Hydrogen Bond Descriptors Research Articles

Quantification of hydrogen bond energy based on equations using spectroscopic, structural, QTAIM-based, and NBO-based descriptors which calibrated by the molecular tailoring approach

ContextHydrogen bonds critically influence the structure and properties of both organic molecules and biomolecules, as well as supramolecular assemblies. For this reason, the development and elaboration of methods for quantitative assessment of hydrogen bond energy is an urgent challenge. In this study, using a large series of hydroxycarbonyl aliphatic compounds with the O‒H···O = C intramolecular hydrogen bond, a bank of hydrogen bond descriptors was created, including spectroscopic, structural, QTAIM-based, and NBO-based parameters. It was shown that the O‒H vibration frequency, OH chemical shift as the spectroscopic descriptors, the O···H hydrogen bond length, O···O distance, and O‒H covalent bond length as the structural descriptors, the electron density and its Laplacian, electron potential energy density in the hydrogen bond critical point, the electron density at the ring critical point as the QTAIM-based descriptors change in a correlated manner. The same correlation is found in change of the charge transfer energy through a hydrogen bond, the occupancy of the O‒H bond antibonding orbital, the Wiberg indices of the O···H hydrogen bond, and the O‒H covalent bond, as well as the polarization of the O‒H bond, which are the NBO-based descriptors. It was also recognized that the specified descriptors from the spectroscopic, structural, QTAIM-based, and NBO-based categories are functionally related to the values of intramolecular hydrogen bond energy, quantified via the molecular tailoring approach. This allowed one to obtain a system of equations for quantitative estimation of intramolecular hydrogen bond energy based on the spectroscopic, structural, QTAIM, and NBO descriptors, which makes such quantification more dependable and reliable.MethodsTo obtain the spectroscopic descriptors, the vibrational spectra and shielding constants were calculated using the GIAO method. Structural descriptors were obtained for the equilibrium geometry of molecules, calculated at the MP2(FC)/6–311 + + (2d,2p) level using the Gaussian 09 program. The QTAIM-based descriptors were calculated using the AIMAll program within the framework of the quantum theory “Atoms in Molecules.” The NBO-based descriptors were calculated using the NBO 3.1 program implemented into Gaussian 09. To quantify the energy of intramolecular hydrogen bonds, molecular fragmentation was used within the molecular tailoring approach.

Green and designable deep eutectic solvents for extraction separation of oxygenated compounds in Fischer-Tropsch oil products: Hydrogen bond descriptors and structure–activity study

In this work, choline fluoride, choline chloride, and 2-fluoroethyl-trimethylammonium bromide containing –F, –Cl, and –Br structures were used as hydrogen bond receptors. Acetamide, urea, trifluoroacetamide, xylitol, ethylene glycol, malonic acid and lactic acid containing –HN2, –COOH, –OH, and –F structures were used as hydrogen bond donors. We constructed functional deep eutectic solvents rich in hydrogen bond donors and acceptors while providing alcohol hydrogen bond attraction sites and aldehyde and ketone hydrogen bond attraction sites. The efficient separation and enrichment of trace alcohols, aldehydes, and ketones in Fischer-Tropsch (F-T) oil products were achieved through hydrogen bond interaction. The mechanism of selective extraction of different types of oxygenated compounds by functionalized deep eutectic solvents was revealed, and the linear relationship among structure, hydrogen bond descriptor, and extraction performance was clarified through quantum chemistry calculations. Further, liquid–liquid extraction was used to extract and separate the oxygenated compounds from high-temperature F-T oil products using the synthesized functional deep eutectic solvent. The experimental results showed that propanol, butyraldehyde, and methylethylketone could be extracted simultaneously and efficiently, and the solvent effects were consistent with the results of quantum chemistry calculation. The excellent extraction and separation effects were due to the large number of hydrogen bonds and oxyphilic atomic forces of deep eutectic solvents. The modern solvent was reasonably designed, which is significant for extracting different oxygenated compounds from high-temperature F-T oil products.

Structure and rotational dynamics of water around hydrogen peroxide

The density functional theory-based molecular dynamics simulations were induced to study various properties of water around different solvation pockets around hydrogen peroxide(H2O2). Our study aims to understand water behavior in the vicinity of H2O2 molecule through analyzing structure, hydrogen bond statistics, orientational and non-diffusive jump profile. A water-like peroxide molecule can form four hydrogen bonds with nearby water molecules: two as a proton donor and two as a proton acceptor, which must disturb the local structure and dynamics of the surrounding water. The presence of two different peak maxima in radial distribution function (RDF) allows us to resolve the solvation environment into three solvation sites: solvation shell I, solvation shell II, and bulk. The probability distribution of the average distance of central water molecule from 4 nearest water molecules shows a shift in the peak for solvation shell I water molecules towards a ∼0.3Å higher value compared to two other solvation shells. This further affects tetrahedral order parameters as water molecules shift from the regular tetrahedron. For the first solvation layer, the water molecules lose their tetrahedrality to a significant extent as qtet probability distribution peaks at 0.5 and broaden in the higher values of qtet without any shoulder. For the second solvation layer, we find the qtet peak at 0.87 with a minor shoulder appearing at qtet = 0.55, a sign of slight loss of tetrahedrality in the unstructured water compared to undisturbed water. Loss of tetrahedrality hints at the change of orientation of H2O molecules in the vicinity of H2O2 and affects the water-water hydrogen bond (HB) formation. A noteworthy reduction in the HB donor/acceptor account and per water HB count shows interference of H2O2. The water molecules prefer H2O2 compared to neighboring water molecules for HB formation. The orientation autocorrelation function provides the rotational pace of water molecules in the different solvation layers. The reorientation time constant difference in the solvation shells I and II fluctuate by mere 0.20 ps, showcasing the trivial nature of hydrogen peroxide and water HBs. Using the HB descriptors, we also report the non-diffusive jump profile involving vicinal water molecules of H2O2. The jump angle profile of solvation shell water molecules is in line with bulk water.

A Comprehensive Theoretical Study of Amide Resonance, Intramolecular Hydrogen Bonding, and π-Electron Delocalization in Diformyl and Dithioformyl Amine

In the present work, a comprehensive theoretical study of diformyl (DFA) and dithioformylamine (DTFA) were performed by various theoretical methods, HF, B3LYP, and MP2 with 6‑311++G(3df,3pd) basis set, and the equilibrium conformations were determined. According to these calculations, tautomeric and conformeric preferences, intramolecular hydrogen bond (IMHB) and π-electron delocalization were investigated. Generally, DAI/DTAI tautomers have extra stability with respect to the AI/TAI ones. Also, among the AI/TAI series, the AI-11/TAI-13 conformer with/without IMHB is the most stable tautomer. Moreover, our computation results reveal that the formation of the intramolecular hydrogen bond is accepted as the origin of conformational preferences. The results of hydrogen bond descriptors, such as HB energy, geometrical, topological, spectroscopic and molecular orbital parameters are in agreement with the related energy values and show that the strength of intramolecular hydrogen bond in DFA is more than DTFA ones. On the other hands, π-electron delocalization of chelated rings was measured using various indices, such as q, λ', λ, and HOMA index. Finally, the orders of hydrogen bond strength and π-electron delocalization, obtained by some of the indices, support the resonance assisted hydrogen bond theory.

Компьютерные регрессионные модели P-гликопротеинового транспорта лекарственных соединений

С использованием методов линейной регрессии, случайного леса и опорных векторов созданы регрессионные модели клеточной субстратной специфичности 177 лекарственных соединений по отношению к P-гликопротеину. QSAR моделирование проведено с помощью полного перебора всех возможных комбинаций из 7 наиболее значимых молекулярных дескрипторов с ясной физико-химической интерпретацией. Полученные модели обладают удовлетворительными статистическими характеристиками, что демонстрируется результатами внутреннего перекрестного контроля и внешнего тестирования с применением 44 новых соединений. Дескрипторы H-связи являются компонентом практически всех наиболее значимых QSAR моделей. Это подтверждает важную роль водородной связи в процессах, связанных с проникновением химических соединений через гематоэнцефалический барьер. Разработанные статистические модели могут быть использованы для оценки P-гликопротеинового транспорта новых неисследованных соединений.

LQTA-R: A new 3D-QSAR methodology applied to a set of DGAT1 inhibitors

The rapid advances in computational methods for the drug design have resulted in the accurate predictions of biological activities of ligands with or without the availability of enzyme structures. 3D-QSAR is one of the computational methods used for such purpose. Currently, freely available 3D-QSAR methods suffer the limitations like complex methodologies, difficulty in the analysis of results, applying the statistical methods and validations of models built. Present work describes simple and novel 3D-QSAR methodology, which uses bash scripts LQTA_R_LJ, LQTA_R_QQ and LQTA_R_HB using freely available R statistical program. These scripts then generate Leenard-Jones, Coulomb and Hydrogen bond descriptors. These descriptors provide the steric 3D property, electrostatic property and hydrogen bond formation capacity respectively. These scripts have been tested for the set of DGAT1 inhibitors and results showed that the 3D-QSAR models built have better predictive abilities in terms of R2 0.735, Q2loo 0.635 and R2ext 0.715. The 3D-QSAR model suggested that the substitutions of the alkyl group at the oxadiazolyl ring at the 6th position of the pyrrolo-pyridazine ring is undesirable, on the contrary, substituted phenyl ring at 7th position is responsible for the improved DGAT1 inhibitory activity. The analysis also suggested that 6th position could be substituted with the oxadiazolyl ring or analogous heterocyclic rings, where the 3rd position of such heterocyclic rings substituted with rigid hydrophobic substitute can improve DGAT1 activity.

The influence of 5-fluorouracil anticancer drug on the DNA base pairs; a quantum chemical study

In the present study, various hydrogen bonded complexes between five-fluorouracil (FU) with AT and GC base pairs were studied. First, to determine the affinity of different sites of the parent structures (FU, AT, and GC) for the hydrogen bond formation, their molecular electrostatic potentials are explored. The complexation energies and the strength of individual HBs of the plausible complexes were evaluated by energetic, geometric, spectroscopic, topologic, and molecular orbital descriptors. Our results reveal that, the FU–GC complexes (34.76–44.42 kcal mol−1) are more stable than the FU–AT ones (21.00–30.35 kcal mol−1). Among the complexes, the FU3–AT1 and FU3–GC3 are the most stable structures in the both series, which can be related to the sites with the highest affinity. Second, a detail analysis of the hydrogen bond descriptors were performed to elucidate the effect of FU on the strength of HB interactions within the base pairs. Interestingly, due to the formation of various interactions between the active sites of basic molecules, the strength of HB within the base pairs in the most cases increase about +2.75 and +.57 kcal mol−1 for the GC and AT nucleobases, respectively. Finally, several aromatic indices (HOMA, FLU, NICS (0) and NICS (1)) were applied to evaluate the significance of π-electron delocalization (π-ED) of 5/6 membered rings. These results clearly show that the π-ED of the benchmark systems increase with the formation or strengthening of the HB, which is in line with the resonance assisted hydrogen bond theory.

Hydrogen Bond Contribution to Drug Bioavailability: cheminformatics approach

A review, based mainly on own publications, is devoted to methods of investigation of “structure-bioavailability” relationships. The first part of this review contains information about classification of hydrogen bond descriptors, original 2D hydrogen bond thermodynamic descriptors, program HYBOT, original 3D hydrogen bonding potentials, original hydrogen bond surface area descriptors. The second part includes the results of applications of the above mentioned of hydrogen bond descriptors for prediction of bioavailability components such as lipophilicity, solubility in water and in physiological fluids, absorption and blood-brain barrier permeability.

Retention behavior of flavonoids on immobilized artificial membrane chromatography and correlation with cell-based permeability.

The aim of the study was to investigate the immobilized artificial membrane (IAM) retention mechanism for a set of flavonoids and to evaluate the potential of IAM chromatography to model Caco-2 permeability. For this purpose, the retention behavior of 41 flavonoid analogs on two IAM stationary phases, IAM.PC.MG and IAM.PC.DD2, was investigated. Correlations between retention factors, logkw(IAM) and octanol-water partitioning (logP) were established and the role of hydroxyl groups of flavonoids to the underlying retention mechanism was explored. IAM retention and logP values were used to establish sound linear models with Caco-2 permeability (logPapp ) taken from the literature. Both stepwise regression and multivariate analysis confirmed the contribution of hydrogen bond descriptors, as additional parameters in the either logkw(IAM) or logP models. Retention factors on both IAM stationary phases showed comparable performance with n-octanol-water partitioning towards Caco-2 permeability.

Comparative study of NH···O and NH···S intramolecular hydrogen bonds in β-aminoacrolein, β-thioaminoacrolein and their halogenated derivatives by some usual methods

We first use the second-order Moller–Plesset theory to optimize β-aminoacrolein, β-thioaminoacrolein and a set of their halogenated derivatives, which involve N–H···O and N–H···S hydrogen bonds. Then, four different methods, namely rotation barrier method (RBM), isodesmic reaction method (IRM), geometry corrected method (GCM) and related rotamers method, (RRM) are utilized to estimate the intramolecular hydrogen bond (IMHB) energies. The linear correlations between the estimated IMHB energies and some hydrogen bond strength descriptors such as geometrical, electron density topological and spectroscopic parameters are obtained. According to our data, RRM and RBM have the best linear correlations with all of the hydrogen bond descriptors, while GCM and IRM do not reveal suitable results. It is assumed that the performance or reliability of the estimating methods is determined based on the value of squared regression coefficients (R 2). By adding the results of the previous studies including OH···O, OH···S and NH···O hydrogen bond units to the present obtained data, the methods can be sorted according to their relative reliability as follows: RRM > RBM ≫ GCM > IRM.

Determination of the molecular structure of gaseous proline by electron diffraction, supported by microwave and quantum chemical data

The molecular structures of the four most stable conformers of neutral proline (pyrrolidine-2-carbonic acid) were investigated by means of gas-phase electron diffraction. The results were used in conjunction with the experimental rotational constants in combined structural analysis. Small differences between similar structural parameters were constrained on the basis of theoretical calculations at the M062X/aug-cc-pVTZ level of theory. Because intramolecular hydrogen bonds play an important role in the molecular structure and conformational stability of amino acids, the hydrogen bond descriptors calculated by natural bond orbital, atoms in molecules, interacting quantum atoms and noncovalent interactions methods were included.

Exploring the correlation between the π-electron delocalization and intramolecular hydrogen bond in malonaldehyde derivatives; a quantum chemical study

The resonance-assisted hydrogen bond (RAHB) theory claims that the intramolecular hydrogen bond and π-electron delocalization (π-ED) are interrelated. In the present study, for the first time, the relation between the π-ED and intramolecular hydrogen bond strength were examined. Along this line, the π-ED of the cis enol forms of malonaldehyde and its halogenated derivatives using the various indicators, such as geometrical factor of Gilli (λ), the harmonic oscillator model of aromaticity (HOMA), the nucleus-independent chemical shift (NICS), the para delocalization index (PDI), the average two center index (ATI), the aromatic fluctuation index (FLU), and the π-fluctuation aromatic index (FLUπ) were evaluated. For checking the relation between the π-ED and hydrogen bond strength, we explored and compared all of the correlations between these indices with various descriptors of hydrogen bond, such as geometrical, spectroscopic, topological, and molecular orbital parameters. Our theoretical results show that the geometrical-based indices (λ and HOMA) have the best linear correlations with all of hydrogen bond descriptors (R ≈ 0.90), while the results of other indices (ATI, PDI, FLU, FLUπ, NICS(0), and NICS(1)) are not appropriate (R ≤ 0.80). Surprisingly, we found that the NICS(0) has the weakest linear dependence with all of the HB descriptors. Consequently, the linear dependence of π-ED indices and HB descriptors are in line with the RAHB theory. Finally, according to the absolute correlation coefficients, the approximate order of linearity is as follows: $$\lambda > {\text{HOMA}} > {\text{FLU}} > {\text{ATI}} \approx {\text{FLU}}\pi > {\text{NICS}}\left( 1\right) > {\text{PDI}} > {\text{NICS}}\left( 0 \right) .$$

A comprehensive theoretical study of tautomeric and conformeric preferences, intramolecular hydrogen bonding, and π-electron delocalization in β-selenoaminoacrolein with its thio and oxo analogs

The quantum chemical study of various aspects of β-selenoaminoacrolein, β-thioaminoacrolein, and β-aminoacrolein was performed at various theoretical levels, HF, B3LYP, and MP2 with 6-311++G(3df,3pd) basis set, and the equilibrium conformations were determined. According to these calculations, tautomeric and conformeric preferences, intramolecular hydrogen bond, and π-electron delocalization (π-ED) were investigated. Among tautomers, enaminic tautomers have extra stability with respect to the iminic ones, with and without π-ED. All of the criteria predict that the origin of tautomeric preferences is mainly due to the greater π-ED in the framework of enaminic tautomers. Moreover, our computational results reveal that the formation of intramolecular hydrogen bond is accepted as the origin of conformational preferences. According to the hydrogen bond descriptors, such as HB energy, geometrical, spectroscopic, topological, and molecular orbital parameters, various HB energy orders were found and interpreted. On the other hand, π-ED of chelated rings were measured using various indices, such as q, HOMA, NICS, PDI, ATI, and FLU π index, and various orders were found. Finally, the orders of hydrogen bond strength and π-ED, obtained by some of indices, support the resonance assisted hydrogen bond theory.

OH···O and OH···S intramolecular interactions in simple resonance-assisted hydrogen bond systems: a comparative study of various models

The energy of intramolecular hydrogen bond (IMHB) is a central subject in chemistry and biochemistry. In contrast with the IMHBs, there is no general accepted procedure to determine the IMHB energy. In the present study, for the first time, we applied all the different adopted models for assessing the energy of IMHB of O–H···O and O–H···S in simple resonance-assisted hydrogen bond systems (the cis enol form of malonaldehyde, thiomalonaldehyde, and a variety of halogenated derivatives), and compared them. The energy of IMHB, by various methods such as related rotamers method (RRM), rotational barrier method (RBM), conformational analysis method (CAM), isodesmic reaction method (IRM), and open–close method (OCM), was estimated. Exploring and comparing the correlations between the IMHB energies with various descriptors of hydrogen bond strength, such as geometrical, topological, molecular orbital, and spectroscopic parameters, were carried out. According to the theoretical results, we found that both RRM and RBM have the best linear correlations with all of the hydrogen bond descriptors (R ≥ 0.90) while the results of other methods (CAM, IRM and OCM) are not suitable (R ≤ 0.80). Surprisingly, we found that the OCM, which has been widely applied in the estimation of the IMHB energy, has the weakest linear dependent with all of the HB descriptors. Consequently, according to the regression coefficients, the order of linearity of these methods is as follows: RRM > RBM > > CAM > IRM > OCM.

How to estimate the intramolecular hydrogen-bond energy of complex RAHB systems? A theoretical study

In the present study, new estimations of the intramolecular hydrogen-bond (IMHB) energy in complex RAHB systems were represented. In this regard the malonaldehyde and its 16 halogenated (F, Cl, Br) derivatives, as a set of model compounds, were used. Various enol forms of these compounds at MP2/6-311++G(3df,3pd) level were optimized. Theoretically, enol forms has three degree of freedom correspond to the rotation around C–C, C=C, and C–O bonds. Same as original related rotamers method (RRM1), which is based on rotation about C–C/C=C bonds, by considering rotations about C–C/C–O and C=C/C–O bonds, we can obtain two different method, RRM2 and RRM3, respectively. These methods were used to estimate the IMHB energies in RAHB systems. Exploring and comparing the correlations between these RRM’s energies with various descriptors of hydrogen-bond strength, such as geometrical, topological, molecular orbital, and spectroscopic properties were carried out. Moreover, we found that the RRM2, as original RRM1, has excellent linear correlations while RRM3 has weak dependence with hydrogen bond descriptors. Consequently, according to the regression coefficients, the order of accuracy of these methods is as follows: $${\text{RRM1}} \approx {\text{RRM2}} > {\text{RRM3}}$$

Algorithms for skin permeability using hydrogen bond descriptors: the problem of steroids.

Several algorithms that use hydrogen bond descriptors have been published for the permeation of compounds from aqueous solution through human stratum corneum. In the present work, all the skin permeability coefficients, Kp in cm s-1, used in these algorithms for non-steroids have been correlated through the Abraham equation to give a new algorithm: [equation: see text] where n is the number of solutes, r is the correlation coefficient, s.d. is the standard deviation, and F is the F-statistic. The solute descriptors are: R2 an excess molar refraction, pi 2H the dipolarity/polarizability, sigma alpha 2H and sigma beta 2H the overall or effective hydrogen-bond acidity and basicity, and Vx the McGowan characteristic volume. Equation 1 is a reasonably good predictor of log Kp values for steroids as given by Johnson et al, but not for those given by Scheuplein.

Computational-Regulatory Developments in the Prediction of Oral Drug Absorption.

Early prediction of human intestinal absorption is important in selection of potential orally administered drugs. Various computational models for prediction of the fraction of dose absorbed, Fa, have been developed. In 1989, a sigmoidal relationship between Fa and drug absorption potential was shown. Since then various physicochemical descriptors of molecules (lipophilicity, polar surface area, hydrogen bond descriptors) have been found to correlate with human intestinal absorption and various attempts in estimating Fa have been reported. Most studies rely on the presupposition that Fa is mainly dependent on drug's solubility, which drives the dissolution rate in the gastrointestinal (GI) fluids, and the rate of passive drug transport across the intestinal membrane. In the same vein, the biopharmaceutics classification system (BCS) and the relevant FDA guideline classify drugs in four categories according to their aqueous solubility and permeability. However, the biopharmaceutics drug disposition classification system (BDDCS) revealed the poor predictability of permeability estimates for Fa and the major role of transporters for GI uptake of drugs. The role of solubility in the reaction limited model of dissolution and the ubiquitous presence of supersaturated solubility-dissolution phenomena in the GI lumen, call for a more physiologically relevant consideration of GI absorption.

Characterization of Mixtures. Part 2: QSPR Models for Prediction of Excess Molar Volume and Liquid Density Using Neural Networks.

In our earlier work, we have demonstrated that it is possible to characterize binary mixtures using single component descriptors by applying various mixing rules. We also showed that these methods were successful in building predictive QSPR models to study various mixture properties of interest. Here in, we developed a QSPR model of an excess thermodynamic property of binary mixtures i.e. excess molar volume (V(E) ). In the present study, we use a set of mixture descriptors which we earlier designed to specifically account for intermolecular interactions between the components of a mixture and applied successfully to the prediction of infinite-dilution activity coefficients using neural networks (part 1 of this series). We obtain a significant QSPR model for the prediction of excess molar volume (V(E) ) using consensus neural networks and five mixture descriptors. We find that hydrogen bond and thermodynamic descriptors are the most important in determining excess molar volume (V(E) ), which is in line with the theory of intermolecular forces governing excess mixture properties. The results also suggest that the mixture descriptors utilized herein may be sufficient to model a wide variety of properties of binary and possibly even more complex mixtures.

Application of QSPR to Mixtures

In this paper we report an attempt to apply the QSPR approach for the analysis of data for mixtures. This is an extension of the conventional QSPR approach to the analysis of data for single molecules. The QSPR methodology was applied to a data set of experimental measured density of binary liquid mixtures compiled from the literature. The present study is aimed to develop models to predict the "delta" value of a mixture i.e., deviation of the experimental mixture density (MED) from the ideal, mole-weighted calculated mixture density (MCD). The QSPR was investigated in two perspectives (QMD-I and QMD-II) with respect to the creation of training and test sets. The study resulted in significant ensemble neural network and k-nearest neighbor models having statistical parameters r2, q2(10cv) greater than 0.9, and pred_r2 greater than 0.75. The developed models can be used to predict the delta and hence the density of a new mixture. The QSPR analysis shows the importance of hydrogen bond, polar, shape, and thermodynamic descriptors in determining mixture density, thus aiding in the understanding of molecular interactions important in molecular packing in the mixtures.

Creation of predictive models of aquatic toxicity of environmental pollutants with different mechanisms of action on the basis of molecular similarity and HYBOT descriptors

Over half of known industrial pollutants have minimal toxic effect, in line with the concept of "baseline toxicity"; such toxicity usually correlates well with lipophilicity. The remainder require additional descriptors in order to model their toxicity by the QSAR approach. Hence, it has not been possible, to date, to develop common stable QSAR models for the toxicity of diverse chemicals with various modes of action on the basis of simple regression relationships. Any new methodology has to take such different modes of action into account. In our work, we used for this purpose an original combination of the similarity concept and physicochemical descriptors calculated by HYBOT, in order to construct stable QSAR models of guppy toxicity. The training set comprised 293 diverse chemicals. Experimental value(s) of one or more nearest related chemicals were used to take structural features and possible modes of toxic action into account. In addition, molecular polarisability and hydrogen bond descriptors for the chemicals of interest and related compounds were used to calculate any additional contribution in toxicity by means of linear regression relationships. Final comparison of calculated and experimental toxicity values gave good results, with standard deviation close to the experimental error.