benzophenone-4 in Hair Shampoos by Hydrophilic Interactions Thin-Layer Chromatography/Densitometry or Derivative UV Spectrophotometry.

Benzophenone-4 (BZ4) was separated from surfactants, dyes, preservatives, and other components of hair shampoos by thin-layer chromatography on silica gel 60 stationary phase, with ethyl acetate-ethanol-water-pH 6 phosphate buffer (15 : 7 : 5 : 1 v/v/v/v) as mobile phase. Densitometry scanning of chromatograms was performed at 285 nm. The densitometric calibration curve for BZ4 was nonlinear (second-degree polynomial), with R > 0.

Comparative (Q)SAR analysis of benzodiazepine derivatives with different biological activity.

211 compounds containing a benzodiazepine moiety (BZD) and belonging to 4 groups of different biological activity (H - inhibitors of reverse transcriptase of HIV-I virus, A - antiarrhythmic agents, G - ligands of benzodiazepine receptor in GABAergic system and C - cholecystokinin receptor antagonists) were subjected to structure-activity relationship (SAR) analysis. SAR investigations of all 211 BZD were based on Discriminant Function Analysis (DFA) of physicochemical data connected with BBB (blood-brain barrier) permeability of studied compounds. DFA was performed with STATISTICA 10.

Evaluation of the lipophilicity of selected sunscreens--a chemometric analysis of thin-layer chromatographic retention data.

The lipophilicities of 22 selected sunscreens, preservatives, and vitamins used in topical skin products were measured by thin-layer chromatography. Lipophilicity was calculated in silico from the sunscreen molecular structures and compared to the experimental octanol/water partition coefficients found in the literature. The retention of the compounds was investigated on an RP-18 stationary phase with mobile phases consisting of water and one of six organic modifiers (dioxane, tetrahydrofuran, acetone, acetonitrile, methanol, and dimethylformamide) at different concentrations.

Quantification of sunscreen ethylhexyl triazone in topical skin-care products by normal-phase TLC/densitometry.

Ethylhexyl triazone (ET) was separated from other sunscreens such as avobenzone, octocrylene, octyl methoxycinnamate, and diethylamino hydroxybenzoyl hexyl benzoate and from parabens by normal-phase HPTLC on silica gel 60 as stationary phase. Two mobile phases were particularly effective: (A) cyclohexane-diethyl ether 1 : 1 (v/v) and (B) cyclohexane-diethyl ether-acetone 15 : 1 : 2 (v/v/v) since apart from ET analysis they facilitated separation and quantification of other sunscreens present in the formulations. Densitometric scanning was performed at 300 nm.