Theoretical Investigation on Atmospheric Chemistry of Nitryl Cyanide: A Novel Fluorine-Free Dielectric Gas.

In view of the significant greenhouse effect of sulfur hexafluoride and the potential biotoxic hazard of perfluorinated substances, we proposed that nitryl cyanide (NCNO2), a nearly nonpolar molecule with a unique combination of two strongly electronegative and polarized functional groups, is a novel fluorine-free replacement to be used as the insulating gas in green electrical grids. Atmospheric chemistry of NCNO2 has been investigated theoretically to assess its environmental impact if emitted into the atmosphere. Potential energy surfaces for the reaction of NCNO2 with OH in the presence of O2 were calculated using the restricted open-shell complete basis set quadratic Becke3 and Gaussian-4 methods on the basis of the density functional (M06-2X) and couple-cluster (CCSD) optimized geometrical parameters. The oxidation of NCNO2 takes place via the nearly zero-barrier association of OH with the cyano-C to form energy-rich adducts NC(OH)NO2, followed by C-N bond rupture to the major HOCN + NO2 and the minor HONO + NCO products. Interception of the adduct by O2 can result in OH-regeneration together with further degradation to CO and NOx. Moreover, photolysis of NCNO2 under tropospheric sunlight conditions might compete with OH-oxidation. The atmospheric lifetime and radiative efficiency of NCNO2 were computed to be far less than those of either nitriles or nitro compounds. The global warming potential of NCNO2 was estimated to be in the range of 0-5 for a 100 year time horizon. However, the secondary chemistry of NCNO2 should be treated with caution in view of the production of NOx in the atmosphere.

Computational Investigations on Reaction Mechanisms of the Covalent Inhibitors Ponatinib and Analogs Targeting the Extracellular Signal-Regulated Kinases.

As an important cancer therapeutic target, extracellular signal-regulated kinases (ERK) are involved in triggering various cellular responses in tumors. Regulation of the ERK signaling pathway by the small molecular inhibitors is highly desired for the sake of cancer therapy. In contrast to the routine inhibitors targeting ERKs through long-range non-bonding interactions, Ponatinib, a covalent inhibitor to ERK2 with a macrocyclic structure characterized by the α,ß-C=C unsaturated ketone, can form the stable -C(S)-C(H)-type complex via the four-center barrier due to the nucleophilic addition reaction of the thiol group of the Cys166 residue of ERK2 with the C=C double bond of Ponatinib with reaction free-energy barrier of 47.2 kcal/mol. Reaction mechanisms for the covalent binding were calculated using QM/MM methods and molecular dynamics simulations. The interaction modes and the corresponding binding free energies were obtained for the non-covalent and covalent complexation. The binding free energies of the non-covalent and covalent inhibitions are 14.8 kcal/mol and 33.4 kcal/mol, respectively. The mechanistic study stimulated a rational design on the modified Ponatinib structure by substituting the C=C bond with the C=N bond. It was demonstrated that the new compound exhibits better inhibition activity toward ERK2 in term of both thermodynamic and kinetic aspects through the covalent binding with a lower reaction free-energy barrier of 23.1 kcal/mol. The present theoretical work sheds new light on the development of the covalent inhibitors for the regulation of ERKs.

6-Iodopurine as a Versatile Building Block for RNA Purine Architecture Modifications.

Natural modified bases in RNA were found to be indispensable for basic biological processes. In addition, artificial RNA modifications have been a versatile toolbox for the study of RNA interference, structure, and dynamics. Here, we present a chemical method for the facile synthesis of RNA containing C6-modified purine. 6-Iodopurine, as a postsynthetic building block with high reactivity, was used for metal-free construction of C-N, C-O, and C-S bonds under mild conditions and C-C bond formation by Suzuki-Miyaura cross-coupling. Our strategy provides a convenient approach for the synthesis of various RNA modifications, especially for oligonucleotides containing specific structures.

Star-Shaped Molecules as Dopant-Free Hole Transporting Materials for Efficient Perovskite Solar Cells: Multiscale Simulation.

On the reported TCP-OH (See Scheme 1), other two star-shaped molecules are theoretically designed by replacement of side group of TCP-OH by N,N-di(4-methoxyphenyl)aniline for TPAP-OH and oxygen-bridged triarylamine for TBOPP-OH. The core group, phenol, is kept in three molecules. Their potential to be hole transport material in perovskite solar cells without dopants is evaluated by multiscale simulations. The properties of isolated molecules are estimated by the frontier molecular orbital, absorption spectrum, and hole mobility. After that, the HTM@CH3 NH3 PbI3 adsorbed system is studied to consider the influence of adsorption on HTM performance. Besides the primary judgment, the glass transition temperature is also simulated to determine the stability of amorphous film. Not only the chemical stability is evaluated but also the amorphous film stability is considered. The latter is almost neglected in previous theoretical studies to evaluate the properties of HTMs. The performance of a designed molecule is evaluated from both the isolated molecules and HTM@CH3 NH3 PbI3 adsorbed system including aforementioned items, which is favorable to build reliable structure-property relationship.

Pharmacophore-based virtual screening, molecular docking and molecular dynamics simulation for identification of potential ERK inhibitors.

As the downstream component of the mitogen-activated protein kinases (MAPK) pathway, the extracellular signal-regulated kinase (ERK) is responsible for phosphorylating a broad range of substrates in cell proliferation, differentiation, and survival. Direct targeting the ERK proteins by the piperidinopyrimidine urea-based inhibitors has been demonstrated to be an effective way to block the MAPK signaling pathway in inhibiting tumor growth. In order to discover better inhibitors, a computer-aided drug design (CADD) approach was employed to reveal the pharmacological characteristics and mechanisms of action. The pharmacophore model was generated on the basis of the compounds with eight features, i.e., four hydrogen bond acceptor atoms, one hydrogen bond donor atom, and three hydrophobic centers. A total of 14 hit compounds were obtained through virtual screening. Two potential inhibitors, namely VS01 and VS02, have been identified by molecular docking and molecular dynamics simulations. Both compounds are capable of attaching to the ERK pocket precisely. The binding free energies of VS01 and VS02 are about 15 kJ/mol and 4 kJ/mol stronger than that of the clinic Ulixertinib because of the characteristic hydrogen bonding, electrostatic, and hydrophilic interactions. The present theoretical investigations shed new light on the rational design of the potential ERK inhibitors to stimulate further experimental tests.Communicated by Ramaswamy H. Sarma.

Rational design of D-π-A organic dyes to prevent "trade off" effect in dye-sensitized solar cells.

It is an easy task to simulate the spectrum properties for the organic dyes applied in dye-sensitized solar cells (DSSCs) if the suitable method is chosen. However, it is still difficult to quantitatively determine the overall performance for them. In this work, the short-circuit photocurrent density (JSC) and open circuit photovoltage (VOC) are quantitatively calculated by combination of the density functional theory and first principle for DSSCs based on four different organic dyes, 2-((4'-((4-(bis(4-methoxyphenyl)amino)phenyl)diazenyl)biphenyl-4-yl)methylene)but-3-ynoic acid (1), 2-((5-(4-((4-(bis(4-methoxyphenyl)amino)phenyl)diazenyl)phenyl)thiophen-2-yl)methylene)but-3-ynoic acid (2), 3-(7-(4-((4-(bis(4-methoxyphenyl)amino)phenyl)diazenyl)-4H-cyclopenta[2,1-b:3,4-b']-dithiophene)-2-cyanoacrylic acid (3), and 3-(7-(4-((4-(bis(4-methoxyphenyl)amino)phenyl)diazenyl)phenyl)-2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-2-cyanoacrylic acid (4), in which the triarylamine is donor and the cyanoacrylic acid is acceptor along with variable π group. The 3 and 4 are new theoretically designed organic dyes on the basis of 1 and 2 with different electron-rich group as π group. Both JSC and VOC of 3 and 4 are improved as compared with those of 1 and 2, which breaks the normal "trade-off" rule. As a result, the power conversion efficiency (PCE) of 3 and 4 is improved, especially for 3. The aggregation effect is also considered to evaluate the overall performance, which is favorable to further enhance the reliability of theoretical design.