Development of binary classification models for grouping hydroxylated polychlorinated biphenyls into active and inactive thyroid hormone receptor agonists.

Some adverse effects of hydroxylated polychlorinated biphenyls (OH-PCBs) in humans are presumed to be initiated via thyroid hormone receptor (TR) binding. Due to the trial-and-error approach adopted for OH-PCB selection in previous studies, experiments designed to test the TR binding hypothesis mostly utilized inactive OH-PCBs, leading to considerable waste of time, effort and other material resources. In this paper, linear discriminant analysis (LDA) and binary logistic regression (LR) were used to develop classification models to group OH-PCBs into active and inactive TR agonists using radial distribution function (RDF) descriptors as predictor variables. The classifications made by both LDA and LR models on the training set compounds resulted in an accuracy of 84.3%, sensitivity of 72.2% and specificity of 90.9%. The areas under the ROC curves, constructed with the training set data, were found to be 0.872 and 0.880 for LDA and LR models, respectively. External validation of the models revealed that 76.5% of the test set compounds were correctly classified by both LDA and LR models. These findings suggest that the two models reported in this paper are good and reliable for classifying OH-PCB congeners into active and inactive TR agonists.

A kinetic study and mechanisms of reduction of N, N'-phenylenebis(salicyalideneiminato)cobalt(III) by L-ascorbic acid in DMSO-water medium.

The kinetics of reduction of N, N 1 -phenylenebis-(salicylideneiminato)cobalt (III), referred to as [Co(Salophen)]+ by L-ascorbic acid (H2A) was studied in mixed aqueous medium (DMSO:H2O; 1:4 v/v) under pseudo-first-order conditions at 33 ± 1 °C, µ = 0.1 mol dm-3 (NaCl) and λ max = 470 nm. L-ascorbic acid was oxidized to dehydroascorbic acid with kinetics that was first order in both the [H2A] and [Co(Salophen)+] and second-order overall. The reaction involves two parallel reaction pathways; an acid-dependent and the inverse acid-dependent pathways. The inverse acid pathway shows that there is a pre-equilibrium step before the rate determining-step in which a proton is lost. The kinetics followed negative Brønsted-Debye salt effect. Evidence was obtained for the presence of free radicals but none to support the formation of an intermediate complex of significant stability during the reaction. Overall, the data obtained suggest an outer-sphere mechanism for the reaction. A plausible mechanism is proposed.

Reaction of N, N 1 -phenylenebis(salicyalideneiminato)cobalt(III) and l-cysteine in mixed aqueous medium: kinetics and mechanism.

The redox kinetics involving the reaction of N, N'-phenylenebis(salicyalideneiminato)cobalt(III) ([CoSalophen]+) and l-cysteine (LSH) was studied using pseudo-first order approach under the following conditions, [H+] = 1.0 × 10-3 mol/dm3, µ = 0.1 C2 mol/dm3 (NaCl), λmax = 470 nm and T = 27 ± 1 °C in DMSO: H2O; 1:4 v: v medium. The redox reaction was 1st order in both [CoSalophen+] and [LSH], with the overall 2nd order. Hydrogen ion concentration effect revealed the activeness of both the protonated and deprotonated form of the reductant, positive Brønsted-Debye salt effect and was also ion catalyzed. There was no evidence suggesting an intermediate complex of significant stability in the reaction. Free radical was detected to take part and as such the reasonable mechanistic pathway for the reaction is suggested to be outer-sphere, hence proposed.