QSAR and ANN for the estimation of water solubility of 209 polychlorinatedtrans-azobenzenes

Abstract

Polychlorinated trans-azobenzenes (PCt-ABs) are less studied a highly toxic impurity in 2,3-dichloroaniline (2,3-D) and some herbicides and are compounds of environmental relevance lacking experimental physical and chemical properties data. In this study, to fulfill gaps on environmentally relevant partitioning properties of PCABs, the values of water solubility (μg/L and log S) have been determined for 209 congeners of chloro-trans-azobenzene (Ct-AB) by means of quantitative structure - property relationship (QSPR) approach and artificial neural networks (ANN) predictive ability. The quantitative structure - property relationship (QSPR) approach used based on geometry optimalization and quantum-chemical structural descriptors, which were computed on the level of density functional theory (DFT) using B3LYP functional and 6-311++G** basis set in Gaussian 03 and the semi-empirical quantum chemistry method for property parameterization (PM6) in the molecular orbital package (MOPAC) software. The predicted solubility of PCt-ABs by PM6 and DFT models and depending on a congener within a homologue class varied between 1995-11481 and 5370-15135 μg/L for mono-; 170-5495 and 138-9332 μg/L for di-; 36-1950 and 209-5248 μg/L for tri-; 15-794 and 41-3715 μg/L for tetra-; 5.5-209 and 39-1259 μg/L for penta-; 1.8-98 and 3.5-1096 μg/L for hexa-; 1.5-34 and 4.7-214 μg/L for hepta-; 0.71-6.2 and 0.76-26 μg/L for octa-; 0.83-1.7 and 0.69-1.2 μg/L for nonaCt-ABs; and between 0.36 and 0.04 μg/L for decaCt-AB, respectively. The calculations by PM6 were highly efficient and inexpensive compared to these by DFT, while both models gave data of similar accuracy.

Differential azobenzene solubility increases equilibrium cis/trans ratio in water

“…Log P values of 3.82 [17] and 4.11 [20] have been reported for 1 and log P = 3.4 for dipeptide 8 [17]. Using the method of Abraham [21] we obtained S w (trans) values of 0.07 and 0.03 mM for AB 1, similar to our results in Table 1 (Table S1). The t R values for the trans isomers fell within a small range, as did values for cis isomers; t R (trans) = 40 ± 4 and t R (cis) = 30.0 ± 4 min.…”

“…Given the number of literature reports on AB-peptide conjugates, it is important to fully understand model systems like 8-10. Chambers and Haworth [21] observed ~30% cis for NMR samples of 8 and 10 in buffered D 2 O; the authors postulated intramolecular stabilization of the cis isomer. Our results do not support this hypothesis; instead we propose a solubility-driven isomerization.…”

“…Because log P of a putative drug is one of the key molecular attributes for pharmacological activity, the pharmaceutical industry has developed models using linear free energy relationships and retention times (t R ) from RP-HPLC [16][17][18]. Log P determination is also used in ground water contamination studies [19][20][21]. Log P values for 1 have been reported but most values are based on computed solubility from a linear free energy relationship.…”

Conformation-independent quantitative structure-property relationships study on water solubility of pesticides

“…They found that solubility was strongly affected by three variables: energy of the lowest unoccupied molecular orbital, most positive atomic partial charge in the molecule, and the quadrupole moment. The water solubility of 209 congeners of chloro-trans-azobenzene was modeled using Genetic Algorithm-Artificial Neural Network (GA-ANN) (Wilczyńska-Piliszek et al, 2012). Non-ionic perfluorinated chemicals were studied using two-dimensional descriptors (Bhhatarai and Gramatica, 2010).…”

Chemometrics tools in QSAR/QSPR studies: A historical perspective

“…GA-ANN has been applied in different studies [175][176][177][178][179][180][181][182][183]. Application of the specific combined versions of ANN with GA can be found in QSAR/QSPR studies.…”