Electrostatic self-organization of robust porphyrin-polyoxometalate films

Strategies to create thin films using layer-by-layer methods use oppositely charged polymeric polyelectrolytes for both or at least one component to beneficially exploit multitopic electrostatic interactions between the deposited layers with opposite charges. In contrast, the electrostatic deposition of tetracationic 5,10,15,20-tetrakis(1'-methyl-4'-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP(4+)) with tetraanionic polyoxometalates such as EuPW(11)O(39)(4-) or SiW(12)O(40)(4-) onto charged substrates, such as mica, or polar substrates, such as glass and indium-tin oxide (ITO), demonstrates that the use of polymeric components is not a priori necessary. The use of molecules in sequential dipping approaches requires a careful balance in the interaction energies between the oppositely charged molecules, as demonstrated by the observation that a tetraanionic porphyrin such as 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin does not form layers with TMPyP(4+). In the present case, these systems require several rounds of dipping to obtain films of uniform coverage and durability. The thin films deposited onto glass, quartz, ITO, and mica are surprisingly robust, since they are not removed by sonication in either organic solvents or 100 mM NaCl.     

TEAD–YAP Interaction Inhibitors and MDM2 Binders from DNA-Encoded Indole-Focused Ugi Peptidomimetics

DNA-encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain of tryptophan plays a prominent role in key, or “hot spot”, regions of protein–protein interactions. A DNA-encoded combinatorial peptoid library was designed based on the Ugi four-component reaction by employing tryptophan-mimetic indole side chains to probe the surface of target proteins. Several peptoids were synthesized on a chemically stable hexathymidine adapter oligonucleotide “hexT”, encoded by DNA sequences, and substituted by azide-alkyne cycloaddition to yield a library of 8112 molecules. Selection experiments for the tumor-relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD-YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.     

LiTFSI structure and transport in ethylene carbonate from molecular dynamics simulations

Molecular dynamics (MD) simulations using a many-body polarizable force field were performed on ethylene carbonate (EC) doped with lithium bistrifluoromethanesulfonamide (LiTFSI) salt as a function of temperature and salt concentration. At 313 K Li+ was coordinated by 2.7-3.2 EC carbonyl oxygen atoms and 0.67-1.05 TFSI- oxygen atoms at EC:Li = 10 and 20 salt concentrations. In completely dissociated electrolytes, however, Li+ was solvated by approximately 3.8 carbonyl oxygen atoms from EC on average. The probability of ions to participate ion aggregates decreased exponentially with an increase in the size of the aggregate. Ion and solvent self-diffusion coefficients and conductivity predicted by MD simulations were in good agreement with experiments. Approximately half of the charge was transported by charged ion aggregates with the other half carried by free (uncomplexed by counterion) ions. Investigation of the Li+ transport mechanism revealed that contribution from the Li+ diffusion together with its coordination shell to the total Li+ transport is similar to the contribution arising from Li+ exchanging solvent molecules in its first coordination shell with solvents from the outer shells.     

Effects of cations on the hydrogen bond network of liquid water: new results from X-ray absorption spectroscopy of liquid microjets

Oxygen K-edge X-ray absorption spectra (XAS) of aqueous chloride solutions have been measured for Li(+), Na(+), K(+), NH(4)(+), C(NH(2))(3)(+), Mg(2+), and Ca(2+) at 2 and 4 M cation concentrations. Marked changes in the liquid water XAS are observed upon addition of the various monovalent cation chlorides that are nearly independent of the identity of the cation. This indicates that interactions with the dissolved monovalent cations do not significantly perturb the unoccupied molecular orbitals of water molecules in the vicinity of the cations and that water-chloride interactions are primarily responsible for the observed spectral changes. In contrast, the addition of the divalent cations engenders changes unique from the case of the monovalent cations, as well as from each other. Density functional theory calculations suggest that the ion-specific spectral variations arise primarily from direct electronic perturbation of the unoccupied orbitals due to the presence of the ions, probably as a result of differences in charge transfer from the water molecules onto the divalent cations.     

Synthetic peptides with selective affinity for apoptotic cells

The appearance of anionic phosphatidylserine (PS) in the outer monolayer of the plasma membrane is a universal indicator of the early/intermediate stages of cell apoptosis. The most common method of detecting PS on a cell surface is to use the protein annexin V; however, in certain applications there is a need for alternative reagents. Recent research indicates that rationally designed zinc 2,2'-dipicolylamine (Zn2+-DPA) coordination complexes can mimic the apoptosis sensing function of annexin V. Here, a series of fluorescently-labelled, tri- and pentapeptides with side chains containing Zn2+-DPA are prepared and shown to selectively bind to anionic vesicle membranes. Fluorescein-labelled versions of the peptides are used to detect apoptotic cells by fluorescence microscopy and flow cytometry.     

UPLC/MS(E); a new approach for generating molecular fragment information for biomarker structure elucidation

A new approach to obtain fragmentation information in liquid chromatography/mass spectrometry (LC/MS) studies of small molecules in complex mixtures is presented using simultaneous acquisition of exact mass at high and low collision energy, MS(E). LC/MS-TOF and LC/MS/MS-TOF are powerful tools for the analysis of complex mixtures, especially those for biological fluids allowing the elucidation of elemental composition and fragmentation information. In this example the composition of rat urine was studied using this new approach, allowing the structures of several endogenous components to be confirmed in one analytical run by the simultaneous acquisition of exact mass precursor and fragment ion data. The spectral data obtained using this new approach are comparable to those obtained by conventional LC/MS/MS as exemplified by the identification of endogenous metabolites present in rat urine.     

Organic-inorganic hybrid nanoparticles: surface characteristics and interactions with a polyester resin

Organic-inorganic hybrid nanoparticles, derived from silica precursors with different organic functionalities (methyl, ethyl, vinyl, and phenyl) synthesized via a modified St?ber method have been investigated. These particles are intended as modifiers for polymers and polymer matrix composites. Therefore, the characteristics of a polyester matrix have also been determined, and the likely interactions with the particles have been proposed. Particles have been characterized using inverse gas chromatography (IGC), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FT-IR). The particles show two different sets of characteristics, with methyl, ethyl, and vinyl modified silicas showing one type of behavior and the phenyl modified silica behaving rather differently. The methyl, ethyl, and vinyl groups exhibit the appearance of uniform coverage, as they are comparatively small and tightly packed, which will prevent interaction of matrix resin with retained silanol groups. The phenyl group, which is comparatively large, is not able to pack as closely, which results in a reduction of the presence and availability of silanol groups, compared to an unmodified fumed silica, but not complete inaccessibility as far as the matrix resin is concerned.     

1H and 13C NMR assignments and X-ray structures for three monocyclic benzoannelated dilactam polyethers

Three monocyclic polyether dilactams, 17,18-dihydro-5H, 9H-dibenzo[e,n]1,4,10,7,13trioxadiazacyclopentadecine-6,10(7H,11H)-dione (1); 9,10,20,21-tetrahydro-5H, 12H-dibenzo[e,q]1,4,10,13,7,16tetraoxadiazacyclooctadecine-6, 13(7H,14H)-dione (2); and 6,7,9,10-tetrahydro-16H, 20H-dibenzo[h,q]1,4,7,13, 10,16tetraoxadiazacyclooctadecine-17, 21(18H,22H)-dione (3) were isolated during the synthesis of several benzoannelated cryptands. The complete assignments of the 1H and 13C NMR spectra of 1, 2 and 3 in CDCl3 were made using gCOSY, gHMBC, gHMQC, HMQC, HSQC, and NOESY 1D techniques. The ortho (H2) benzene protons show significant downfield shifts (1.16-1.43 ppm) that are consistent with an exodentate orientation for the amide carbonyl groups. The X-ray crystal structures of 1, 2 and 3 show that the carbonyl groups adopt an exodentate conformation in the solid state.     

Lithium amide conjugate addition for the asymmetric synthesis of 3-aminopyrrolidines

Conjugate addition of homochiral lithium amides to methyl 4-(N-benzyl-N-allylamino)but-2-enoate, chemoselective N-deprotection and concomitant cyclisation, followed by enolate functionalisation and deprotection allows access to syn- and anti-3,4-disubstituted aminopyrrolidines in > 98% d.e. and > 98% e.e.