Soft X-ray microscopy and spectroscopy at the molecular environmental science beamline at the Advanced Light Source

We present examples of the application of synchrotron-based spectroscopies and microscopies to environmentally relevant samples. The experiments were performed at the molecular environmental science beamline (11.0.2) at the Advanced Light Source, Lawrence Berkeley National Laboratory. Examples range from the study of water monolayers on Pt(1 1 1) single crystal surfaces using X-ray emission spectroscopy and the examination of alkali halide solution/water vapor interfaces using ambient pressure photoemission spectroscopy, to the investigation of actinides, river water biofilms, Al-containing colloids and mineral–bacteria suspensions using scanning transmission X-ray spectromicroscopy. The results of our experiments show that spectroscopy and microscopy in the soft X-ray energy range are excellent tools for the investigation of environmentally relevant samples under realistic conditions, i.e., with water or water vapor present at ambient temperature.     

Crizotinib attenuates cancer metastasis by inhibiting TGFβ signaling in non-small cell lung cancer cells

Crizotinib is a clinically approved tyrosine kinase inhibitor for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EML4-ALK fusion. Crizotinib was originally developed as an inhibitor of MET (HGF receptor), which is involved in the metastatic cascade. However, little is known about whether crizotinib inhibits tumor metastasis in NSCLC cells. In this study, we found that crizotinib suppressed TGFβ signaling by blocking Smad phosphorylation in an ALK/MET/RON/ROS1-independent manner in NSCLC cells. Molecular docking and in vitro enzyme activity assays showed that crizotinib directly inhibited the kinase activity of TGFβ receptor I through a competitive inhibition mode. Cell tracking, scratch wound, and transwell migration assays showed that crizotinib simultaneously inhibited TGFβ- and HGF-mediated NSCLC cell migration and invasion. In addition, in vivo bioluminescence imaging analysis showed that crizotinib suppressed the metastatic capacity of NSCLC cells. Our results demonstrate that crizotinib attenuates cancer metastasis by inhibiting TGFβ signaling in NSCLC cells. Therefore, our findings will help to advance our understanding of the anticancer action of crizotinib and provide insight into future clinical investigations.Subject terms: Non-small-cell lung cancer, Targeted therapies     

Hydroxypropylation of Polyphenol-Rich Alkaline Extracts from Pinus radiata Bark and Their Physicochemical Properties

Pinus radiata bark is a rich source of polyphenols, which are mainly composed of proanthocyanidins. This study aimed to utilize P. radiata bark as a polyol source for bio-foam production in the future. Polyphenol-rich alkaline extracts (AEs) from P. radiata bark were prepared by mild alkaline treatment and then derivatized with propylene oxide (PO). Hydroxypropylated alkaline extracts (HAEs) with varying molar substitutions (MS 0.4–8.0) were characterized by FT-IR, NMR, GPC, TGA, and DSC. The hydroxyl value and solubility in commercial polyols were also determined. The molecular weights of the acetylated HAEs (Ac-HAEs) were found to be 4000 to 4900 Da. Analyses of FT-IR of HAEs and ¹H NMR of Ac-HAEs indicated that the aromatic hydroxyl groups were hydroxypropylated and showed an increase in aliphatic hydroxyl group content. The glass transition temperature (T_g) of AE and HAEs were 58 to 60 °C, showing little difference. The hydroxyl value increased as the hydroxypropylation proceeded. Although salts were produced upon neutralization after hydroxypropylation, HAEs still showed suitable solubility in polyether and polyester polyols; HAEs dissolved well in polyether polyol, PEG#400, and solubility reached about 50% (w/w). This indicated that neutralized HAEs could be directly applied to bio-foam production even without removing salts.     

Direct functionalization of cell-adhesion promoters to hydrogel microparticles synthesized by stop-flow lithography

Polyethylene glycol (PEG) hydrogel microparticles generated via stop-flow lithography can be utilized for efficient microparticle-based cell culture processes because of their high biocompatibility, the molecular diffusion capability in the gel structure, and the tunability of their shape and size. However, the typical functionalization process of PEG microparticles with cell-adhesion promoters has inevitable limitations, requiring additional linker molecules and the preconjugation of linkers to cell-adhesion promoters and microparticles. In this study, a simple and direct cell-adhesion promoter functionalization process of the PEG microparticles is presented by use of aza-Michael reaction between remnant unreacted acrylate groups in particles and amine groups in cell-adhesion promoters. On the basis of proposed process, particles are directly conjugated with poly-l -lysine (PLL), a typical cell-adhesion promoter that can electrostatically interact with cellular membranes, in a controllable manner. We demonstrate enhanced cell-adhesion capabilities of the particles along with the increased amount of conjugated PLL in the particles. Furthermore, to validate extended applicability, the particles are directly conjugated with Gly-Arg-Gly-Asp-Ser (GRGDS) peptides, in which RGD sequence is involved in the cell-adhesion behavior of extracellular matrix proteins, including fibronectin. The introduced GRGDS peptides increase the cell-adhesion capacity of the microparticles binding to integrin proteins in cellular membranes.     

Intermacromolecular interactions involving linear and network polyacids and nonionic polymers

Interactions between linear and network polymers are studied in the case when one component is a polyacid and the other component is an uncharged polymer. It is shown that, under different reaction conditions, swelling or contraction of the polymer network can be observed for the same pair of reagents. It is found that, during consideration of the formation of an interpolymer complex between network and linear polymers, a distinction should be made between a semi-interpenetrating network and a hydrogel with a modified surface. The latter forms under conditions when the linear polymer practically does not penetrate the network and the complexation occurs predominantly on the sample surface.     

Oxoammonium salt-mediated oxidative nitriles synthesis from aldehydes with ammonium acetate

An efficient and scalable route for the synthesis of nitriles was developed by oxoammonium salt (4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) mediated oxidative conversion of aldehydes with NH₄OAc. A variety of aliphatic aldehydes as well as benzaldehydes were converted into the corresponding nitriles in high yields. The nitroxyl radical which is the reduced species of the used oxoammonium salt was recovered by simple acid-base extraction for the recycling.     

Photon recoil momentum in dispersive media

A systematic shift of the photon recoil momentum due to the index of refraction of a dilute gas of atoms has been observed. The recoil frequency was determined with a two-pulse light grating interferometer using near-resonant laser light. The results show that the recoil momentum of atoms caused by the absorption of a photon is n variant Planck's k, where n is the index of refraction of the gas and k is the vacuum wave vector of the photon. This systematic effect must be accounted for in high-precision atom interferometry with light gratings.     

Performance of ionic liquid as catalyst in the copolymerization of phenyl glycidyl ether with carbon dioxide

Summary Selective ammoxidation of ethylene over Co-ZSM-5 prepared by aqueous and solid-state ion exchange has been studied. The catalyst prepared using solid-state exchange showed higher activity and selectivity to acetonitrile. Catalysts tested in the ammoxidation of ethylene were previously characterized by chemical analysis, XRD, N₂-BET measurements and FTIR. TPD of ammonia and FTIR of pyridine used as probe molecule showed that solid-state ion exchange of H-ZSM-5 with cobalt generates new Lewis acid sites which seem to play a role in the ammoxidation reaction.     

Synthesis of 2,3-disubstituted indole on solid phase by the Fischer indole synthesis

2,3-Disubstituted indoles were synthesized by solid-phase reaction using the Fischer indole synthesis. A "traceless" silicon linker was employed with the silicon-carbon bonding being cleaved with TFA. An oxygen atom was placed into the middle of the spacer/linker so as to enhance solid-phase synthesis by better solvation.     

Angustilodine,an Unusual Pentacyclic Indole Alkaloid from Alstonia

Two new indole alkaloids, angustilodine ( 1 ), with an unprecedented pentacyclic carbon skeleton, and angustilocine ( 2 ), belonging to the seco‐angustilobine‐B group of alkaloids, were obtained from the leaf extract of the Malayan species Alstonia angustiloba, and their structures were established by spectroscopic analysis.