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Research is done on tandem mass spectrometry which is used to show that low energy collisions of ionized halocarbenes, including CBr2(super .+) and CBrCl(super .+), with molecular oxygen lead to decarbonation with formation of the dihalogen molecular cation and oxygenolysis yielding BrCO(super +). Insights into the energetics of the reactions of CBr2(super .+) with O2 are obtained from ab initio molecular orbital theory.

The value of low-energy ionic collisions for selective surface analysis is shown by the fact that reactive scattering allows differentiation of isomeric chemisorbates. Reactions of [Cr.sup.[center dot]+] and Cr-containing cations at chlorobenzyl mercaptan (CBM) monolayers on Au surfaces show different reaction products, depending on the position of chlorine substitution in the phenyl ring. The chlorine atom abstraction product, Cr[Cl.sup.+], is observed at 45-eV collision in 4-CBM and is completely absent in 2-CBM at the same energy. The sensitivity of reactive ion scattering to the isomeric adsorbate is further demonstrated by the fact that the peak corresponding to [Cr.sup.[center dot]+] addition and Cl loss via Cl-C bond cleavage, [C.sub.7][H.sub.6]S[Cr.sup.+], is large in the monolayer formed from 4-CBM, but weak in the 2-CBM monolayer, suggesting that the chlorine is below the first layer of atoms in the latter case. The inverse intensity relationship applies for the dehydrohalogenation product [C.sub.7][H.sub.5][Cr.sup.+] where the Cl atom at the ortho position in 2-CBM facilitates the intramolecular elimination of HCl. The 85-eV [Xe.sup.[center dot]+] chemical sputtering mass spectra are the same for both surfaces, indicating similarities in the electrontransfer and momentum-transfer processes. A related set of isomers, 2-, 3- and 4-chlorothiophenol, chemisorbed on gold, shows no differences in ion/surface reactions or chemical sputtering.

Ion/surface reactive collisions and charge exchange leading to chemical sputtering are sensitive to chemisorbate structure of aromatic compounds. The differences in adsorption geometry were investigated using self-assembled monolayers of 1,2-, 1,3- and 1,4-benzenedimethanethiol adsorbed in gold and silver thin films as target surfaces. Results suggested that the difference in adsorbate geometry is due to the presence of aromatic C-H and S-H chains and an S-C-H bend from the gold monolayer and the absences of these in the silver monolayer.

The role of peptide inhibitors when delivered into cells, which inhibit cellular Akt activity and cell growth, is discussed. The Akt specific peptide inhibitors are useful in the treatment of cancer; they dissect the cellular function of Akt and provide prototypes for peptide mimetic drugs.

Direct, reactive incorporation of molecular groups into surfaces was demonstrated to be a new surface modification method. Reactive soft-landing of ion beams provided a means of covalently attaching intact molecular moieties to give-well defined products in contrast to earlier experiments using ion treatment. The fragmentation of the reactive projectiles was reduced or prevented by the very low collision energies used in the experiments. A superficial similarity to the classical Kolbe alkane synthesis labels the results an interfacial Kolbe reaction.

The development of bromodomain and extraterminal domain (BET) bromodomain inhibitors and their examination in clinical studies, particularly in oncology settings, has garnered substantial recent interest. An effort to generate novel BET bromodomain inhibitors with excellent potency and drug metabolism and pharmacokinetics (DMPK) properties was initiated based upon elaboration of a simple pyridone core. Efforts to develop a bidentate interaction with a critical asparagine residue resulted in the incorporation of a pyrrolopyridone core, which improved potency by 9-19-fold. Additional structure-activity relationship (SAR) efforts aimed both at increasing potency and improving pharmacokinetic properties led to the discovery of the clinical candidate 63 (ABBV-075/mivebresib), which demonstrates excellent potency in biochemical and cellular assays, advantageous exposures and half-life both in animal models and in humans, and in vivo efficacy in mouse models of cancer progression and inflammation.

There is a great need to develop multifunctional nanoparticles (MFNPs) for cancer biomarker-based detection and highly selective therapeutic treatment simultaneously. Here we describe a facile approach of layer-by-layer-assembled MFNPs conjugated with monoclonal antibody anti-HER2, demonstrating the specific detection of breast cancer BT474 cells (biomarker HER2 positive) with a high signal-to-noise ratio. The MFNPs contain a well-defined core-shell structure of UCNP@Fe3O4@Au coated by poly(ethylene glycol) (PEG) and anti-HER2 antibody, displaying excellent dispersity in various aqueous solutions. This unique combination of nanoparticles and ligand molecules allows us to perform photothermal treatment (PTT) of the cancer cells, while simultaneously quantifying the distribution of MFNPs on a cancer cell surface induced by antigen-antibody binding events. An important finding is that cancer cells adjacent to each other or in physical proximity within micrometers may end up with different fates of survival or death in PTT. This dramatic difference is determined by the antigen-antibody binding events at the interface of MFNPs and cells because of tumor cell heterogeneity. Therefore, our experiments reveal a new scale of the highly localized feature of the photothermal effect at the single-cell level illuminated by a continuous-wave near-IR laser.

A facile approach was developed to fabricate patterned substrates of nano-graphene oxide, demonstrating highly localized and efficient gene delivery to multiple cell lines in a substrate-mediated manner. The GO substrates served as a valid platform to preconcentrate PEI/pDNA complexes and maintain their gradual releasing for a relatively long period of time. Our approach allowed successful gene delivery in selected groups of cells on the stripe-patterned GO substrates, without transfecting their neighbor cells directly cultured on glass. These GO substrates exhibited excellent biocompatibility and enabled effective gene transfection for various cell lines including stem cells, thus promising important applications in stem cell research and tissue engineering.

Ion channels play critical roles in signaling processes and are attractive targets for treating various diseases. Here we describe an NMR-based strategy for structural analyses of potassium channel-ligand complexes using KcsA (residues 1-132, with six mutations to impart toxin binding and to mimic the eukaryotic hERG channel). Using this approach, we determined the solution structure of KcsA in complex with the high-affinity peptide antagonist charybdotoxin. The structural data reveal how charybdotoxin binds to the closed form of KcsA and makes specific contacts with the extracellular surface of the ion channel, resulting in pore blockage. This represents the first direct structural information about an ion channel complexed to a peptide antagonist and provides an experimental framework for understanding and interpreting earlier mutational analyses. The strategy presented here overcomes many of the limitations of conventional NMR approaches to helical membrane protein structure determination and can be applied in the study of the binding of druglike molecules to this important class of proteins.