Tackling Remote sp3 C−H Functionalization via Ni-Catalyzed “chain-walking” Reactions

Nickel catalysts have recently played an important role for rapidly and reliably converting feedstock chemicals into valuable compounds of interest for both pharmaceutical and academic laboratories. Herein, we summarize the recent advances on the ability of nickel catalysts to trigger olefin isomerization via “chain-walking”, causing a displacement of the nickel catalyst throughout the alkyl chain while opening up new grounds for forging C−C and C-heteroatom linkages at remote, yet unfunctionalized, sp³ C−H bonds.     

Surface and interface morphology and structure of amorphous carbon thin and multilayer films

We review the implementation of X-ray reflection (reflectivity and scattering) techniques for the study of amorphous Carbon (a-C, a-C:H, ta-C) thin and multilayer films and in particular in the determination of the film density and surface and interface morphology, which are intrinsically significant for ultra-thin films. We present studies of various a-C and a-C:H films, which include in particular: i) the morphology of a-C/Si interface, ii) the surface morphology and density evolution during sputter growth of a-C, iii) the morphology of the sp²-rich a-C/sp³-rich a-C interfaces in multilayer a-C films, iv) the universal correlation between the film density and the refractive index of a-C and a-C:H films. We also compare and validate the experimental results with relative results from Monte-Carlo simulations within an empirical potential scheme. The computational results shed light on the atomistic mechanisms determining the structure and morphology of the a-C interfaces between individual sp²- and sp³-rich a-C layers and between a-C and Si substrates.     

Substrate temperature effects on the microhardness and adhesion of diamond-like thin films

Diamond-like films were deposited on silicon substrates by r.f. plasma-enhanced chemical vapor deposition from gas methane. In this study, the substrate temperature, T_S, was varied in a wide range from 20 to 370°C while maintaining fixed other important process parameters such as r.f. power (70 W) or pressure (2.5 Pa). The increase of T_S causes an increase of the sp²/(sp²+sp³) bonded carbon ratio and a decrease of the hydrogen content. These changes produce a great modification of the mechanical properties: microhardness, friction coefficient and adhesion. The variations of mechanical properties with T_S correlate well with the sp²/(sp²+sp³) bonded carbon ratio and the hydrogen content in the films showing a gradual transformation of the diamond-like structure into a more sp²-rich one.     

Interpretation of the Raman spectra of ultrananocrystalline diamond

It has long been known that by slightly altering the deposition conditions for diamond in plasma-enhanced chemical vapor deposition (PECVD), a transition from a microcrystalline to a nanocrystalline diamond morphology can be affected. The method of this transition, however, is not clear. This work investigates that transition by using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and Raman spectroscopy. These experiments show that far from being a continuous transition, there is competitive growth between microcrystalline and nanocrystalline diamonds. Additionally, this work confirms the interpretation that certain peaks in the Raman spectrum previously attributed to “nanocrystalline diamond” are indeed due to the presence of hydrogen at the grain boundaries. For ultrananocrystalline diamond (UNCD) films, we verify that none of the spectral features observed using visible Raman spectroscopy can be attributed to sp³-bonded carbon, although the sample is composed of ∼95% sp³-bonded carbon. Thus, the Raman signal in UNCD can be considered to be solely due to the disordered sp²-bonded carbon at the grain boundaries.     

Structural,electronic, and elastic properties of Y-diamonds and their BN analogues

The structural, elastic, and electronic properties of yne-diamonds — a new group of covalent frameworks formed by sp¹ and sp³ C atoms as well as their BN analogues are studied within the density-functional tight-binding method. The presence of very anisotropic non-equivalent covalent bonds (sp¹–sp³)/(sp¹–sp¹) in diamond-like skeletons of these materials leads to drastic changes in their properties as compared with the parent phases: diamond and c-BN. The most surprising finding concerns “pseudo-metallic” mechanical properties of examined yne-diamond-like C, BN crystals, since these wide-band-gap semiconductors behave as very soft, high-compressible, and ductile materials, showing a positive Cauchy pressure, quite high Poisson's ratio, and very small bulk moduli typical of metals.     

Surface roughness evolution and growth mechanism of carbon films from hyperthermal species

The roughness evolution of carbon films deposited from hyperthermal species was investigated by AFM. 10 eV C deposition at normal incidence angle starts with formation of 10 nm high islands followed by continuous, sp² rich films at larger doses with essentially the same feature height and film roughness. 40 eV C deposition at normal incidence angle (0°) forms sp³ rich, atomically smooth films, which become sp² rich and rough at oblique angles (≥ 60°). The limitations of currently available molecular dynamic simulations prevent their use to describe the island formation during 10 eV C bombardment. Dedicated calculations probing the effect of incidence angle on 40 eV C deposition exhibit similar trends to the experimental data i.e. decrease of the sp³ fraction and increase of the roughness with increasing incidence angle. The results are in accord with the “subplantation” scheme, linking roughness and sp² bonding to surface entrapment. Implications on recent works discussing growth mechanisms or surface smoothening are given.     

Hard and sp2-rich amorphous carbon structure formed by ion beam irradiation of fullerene,a-C and polymeric a-C:H films

In this work, we present a comparative study of the ion irradiation effect on the mechanical and optical properties of fullerene, amorphous carbon (a-C) and polymeric hydrogenated amorphous carbon (a-C:H) films, irradiated with N ions at 400 keV in the fluence range from 10¹³ to 3×10¹⁶ N cm⁻². Modifications in the carbon structure, as function of the irradiation fluence, were investigated using the Rutherford backscattering spectrometry (RBS), nuclear reaction analysis (NRA), Fourier transform infrared (FTIR), Raman spectroscopy, UV–Vis–near infrared (NIR) spectrophotometry and nanoindentation techniques. After high fluence, the three carbon samples are transformed into very similar hard (≈14 GPa) and non-hydrogenated amorphous carbon layers with very low optical gap (≈0.2 eV) and an unusual sp²-rich bonded atomic network. The mechanical properties of the irradiated films correlated with the bonding topologies of this new sp² carbon phase are investigated through the constraint-counting model. The results show that the structural modifications and the unusual rigidity were achieved by the distortion of the sp² carbon bond angles, giving origin to a constrained three-dimensional sp² carbon bonded network.     

Structural changes in carbon nanofibers induced by ball milling

A nested cones type carbon nanofiber (CNF) was exposed to ball milling with different milling times. Ball milled CNFs were investigated by transmission electron microscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and thermogravimetric analysis. It was suggested that the milling energy could be consumed by CNF grinding and aggregating. The effect of mechanical stress causes a “flattening” of the CNFs with the loss of the nanofibrous structure, and the amount of carbon layers in crystallite decreases. Multiple structural changes induced by ball milling lead to fluctuations of sp³/sp² and O/C ratios.     

Growth,electronic properties and applications of nanodiamond

Nanodiamond or nanocrystalline diamond is a broad term used to describe a plethora of materials. It is generally accepted that nanocrystalline diamond (NCD) consists of facets less than 100 nm in size, whereas a second term “ultrananocrystalline diamond” (UNCD) has been coined to describe material with grain sizes less than 10 nm. These differences in morphology originate in the growth process. Conventional hydrogen rich gas phases produce facetted diamond with grain size proportional to film thickness and low sp² content. If these films are thin the grains can be less than 100 nm and hence NCD. By starving the plasma of hydrogen, the reduction in etching of sp² can lead to re-nucleation. At the extreme this results in very small grain sizes of around 3–5 nm, UNCD.The electronic properties of these two materials are vastly different. NCD is basically very thin microcrystalline diamond and thus can be doped with boron. It is intrinsically transparent, with absorption increasing with doping level. UNCD is highly absorbing due to its higher sp² content, and exhibits a reduced bandgap due to disorder. By adding nitrogen to the gas phase, the density of states within the bandgap increases and ultimately metallic conductivity can be achieved. This conductivity is n-type but not doping.     

Inhibition of Eimeria tenella CDK‐Related Kinase 2: From Target Identification to Lead Compounds

Apicomplexan parasites encompass several human‐ and animal‐pathogenic protozoans such as Plasmodium falciparum, Toxoplasma gondii, and Eimeria tenella. E. tenella causes coccidiosis, a disease that afflicts chickens, leading to tremendous economic losses to the global poultry industry. The considerable increase in drug resistance makes it necessary to develop new therapeutic strategies against this parasite. Cyclin‐dependent kinases (CDKs) are key molecules in cell‐cycle regulation and are therefore prominent target proteins in parasitic diseases. Bioinformatics analysis revealed four potential CDK‐like proteins, of which one—E. tenella CDK‐related kinase 2 (EtCRK2)—has already been characterized by gene cloning and expression. 1 By using the CDK‐specific inhibitor flavopiridol in EtCRK2 enzyme assays and schizont maturation assays (SMA), we could chemically validate CDK‐like proteins as potential drug targets. An X‐ray crystal structure of human CDK2 (HsCDK2) served as a template to build protein models of EtCRK2 by comparative homology modeling. Structural differences in the ATP binding site between EtCRK2 and HsCDK2, as well as chicken CDK3, were addressed for the optimization of selective ATP‐competitive inhibitors. Virtual screening and “wet‐bench” high‐throughput screening campaigns on large compound libraries resulted in an initial set of hit compounds. These compounds were further analyzed and characterized, leading to a set of four promising lead compounds for development as EtCRK2 inhibitors.     

Benzocyclobutane,Benzocycloheptane and Heptene Derivatives as Melatonin Agonists and Antagonists

Two series of analogues were designed, synthesised and evaluated as potential human melatonin type 1 and 2 receptor (hMT₁ and hMT₂) ligands. Their biological effects were assessed by a well‐established, specific model of melatonin action, the pigment response of Xenopus laevis melanophores. Compounds containing a benzocyclobutane scaffold and a methoxy group in the “melatonin” orientation were found to be potent agonists, with one of the analogues exhibiting activity comparable to melatonin. In contrast, analogues with a methoxy group in non‐melatonin positions or with multiple methoxy groups showed either weaker agonist activity or were antagonists. Benzocycloheptene derivatives with one methoxy group are found to be weak agonists, whereas those with two methoxy groups were found to be antagonists, as were all of the benzocycloheptane derivatives evaluated. The most active compounds were assessed in a human receptor radio ligand binding assay but showed little discrimination between MT₁ and MT₂. These results again show that the indole nitrogen of melatonin is not a necessary component for analogue activity and also illustrate that replacement of the indole ring with a 4‐membered carbocycle can provide highly active compounds when the methoxy group is in the melatonin position.     

Hydrogel capsules for sustained drug release

Interpenetrating polymer networks (IPNs) based on polyacrylamide and polyvinyl alcohol for hydrogel capsules were synthesized. These polymer networks were evaluated as drug-delivery devices using Crystal Violet and Bromothymol Blue as model drugs. The observed drug release is higher for semi-II-IPN than full-IPN. The drug-release behaviors from these capsules were analyzed by the exponent relation Mt/Mα = Ktⁿ, where “K” and “n” are constants and Mt/Mα is the fraction of the drug released until time “t.” The constant “n” was found to be above 0.5, which suggests that the release of drug from the capsules follows the non-Fickian diffusional model. The mechanical behavior of hydrogel disks were also analyzed. © 1994 John Wiley & Sons, Inc.     

PAF receptor structure: A hypothesis

Different hypotheses of the structure of platelet-activating factor (PAF) receptor based on structure-activity relationships of agonists and antagonists are reviewed. For an agonistic effect, strong hydrophobic interactions and an ether function are required in position-1 of the glycerol backbone; chain length limitations and steric hindrance demand a small group in position-2. The unusual structural properties of non-PAF-like antagonists required 3-D electrostatic potential calculations. This method applied to seven potent antagonists suggests a strong “Cache-oreilles” (ear-muff) effect,i.e., two strong electronegative wells (isocontour at ?10 Kcal/mole) are located at 180° to each other and at a relatively constant distance. Initial consideration of the “Cache-oreilles” effect implied the structure of a bipolarized cylinder of 10–12 Å diameter for the receptor. However, very recent results on studies with agonists and antagonists structurally similar to PAF suggest that the receptor may in fact be a multi-polarized cylinder.     

Scaling-down characteristics of nanoscale diamond-like carbon based resistive switching memories

A nonvolatile resistive switching random access memory (RRAM) device based on the diamond-like carbon (DLC) films and the inert metal electrodes was demonstrated. A typical unipolar resistive switching (RS) behavior without high voltage “forming process” is observed. It exhibits good scaling-down properties when negligible dependence upon the cell area is observed for V_SET and I_RESET decreases with the reduction of the cell area, which is suitable for practical nonvolatile memory applications. Investigations on the electron transport characteristics at HRS and LRS indicate that Frenkel–Poole emission and Ohmic Laws dominate the LRS and HRS states, respectively. Based on the conduction mechanism studies, the RS behavior is found to arise from the formation and rupture of conductive sp²-like graphitic filaments originating from the connection of conductive sp²-like carbon bonds in the predominantly sp³-like insulating carbon matrix through the electric field induced dielectric breakdown process and thermal fuse effects.     

Ozone treatment process for the removal of pharmaceuticals and personal care products in wastewater

This study investigated the degradability of pharmaceuticals and personal care products (PPCPs) by ozonation for the treatment of secondary effluent of a municipal wastewater treatment plant. A set of experiments were conducted in a laboratory using a pilot-scale process consisting of three flow-through reactors in series, by varying the ozone dose (1–9 mg L^?1), the hydraulic retention time (5–15 min), and the concentration of ozone injected into the reactors (14–42 mg L^?1). Thirty-seven PPCPs were detected in the secondary effluent, which belongs to the use categories of antibiotics, analgesics, antiarrhythmic agents, anticonvulsants, vasodilators, lipid modifying agents, anti-itch drugs, anti-psychotic drugs, insect repellents, bronchodilators, diuretics, peptic ulcer drugs, NMDA receptor antagonists, antifungal drugs, antimicrobial drugs, and antineoplastic agents. These PPCPs were broadly classified into five groups ranging from “sensitive” to ozone (O₃) or “unstable” in the ozonation process, to the group of “insensitive” to O₃ or “very stable” in the ozonation process. These groups are based on the PPCP concentrations after the ozone treatment and their limit of detection (LOD). Furthermore, this study examined comparatively the effects of the ozone dose, the retention (reaction) time, and the concentration of O₃ supplied to the reactors on the degradability of the PPCPs.     

Electronic and bonding properties of Fe- and Ni based hydrogenated amorphous carbon thin films by X-ray absorption, valence-band photoemission and Raman spectroscopy

Electronic and bonding properties of Me-based hydrogenated amorphous carbon (a-CH:Me, Me = Fe, Ni) thin films have been studied by X-ray absorption near-edge structure (XANES), valence-band photoemission (VB-PES) and Raman spectroscopy. Raman and XANES results show enhancement of the content of sp³-rich diamond-like carbon (DLC) by doping with Fe and Ni. The VB-PES spectrum of a-CH:Fe shows emergence of a prominent feature due to states of sp³-bonded clusters, indicating that a-CH:Fe induced enhancement of DLC structure. The nano-indentation measurement reveals that a-CH:Fe has a greatly enhanced hardness, while electrical resistance measurement shows that a-CH:Me reduces resistivity.     

Mechanical properties of bilayer graphene sheets coupled by sp bonding

The mechanical properties, such as the Young’s modulus, the interlayer shear modulus and the ultimate tensile strength, of bilayer graphene sheets (GS) coupled by sp³ bonding are investigated by molecular dynamics simulations. These mechanical properties are found to be sensitive to the presence of sp³ bonds in the bilayer GS. The sp³ bonds exert a strengthening influence on the interlayer shear modulus as well as the load transfer rate, thereby enhancing the stability capacity of GS under axial compression. However, the presence of sp³ bonds also leads to a reduction in the Young’s modulus, ultimate tensile strength and the associated facture strain. The adverse and strengthening effects induced by the sp³ bonds are also strongly dependent of their distributions. Simulation results suggest that a small amount of sp³ bonds can be introduced in GS to improve its load transfer rate and stability substantially at the expense of a marginal deterioration in the Young’s modulus and tensile strength.     

Rearrangements of sp/sp hybridized bonding with phosphorus incorporation in pulsed laser deposited semiconducting carbon films by X-ray photoelectron spectroscopic analysis

The carbon films were grown on p-type silicon substrate at room temperature by pulsed (XeCl) laser deposition technique using camphoric carbon target containing 1%, 3%, 5% and 7% of phosphorus (P) by mass. The analysis of X-ray photoelectron spectroscopy spectra of the C1s region in these films shows the presence of sp² and sp³ hybridized carbon and a sp² satellite peak due to π–π shake up. The sp² content is seen to remain almost constant with P content. The FWHM of the sp² peak increases up to 5% P but decreases for 7% P probably due to clustering of sp² chains and this clustering in the sp² phase probably decreases the band gap for the 7% P film. With P incorporation, the tetrahedral bonding configurations of the carbon network do not change appreciably, therefore, suggesting the scope of phosphorus as a potential dopant in carbon films.     

Sigma‐2 Receptor Agonists as Possible Antitumor Agents in Resistant Tumors: Hints for Collateral Sensitivity

With the aim of contributing to the development of novel antitumor agents, high‐affinity σ₂ receptor agonists were developed, with 6,7‐dimethoxy‐2‐[4‐[1‐(4‐fluorophenyl)‐1H‐indol‐3‐yl]butyl]‐1,2,3,4‐tetrahydroisoquinoline ( 15 ) and 9‐[4‐(6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinolin‐2‐yl)butyl]‐9H‐carbazole ( 25 ) showing exceptional selectivity for the σ₂ subtype. Most of the compounds displayed notable antiproliferative activity in human MCF7 breast adenocarcinoma cells, with similar activity in the corresponding doxorubicin‐resistant MCF7adr cell line. Surprisingly, a few compounds, including 25 , displayed enhanced activity in MCF7adr cells over parent cells, recalling the phenomenon of collateral sensitivity, which is under study for the treatment of drug‐resistant tumors. All of the compounds showed interaction with P‐glycoprotein (P‐gp), and 15 and 25 , with the greatest activity, were able to revert P‐gp‐mediated resistance and reestablish the antitumor effect of doxorubicin in MCF7adr cells. We therefore identified a series of σ₂ receptor agonists endowed with intriguing antitumor properties; these compounds deserve further investigation for the development of alternate strategies against multidrug‐ resistant cancers.