Predicting the Redox Potentials of Phenazine Derivatives using DFT Assisted Machine Learning

Here, four machine-learning models were employed to predict the redox potentials of phenazine derivatives in DME using DFT. A small dataset of 189 phenazine derivatives having only one type of functional group per molecule (20 unique groups) was used for the training. Models were validated on the external test-set containing new functional groups and diverse molecular structures and achieved reasonable accuracies (R2 > 0.57). Despite being trained on the molecules with a single type of functional group, models were able to predict the redox potentials of derivatives containing multiple and different types of functional groups with reasonable accuracy (R2 > 0.6). This type of performance for predicting redox potential from such a small and simple dataset of phenazine derivatives has never been reported before. Redox Flow Batteries (RFBs) are emerging as promising candidates for energy storage systems. However, new green and efficient materials are required for their widespread usage. We believe that the hybrid DFT-ML approach demonstrated in this report would help in accelerating the virtual screening of phenazine derivatives saving computational and experimental resources. This approach could potentially identify novel molecules for green energy storage systems such as RBF

Insights into nucleation, growth and phase selection of WO3: morphology control and electrochromic properties

Electrochromic application of nanoscale WO3 demands stringent control in terms of phase-purity and morphology. Here, we show that two different phases of WO3 with distinct morphologies ( viz. 2D plates of orthorhombic phase and 1D rods of hexagonal phase) can be obtained by tuning the solvothermal reaction conditions. Control experiments along with density functional theory based ab initio calculations show that the reaction pathway critically depends on the capping agent used in the reaction. Using this concept in conjunction with crystallographic arguments, we rationalize the morphology evolution of the two phases. Furthermore, the synthesized phases exhibit very different electrochromic properties in terms of H+ diffusion, which can be rationalized by the calculated trend in the H+-intercalation energies

Pharmacokinetic Study of Withanosides and Withanolides from Withania somnifera Using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS)

Withania somnifera is a traditional Indian herb described under the ‘Rasayana’ class in Ayurveda, which gained immense popularity as a dietary supplement in the USA, Europe, Asia, and the Indian domestic market. Despite enormous research on the pharmacological effect of withanosides and withanolides, bioanalytical method development and pharmacokinetics remained challenging and unexplored for these constituents due to isomeric and isobaric characteristics. In current research work, molecular descriptors, pharmacokinetic, and toxicity prediction (ADMET) of these constituents were performed using Molinspiration and admetSAR tools. A rapid, selective, and reproducible bioanalytical method was developed and validated for seven withanosides and withanolides as per USFDA/EMA guidelines, further applied to determine pharmacokinetic parameters of Withania somnifera root extract (WSE) constituents in male Sprague Dawley rats at a dose of 500 mg/kg. Additionally, an ex vivo permeability study was carried out to explore the absorption pattern of withanosides and withanolides from the intestinal lumen. In silico, ADMET revealed oral bioavailability of withanosides and withanolides following Lipinski’s rules of five with significant absorption from the gastrointestinal tract and the ability to cross the blood-brain barrier. Upon oral administration of WSE, Cmax was found to be 13.833 ± 3.727, 124.415 ± 64.932, 57.536 ± 7.523, and 7.283 ± 3.341 ng/mL for withanoside IV, withaferin A, 12-Deoxy-withastramonolide, and withanolide A, respectively, with Tmax of 0.750 ± 0.000, 0.250 ± 0.000, 0.291 ± 0.102, and 0.333 ± 0.129 h. Moreover, at a given dose, withanoside V, withanolide B, and withanone were detected in plasma; however, the concentration of these constituents was found below LLOQ. Thus, these four major withanoside and withanolides were quantified in plasma supported by ex vivo permeation data exhibiting a time-dependent absorption of withanosides and withanolides across the intestinal barrier. These composite findings provide insights to design a clinical trial of WSE as a potent nutraceutical