Peptide Amphiphile Supramolecular Nanostructures as a Targeted Therapy for Atherosclerosis

The rising prevalence of cardiovascular disease worldwide necessitates novel therapeutic approaches to manage atherosclerosis. Intravenously administered nanostructures are a promising noninvasive approach to deliver therapeutics that reduce plaque burden. The drug liver X receptor agonist GW3965 (LXR) can reduce atherosclerosis by promoting cholesterol efflux from plaque but causes liver toxicity when administered systemically at effective doses, thus preventing its clinical use. The ability of peptide amphiphile nanofibers containing apolipoprotein A1–derived targeting peptide 4F to serve as nanocarriers for LXR delivery (ApoA1‐LXR PA) in vivo is investigated here. These nanostructures are found to successfully target atherosclerotic lesions in a mouse model within 24 h of injection. After 8 weeks of intravenous administration, the nanostructures significantly reduce plaque burden in both male and female mice to a similar extent as LXR alone in comparison to saline‐treated controls. Furthermore, they do not cause increased liver toxicity in comparison to LXR treatments, which may be related to more controlled release by the nanostructure. These findings demonstrate the potential of supramolecular nanostructures as safe, effective drug nanocarriers to manage atherosclerosis.     

Ionic Liquid-Driven Formation of and Cation Exchange in Layered Sulfido Stannates – a CH2 Group Makes the Difference

Two types of layered sulfido stannates or a molecular cluster compound are obtained upon ionothermal treatment of the simple sulfido stannate salt K₄[SnS₄] 4H₂O that is based on binary tetrahedral [SnS₄]⁴⁻ anions. The formation of the respective products, novel compounds (C₄C₁C₁Im)₂[Sn₃S₇] ( 1 a ), (C₄C₁C₂Im)₂[Sn₃S₇] ( 1 b ), and (C₄C₁C₂Im)₂[Sn₄S₉] ( 2 ) with layered anionic substructures, or the recently reported compound (C₄C₁C₁Im)_4+x[Sn₁₀O₄S₁₆(SMe)₄][An]_x ( A ) comprising a molecular cluster anion, is controlled by both the choice of the ionic liquid cation and the reaction temperature. We report the scale-up of the syntheses by a factor of 100 with regard to other reported ionothermal syntheses of related compounds, and a procedure of how to isolate them in phase-pure form – both being rare observations in chalcogenido stannate chemistry in ionic liquids. Moreover, the synthesis of compound 1 a can be achieved by rapid cation exchange starting out from 1 b , which has not been reported for organic cations in any chalcogenido stannate salt to date.     

Linear Tetraphenylmethane‐Based Thioether Oligomers Stabilising an Entire Gold Nanoparticle by Enwrapping

The design and synthesis of a novel linear thioether‐based ligand subunit with a tetraphenylmethane core used in the stabilisation of gold nanoparticles (AuNPs) are presented. Mono‐, tri, penta‐ and heptamers of the ligand have been synthesised and used to stabilise AuNPs by enwrapping. With the exception of the monomer, all ligands provide reliable long‐term stability and redispersibility for the coated nanoparticles in common organic solvents. Despite variation of the oligomer length, all stable particles were of the same size within error tolerance (1.16±0.32 nm for the trimer, 1.15±0.30 nm for the pentamer, 1.17±0.34 nm for the heptamer), as investigated by transmission electron microscopy (TEM). These findings suggest that not only the number of sulfur atoms in the ligand, but also its bulkiness play a crucial role in stabilising the AuNPs. These findings are supported by thermogravimetric analysis (TGA), showing that AuNPs stabilised by the penta‐ or heptamer are passivated by a single ligand. Thermal stability measurements suggest a correlation between ligand coverage and thermal stability, further supporting these findings.     

A Methylated Oxo-Thio Stannate Cluster from a Non-Innocent Ionic Liquid

A new salt of the alkylated oxo-thio stannate cluster [Sn₁₀O₄S₁₆(SMe)₄]^4–, (C₄C₄C₁Im)₄[Sn₁₀O₄S₁₆(SMe)₄] ( 1 ), was obtained by ionothermal treatment of K₄[SnS₄] · 4H₂O. The reaction was carried out in the ionic liquid 1,3-dibutyl-2-methylimidazolium chloride, (C₄C₄C₁Im)Cl, which proved to be non-innocent against the chalcogenido metallate species in the reaction mixture. In continuation of our first studies on alkylation of very weakly nucleophilic chalcogenido metalate anions, this study served to prove that an N-bonded alkyl group is selectively released from the imidazolium cation of the ionic liquid, and it served to show that methylation is favored over butylation. The title compound is one of the rare cases, in which the cations of the salt, which stem from the ionic liquid, could be crystallographically determined without problems.     

Strong field ionization of many electron systems: A quantum chemical challenge

A non-variational Time-Dependent Multiconfiguration Self-Consistent Field (TDMCSCF) scheme has been developed [Nguyen-Dang T.T., Peters M., Wang S.-M., Sinelnikov E., and Dion F., J. Chem. Phys. 127, 174107 (2007)] to describe, by an ab-initio approach, the time-resolved electron dynamics of a laser-driven many-electron atomic or molecular system. As an L ² method, this approach faces severe challenges when ionization and large-amplitude electronic motions are addressed. We present here an extension of this TDMCSCF scheme to include multiple ionization processes, using a Feschbach state-partitioning formalism, allowing the bound electrons’ dynamics to be treated by the L ²-TDMCSCF method, while the ionized electrons can be treated separately by an alternative approach. We present results of proof-of-principle calculations pertaining to the single and double ionizations of H ₂ and discuss methodological issues such as the systematic corrections that could be brought, using this approach, to the strong field approximation (SFA).     

3,3-Bis(3,5-dimethylpyrazol-1-yl)propionic acid: A tripodal N,N,O ligand for manganese and rhenium complexes - Syntheses and structures

The tripodal N,N,O ligands 3,3-bis(3,5-dimethylpyrazol-1-yl)propionic acid (Hbdmpzp) (1) and 3,3-bis(pyrazol-1-yl)propionic acid (Hbpzp) (2) form the “missing link” between the well-known bis(pyrazol-1-yl)acetic acids and related ligands with a longer “carboxylate arm”. To illustrate the reactivity of this ligand, manganese and rhenium complexes bearing the ligand bdmpzp are reported. The complexes are compared to related compounds bearing other tripod ligands such as bis(3,5-dimethylpyrazol-1-yl)acetate (bdmpza) and 3,3-bis(1-methylimidazol-2-yl)propionate (bmip). Spectroscopic and structural data are used as a basis for comparison, as well as DFT calculations. Both ligands 1 and 2 and the complexes fac-[Mn(bdmpzp)(CO)₃] (3) and fac-[Re(bdmpzp)(CO)₃] (4) were characterised by X-ray crystallography.     

Thin Pd–23%Ag/stainless steel composite membranes: Long-term stability,life-time estimation and post-process characterisation

The long-term stability of Pd–23%Ag/stainless steel composite membranes has been examined in H₂/N₂ mixtures as a function of both temperature and feed pressure. During continuous operation, the membrane shows a good stability at 400 °C while the N₂ leakage increases very slowly at a temperature of 450 °C (P_feed = 10 bar). After 100 days of operation (P_feed = 5–20 bar, T = 350–450 °C), the N₂ permeance equals 7.0 × 10⁻⁹ mol m⁻² s⁻¹ Pa⁻¹, which indicates that the H₂/N₂ permselectivity still lies around 500, based on a H₂ permeance equal to 3.0 × 10⁻⁶ mol m⁻² s⁻¹ Pa⁻¹. Despite the generation of small pinholes, a membrane life-time of several (2–3) years (T ≤ 425 °C) is estimated for the experimental conditions employed based on long-term stability tests over 100 days. Post-process characterisation shows a considerable grain growth and micro-strain relaxation in the Pd–23%Ag membrane after the prolonged permeation experiment. Changes in surface area are relatively small. In addition, segregation of Ag to the membrane surfaces is observed. The formation of pinholes is identified as the main source for the increased N₂ leakage during testing at higher temperature.     

A motivic study of generalized Burniat surfaces

Generalized Burniat surfaces are surfaces of general type with \(p_g=q\) and Euler number \(e=6\) obtained by a variant of Inoue’s construction method for the classical Burniat surfaces. I prove a variant of the Bloch conjecture for these surfaces. The method applies also to the so-called Sicilian surfaces introduced by Bauer et al. in (J Math Sci Univ Tokyo 22(2–15):55–111, 2015. arXiv:1409.1285v2). This implies that the Chow motives of all of these surfaces are finite-dimensional in the sense of Kimura.