Synthesis of pyrido[3′,2′:4,5]thieno[2,3-c]cinnolines — A new heterocyclic system

Pyrido[3,2:4,5]thieno[2,3-c]cinnolines, new heterocyclic compounds, were obtained in three steps: 1) alkylation of 3-cyanopyridine-2(1H)-thiones by o-nitrobenzyl bromide to give 2-(o-nitrobenzyl)thio-3-cyanopyridines, 2) closure of the thiophene ring in these intermediates to give 3-amino-2-(o-nitrophenyl)thieno[2,3-b]pyridines, and 3) closure of the pyridazine ring by condensation of the amino and nitro groups in triethyl phosphite, leading to the final heterocyclic system.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 104–109, January, 1998.     

Properties of multiplicity distributions in νA and\bar v A intersections atE_{\begin{array}{*{20}c} {( - )} \\ v \\ \end{array} }< 30GeV

We present data on the multiplicity structure of inclusive charged hadron production in charged current neutrino and antineutrino freon interactions in the energy range 3–30 GeV resulting from an experiment with the bubble chamber SKAT. Average multiplicities, dispersions and correlation coefficients are investigated. Furthermore, KNO-scaling is studied and average net charges are calculated in different kinematical regions. Our data are compared with results from \(\begin{array}{*{20}c} {( - )} \\ v \\ \end{array} \) -interactions on an isoscalar target of “free” nucleons to study the influence of nuclear effects.     

Semiempirical andab initio calculations of the full configuration interaction using iterated Krylov’s spaces

The algorithm proposed previously for calculating the full configuration interaction using the variation matrix of the wave operator involves the numerical solution of the corresponding incomplete eigenvalue problem based on iterated Krylov’s subspaces. In practice, that means using the multistep gradient method as a special version of the Lanczos method. The high efficiency of this algorithm, which can readily be used in personal computer calculations, is proved by particular ab initio calculations of the full configuration interaction for the helium and beryllium atoms as well as by semiempirical calculations of π-shells for naphthalene and diphenylene. The algorithm is of particular assistance in obtaining numerous excited states, which are used for determining various spectral sums (polarizability, van der Waals interaction constants, and photoionization cross sections). Translated fromZhumal Struktumoi Khimii, Vol. 38, No. 1, pp. 14–22, January–February, 1997.     

Inhibition and labeling of enzymes and abzymes by phosphonate diesters

Reactive phosphonate diesters were designed and prepared as inhibitors of serine proteases and esterases. Inactivation of trypsin, chymotrypsin, and butyrylcholinesterase was determined by residual enzymaticactivity as well as by the release of a chromogenic or fluorogenic product of the inhibition reaction. Second-order rate constants were determined from rates of nitrophenol formation. Application of the reaction for active-site titration of enzyme preparations is demonstrated. A basic functional group present in the nitrophenyl tropane phosphonate diester was shown to confer selectivity for inactivation of try psin and chymotrypsin. Biotinylated derivatives of the phosphonate diesters were prepared to permitanalysis of proteins modified in the inhibition reaction. Labeled polypeptides were resolved by SDSPAGE, electroblotted, and detected by streptavidin-peroxidase staining. A detection limit of less than 4 ng, corresponding to 20 nM of trypsin, was demonstrated. Pretretment of enzymes with DFP or nonbiotinylated phosphonates specifically blocks the labeling. This technique permits identification of serine proteases in complex mixtures with good sensitivity and specificity.     

Homotopy of spaces of diffeomorphisms of some three-dimensional manifolds

The goal of the paper is to calculate the homotopy type of the space of diffeomorphisms for most orientable three-dimensional manifolds with finite fundamental group containing the Klein bottle. The fundamental group of such a manifold Q has the form <a, b ¦abab ^–1=1,a ^mb²ⁿ=1>. As m and n one can have any relatively prime natural numbers; these numbers m, n determine the manifold Q up to diffeomorphism. Let K be a Klein bottle lying in Q and let P be a closed tubular neighborhood in Q of this Klein bottle K. We denote by Diff_o(Q) the connected component of the space of diffeomorphisms QQ containing id Q, and by E₀(K, Q) the connected component of the space of imbeddings KQ containing the inclusion KQ; analogously we define E₀(K, P). The main results of the paper are the following two theorems. THEOREM 1. If m, n1, then the space Diff_o(Q) is homotopy equivalent with a circle. THEOREM 2. If m, n1, then the inclusion E₀(K, P) E₀(K, Q) is a homotopy equivalence. With the help of familiar results on spaces of diffeomorphisms of irreducible manifolds which are sufficiently large, Theorem 1 reduces without difficulty to Theorem 2. The main difficulty is the proof of Theorem 2. This proof develops a technique of Hatcher and the author which deals with spaces of PL-homeomorphisms and diffeomorphisms of irreducible manifolds which are sufficiently large. In the paper we use a different structure definition of the class of manifolds considered. It is easy to verify that these definitions are equivalent.Translated from Zapiski Nauchnykh Seminarov Leningradskogo Otdeleniya Matematicheskogo Instituta im. V. A. Steklova AN SSSR, Vol. 122, pp. 72–103, 1982.     

Rational approximations of real numbers

For anyx ∈ r put $$c(x) = \overline {\mathop {\lim }\limits_{t \to \infty } } \mathop {\min }\limits_{(p,q\mathop {) \in Z}\limits_{q \leqslant t} \times N} t\left| {qx - p} \right|.$$ . Let [x₀; x₁,..., x_n, ...] be an expansion of x into a continued fraction and let \(M = \{ x \in J,\overline {\mathop {\lim }\limits_{n \to \infty } } x_n< \infty \}\) .Forx∈M put D(x)=c(x)/(1?c(x)). The structure of the set \(\mathfrak{D} = \{ D(x),x \in M\}\) is studied. It is shown that $$\mathfrak{D} \cap (3 + \sqrt 3 ,(5 + 3\sqrt 3 )/2) = \{ D(x^{(n,3} )\} _{n = 0}^\infty \nearrow (5 + 3\sqrt 3 )/2,$$ where \(x^{(n,3)} = [\overline {3;(1,2)_n ,1} ].\) This yields for \(\mu = \inf \{ z,\mathfrak{D} \supset (z, + \infty )\}\) (“origin of the ray”) the following lower bound: μ?(5+3√3)/2=5.0n>(5 + 3/3)/2=5.098.... Suppose a∈n. Put \(M(a) = \{ x \in M,\overline {\mathop {\lim }\limits_{n \to \infty } } x_n = a\}\) , \(\mathfrak{D}(a) = \{ D(x),x \in M(a)\}\) . The smallest limit point of \(\mathfrak{D}(a)(a \geqslant 2)\) is found. The structure of (a) is studied completely up to the smallest limit point and elucidated to the right of it.     

Single-molecule nanopore sensing of actin dynamics and drug binding

Actin is a key protein in the dynamic processes within the eukaryotic cell. To date, methods exploring the molecular state of actin are limited to insights gained from structural approaches, providing a snapshot of protein folding, or methods that require chemical modifications compromising actin monomer thermostability. Nanopore sensing permits label-free investigation of native proteins and is ideally suited to study proteins such as actin that require specialised buffers and cofactors. Using nanopores, we determined the state of actin at the macromolecular level (filamentous or globular) and in its monomeric form bound to inhibitors. We revealed urea-dependent and voltage-dependent transitional states and observed the unfolding process within which sub-populations of transient actin oligomers are visible. We detected, in real-time, filament-growth, and drug-binding at the single-molecule level demonstrating the promise of nanopore sensing for in-depth understanding of protein folding landscapes and for drug discovery.

Nanopipettes were used for real-time investigation into actin dynamics and drug binding at single-molecule resolution, showing promise for a better understanding of the mechanism of protein–protein interactions and drug discovery.     

Reactions of 4-Aryl-2-hydrazino-3-nitro-6-R-quinolines with HNO2

The reaction of 4-aryl-2-hydrazino-3-nitro-6-R-quinolines with NaNO₂ in AcOH gives the corresponding tetrazolo[1,5-a]quinolines. In contrast to tetrazolo[1,5-c]pyrimidines they cannot be converted to 6-R-4-phenyl[1,2,5]oxadiazolo[3,4-b]quinoline-3-oxides by heating in THF, toluene, or AcOH. Total energy quantum-chemical calculations using the MINDO/3 and MNDO methods show that [1,2,5]oxadiazolo[3,4-b]quinoline-3-oxides are significantly higher in energy (230-280 kcal/mol) than the mentioned tetrazolo[1,5-a]quinolines and hence their formation is unlikely.     

Kinetic model ofCO oxidation on nonuniform surface analyzed regardingCOads spillover, 2. homotopic method. Effect ofm1 surface portion

The homotopic method has been used to analyze the kinetic model of three-stageCO oxidation on two nonuniform surface patches conjugated byCO ₂ spillover. Diagrams of steady states depending on the portion of surface patchm ₁ at various temperatures and pressure ratiosP(O ₂)/P(CO) have been constructed. The ratios of different type patches corresponding to the maximum overall reaction rate have been found.     

New approaches to the synthesis of functionally substituted pyrido[3′,2′:4,5]thieno[3,2-b]pyridines and the structure of the products obtained

Substituted pyrido,[3',2':4,5]thieno[3,2-b]pyndines were obtained by the reaction of 3-amino-2-benzoylthieno [2,3-b]pyridines with malononitrile and the reaction of 3-cyanopyridine-2(IH)-thiones with 2-aryl-3-bromo-I,I-dicyanopropene. 2-Amino-4-(4-bromophenyl)-7, 9-dimethyl-3-cyanopyrido [3',2':4,5]thieno[3, 2-b]-pyridine was used for the synthesis of a derivative of pyrido[3",2":4', 5']thieno[2',3':5,6]pyrido[2,3-d]-pyrimidine. The structure of these compounds was confirmed by spectral data and x-ray diffraction structural analysis.Deceased.