Linear Solvation Energy Relationship Equation Research Articles

Preparation of ionic liquid stationary phase copolymerized with anion and cation for mixed-mode liquid chromatography

Ionic liquids (ILs) are a promising material to develop stationary phases for mixed-mode chromatography (MMC). In order to investigate the effect of anion type and polymerization method of ionic liquid, this work prepared and compared two stationary phases (Sil-IM-Br and Sil-IM-SAG) based on the polymeric ionic liquid, one of which copolymerized cation and anion. Two stationary phases were characterized and provided satisfactory retention repeatability (RSD < 0.3 %) and column efficiency (84600 plates/m). Chromatographic conditions (ACN content, salt concentration, and pH) were varied to reveal the retention characters and interactions between stationary phases and solutes. The results showed that both two developed stationary phases can operate under the mixed mode of RPLC/HILIC/IEC, but diverse selectivity was provided. So, the retention mechanisms were studied by linear solvation energy relationship equation (LSER) and thermodynamic research. Two stationary phases showed totally different retention towards carboxylic acids, which resulted from the effect of anion bonded. Lastly, the developed stationary phases were applied to separate alkylbenzenes and polycyclic aromatic hydrocarbons (PAHs) under RPLC. Furthermore, 7 carboxylic acids and 7 nucleosides and bases and complex samples were successfully separated under HILIC mode, Sil-IM-Br and Sil-IM-SAG provide better performances and different selectivity when compared with commercial mixed-mode columns. This work proves that cationic and anionic copolymerization provides a new method for stationary phase design, and better selectivity can be obtained by changing the anions.

Adsorption modeling of organic compounds (OCs) by carbon nanotubes (CNTs): role of OC and CNT properties on the linear solvation energy relationship.

This study evaluated a comprehensive database for the adsorption of polar and nonpolar organic compounds (OCs) by carbon nanotubes (CNTs) and to use the linear solvation energy relationship (LSER) technique for developing predictive adsorption models of OCs by multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs). The results showed that coefficient of determinations (R2) values for all compounds are higher variability in the 200 g/mol molecular weight cutoff (74-99%). When the molecular weight cutoff of all OCs is higher than 200 g/mol, the trend of their R2 values is decreased (less than 70%). Among all adsorbate descriptor coefficients, V and B terms are the most significant descriptors (p-values ≤ 0.05) in LSER equations for adsorption of low molecular weight polar and nonpolar OCs by both CNTs. Besides, KOW normalization of all Kd values did not have significant impact on the regression of the LSER model, indicating that hydrophobic interactions are not sole mechanism for the adsorption of OCs on CNTs. Lastly, SWCNTs exhibited higher polar OCs uptake than MWCNTs, which was attributed to more polar surface of SWCNTs as suggested by its high oxygen content (%10).

Synthesis of 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazol-5(4H)-one and 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazole-5(4H)-thione and solvent effects on their infrared spectra in organic solvents

In the present study novel 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazol-5(4H)-one (compound (4)) and 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazole-5(4H)-thione (compound (5)) were synthesized. These oxadiazole ring derivatives were characterized by IR, 1H NMR, 13C NMR and HRMS analyses. The solvent effects on CO, CN and CS stretching vibrational frequencies (ν(CO), ν(CN) and ν(CS)) of synthesized compounds were investigated experimentally using attenuated total reflection (ATR) infrared spectroscopy and compared with the theoretical results assigned using the potential energy distribution (PED) contributions. Furthermore, the ν(CO), ν(CN) and ν(CS) of compound (4) and compound (5) were correlated with empirical solvent parameters such as the solvent acceptor numbers, the Swain equation, the Kirkwood-Bauer-Magat equation, and the linear solvation energy relationships. Apart from the linear effects investigated in similar studies, solvent-induced vibrational shifts were investigated using the quadratic equation. The prediction capabilities of empirical solvent parameters were statistically compared. It was found that the linear solvation energy relationships show better correlation than the other empirical solvent parameters. Additionally, the quadratic equation provided more accurate predictions for the vibrational frequency locations than the Swain and the linear solvation energy relationships equations.

Exploring electronic structure, and substituent effect of some biologically active benzimidazole derivatives: Experimental insights and DFT calculations

A series of (1H-benzimidazol-2-ylmethyl)-N-(4-phenyl)amine derivatives incorporating different electron-donating and withdrawing groups (X = 4OCH3 (1), 4CH3 (2), H (3), 4Cl (4), and 4Br (5)) on the para-position of the phenyl substituent was prepared, characterized and screened for their potential antimicrobial activity against some microbes. The substituent effect on the spectroscopic data (vibrational modes and NMR resonances) is well established by fitting with the Hammett constant. The unsubstituted derivative 4 exhibited comparable activity (MIC = 0.26 μM) to the standard tetracycline (MIC = 0.18 μM) against Staphylococcus aureus. Introduction of a substituent to the phenyl ring led to diminishing of the antibacterial activity. The substituent effect on the electron structure of 1–5 was investigated by TDDFT calculations. The acid dissociation constants of the ionizable NH group correlate well with Kubota's σ− parameter (R2 = 0.9196). The solvatochromism behavior of 1–5, in solvents of different polarity and hydrogen-bond tendency, was investigated by linear solvation–energy relationship equation analysis. Correlation between various quantum chemical descriptors, and antibacterial activity was carried out to verify a structural activity relation for this series of benzimidazole derivatives.

Effects of high concentrations of mobile phase additives on retention and separation mechanisms on a teicoplanin aglycone stationary phase in supercritical fluid chromatography

The objective of this study is to understand the behavior of a peptide in a medium containing supercritical carbon dioxide mixed with an alcohol (methanol) and acidic or basic additives in uncommonly high concentrations. Chirobiotic TAG is a chromatographic column made of silica bonded with a macrocyclic peptide, teicoplanin aglycone. With this stationary phase, two additives (trifluoroacetic acid and isopropylamine) were tested under extreme concentration conditions to observe the behavior of this peptide. Indeed, concentrations exceeding 1 M in the methanol co-solvent (>0.1 M overall concentration in the CO2-methanol mixture) were used whereas usual additive concentrations employed in supercritical fluid chromatography (SFC) rarely exceed 50 mM in the co-solvent. One purpose was to modify the apparent pH of the fluid, which is normally slightly acidic (around 5) and consequently possibly changing the ionization state of the peptide. Firstly, the effect of acidic and basic additives on the polarity and the apparent pH were evaluated with the help of color indicators. This served to assess the ionization state of the peptide under the selected operating conditions. Secondly, 54 achiral and 24 chiral molecules were injected in the chromatographic column at different levels of additives. The achiral species served at establishing retention models based on linear solvation energy relationships (LSER), while the chiral species were examined for their enantioresolution. From the LSER equations and observation of chromatograms, it appeared that specific interactions between the peptide-based stationary phase and the analytes evolved when increasing the concentration of additives, particularly hydrogen bonds and ionic interactions. A bare silica stationary phase (Acquity BEH) served as reference to deconvolute the contributions of silica support and bonded peptide. This study, with these extreme conditions of mobile phase, could be useful to understand the behavior of such peptides in SFC mobile phases and also improve the knowledge of the effects of additives in SFC, which should be helpful in the future prospect of analyzing large biomolecules in SFC.

Prediction of solvent effect on enzyme enantioselectivity

Enantiomeric ratios for the esterification reaction of 2-phenylpropionic acid with 1-octanol catalyzed by immobilized Candida antarctica lipase B in sixteen organic solvents have been measured. Correlation equations that relate the enzyme enantioselectivity with the van der Waals volume (Vw), the van der Waals area (Aw), and the Hildebrand solubility parameters (δ2) of the solvents were obtained, and they were compared with linear solvation energy relationship (LSER) correlation equations, which relates the enzyme enantioselectivity with polarity, acidity, basicity, and Hildebrand solubility parameters of the solvents. Statistical analysis of the experimental data for the esterification reaction investigated here as well as for seven other reactions taken from the literature showed that the pure solvent Vw, Aw and δ2 parameters, sufficiently describe the dependence of enzyme enantioselectivity on the properties of the solvent, yielding better results than the LSER equations that use one more parameter. Furthermore, the enzyme enantioselectivity has been related to the infinite dilution activity coefficients of substrates in the solvent, which are predicted by the COSMO-RS model. It is shown that the predicted by COSMO-RS ratios of infinite dilution activity coefficients of the two enantiomers can be used to correlate satisfactorily the enantiomeric ratios.

Adsorption of volatile organic vapors by activated carbon derived from rice husk under various humidity conditions and its statistical evaluation by linear solvation energy relationships

The adsorption of sixteen volatile organic compounds (VOCs) in the gas phase by activated carbon (AC) generated from waste rice husk was investigated under two different levels of relative humidity (RH) by inverse gas chromatography (IGC). R850 AC had the largest surface area and was characterized. Linear solvation energy relationship (LSER) was employed to understand the interactions between R850 AC and VOCs. The major functional groups on the surface of R850 AC were CC, SiOSi, OH, and CO(H). IGC indicated that the gas/solid adsorption coefficients (log Kd) for the 16 VOCs lied in the range 4.0–6.1 (g g−1)/(g mL−1) under medium RH (around 55%), but decreased under high RH (90%). Moreover, the log Kd value predicted from our LSER equations was highly correlated to the experimental log Kd of the R850 AC. This study demonstrates that R850 AC is a promising material for VOC removal and the established LSER equations are useful to estimate VOC adsorption.

Characterization of volatile organic compound adsorption on multiwall carbon nanotubes under different levels of relative humidity using linear solvation energy relationship

Multiwall carbon nanotubes (MWCNTs) have been used as an adsorbent for evaluating the gas/solid partitioning of selected volatile organic compounds (VOCs). In this study, 15 VOCs were probed to determine their gas/solid partitioning coefficient (LogKd) using inverse gas chromatography at different relative humidity (RH) levels. Interactions between MWCNTs and VOCs were analyzed by regressing the observed LogKd with the linear solvation energy relationship (LSER). The results demonstrate that the MWCNT carbonyl and carboxyl groups provide high adsorption capacity for the VOCs (LogKd 3.72–5.24g/kg/g/L) because of the π-/n-electron pair interactions and hydrogen-bond acidity. The increasing RH gradually decreased the LogKd and shifted the interactions to dipolarity/polarizability, hydrogen-bond basicity, and cavity formation. The derived LSER equations provided adequate fits of LogKd, which is useful for VOC-removal processes and fate prediction of VOC contaminants by MWCNT adsorption in the environment.

Combined 1H NMR and LSER study for the compound-specific interactions between organic contaminants and organobentonites

The compound-specific mechanisms for the sorption of organic contaminants onto cetyltrimethylammonium-saturated bentonite (i.e., CTMA-Bentonite) in water were evaluated by 1H NMR study and Linear Solvation Energy Relationship (LSER) approach. In 1H NMR study, comparing with pure CTMAB, the up-field shifts of hydrogen peaks for CH2N+ and CH3N+ of CTMA+ in CTMAB-aromatics (1-naphtylamine, aniline and phenol) mixtures are much greater than that in CTMAB-aliphatics (cyclohexanone and cyclohexanol) mixtures. Meanwhile, the peak position of hydrogen on amino- and hydroxyl-groups of aromatic compounds also changes greatly. 1H NMR data demonstrated the strong molecular interaction between the positive ammonium group of CTMA+ and the delocalized π-systems of aromatic solutes, whereas the interactions of CTMA+ with aliphatic compounds having electron-donating groups (such as cyclohexanol and cyclohexanone) or aromatic ring substituted by electron-withdrawing groups (i.e., nitrobenzene) or nonpolar aromatic compounds with single phenyl ring (i.e., toluene) are weak. The derived LSER equation was obtained by a multiple regression of the solid–water sorption coefficients (Kd) of 16 probe solutes upon their solvation parameters, and demonstrates aromatics sorption onto CTMA-Bentonite is concurrently governed by the π-/n-electron pair donor–accepter interaction and the cavity/dispersion interaction, while the predominant mechanism for aliphatic compounds is the cavity/dispersion interaction, consisting with the 1H NMR results.

Cooperativity between various types of polar solute–solvent interactions in aqueous media

Partition coefficients of seven low molecular weight compounds were measured in multiple aqueous two-phase systems (ATPSs) formed by pairs of different polymers. The ionic composition of each ATPS was varied to include 0.01M sodium phosphate buffer (NaPB), pH 7.4 and 0.1M Na2SO4, 0.15M NaCl, and 0.15M NaClO4 all in 0.01M NaPB, pH 7.4. The differences between the solvent features of the coexisting phases in all the ATPSs were estimated from partitioning of a homologous series of dinitrophenylated-amino acids and by the solvatochromic method. The solute-specific coefficients for the compounds examined were determined by the multiple linear regression analysis using the modified linear solvation energy relationship equation. It is established that the solute specific coefficients characterizing different types of the solute–water interactions (dipole–dipole, dipole–ion, and H-bonding) for a given solute change in the presence of different salt additives in the solute specific manner. It is also found that these characteristics are linearly interrelated. It is suggested that there is a cooperativity between various types of solute–water interactions governed by the solute structure.

Characterization of surface confined ionic liquid stationary phases: Impact of cation revisited

Modification of the Linear Solvation Energy Relationship (LSER) equation to account for ionic interactions in the retention of ionizable compounds has enabled the elucidation in the effect of the imidazolium cation identity on retention. Three Surface Confined Ionic Liquid stationary phases were synthesized from an octylbromide phase on silica: 1-octyl-3-methylimidazolium bromide (MIM), 1-octyl-3-butylimidazolium bromide (BIM), and 1-octyl-3-benzylimidazolium bromide (BzIM). These phases were probed via a 35 analyte probe set, including 6 phenolic acids, 5 anilinic bases, and 2 pyridinic bases, and the resulting column parameters compared with previously reported interactions of ionic liquids or Surface Confined Ionic Liquids. The correlation between experimental and calculated retention for the conventional, 6-parameter LSER equation was very poor: r2=0.64 (MIM), 0.60 (BIM), and 0.62 (BzIM). By accounting for the ionic interactions between stationary phase and analytes, linearity for the modified, 8 parameter LSER equation was significantly improved to r2=0.997 (MIM), 0.996 (BIM), and 0.997 (BzIM). The primary difference between cation identities is within the retention of acids where BIM>BzIM>MIM. We conjecture that the accessibility of bulky, acidic analytes to the on-top interaction of the imidazolium ring is the major contributor to increased anion retention.

A novel method for characterization and comparison of reversed-phase column selectivity

Characterization of reverse-phase column selectivity is helpful for chromatographers to select an optimal column. A novel method, based on linear solvation energy relationships (LSERs) combined with fundamental retention equations, was developed to characterize and compare reversed-phase column selectivity. The retention times of 25 elaborately selected solutes on 12 reversed-phase columns were determined in three linear gradient elutions. Using these retention times, fundamental retention equations were acquired by a complex sample analysis software system (CSASS). When 0%, 10%, 20%, 30%, 40% and 50% acetonitrile were introduced into the fundamental retention equations, the corresponding retention factors were predicted and used to obtain LSER equations by multiple linear regression. In the gradient elution, the retention times of solutes could be accurately determined and the excessively long or short analysis time could be avoided. As the retention factor (lnkw) at a hypothetical 0% organic modifier closely reflected properties of columns, coefficients of LSERs equations obtained based on lnkw were employed to discuss the properties of different stationary phases. An angle and a spider diagram based on solvation energy vectors were used to compare selectivity differences between stationary phases, which provided a visual means for users to select appropriate columns with orthogonal or similar selectivity. These results of column selectivities were compared with those obtained by geometric orthogonality approach, and a consistent result was acquired. Finally, Click TE-CD and XCharge C18PN with highest difference in column selectivity were applied to the separation of Psoralea corylifolia extraction.

Application of the LSER method for investigation of intermolecular interactions of porous polymer surface with organic molecules

The contributions of intermolecular interactions into the molar change of free energy -ΔF of sorption on the surface of porous polymers of various natures were studied by the linear solvation-energy relationship (LSER) method. It was shown that a high correlation coefficient does not ensure reliability of the results obtained. The applicability of the LSER equations for investigation of the polarity of polymer sorbents was analyzed.

Analysis of amino acid–water interactions by partitioning in aqueous two-phase systems. I—Amino acids with non-polar side-chains

Partition ratios of 10 l-amino acids with non-polar side chains (Gly, Ala, Val, nor-Val, Ile, Leu, nor-Leu, Phe, Trp and Pro) were measured in ten different polymer/polymer aqueous two-phase systems (ATPS) containing 0.15M NaCl in 0.01M phosphate buffer, pH 7.4. The solute-specific coefficients representing the solute dipole–dipole, hydrogen bonding and electrostatic interactions with aqueous environment for the compounds examined were determined by the multiple linear regression analysis using the modified linear solvation energy relationship equation. It is shown that linear combinations of these coefficients are correlated with the amino acid lipophilicity/hydrophobicity scales reported in the literature. The results obtained imply that the solute-specific coefficients may be used as solute descriptors for quantitative structure–property relationship (QSPR) analysis.

Solvatochromic relationship: Prediction of distribution of ionic solutes in aqueous two-phase systems

Partition ratios of several ionic compounds in 20 different polymer/polymer aqueous two-phase systems (ATPS) containing 0.15M NaCl in 0.01M phosphate buffer, pH 7.4, were determined. The differences between the electrostatic properties of the phases in all the ATPS were estimated from partitioning of the homologous series of dinitrophenylated-amino acids. Also the solvatochromic solvent parameters characterizing the solvent dipolarity/polarizability (π*), solvent hydrogen-bond donor acidity (α), and solvent hydrogen-bond acceptor basicity (β) of aqueous media were measured in the coexisting phases of the ATPS. The solute-specific coefficients for the compounds examined were determined by the multiple linear regression analysis using the modified linear solvation energy relationship equation. The minimal number of ATPS necessary for determination of the coefficients was established and 10 ATPS were selected as a reference ATPS set. The solute-specific coefficients values obtained with this reference set of ATPS were used to predict the partition ratios for the compounds in 10 ATPS not included in the reference set. The predicted partition ratios values were compared to those determined experimentally and found to be in good agreement. It is concluded that the presented model of solute–solvent interactions as the driving force for solute partitioning in polymer/polymer ATPS describes experimental observations with 90–95% accuracy.

Predictive Model Development for Adsorption of Aromatic Contaminants by Multi-Walled Carbon Nanotubes

In the present study, Quantitative Structure-Activity Relationship (QSAR) and Linear Solvation Energy Relationship (LSER) techniques were used to develop predictive models for adsorption of organic contaminants by multi-walled carbon nanotubes (MWCNTs). Adsorption data for 29 aromatic compounds from literature (i.e., the training data) including some of the experimental results obtained in our laboratory were used to develop predictive models with multiple linear regression analysis. The generated QSAR (r(2) = 0.88), and LSER (r(2) = 0.83) equations were validated externally using an independent validation data set of 30 aromatic compounds. External validation accuracies indicated the success of parameter selection, data fitting ability, and the prediction strength of the developed models. Finally, the combination of training and validation data were used to obtain a combined LSER equation (r(2) = 0.83) that would be used for predicting adsorption of a wide range of low molecular weight aromatics by MWCNTs. In addition, LSER models at different concentrations were generated, and LSER parameter coefficients were examined to gain insights to the predominant adsorption interactions of low molecular weight aromatics on MWCNTs. The molecular volume term (V) of the LSER model was the most influential descriptor controlling adsorption at all concentrations. At higher equilibrium concentrations, hydrogen bond donating (A) and hydrogen bond accepting (B) terms became significant in the models. The results demonstrate that successful predictive models can be developed for the adsorption of organic compounds by CNTs using QSAR and LSER techniques.

Characterization of Adsorption Mechanisms of Volatile Organic Compounds with Montmorillonite at Different Levels of Relative Humidity via a Linear Solvation Energy Relationship Approach

The sorption mechanisms of volatile organic compounds (VOCs) with montmorillonite, a clay, need to be studied adequately to predict the fate of VOCs in the environment and to fully employ the sorption characteristics of clays to control VOC pollution. The sorption of VOCs as vapors to a typical montmorillonite, STx-1, at different levels of relative humidity were characterized using a linear solvation energy relationship (LSER). The fitted LSER equation was obtained by a multiple regression of the partition coefficients of 22 probe chemicals against their solvation parameters. The coefficients of the five-parameter LSER equations show that montmorillonite interacts with VOC molecules mainly through dispersion, partly through dipolarity/polarizability and hydrogen bonds, and with negatively π-/n-electron pair interaction under dry conditions. With an increase of relative humidity, hydrated montmorillonite behaves both as a hydrogen-bond donor (HBD) and hydrogen-bond acceptor (HBA) and interacts with chemic...

Experimental Determination of LSER Parameters for a Set of 76 Diverse Pesticides and Pharmaceuticals

Linear solvation energy relationships (LSERs) have more recently been proposed as the method of choice to describe and/or predict the partitioning behavior of neutral organic compounds over a large range of environmental matrices and for a broad variety of compounds in a consistent manner. However, when dealing with more complex, polar compounds with multiple functional groups, it has also been noted that there is a severe lack of substance descriptors quantifying the different intermolecular interactions that these compounds may undergo. In this study, we used a system of eight reversed phase, normal phase, and hydrophilic interaction HPLC systems to determine the substance descriptors for H-bond donor (A) and acceptor (B) interactions and for polarizability and dipolarity (S) for a set of 76 complex compounds containing multiple functional groups, comprising mainly pesticides and some pharmaceuticals. The obtained substance descriptors for most compounds are unique in that values of A, S, and B are high and lie at the very upper end of the numerical range of currently known substance descriptors. The substance descriptors have been cross-compared against literature values of the octanol-water (Kow) and air-water (Kaw) partition coefficients and against a set of heptan-methanol partition coefficients (Khm) experimentally determined with a consistent methodology herein. The comparison confirmed plausibility of the substance descriptors of all except six tested compounds. The newly determined substance descriptors promise to be highly valuable in chemicalfate modeling, allowing, in conjunction with available phase descriptors, for a better representation of partitioning of polar compounds in those models. The results also reveal a systematic deviation of the log Kow values predicted with our substance descriptors from the literature values. The deviation points toward a possible problem when existing LSER equations are applied to polar, multifunctional compounds with high values of A, S, and B. Hence, the substance descriptors determined herein should also be helpful in revisiting the validity of existing LSERs for complex, polar compounds.

Characterization of sorption mechanisms of solid-phase microextraction with volatile organic compounds in air samples using a linear solvation energy relationship approach

The linear solvation energy relationship (LSER) model was used to characterize interactions responsible for sorption of volatile organic compounds (VOCs) in air samples on six different solid-phase microextraction (SPME) fibers at 296 K and zero relative humidity. The polydimethylsiloxane and polyacrylate fibers sorption data were also modeled at different relative humidities in the range of 10–90% and influence of water vapors on the extraction process is discussed. The LSER equations were obtained by a multiple regression of the distribution coefficients of 14 probe solutes on an appropriate SPME fiber against the solvation parameters of the solutes. The derived LSER equations successfully predicted the VOC distribution coefficients and the selectivity of individual SPME fibers for the various volatile solutes. The LSER approach coupled with SPME is a relatively simple and reliable tool to rapidly characterize the sorption mechanism of VOCs with various stationary phases and may potentially be applied to design and test new chromatographic materials for sampling or separation of VOCs.

Predicting dermal permeability of biocides in commercial cutting fluids using a LSER approach

The aim of this study is to predict dermal permeability of four phenolic biocides in four different formulations using a linear solvation energy relationship (LSER) approach, with a calibrated flow through diffusion cell system. Mathematical descriptors were determined in the laboratory, by mathematical computations, and by statistical methods. Infinite doses of 4 biocides and 25 probe chemicals in water, 17% methanol and 2 commercial metalworking fluids namely Astrocut–C ® and Tapfree 2 ® were applied to porcine skin flow through diffusion cells. The strength coefficients for the 25 probe compounds for each system were determined from multiple linear regression analysis and plugged into the Abraham's LSER equation to predict permeability values for biocides. Biocide permeability significantly decreased in methanol, Astrocut–C ® and Tapfree 2 ® when compared to water. The strength coefficients revealed that hydrophobicity played an important role in explaining the reduced permeability in vehicles compared to water. This finding is important for selection of biocides and cutting fluids formulation. The R 2 between experimental and predicted log Kp of probe solutes for water, methanol, Astrocut–C ® and Tapfree 2 ® were 0.70, 0.78, 0.89 and 0.84, respectively. In conclusion, the LSER approach adequately predicted the dermal permeability of four biocides in commercial cutting fluids and also shed light on the chemical interactions resulting in reduced permeability.