Antioxidant activity of erlotinib and gefitinib: theoretical and experimental insights.

Erlotinib and gefitinib are quinazoline derivatives with antineoplastic properties. Usually, intake of antineoplastic agents results in much a greater degree of oxidative stress, i.e. the production of free radicals, than induced by cancer itself. Hence, anticancerous drugs must also exhibit antioxidant activity but this has not been studied thus far. In this study, the antioxidant activity of erlotinib and gefitinib was examined by experimental and computational studies. It was found that erlotinib and gefitinib exhibit good 2,2-dipheny l-1-picrylhydrazyl (DPPH) radical and hydroxyl radical scavenging (HRS) activities. In DPPH assay, the IC50 for erlotinib and gefitinib were 0.584 and 0.696 mM, respectively, while IC50 for HRS assay were 0.843 and 1.03 mM for erlotinib and gefitinib, respectively. Structural characteristics such as frontier molecular orbitals (FMOs), molecular electrostatic potential maps (MESPs), and global descriptive parameters were calculated at DFT/B3LYP/6-311++G (d,p) on the optimized geometries of erlotinib and gefitinib. UV-visible spectroscopy revealed the possible electronic transitions between the FMOs and their associated excitation energies of both drugs and found that erlotinib has π to π* transitions while gefitinib has π to π* and σ to π* transitions. To elucidate the antioxidant activity of erlotinib and gefitinib, three mechanisms namely hydrogen atom transfer (HAT), single electron transfer proton transfer (SETPT), and sequential proton-loss electron-transfer (SPLET) were employed and articulated the results in arithmetic parameters like bond dissociation energy (BDE), proton affinity (PA), ionization potential (IP), electron transfer enthalpy (ETE), and proton dissociation enthalpy (PDE). Further, molecular docking studies have been carried out to have a better understanding of binding sites and modes of interaction with a well-known antioxidant target protein monoamine oxidase-B (MAO-B) employing docking scores and types of interactions. All the calculated parameters point out that though gefitinib and erlotinib were interchangeable, erlotinib requires a lesser amount of energy for proton transfer and electron transfer, moreover it scavenges radicals easily.

Theoretical insights into the radical scavenging activity of glipizide: DFT and molecular docking studies.

Glipizide is an N-sulfonylurea compound used in the treatment of hyperglycemia in patients with type 2 diabetes mellitus. In the present study, DFT-based computational methods and molecular docking studies have been performed to systematically evaluate the radical scavenger behavior of the title molecule. Structural characteristics such as molecular descriptors, frontier molecular orbitals, molecular potential mapping, and Mulliken charge population have been investigated. Thermodynamic parameters like proton affinity (PA), ionization potential (IP), bond dissociation energy (BDE), electron transfer enthalpy (ETE), and proton dissociation enthalpy (PDE) related to three antiradical mechanisms namely hydrogen atom transfer (HAT), sequential electron transfer proton transfer (SETPT) and sequential proton loss electron transfer (SPLET) have been studied. Also, molecular docking studies have been carried out to have a theoretical understanding of the molecular mechanism and for the elucidation of binding mode/modes of a compound targeted through non-covalent interactions. The obtained results are of great significance in better understanding the reaction mechanism of the title molecule and opens a new perspective for the design of potent antioxidant agents.

The Interplay between Charge Transport and CO2 Capturing Mechanism in [EMIM][SCN] Ionic Liquid: A Broadband Dielectric Study.

The hoisted increment in the CO2 emission in the atmosphere is a noteworthy environmental problem. Gas-liquid absorption is a well-known strategy that can be used to control CO2 emissions from an increased rate of fossil fuel industrializations. In this work, a combination of broadband dielectric spectroscopy, Fourier infrared (FTIR) spectroscopy, and quantum chemical calculations were used to study the absorption, desorption and kinetic mechanism of a room temperature imidazolium ionic liquid (IL) with cyanide anion, 1-ethyl-3-methylimidazolium thiocyanate ([EMIM][SCN]) on CO2 exposure. Initially, the charge transport and glassy dynamics of [EMIM][SCN] is investigated in a wide frequency and temperature range using broadband dielectric spectroscopy and differential scanning calorimetry. The conductivity relaxation was well fitted with Havriliak-Negami function in the modulus formalism, while the dc conductivity correlated well with the Barton-Nakajima-Namikawa relation. Then, the conductometric approach was taken to monitor the interplay between the ionic conductivity of [EMIM][SCN] and diffusion of captured CO2 in it. The resistance of the IL increases upon CO2 exposure, indicating a chemical change at the molecular level of [EMIM][SCN]. The possible CO2 capturing mechanisms for [EMIM][SCN] were investigated with density functional theory calculations and FTIR spectroscopy. Thus, this work proposes a new strategy to explain the mechanism underlined in chemisorption of CO2 in the [EMIM][SCN]. This can be extended to more promising CO2 capturing materials including ionic liquids especially imidazolium-based ionic liquids with cyanide anions like dicyanimide, tricyanometanide, tetracyanoborate, etc.

Molecular dynamics and the translational-rotational coupling of an ionically conducting glass-former: amlodipine besylate.

We studied the conductivity relaxation originating from a glass-former composed of cations and anions, and the relation to the structural α-relaxation at temperatures above and below the glass transition temperature. The material chosen was amorphous amlodipine besylate (AMB), which is also a pharmaceutical with a complex chemical structure. Measurements were made using differential scanning calorimetry (DSC), broadband dielectric spectroscopy (BDS) and X-ray diffraction, and the characterization was assisted using density functional theory (DFT). The X-ray diffraction pattern confirms the amorphous nature of vitrified AMB. Both the ionic and dipolar aspects of the dynamics of AMB were examined using these measurements and were used to probe the nature of the secondary conductivity and dipolar relaxations and their relation to the conductivity α-relaxation and the structural α-relaxation. The coupling model predictions and quantum mechanical simulations were used side by side to reveal the properties and nature of the secondary conductivity relaxation and the secondary dipolar relaxation. Remarkably, the two secondary relaxations have the same relaxation times, and are one and the same process performing dual roles in conductivity and dipolar relaxations. This is caused by the translation-rotation coupling of the AMB molecule. Thus, AMB has both conductivity α- and ß-relaxations, and application of the coupling model shows that these two relaxations are related in the same way as the structural α-relaxation and the Johari-Goldstein ß-relaxation are. This important result has an impact on the fundamental understanding of the dynamics of ionic conductivity.

Polyaniline modified lignocellulosic fibers from sago seed shell powder for electrochemical devices.

We report the development of a novel electrode material from agrarian waste, sago (Cycas circinalis) seed shell powder (SSP). Lignocellulosic fibers obtained from sago seed shell powder were modified with polyaniline (PANI) by an in situ oxidative polymerization technique. Morphological changes, thermal stability and crystallinity of modified SSP were investigated using FTIR, XRD, SEM, TGA and DSC techniques. The structural organization of SSP with the monomer of PANI significantly influenced the thermal and electrical properties of resulting PANI-SSP composite material. The developed PANI-SSP composite showed enhanced thermal stability up to 308 °C with appreciable dc-conductivity in the range of 10-1 S cm-1 having very low activation energy of 0.0153 eV. The I-V characteristics of the composite exhibited nonohmic behaviour similar to a diode. Thus, the chemical modification of lignocelluloses fibers opens up a new avenue for fabricating cheap, eco-friendly substrates for energy storage devices, disposable electronic applications and diverse scopes for research and development.