Isolation, dynamic NMR study and X-ray characterisation of a bis sulfonium zirconocene-ate dimer

The novel dimer [Cp(2)Zr[upper bond start]([minus sign in circle])S([plus sign in circle])CH(Ph)CH[double bond]C[upper bond end]PPh(2)](2), the first example of a structurally characterised sulfur-bridged binuclear zirconathiolane complex, was prepared, characterised by NMR spectroscopy and X-ray crystallography, and some aspects of its solution behaviour were studied.     

Fentanyl and its analogue N-(1-phenylpyrazol-3-yl)-N-[1-(2-phenylethyl)-4-piperidyl]propanamide: 1H- and 13C-NMR spectroscopy,X-ray crystallography,and theoretical calculations

The oxalate salts and free bases of fentanyl and N-[1-(2-phenylethyl)-4-piperidyl]-N-(1-phenyl-4-pyrazolyl)propanamide, a new lead compound for long-acting analgesia, have been characterized by (1)H- and (13)C-NMR spectroscopy. The crystal structure of the hydrochloride of N-[1-(2-phenylethyl)-4-piperidyl]-N-(1-phenyl-4-pyrazolyl)propanamide monohydrate has been determined. Two centrosymmetrically related cations, joined through C(phenyl)-H em leader pi contacts, encapsulate a large void that contains pairs of anions and bridged water molecules into a zero-dimensional (0D) supramolecular motif. The cations are linked to this framework via N(+)H em leader Cl(-) contacts. GIAO/B3LYP calculations have been carried out to compare the experimental (13)C chemical shifts with the absolute shieldings thus calculated. The protonation of both molecules takes place on the piperidine ring (axial protonation), as has been verified both in the solid state (X-ray) and in solution (NMR).     

Study of the structure of 1‐hydroxymethylindazole and 1‐hydroxymethylbenzotriazole by X‐ray crystallography,multinuclear NMR in solution and DFT calculations

1‐Hydroxymethylindazole and 1‐hydroxymethylbenzotriazole have been studied in solution by ¹H, ¹³C and ¹⁵N NMR spectroscopy and the X‐ray structure of the second compound determined. DFT and GIAO calculations have been used to discuss geometries, energies (comparatively with 2‐substituted isomers) and NMR chemical shifts.     

Cw-laser thermal lens spectrometry in binary mixtures of water and organic solvents: composition dependence of the steady-state and time-resolved signals

The thermal lens effect obtained in binary liquid systems composed of water and ethanol, propanol and acetonitrile has been investigated. The dependence of dn/dT upon the solvent volume fraction follows polynomials up to sixth order and cannot be precisely predicted using the additive rule. The sensitivity of the thermal lens method upon the addition of organic solvent in water varies as the temperature-dependent refractive index gradient to thermal conductivity ratio of the mixture provided that the signal is sampled correctly. Otherwise, especially when steady-state experiments are carried out, the thermally induced concentration gradient, known as the Soret effect, can change the thermo-optical properties of the solution locally in the irradiated area and produce an additional signal. This effect depends on the solvent and is maximum at low solvent composition. At the critical solvent volume fraction of 0.1-0.15, the Soret component may represent up to 25% of the pure thermal lens signal and has a time constant which is 200-400 times greater than the characteristic time constant of the thermal lens.     

Preclinical Investigation in Neuroprotective Effects of the GPR55 Ligand VCE-006.1 in Experimental Models of Parkinson’s Disease and Amyotrophic Lateral Sclerosis

Cannabinoids act as pleiotropic compounds exerting, among others, a broad-spectrum of neuroprotective effects. These effects have been investigated in the last years in different preclinical models of neurodegeneration, with the cannabinoid type-1 (CB₁) and type-2 (CB₂) receptors concentrating an important part of this research. However, the issue has also been extended to additional targets that are also active for cannabinoids, such as the orphan G-protein receptor 55 (GPR55). In the present study, we investigated the neuroprotective potential of VCE-006.1, a chromenopyrazole derivative with biased orthosteric and positive allosteric modulator activity at GPR55, in murine models of two neurodegenerative diseases. First, we proved that VCE-006.1 alone could induce ERK1/2 activation and calcium mobilization, as well as increase cAMP response but only in the presence of lysophosphatidyl inositol. Next, we investigated this compound administered chronically in two neurotoxin-based models of Parkinson’s disease (PD), as well as in some cell-based models. VCE-006.1 was active in reversing the motor defects caused by 6-hydroxydopamine (6-OHDA) in the pole and the cylinder rearing tests, as well as the losses in tyrosine hydroxylase-containing neurons and the elevated glial reactivity detected in the substantia nigra. Similar cytoprotective effects were found in vitro in SH-SY5Y cells exposed to 6-OHDA. We also investigated VCE-006.1 in LPS-lesioned mice with similar beneficial effects, except against glial reactivity and associated inflammatory events, which remained unaltered, a fact confirmed in BV2 cells treated with LPS and VCE-006.1. We also analyzed GPR55 in these in vivo models with no changes in its gene expression, although GPR55 was down-regulated in BV2 cells treated with LPS, which may explain the lack of efficacy of VCE-006.1 in such an assay. Furthermore, we investigated VCE-006.1 in two genetic models of amyotrophic lateral sclerosis (ALS), mutant SOD1, or TDP-43 transgenic mice. Neither the neurological decline nor the deteriorated rotarod performance were prevented with this compound, and the same happened with the elevated microglial and astroglial reactivities, albeit modest spinal motor neuron preservation was achieved in both models. We also analyzed GPR55 in these in vivo models and found no changes in both TDP-43 transgenic and mSOD1 mice. Therefore, our findings support the view that targeting the GPR55 may afford neuroprotection in experimental PD, but not in ALS, thus stressing the specificities for the development of cannabinoid-based therapies in the different neurodegenerative disorders.     

ansa‐[(tert‐Butylamino)(isodicyclo­pentadienyl)dimethylsilane]Zr(NMe2)2 prepared by an amine‐elimination reaction

An amine‐elimination reaction was used to obtain the title compound, i.e. (N‐tert‐butyl‐N‐{[(1,2,3,3a,7a‐η)‐4,5,6,7‐tetra­hydro‐4,7‐methano‐1H‐inden‐2‐yl]­di­methyl­silyl}amido‐κN)bis(N‐methyl­methanaminato‐κN)­zirconium(IV) or [isodiCpSiMe₂N‐tert‐butyl]Zr(NMe₂)₂ (Cp is cyclo­penta­dienyl), [Zr(C₁₆H₂₅NSi)(C₂H₆N)₂], in very good yield. Treatment of isodiCpHSiMe₂NH‐tert‐butyl with Zr(NMe₂)₄ leads to the formation of a yellow solid that can be purified by sublimation. The single‐crystal structure of the product shows the exo complexation of the isodi­cyclo­penta­dienyl ligand to the Zr atom. The Cp portion of this ligand is bonded to the Zr atom in a η⁵ manner, with a Zr—Cg (Cg is the ring centroid) distance of 2.2352 (10) Å. The isodiCpSiMe₂N‐tert‐butyl ligand has a constrained geometry, which is exhibited by the small angle of 95.55 (10)° for N—Si—C_Cp.     

Atmospheric organic aerosol production by heterogeneous acid-catalyzed reactions.

Exploratory evidence from our laboratories shows that acidic surfaces on atmospheric aerosols lead to very real and potentially multifold increases in secondary organic aerosol (SOA) mass and build-up of stabilized nonvolatile organic matter as particles age. One possible explanation for these heterogeneous processes are the acid-catalyzed (e.g., H2SO4 and HNO3) reactions of atmospheric multifunctional organic species (e.g., multifunctional carbonyl compounds) that are accommodated onto the particle phase from the gas phase. Volatile organic hydrocarbons (VOCs) from biogenic sources (e.g., terpenoids) and anthropogenic sources (aromatics) are significant precursors for multifunctional organic species. The sulfur content of fossil fuels, which is released into the atmosphere as SO2, results in the formation of secondary inorganic acidic aerosols or indigenous acidic soot particles (e.g., diesel soot). The predominance of SOAs contributing to PM2.5 (particulate matter, that is, 2.5 microm or smaller than 2.5 microm), and the prevalence of sulfur in fossil fuels suggests that interactions between these sources could be considerable. This study outlines a systematic approach for exploring the fundamental chemistry of these particle-phase heterogeneous reactions. If acid-catalyzed heterogeneous reactions of SOA products are included in next-generation models, the predicted SOA formation will be much greater and have a much larger impact on climate-forcing effects than we now predict. The combined study of both organic and inorganic acids will also enable greater understanding of the adverse health effects in biological pulmonary organs exposed to particles.     

Alteration of bacterial nanocellulose structure by in situ modification using polyethylene glycol and carbohydrate additives

Bacterial nanocellulose (BC) is characterized by an exciting interconnection of the important and well-known cellulose properties with the outstanding features of nano-scale materials. As a remarkable benefit of BC the property-controlling fiber network and pore system formed by self-assembly of the cellulose molecules can be modified in situ using additives during biosynthesis. The addition of polyethylene glycol (PEG) 4000 causes a pore size decrease. In presence of β-cyclodextrin or PEG 400 remarkably increased pores can be achieved. Surprisingly, these co-substrates act as removable auxiliaries not incorporated in the BC samples. In contrast, carboxymethyl cellulose and methyl cellulose as additives lead to structural modified composite materials. Using cationic starch (2-hydroxy-3-trimethylammoniumpropyl starch chloride, TMAP starch) double-network BC composites by incorporation of the starch derivative in the BC prepolymer were obtained.     

Die Wirkung grenzflächenaktiver Stoffe auf die Kristallisationsvorgänge in den Liesegang'schen Ringen

Ohne Zusammenfassung II. Abh.: P. Rehbinder und E. Wenstr?m, Koll.-Ztschr.53, 145 (1930). Zum Schlu? fühle ich mich verpflichtet, meinen herzlichsten Dank dem Herrn Professor P. Rehbinder für die überlassung des Themas und die Leitung meiner Arbeit auszudrücken.     

Neue Wege zu Pentalen-Vorstufen

New Pathways to Precursors of Pentalene Pentalene dimers 2 and 3 are easily available in moderate yields by CuCl₂-induced oxidative coupling of dilithium-pentalenediide ( 5 ) (Scheme 1). On the other hand, NBS bromination of 1,5-dihydropentalene ( 4 ) or of 1,2-dihydropentalene ( 8 ) gives unstable 1-bromo-1,2-dihydropentalene ( 9 ), while subsequent in-situ elimination with Et₃N exclusively gives syn-cis-pentalene dimer 2 in moderate yields (Scheme 3). NMR-Spectroscopic evidence for compounds 2 , 3 , and 9 is presented, and mechanistic alternatives for the formation of pentalene dimers 2 and 3 are discussed.