Nitropyrazoles

A preparative method ofN-amination of pyrazoles bearing nitro groups and other electron withdrawing substituents in the pyrazole ring with hydroxylamine-O-sulfonic acid involving control of the pH of the medium has been elaborated. A series of previously unknown pyrazoles has been prepared. Basicities of 1-aminopyrazole and 1-amino-4-nitropyrazole have been measured and differences between the basicities of theC- andN-amino groups for the pyrazole series have been revealed.For part 3, see ref. 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1434–1436, August, 1993.     

Identification of extracellular nanoparticle subsets by nuclear magnetic resonance

Exosomes are a subset of secreted lipid envelope-encapsulated extracellular vesicles (EVs) of 50–150 nm diameter that can transfer cargo from donor to acceptor cells. In the current purification protocols of exosomes, many smaller and larger nanoparticles such as lipoproteins, exomers and microvesicles are typically co-isolated as well. Particle size distribution is one important characteristics of EV samples, as it reflects the cellular origin of EVs and the purity of the isolation. However, most of the physicochemical analytical methods today cannot illustrate the smallest exosomes and other small particles like the exomers. Here, we demonstrate that diffusion ordered spectroscopy (DOSY) nuclear magnetic resonance (NMR) method enables the determination of a very broad distribution of extracellular nanoparticles, ranging from 1 to 500 nm. The range covers sizes of all particles included in EV samples after isolation. The method is non-invasive, as it does not require any labelling or other chemical modification. We investigated EVs secreted from milk as well as embryonic kidney and renal carcinoma cells. Western blot analysis and immuno-electron microscopy confirmed expression of exosomal markers such as ALIX, TSG101, CD81, CD9, and CD63 in the EV samples. In addition to the larger particles observed by nanoparticle tracking analysis (NTA) in the range of 70–500 nm, the DOSY distributions include a significant number of smaller particles in the range of 10–70 nm, which are visible also in transmission electron microscopy images but invisible in NTA. Furthermore, we demonstrate that hyperpolarized chemical exchange saturation transfer (Hyper-CEST) with ¹²⁹Xe NMR indicates also the existence of smaller and larger nanoparticles in the EV samples, providing also additional support for DOSY results. The method implies also that the Xe exchange is significantly faster in the EV pool than in the lipoprotein/exomer pool.

Diffusion and xenon NMR based methods to determine a very broad range of sizes and sub-sets of extracellular vesicles.     

Density functional based structure optimization for molecules containing heavy elements: analytical energy gradients for the Douglas-Kroll-Hess scalar relativistic approach to the LCGTO-DF method

The self-consistent scalar-relativistic linear combination of Gaussian-type orbitals density functional (LCGTO-DF) method has been extended to calculate analytical energy gradients. The method is based on the use of a unitary second order Douglas-Kroll-Hess (DKH) transformation for decoupling large and small components of the full four-component Dirac-Kohn-Sham equation. The approximate DKH transformation most common in molecular calculations has been implemented; this variant employs nuclear potential based projectors and it leaves the electron-electron interaction untransformed. Examples are provided for the geometry optimization of a series of heavy metal systems which feature a variety of metal-ligand bonds, like Au₂, AuCl, AuH, Mo(CO)₆ and W(CO)₆ as well as the d¹⁰ complexes [Pd(PH₃)₂O₂] and [Pt(PH₃)₂O₂]. The calculated results, obtained with several gradient-corrected exchange-correlation potentials, compare very well with experimental data and they are of similar or even better accuracy than those of other high quality relativistic calculations reported so far.     

New Synthetic Approaches to Functionally Substituted 4,5-Dihydro-1,2,3-oxadiazole 2-Oxides

A practical procedure has been proposed for the synthesis of functionally substituted 4,5-dihydro-1,2,3-oxadiazole 2-oxides on the basis ofsulfamic acid derivatives.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 121–123.Original Russian Text Copyright © 2005 by Tartakovskii, Ermakov, Strelenko, Vinogradov, Petrov.     

Studies of reaction heats and structure of complexes formed between strong N-bases and phenols

The heats of reactions between various phenols and two strong N-bases of guanidine-like character in acetonitrile, are determined. The values can be used as a measure of self-assembly abilities of the phenol molecules in the interactions with strong N-bases, playing a very important role in biological systems. In the case of TBD complexes with corresponding nitrophenols, the protonated N-base is hydrogen-bonded to the nitro group excluding the self-assembly process of the phenols. In the case of other phenols, the self-assembly abilities are dependent on pK_a values of phenols. With increasing acidity of phenols their ability to form the hydrogen-bonded chains decreases. The maximum of length of the chains is observed for 4-methylphenol, which has a similar pK_a value to that in the tyrosine residue in biological systems.     

Synthesis, structure and reactivity of binuclear metal-metal bonded molybdenum(V) and tungsten(V) thioselenohalides: Molecular structure of Mo2(μ-S2)2Cl6(SeCl2)2 and W2(μ-S2)2Cl6(SeCl2)2

Thioselenohalide complexes Mo₂(μ-S₂)₂Cl₆(SeCl₂)₂ (I), Mo₂(μ-S₂)₂Br₆(SeBr₂)₂ (II), and W₂(μ-S₂)₂Br₆(SeBr₂)₂ (III) were synthesized by the reactions of corresponding metal halides or carbonyls or molybdenum metal with excesses of S₂ X ₂+Se₂ X ₂ mixtures. The complex W₂(μ-S₂)₂Cl₆(SeCl₂)₂ (IV) was obtained by an exchange reaction between (III) and excess of Se₂Cl₂. Coordination of the neutral SeX ₂ ligands to thiohalidesM ₂(μ-S₂)₂ X ₆ results in higher thermal stability, and suggests the possibility to synthesize SeX ₂ complexes of the unstable parent tungsten thiohalides. An unusual oxidative addition reaction of (I) was detected: {fx27-1} Both (I) and (IV) were characterized by X-ray crystal structure analysis. They are isostructural and form discrete molecules. Bridging S ₂ ^2? ligands are coordinated perpendicularly to the metal-metal bond;d(M?M)=2.8066 Å and 2.793 Å for I and IV, respectively. Nonequivalence of chlorine atoms which are bound to the metal atom, relate to nonequivalence of halogen atoms in the complexesM ₂(μ?S₂)₂ X ₈ ^2? . Chlorine atomstrans to SeCl₂ ligands form short bonds with the metal; the corresponding³⁵Cl NQR frequency is increased. The selenium dichloride ligand is ambidentate. The selenium atom binds as a donor to the metal and as an acceptor to two chlorine atoms which are also bound covalently to the same metal atom.     

Linked crystallites in the conducting topmost layer of polymer bilayer films controlled by temperature: from micro- to nanocrystallites.

Temperature has great impact on the structure and size of the linked crystallites of the conducting topmost layer formed at the surface of a polycarbonate film via the reaction BEDT-TTF+IBr [BEDT-TTF=bis(ethylenedithio)tetrathiafulvalene]. We show that fine temperature control permits formation of a semiconducting topmost layer of alpha'-(BEDT-TTF)(2)(I(x)Br(1-x))(3) crystallites with either micro- or nanometre size, a result that opens a route to miniaturized conducting plastic materials.     

Comparison of the Temperature Effect on the π∗←n and π∗←π Electronic Transition Bands of NO<Subscript>3</Subscript><Superscript>−</Superscript>(aq)

The effect of temperature on the π∗←π transition band in the UV absorption spectrum of NO₃⁻(aq) centered at ≈200 nm was studied in the temperature range 10–70 ^∘C. The observed temperature independence of this band was in contrast to the significant influence of temperature on the nitrate π∗←n transition reported recently by us. However, taking into account the electronic states involved in both the transitions, it was concluded that this finding was in accordance with our previous assumption that interconversion between spectrally distinct (with respect to π∗←n band) nitrate species included the rupture/formation of hydrogen bond(s) in the hydration shell of the nitrate ion.     

Addition of secondary phosphines to N-vinylpyrroles

Secondary phosphines 1-3 react readily with N-vinylpyrroles 4 and 5 under radical initiation to give regiospecifically anti-Markovnikov adducts, diorganyl-2-(1-pyrrolyl)ethylphosphines 6a-d, highly reactive building blocks for organic synthesis, in 88-91% yields.