Interfacial behavior and film patterning of redox-active cationic copper(II)-containing surfactants

Herein, we describe the synthesis and characterization of a novel series of single-tail amphiphiles LPyCn (Py=pyridine, Cn=C18, C16, C14, C10) and their copper(II)-containing complexes, which are of relevance for patterned films. The N-(pyridine-2-ylmethyl)alkyl-1-amine ligands and their complexes [CuIICl2(LPyC18)] (1), [CuIICl2(LPyC16)] (2), [CuIICl2(LPyC14)] (3), [CuIIBr2(LPyC18)] (4), [CuIIBr2(LPyC16)] (5), and [CuIIBr2(LPyC10)] (6) were synthesized, isolated, and characterized by means of mass spectrometry, IR and NMR spectroscopies, and elemental analysis. Complexes 1, 2, 3, and 6 had their molecular structure solved by X-ray diffraction methods, which showed that the local geometry around the metal center is distorted square planar. With the aim of using these species as precursors for redox-responsive films, an assessment of their electrochemical properties involved cyclic voltammetry in different solvents, with different supporting electrolytes and scan rates. Density functional theory calculations of relevant species in bulk and at interfaces were used to evaluate their electronic structure and dipole moments. The morphology and order of the resulting films at the air/water interface were studied by isothermal compression and Brewster angle microscopy. Biphasic patterned Langmuir films were observed for all complexes except 3 and 6, and dependence on the chain length and the nature of the halogen coligand determine the characteristics of the isotherms and their intricate topology. Complexes 3 and 6, which have shorter chain lengths, failed to exhibit organization. These results exemplify the first comprehensive study of the behavior of single-tail metallosurfactants, which are likely to lead to high-end technological applications based on their patterned films.     

A Frustrated and Confused Lewis Pair

We report a new class of frustrated Lewis pairs (FLPs) by the hydroboration of bulky isocyanates ^iPr2ArNCO (^iPr2Ar=2,6‐iPr₂C₆H₃) and ^Ph2tBuArNCO (^Ph2tBuAr=2,6‐Ph₂‐4‐tBuC₆H₂) with Piers’ borane (HB(C₆F₅)₂). While hydroboration of smaller isocyanates such as ^iPr2ArNCO leads to isocyanate—N/B FLP adducts, hydroboration of the bulkier ^Ph2tBuArNCO allows isolation of the substrate‐free aminoborane with a short, covalent N?B bond. This confused FLP reversibly binds unsaturated substrates such as isocyanates and isocyanides, suggesting the intermediacy of a “normal” FLP along the reaction pathway, supported by high‐level DFT studies and variable‐temperature NMR spectroscopy. These results underscore the possibility of FLP behavior in systems that possess no obvious frustrated Lewis acid–base interaction.     

Redox Non‐Innocence of Nitrosobenzene at Nickel

Nitrosobenzene (PhNO) serves as a stable analogue of nitroxyl (HNO), a biologically relevant, redox‐active nitric oxide derivative. Capture of nitrosobenzene at the electron‐deficient β‐diketiminato nickel(I) complex [ⁱPr₂NN_F6]Ni results in reduction of the PhNO ligand to a (PhNO)^./? species coordinated to a square planar Ni^II center in [ⁱPr₂NN_F6]Ni(η²‐ONPh). Ligand centered reduction leads to the (PhNO)^2? moiety bound to Ni^II supported by XAS studies. Systematic investigation of structure–reactivity patterns of (PhNO)^./? and (PhNO)^2? ligands reveals parallels with superoxo (O₂)^./? and peroxo (O₂)^2? ligands, respectively, and forecasts reactivity patterns of the more transient HNO ligand.     

Benzimidazole- and benzothiazole-quinones: excellent substrates for NAD(P)H:quinone oxidoreductase 1

A series of benzimidazole- and benzothiazole-quinones has been synthesized. The ability of these heterocyclic quinones to act as substrates for recombinant human NAD(P)H:quinone oxidoreductase (NQO1), a two-electron reductase upregulated in tumour cells, was determined. Overall, the quinones were excellent substrates for NQO1.     

Self-assembled ionophores from isoguanosine: diffusion NMR spectroscopy clarifies cation's and anion's influence on supramolecular structure

Cation-templated self-assembly of the lipophilic isoguanosine (isoG 1) with different monovalent cations (M(+)=Li(+), Na(+), K(+), NH(4) (+), and Cs(+)) was studied in solvents of different polarity by using diffusion NMR spectroscopy. Previous studies that did not use diffusion NMR techniques concluded that isoG 1 forms both pentamers (isoG 1)(5)M(+) and decamers (isoG 1)(10)M(+) in the presence of alkali-metal cations. The present diffusion NMR studies demonstrate, however, that isoG 1 does not form (isoG 1)(5)M(+) pentamers. In fact, the diffusion NMR data indicates that both doubly charged decamers of formula (isoG 1)(10)2 M(+) and singly charged decamers, (isoG 1)(10)M(+), are formed with lithium, sodium, potassium, and ammonium tetraphenylborate salts (LiB(Ph)(4), KB(Ph)(4), NaB(Ph)(4) and NH(4)B(Ph)(4)), depending on the isoG 1:salt stoichiometry of the solution. In the presence of CsB(Ph)(4), isoG 1 affords only the singly charged decamers (isoG 1)(10)Cs(+). By monitoring the diffusion coefficient of the B(Ph)(4) (-) ion in the different mixtures of solvents, we also concluded that the anion is more strongly associated to the doubly charged decamers (isoG 1)(10)2 M(+) than to the singly charged decamers (isoG 1)(10)M(+). The (isoG 1)(10)2 M(+) species can, however, exist in solution without the mediation of the anion. This last conclusion was supported by the finding that the doubly charged decamers (isoG 1)(10)2 M(+) also prevail in 1:1 CD(3)CN:CDCl(3), a solvent mixture in which the B(Ph)(4) (-) ion does not interact significantly with the self-assembled complex. These diffusion measurements, which have provided new and improved structural information about these decameric isoG 1 assemblies, demonstrate the utility of combining diffusion NMR techniques with conventional NMR methods in seeking to characterize labile, multicomponent, supramolecular systems in solution, especially those with high symmetry.     

Evidence for a SN2-type pathway for phosphine exchange in phosphine-phosphenium cations, [R2P--PR'3]+

Abstraction of a Cl(-) ion from the P-chlorophospholes, R4C4PCl (R=Me, Et), produced the P--P bonded cations [R4C4P--P(Cl)C4R4]+, which reacted with PPh3 to afford X-ray crystallographically characterised phosphine-phosphenium cations [R4C4P(PPh3)]+ (R=Me, Et). Examination of the 31P-{1H} NMR spectrum of a solution (CH2Cl(2)) of [Et4C4P-(PPh3)]+ and PPh3 revealed broadening of the resonances due to both free and coordinated PPh3, and importantly it proved possible to measure the rate of exchange between PPh3 and [Et4C4P-(PPh3)]+ by line shape analysis (gNMR programmes). The results established second-order kinetics with DeltaS( not equal)=(-106.3+/-6.7) J mol(-1) K(-1), DeltaH( not equal)=(14.9+/-1.6) kJ mol(-1) and DeltaG( not equal) (298.15 K)=(46.6+/-2.6) kJ mol(-1), values consistent with a SN2-type pathway for the exchange process. This result contrasts with the dominant dissociative (S(N)1-type) pathway reported for the analogous exchange reactions of the [ArNCH2CH2N(Ar)P(PMe3)]+ ion, and to understand in more detail the factors controlling these two different reaction pathways, we have analysed the potential energy surfaces using density functional theory (DFT). The calculations reveal that, whilst phosphine exchange in [Et4C4P(PPh3)]+ and [ArNCH2CH2N(Ar)P(PMe3)](+) is superficially similar, the two cations differ significantly in both their electronic and steric requirements. The high electrophilicity of the phosphorus center in [Et4C4P]+, combined with strong pi-pi interactions between the ring and the incoming and outgoing phenyl groups of PPh3, favours the SN2-type over the SN1-type pathway in [Et4C4P(PPh3)]+. Effective pi-donation from the amide groups reduces the intrinsic electrophilicity of [ArNCH2CH2N(Ar)P]+, which, when combined with the steric bulk of the aryl groups, shifts the mechanism in favour of a dissociative SN1-type pathway.     

Ab initio molecular dynamics of hydrogen dissociation on metal surfaces using neural networks and novelty sampling

We outline a hybrid multiscale approach for the construction of ab initio potential energy surfaces (PESs) useful for performing six-dimensional (6D) classical or quantum mechanical molecular dynamics (MD) simulations of diatomic molecules reacting at single crystal surfaces. The algorithm implements concepts from the corrugation reduction procedure, which reduces energetic variation in the PES, and uses neural networks for interpolation of smoothed ab initio data. A novelty sampling scheme is implemented and used to identify configurations that are most likely to be predicted inaccurately by the neural network. This hybrid multiscale approach, which couples PES construction at the electronic structure level to MD simulations at the atomistic scale, reduces the number of density functional theory (DFT) calculations needed to specify an accurate PES. Due to the iterative nature of the novelty sampling algorithm, it is possible to obtain a quantitative measure of the convergence of the PES with respect to the number of ab initio calculations used to train the neural network. We demonstrate the algorithm by first applying it to two analytic potentials, which model the H2/Pt(111) and H2/Cu(111) systems. These potentials are of the corrugated London-Eyring-Polanyi-Sato form, which are based on DFT calculations, but are not globally accurate. After demonstrating the convergence of the PES using these simple potentials, we use DFT calculations directly and obtain converged semiclassical trajectories for the H2/Pt(111) system at the PW91/generalized gradient approximation level. We obtain a converged PES for a 6D hydrogen-surface dissociation reaction using novelty sampling coupled directly to DFT. These results, in excellent agreement with experiments and previous theoretical work, are compared to previous simulations in order to explore the sensitivity of the PES (and therefore MD) to the choice of exchange and correlation functional. Despite having a lower energetic corrugation in our PES, we obtain a broader reaction probability curve than previous simulations, which is attributed to increased geometric corrugation in the PES and the effect of nonparallel dissociation pathways.     

Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis

Background

While there is a general agreement that picture-plane inversion is more detrimental to face processing than to other seemingly complex visual objects, the origin of this effect is still largely debatable. Here, we address the question of whether face inversion reflects a quantitative or a qualitative change in processing mode by investigating the pattern of event-related potential (ERP) response changes with picture plane rotation of face and house pictures. Thorough analyses of topographical (Scalp Current Density maps, SCD) and dipole source modeling were also conducted.

Results

We find that whilst stimulus orientation affected in a similar fashion participants' response latencies to make face and house decisions, only the ERPs in the N170 latency range were modulated by picture plane rotation of faces. The pattern of N170 amplitude and latency enhancement to misrotated faces displayed a curvilinear shape with an almost linear increase for rotations from 0° to 90° and a dip at 112.5° up to 180° rotations. A similar discontinuity function was also described for SCD occipito-temporal and temporal current foci with no topographic distribution changes, suggesting that upright and misrotated faces activated similar brain sources. This was confirmed by dipole source analyses showing the involvement of bilateral sources in the fusiform and middle occipital gyri, the activity of which was differentially affected by face rotation.

Conclusion

Our N170 findings provide support for both the quantitative and qualitative accounts for face rotation effects. Although the qualitative explanation predicted the curvilinear shape of N170 modulations by face misrotations, topographical and source modeling findings suggest that the same brain regions, and thus the same mechanisms, are probably at work when processing upright and rotated faces. Taken collectively, our results indicate that the same processing mechanisms may be involved across the whole range of face orientations, but would operate in a non-linear fashion. Finally, the response tuning of the N170 to rotated faces extends previous reports and further demonstrates that face inversion affects perceptual analyses of faces, which is reflected within the time range of the N170 component.     

Structural Factors and Mechanisms Underlying the Improved Photodynamic Cell Killing with Silicon Phthalocyanine Photosensitizers Directed to Lysosomes Versus Mitochondria

The phthalocyanine photosensitizer Pc 4 has been shown to bind preferentially to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components, especially Bcl-2, are photodamaged and apoptosis, as indicated by activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase, is triggered. A series of analogs of Pc 4 were synthesized, and the results demonstrate that Pcs with the aminopropylsiloxy ligand of Pc 4 or a similar one on one side of the Pc ring and a second large axial ligand on the other side of the ring have unexpected properties, including enhanced cell uptake, greater monomerization resulting in greater intracellular fluorescence and three-fold higher affinity constants for liposomes. The hydroxyl-bearing axial ligands tend to reduce aggregation of the Pc and direct it to lysosomes, resulting in four to six times more killing of cells, as defined by loss of clonogenicity, than with Pc 4. Whereas Pc 4-PDT photodamages Bcl-2 and Bcl-xL, Pc 181-PDT causes much less photodamage to Bcl-2 over the same dose–response range relative to cell killing, with earlier cleavage of Bid and slower caspase-3-dependent apoptosis. Therefore, within this series of photosensitizers, these hydroxyl-bearing axial ligands are less aggregated than is Pc 4, tend to localize to lysosomes and are more effective in overall cell killing than is Pc 4, but induce apoptosis more slowly and by a modified pathway.     

Cigarette smoke extract induced protein phosphorylation changes in human microvascular endothelial cells in vitro

Phosphorylation is the most widely studied posttranslational modification (PTM) and is an important regulatory mechanism used during cellular responses to external stimuli. The kinases and phosphatases that regulate protein phosphorylation are known to be affected in many human diseases. Cigarette smoking causes cardiovascular disease (CVD). Endothelial cells play a pivotal role in CVD initiation and development; however, there have been limited investigations of the specific signaling cascades and protein phosphorylations activated by cigarette smoke in endothelial cells. The purpose of this research was to better understand the differential protein phosphorylation in endothelial cells stimulated with extracts of cigarette smoke total particulate matter (CS-TPM) in vitro. Human microvascular endothelial cells were exposed in vitro to CS-TPM at concentrations that were shown to cause endothelial cell dysfunction. The phosphorylated proteins were isolated using phosphoprotein-specific chromatography, followed by enzymatic digestion and nano-flow capillary liquid chromatography (ncap-LC) coupled to high resolution mass spectrometry. This study putatively identified 94 proteins in human microvascular endothelial cells that were differentially bound to a phosphoprotein-specific chromatography column following exposure to CS-TPM suggesting differential phosphorylation. Pathway analysis has also been conducted and confirmations of several observations have been made using immunoaffinity-based techniques (e.g., Western blotting). Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.