Ultrafast Dynamics of Photoinduced Electron Transfer in Bay-Aryl-Substituted Perylene Diimide Derivatives.

Blends of donors and acceptors have been widely used in bulk-heterojunction solar cells to have exciton formation and charge separation by photoinduced electron transfer (PET). In this work, we have synthesized perylene diimide (PDI)-based materials having different aryl substituents at the bay positions (4-Anisyl-PDI, CBZ-N-Ph-PDI, and 4-Pyridyl-PDI) to understand the excited-state dynamics of electron transfer. The detailed photophysics was studied using steady-state as well as ultrafast dynamics of the excited states in different solvents. CBZ-N-Ph-PDI showed tremendous effects of the solvent on the electronic properties compared with the other two derivatives. The emission quantum yield of CBZ-N-Ph-PDI decreases drastically in dichloromethane and other polar solvents, indicating strong electron transfer. DFT calculations showed that in CBZ-N-Ph-PDI the HOMO is centered mostly on the N-phenylcarbazole and the LUMO is on the electron-poor PDI moieties. In addition, the energy levels of the HOMO and HOMO-1 in CBZ-N-Ph-PDI are estimated to be identical. The free energy change for charge separation (ΔGCS) was calculated using electrochemical and photophysical data and found to be negative for CBZ-N-Ph-PDI. The ground- and excited-state dipole moment ratios suggest that the excited state of 4-Pyridyl-PDI (1.90) is less polar than that of 4-Anisyl-PDI (3.67), which provides an idea of the lower possibility of charge separation in 4-Anisyl-PDI and 4-Pyridyl-PDI. Ultrafast photodynamics studies of 4-Anisyl-PDI, CBZ-N-Ph-PDI, and 4-Pyridyl-PDI showed fast electron transfer only in CBZ-N-Ph-PDI and not in the other PDI derivatives. It was also observed that electron transfer is faster in DCM and THF than in toluene. Ultrafast dynamics studies showed the presence of an equilibrium between electron transfer and decay from the singlet excited state. Ultrafast studies also showed the features of the N-phenylcarbazole cation and PDI anion, further confirming the intramolecular electron transfer in CBZ-N-Ph-PDI.

Blue-red emitting materials based on a pyrido[2,3-b]pyrazine backbone: design and tuning of the photophysical, aggregation-induced emission, electrochemical and theoretical properties.

Pyrido[2,3-b]pyrazine-based donor-acceptor-donor (D-A-D) molecules were designed by altering donor amines and synthesized using the Buchwald-Hartwig C-N coupling reaction. Further, the tunable opto-electrochemical properties of the dyes were studied in detail. The dye possesses intramolecular charge transfer (ICT) transition (412-485 nm), which marked the D-A architecture and induces a broad range of emissions from blue to red (486-624 nm) in the solution and solid state. Some of the dyes show aggregation-induced emission (AIE) features and formation of nanoparticles in the THF/H2O mixture, as confirmed by DLS and FEG-SEM (of 7) analysis. The AIE characteristics indicate its solid/aggregate-state application in organic electronics. The molecules exhibit high thermal stability, low band gap (1.67-2.36 eV) and comparable HOMO (-5.34 to -5.97 eV) and LUMO (-3.61 to -3.70 eV) energy levels with those of reported ambipolar materials. The relationship between the geometrical structure and optoelectronic properties of the dyes, as well as their twisted molecular conformation and small singlet and triplet excitation energy difference (ΔE ST = 0.01-0.23 eV) were analyzed using the DFT/TDDFT method. Thus, potential applications of the dyes are proposed for optoelectronic devices.

Hydrogenated-Graphene-Encapsulated Graphene: A Versatile Material for Device Applications.

Graphene and its heterostructures exhibit interesting electronic properties and are explored for quantum spin Hall effect (QSHE) and magnetism-based device applications. In present work, we propose a heterostructure of graphene encapsulated by hydrogenated-graphene, which could be a promising candidate for a variety of device applications. We have carried out DFT calculations on this system to check its feasibility to be a versatile material. We found that electronic states of multilayer pristine graphene, especially the Dirac cone, an important feature to host QSHE, can be preserved by sandwiching it by fully hydrogenated graphene. The interference of electronic states of hydrogenated graphene was insignificant with those of graphene. States of graphene were also found to be stable upon application of an electric field up to ±2.5 V/nm. For device applications, multilayer graphene or its heterostructures are required to be deposited on a substrate, which interacts with the system opening up a gap at the Dirac cone making it less suitable for QSHE applications, and hydrogenated graphene can prevent it. Magnetization in these hydrogenated-graphene-sandwiched graphene systems may be induced by creating vacancies or distortions in hydrogenated graphene, which was found to have a minimal effect on graphene's electronic states, thus providing an additional degree of manipulation. We also performed a set of calculations to explore its applicability for detecting some molecules. Our results on trilayer graphene encapsulated by hydrogenated graphene indicate that all these observations can be generalized for systems with a larger number of graphene layers, indicating that multilayer graphene sandwiched between two hydrogenated graphene is a versatile material that can be used in QSHE and sensor devices.

Targeting the intersubunit cavity of Plasmodium falciparum glutathione reductase by a novel natural inhibitor: computational and experimental evidence.

Glutathione reductase (GR), a homodimeric FAD-dependent disulfide reductase, is essential for redox homeostasis of the malaria parasite Plasmodium falciparum and has been proposed as an antimalarial drug target. In this study we performed a virtual screening against PfGR, using the structures of about 170,000 natural compounds. Analysis of the two top-scoring molecules, TTB and EPB, indicated that these ligands are likely to interact with the homodimer intersubunit cavity of PfGR with high binding energy scores of -9.67 and -9.60kcal/mol, respectively. Both compounds had a lower affinity for human GR due to differences in structure and electrostatic properties. In order to assess the putative interactions in motion, molecular dynamics simulations were carried out for 30ns, resulting in TTB being more dynamically and structurally favored than EPB. A closely related compound MDPI 21618 was tested on recombinant PfGR and hGR, resulting in IC50 values of 11.3±2.5µM and 10.2±1.7µM, respectively. Kinetic characterization of MDPI 21618 on PfGR revealed a mixed-type inhibition with respect to glutathione disulfide (Ki=9.7±2.3µM) and an uncompetitive inhibition with respect to NADPH. Furthermore, MDPI 21618 was found to inhibit the growth of the chloroquine-sensitive P. falciparum strain 3D7 with an IC50 of 3.2±1.9µM and the chloroquine-resistant Dd2 strain with an IC50 of 3.2+1.6µM. In drug combination assays with chloroquine, artemisinin, or mefloquine MDPI 21618 showed an antagonistic action, which might suggest partially overlapping routes of action. This study further substantiates research on PfGR as a potential antimalarial drug target.

Mechanistic insights into mode of actions of novel oligopeptidase B inhibitors for combating leishmaniasis.

Leishmaniasis is an endemic disease caused by infection with one of several different species of protozoan parasite Leishmania. Oligopeptidase B (OPB) is a serine peptidase which plays a vital role in survival of the Leishmania parasite in the host (human) macrophage and help in attaining complete virulence. Inhibition of this peptidase would check the parasite growth inside the host organism and would thus control its infection. Lack of efficient and cheap drugs has led to an urgent need for development of new anti-leishmanial drugs and this study is a step forward in this direction. Using a structure-based approach we virtually screened a large naturally-occurring compound library against OPB and subjected two top scoring compounds with high binding affinity to molecular dynamics simulations which showed a stable RMSD trajectory. The first compound COP (Glide score: -13.183) was found stable for 15 ns at RMSD of 2.5 Å while the second compound TOA (Glide score: -10.308) was stable for 8 ns at RMSD of 1.5 Å. The screened compounds interacted with some crucial residues of OPB such as COP interacted with Ser577 and His697 (part of the catalytic triad), Tyr499 (responsible for substrate stability), Arg576 (conserved in protozoan family) and Arg664 (plays a role in stabilization of the bound inhibitor). TOA also interacted with Glu669 (conserved in protozoan family) in addition to the residues interacted with COA. These interactions are crucial for OPB inhibition. This study identified naturally-occurring compound leads against OPB with good binding affinity and low toxicity to human cells.

Novel natural structure corrector of ApoE4 for checking Alzheimer's disease: benefits from high throughput screening and molecular dynamics simulations.

A major genetic suspect for Alzheimer's disease is the pathological conformation assumed by apolipoprotein E4 (ApoE4) through intramolecular interaction. In the present study, a large library of natural compounds was screened against ApoE4 to identify novel therapeutic molecules that can prevent ApoE4 from being converted to its pathological conformation. We report two such natural compounds PHC and IAH that bound to the active site of ApoE4 during the docking process. The binding analysis suggested that they have a strong mechanistic ability to correct the pathological structural orientation of ApoE4 by preventing repulsion between Arg 61 and Arg 112, thus inhibiting the formation of a salt bridge between Arg 61 and Glu 255. However, when the molecular dynamics simulations were carried out, structural changes in the PHC-bound complex forced PHC to move out of the cavity thus destabilizing the complex. However, IAH was structurally stable inside the binding pocket throughout the simulations trajectory. Our simulations results indicate that the initial receptor-ligand interaction observed after docking could be limited due to the receptor rigid docking algorithm and that the conformations and interactions observed after simulation runs are more energetically favored and should be better representations of derivative poses in the receptor.

A plausible mechanism for the antimalarial activity of artemisinin: A computational approach.

Artemisinin constitutes the frontline treatment to aid rapid clearance of parasitaemia and quick resolution of malarial symptoms. However, the widespread promiscuity about its mechanism of action is baffling. There is no consensus about the biochemical target of artemisinin but recent studies implicate haem and PfATP6 (a calcium pump). We investigated the role of iron and artemisinin on PfATP6, in search of a plausible mechanism of action, via density functional theory calculations, docking and molecular dynamics simulations. Results suggest that artemisinin gets activated by iron which in turn inhibits PfATP6 by closing the phosphorylation, nucleotide binding and actuator domains leading to loss of function of PfATP6 of the parasite and its death. The mechanism elucidated here should help in the design of novel antimalarials.

Resisting resistant Mycobacterium tuberculosis naturally: mechanistic insights into the inhibition of the parasite's sole signal peptidase Leader peptidase B.

Tuberculosis (TB) is the second highest cause of mortality after HIV/AIDS and is one of the leading public health problems worldwide. The growing resistance to anti-TB drugs and the recalcitrant nature of tenacious infections present arduous challenges for the treatment of TB. Thus, the need to develop therapeutics against novel drug targets to help overcome multi-drug resistant TB is inevitable. Leader peptidase B (LepB), the sole signal peptidase of Mycobacterium tuberculosis (MTb), is one such potential drug target. The present work aims at identifying potential inhibitors of LepB, so as to repress the formation of the functional proteins essential for the growth and pathogenesis of MTb. In this study, we screened a large dataset of natural compounds against LepB using a high throughput approach. The screening was directed toward a binding pocket consisting of residues, some of which are critical for the catalytic activity of the enzyme, while others are part of the conserved domains of the signal peptidases. We also carried out molecular dynamics simulations of the two top-scoring compounds in order to study their molecular interactions with the active site functional residues of LepB and also to assess their dynamic behavior. We report herein two prospective non-covalent type inhibitory drugs of natural origin which are active against tuberculosis. These lead molecules possess improved binding properties, have low toxicity and are specific against MTb.

Ferromagnetism in carbon-doped zinc oxide systems.

We report spin-polarized density functional calculations of ferromagnetic properties for a series of ZnO clusters and ZnO solid containing one or two substitutional carbon impurities. We analyze the eigenvalue spectra, spin densities, molecular orbitals, and induced magnetic moments for ZnC, Zn(2)C, Zn(2)OC, carbon-substituted Zn(n)O(n) (n = 3-10, 12) clusters and the bulk ZnO. The results show that the doping induces magnetic moment of approximately 2 mu(B) in all the cases. All systems with two carbon impurities show ferromagnetic interaction, except when carbon atoms share the same zinc atom as the nearest neighbor. This ferromagnetic interaction is predominantly mediated via pi-bonds in the ring structures and through pi- and sigma-bonds in the three-dimensional structure. The calculations also show that the interaction is significantly enhanced in the solid, bringing out the role of dimensionality of the Zn-O network connecting two carbon atoms.