Plasma desorption mass spectrometry of transition metal complexes of thio- and selenosemicarbazones of 2-acetylpyridines

Summary Californium-252 plasma desorption mass spectra were recorded for complexes of the anions of various thio-and seleno-semicarbazones of 3-acetylpyridines(1–4) with the transition metal ions iron(III) and cobalt(II). Positive ion spectra gave clear evidence of the cation present and fragmentation with loss of ligands or parts of ligands was straightforward. Negative ion spectra likewise provided evidence of the intact anion except with tetracoordinate metal halide systems [MX₄]^– which lost one or more halide atoms. Evidence of fragmentation of the ligand and recombination of the fragments with the metal ion was also observed in the negative ion mode. Spectra were used to revise the structure of a complex previously reported as [FeLCl₂]⁽¹⁾ to [FeL₂]⁺[FeCl₄]^–.     

An Efficient Strategy to Orthogonally Protected (R)- and (S)-alpha-Methyl(alkyl)serine-Containing Peptides via a Novel Azlactone/Oxazoline Interconversion Reaction

A novel strategy for the synthesis of (R)- and (S)-alpha-methyl(alkyl)serine-containing peptides is presented. Using (S)-phenylalanine cyclohexylamide 6 as chiral auxiliary, the optically pure azlactones (R)- and (S)-2 were synthesized via a novel azlactone/oxazoline interconversion reaction (Figures 3 and 6). These azlactones constitute fully protected and activated synthetic equivalents of (R)- and (S)-alpha-methylserine and can be directly incorporated into peptides without further protective group manipulations. Like other alpha,alpha-dialkylated glycines, optically pure alpha-alkylserines can be used to stabilize beta-turn and alpha-helical conformations in short peptides.     

Bile acids LXIX. Selective K-Selectride reduction of 3,7-diketo steroids

The K-Selectride reduction at low temperature (-45°C) of 7-oxo-5α-holestan-3β-yl acetate and methyl 7-oxo-3α-hydroxy-5(β-cholanoate resulted in almost quantitative yield of the 7α-alcohol in the 5α-compound but only moderate yield of the 5β-analog. The simultaneous reduction of two carbonyl groups in the 3 and 7 positions afforded good to excellent yields of the diaxial diol in planar steroids (methyl 3,7-dioxo-5α-cholanoate, 3,7-dioxo-5α-cholestane and methyl 3,7-dioxo-5α-cholestan-27-oate) and only 14% of 3α,7α-(OH)₂ from methyl 3,7-dioxo-5β-cholanoate.     

Cobalt Chalcogenide Clusters. Synthesis,Characterization and DFT Calculations of [Co4Se2(CO)10] and [Co4Te2(CO)11]. Crystal Structure of [Co8Se4(CO)16(μ‐dppa)2]

The reactions of [Co₂(CO)₈] with E(SiMe₃)₂ (E = Se, Te) in CH₂Cl₂ result in the formation of the compounds [Co₄Se₂(CO)₁₀]> ( 1 ) and [Co₄Te₂(CO)₁₁] ( 2 ), respectively. Both cluster complexes have similar molecular structures in which the cobalt atoms form four‐membered rings with μ₄‐bridging chalcogen atoms (Se and Te) above and below the plane of the metal atoms and the carbonyl ligands as either terminal or μ₂‐bridging ligands. DFT‐calculations for both compounds have been carried out in order to obtain some more information about their electronic distribution. In the presence of the phosphine Ph₂PC≡CPPh₂ (dppa), the reaction of [Co₂(CO)₈] with Se(SiMe₃)₂ leads to the formation of [Co₈Se₄(CO)₁₆(μ‐dppa)₂] ( 3 ). During the reaction two molecules of [Co₂(CO)₈] have been added to the acetylene groups of the dppa ligands, whilst the remaining cobalt atoms coordinate to the phosphorus atoms of the phosphine. In this compounds the selenium atoms act as μ₃‐ligands, bridging the metal atoms bonded to the phosphorus with those bonded to the acetylene groups.     

Redetermination of the lanthanum iron sulfide La52Fe12S90

A redetermination of the structure of `La_32.66Fe₁₁S₆₀' in the trigonal space group Rm led to the new formula La₅₂Fe₁₂S₉₀ and to a redefinition of the structure type. In the structure, the Fe²⁺ cations occur in Fe₂S₉ dimers of face‐sharing octa­hedra (with 3m symmetry). The dimers are linked by face‐ and vertex‐sharing bi‐ and tricapped LaS₆ trigonal prisms (with m symmetry) to form a three‐dimensional network containing two types of cubocta­hedral cavities. The larger cavities remain empty, while the smaller ones accommodate alternative sites for disordered La³⁺ cations.     

Aromatic polyethers,polysulfones, and polyketones as laminating resins. IV. Polymers with p-cyclophane units for crosslinking

1,3-Bis(p-phenoxybenzenesulfonyl)benzene, 4,4′-bis(p-phenoxybenzenesulfonyl)diphenyl ether, and 4,4′-diphenoxydiphenyl sulfone were polymerized with isophthaloyl or terephthaloyl chlorides in Friedel-Crafts type polymerizations. These polymers had [2,2]p-cyclophane units in the backbone, introduced by employing 3,9-bis(p-phenoxybenzoyl) [2.2]p-cyclophane as part of the polyaryl ether component. Thermolysis of the dimethylene bridge of the [2.2]p-cyclophane monomer produced diradicals which combined across polymer chains to provide crosslinks. p-Cyclophane polymers with 1,3-bis-(p-phenoxybenzenesulfonyl)benzene showed potential as high performance, thermally stable laminating resins.     

Novel Iron Oxide Nanoparticles Induce Ferroptosis in a Panel of Cancer Cell Lines

The use of nanomaterials rationally engineered to treat cancer is a burgeoning field that has reported great medical achievements. Iron-based polymeric nano-formulations with precisely tuned physicochemical properties are an expanding and versatile therapeutic strategy for tumor treatment. Recently, a peculiar type of regulated necrosis named ferroptosis has gained increased attention as a target for cancer therapy. Here, we show for the first time that novel iron oxide nanoparticles coated with gallic acid and polyacrylic acid (IONP–GA/PAA) possess intrinsic cytotoxic activity on various cancer cell lines. Indeed, IONP–GA/PAA treatment efficiently induces ferroptosis in glioblastoma, neuroblastoma, and fibrosarcoma cells. IONP–GA/PAA-induced ferroptosis was blocked by the canonical ferroptosis inhibitors, including deferoxamine and ciclopirox olamine (iron chelators), and ferrostatin-1, the lipophilic radical trap. These ferroptosis inhibitors also prevented the lipid hydroperoxide generation promoted by the nanoparticles. Altogether, we report on novel ferroptosis-inducing iron encapsulated nanoparticles with potent anti-cancer properties, which has promising potential for further in vivo validation.     

Functional Bacterial Amyloids: Understanding Fibrillation,Regulating Biofilm Fibril Formation and Organizing Surface Assemblies

Functional amyloid is produced by many organisms but is particularly well understood in bacteria, where proteins such as CsgA (E. coli) and FapC (Pseudomonas) are assembled as functional bacterial amyloid (FuBA) on the cell surface in a carefully optimized process. Besides a host of helper proteins, FuBA formation is aided by multiple imperfect repeats which stabilize amyloid and streamline the aggregation mechanism to a fast-track assembly dominated by primary nucleation. These repeats, which are found in variable numbers in Pseudomonas, are most likely the structural core of the fibrils, though we still lack experimental data to determine whether the repeats give rise to β-helix structures via stacked β-hairpins (highly likely for CsgA) or more complicated arrangements (possibly the case for FapC). The response of FuBA fibrillation to denaturants suggests that nucleation and elongation involve equal amounts of folding, but protein chaperones preferentially target nucleation for effective inhibition. Smart peptides can be designed based on these imperfect repeats and modified with various flanking sequences to divert aggregation to less stable structures, leading to a reduction in biofilm formation. Small molecules such as EGCG can also divert FuBA to less organized structures, such as partially-folded oligomeric species, with the same detrimental effect on biofilm. Finally, the strong tendency of FuBA to self-assemble can lead to the formation of very regular two-dimensional amyloid films on structured surfaces such as graphite, which strongly implies future use in biosensors or other nanobiomaterials. In summary, the properties of functional amyloid are a much-needed corrective to the unfortunate association of amyloid with neurodegenerative disease and a testimony to nature’s ability to get the best out of a protein fold.     

Screening an In-House Isoquinoline Alkaloids Library for New Blockers of Voltage-Gated Na+ Channels Using Voltage Sensor Fluorescent Probes: Hits and Biases

Voltage-gated Na⁺ (Na_V) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel Na_V channel ligands. With the objective of discovering new blockers of Na_V channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of Na_V channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC₅₀. These five alkaloids were then assayed using the Na⁺ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNa_V1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na⁺ currents elicited by the hNa_V1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na⁺ currents elicited by the hNav1.2 and hNav1.6 channels, with IC₅₀ values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block Na_V channels, with promising therapeutical applications.     

Electronic structure of strongly correlated systems: recent developments in multiconfiguration pair-density functional theory and multiconfiguration nonclassical-energy functional theory

Strong electron correlation plays an important role in transition-metal and heavy-metal chemistry, magnetic molecules, bond breaking, biradicals, excited states, and many functional materials, but it provides a significant challenge for modern electronic structure theory. The treatment of strongly correlated systems usually requires a multireference method to adequately describe spin densities and near-degeneracy correlation. However, quantitative computation of dynamic correlation with multireference wave functions is often difficult or impractical. Multiconfiguration pair-density functional theory (MC-PDFT) provides a way to blend multiconfiguration wave function theory and density functional theory to quantitatively treat both near-degeneracy correlation and dynamic correlation in strongly correlated systems; it is more affordable than multireference perturbation theory, multireference configuration interaction, or multireference coupled cluster theory and more accurate for many properties than Kohn–Sham density functional theory. This perspective article provides a brief introduction to strongly correlated systems and previously reviewed progress on MC-PDFT followed by a discussion of several recent developments and applications of MC-PDFT and related methods, including localized-active-space MC-PDFT, generalized active-space MC-PDFT, density-matrix-renormalization-group MC-PDFT, hybrid MC-PDFT, multistate MC-PDFT, spin–orbit coupling, analytic gradients, and dipole moments. We also review the more recently introduced multiconfiguration nonclassical-energy functional theory (MC-NEFT), which is like MC-PDFT but allows for other ingredients in the nonclassical-energy functional. We discuss two new kinds of MC-NEFT methods, namely multiconfiguration density coherence functional theory and machine-learned functionals.

This feature article overviews recent work on active spaces, matrix product reference states, treatment of quasidegeneracy, hybrid theory, density-coherence functionals, machine-learned functionals, spin–orbit coupling, gradients, and dipole moments.