Compound 1(Phenikaa University)

An innovative electrochem. redox response of hydroquinone (HQN) and catechol (CCL) was analyzed using a bare graphite and graphene composite paste electrode (BGGCPE) and polymerised L-leucine modified graphite and graphene composite paste electrode (LCN-MGGCPE) was successfully developed in 0.2 M phosphate buffer solution (PBS) with pH 6.0 at a 0.1 V/s scan rate.Fabricated electrode using simple and cost-effective method, the polymerised LCN-MGGCPE surface shows more electrochem. activity, sensitivity and selectivity towards the determination for HQN and CCL.Cyclic voltammetry (CV), linear sweep voltammetry (LSV), Differential pulse voltammetry (DPV), and electrochem. impudence spectroscopy (EIS) were utilized as anal. techniques while LCN-MGGCPE and BGGCPE surface characterization were studied using a SEM (SEM) technique.LCN-MGGCPE exhibited superior electrochem. activity compared to BGGCPE towards the oxidation responses of both HQN and CCL.Addnl., the effect of pH studies, scan rate change for HQN, and concentration change of analyte mol. were examined, with the 0.025 to 0.500 V/s scan rate varied and revealing an adsorption-controlled process.The concentration changes of CVs methods ranged from 0.2 to 320 μM, DPVs ranged from 0.2 to 1100 μM and LSVs ranged from 0.2 to 850 μM, the calculated a limit of detection (LOD) of CV, DPV, and LSV, is 0.020 μM, 0.026 μM, and 0.011 μM and a limit of quantification (LOQ) of 0.068 μM, 0.088 μM, and 0.035 μM.The electrochem. developed LCN-MGGCPE shows good reproducibility, repeatability, stability, sensitivity and simultaneous anal. of analyte mols. were studied.This study presents a promising pathway for the growth of effective sensors for the determination of HQN in medicinal and water sample applications.

In a step towards understanding the structure-property relationship among Synthetic Cathinones (SCs), a combined methodology based on Density Functional Theory (DFT), Administration, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictions, docking and molecular dynamics simulations have been applied to correlate physicochemical descriptors of various SCs to their biological activity. The results from DFT and molecular docking studies correlate well with each other explaining the biological activity trends of the studied SCs. Quantum mechanical descriptors viz. polarizability, electron affinity, ionization potential, chemical hardness, electronegativity, molecular electrostatic potential, and ion interaction studies unravel the distinguishingly reactive nature of Group D (pyrrolidine substituted) and Group E (methylenedioxy and pyrrolidine substituted) compounds. According to ADMET analysis, Group D and Group E molecules have a higher probability of permeating through the blood-brain barrier. Molecular docking results indicate that Phe76, Ala77, Asp79, Val152, Tyr156, Phe320, and Phe326 constitute the binding pocket residues of hDAT in which the most active ligands MDPV, MDPBP, and MDPPP are bound. Finally, to validate the derived quantum chemical descriptors and docking results, Molecular Dynamics (MD) simulations are performed with homology-modelled hDAT (human dopamine transporter). The MD simulation results revealed that the majority of SCs remain stable within the hDAT protein's active sites via non-bonded interactions after 100 ns long simulations. The findings from DFT, ADMET analysis, molecular docking, and molecular dynamics simulation studies complement each other suggesting that pyrrolidine-substituted SCs (Group D and E), specifically, MPBP and PVN are proven potent SCs along with MDPV, validating various experimental observations.