Elastic Light Tunable Tissue Adhesive Dendrimers

Development of bioadhesive formulations for tissue fixation remains a challenge. The major drawbacks of available bioadhesives are low adhesion strength, toxic byproducts, and complexity of application onto affected tissues. In order to address these problems, this study has developed a hydrogel bioadhesive system based on poly amido amine (PAMAM) dendrimer, grafted (conjugated) with UV‐sensitive, 4‐[3‐(trifluoromethyl)‐3H‐diazirin‐3‐yl] benzyl bromide (PAMAM‐g‐diazirine). This particular diazirine molecule can be grafted to the surface amine groups of PAMAM in a one‐pot synthesis. Diazirine functionalities are carbene precursors that form covalent crosslinks with hydrated tissues after low‐power UV activation without necessity of free‐radical initiators. The rheological properties and adhesion strength to ex vivo tissues are highly controllable depending on diazirine grafting, hydrogel concentration, and UV dose intensity fitting variety types of tissues. Covalent bonds at the tissue/bioadhesive interface provide robust adhesive and mechanical strength in a highly hydrated environment. The free flowing hydrogel conversion to elastic adhesive after UV activation allows intimate contact with the ex vivo swine tissue surfaces with low in vitro cytotoxicity observed, making it a promising bioadhesive formulation toward clinical applications.

     

3-Fluoroalkyl (CF3, CHF2, CH2F) Cyclobutane-Derived Building Blocks for Medicinal Chemistry: Synthesis and Physicochemical Properties

Synthesis and physicochemical characterization of all possible cis- and trans-1,3-disubstituted cyclobutane-derived amines and carboxylic acids bearing mono-, di- and trifluoromethyl groups at the C-3 position is disclosed. Tetramethylammonium fluoride (TMAF)- or morpholinosulfur trifluoride (Morph-DAST)-mediated nucleophilic fluorination of appropriate cis- and trans-diastereomeric substrates was used as the key step for the preparation of CH₂F- and CHF₂-substituted derivatives. To obtain the corresponding cis- and trans-isomeric CF₃-substituted derivatives, resolution of known 3-(trifluoromethyl)cyclobutanecarboxylic acid (obtained as a mixture of diastereomers) was applied. The proposed procedures were suitable for the preparation of corresponding fluoroalkyl-substituted cyclobutane-derived amines and carboxylic acids on up to 50 g scale. All 12 building blocks obtained were characterized by measuring dissociation constants (pK_a) and lipophilicities (LogP, for model derivatives) to evaluate the effect of the fluoroalkyl substituents on their physicochemical properties relevant to further drug discovery applications.     

Multigram Synthesis of α- and γ-((Hetera)cyclo)alkylpyridines through α-Arylation of (Hetero)aliphatic Nitriles

A systematic study on the S_nAr reaction of halogenated fluoropyridines and (hetero)aliphatic nitrile anions as an approach to the synthesis of functionalized pyridines bearing a (cyclo)alkyl or saturated heterocyclic substituent by is described. The scope of the method was demonstrated on a wide range of (hetero)aliphatic nitriles (including three- to six-membered cycloalkane derivatives and N-, O-, S-containing saturated heterocycles) and all isomeric halogenated 2-and 4-fluoropyridines. High chemo- and regioselectivity (i. e., exclusive substitution of the fluorine atom), as well as excellent scalability of the proposed reaction sequence were demonstrated (up to 450 g for the arylation step or up to 77 g of cycloalkylpyridine over two steps in a single run). The utility of the synthesized products was illustrated in the additional functional group transformations resulting in synthetically valuable pyridine-containing building blocks.     

Oscillation of solutions of second-order linear differential equations and corresponding difference equations

In this paper, we present conditions ensuring that solutions of linear second-order differential equations oscillate, provided solutions of corresponding difference equations oscillate. We also establish the converse result, namely, when oscillation of solutions of difference equations implies oscillation of solutions of corresponding differential equations.     

Existence and Uniqueness of Invariant Measures for Stochastic Reaction–Diffusion Equations in Unbounded Domains

In this paper, we investigate the long-time behavior of stochastic reaction–diffusion equations of the type \(\text {d}u = (Au + f(u))\text {d}t + \sigma (u) \text {d}W(t)\), where \(A\) is an elliptic operator, \(f\) and \(\sigma \) are nonlinear maps and \(W\) is an infinite-dimensional nuclear Wiener process. The emphasis is on unbounded domains. Under the assumption that the nonlinear function \(f\) possesses certain dissipative properties, this equation is known to have a solution with an expectation value which is uniformly bounded in time. Together with some compactness property, the existence of such a solution implies the existence of an invariant measure, which is an important step in establishing the ergodic behavior of the underlying physical system. In this paper, we expand the existing classes of nonlinear functions \(f\) and \(\sigma \) and elliptic operators \(A\) for which the invariant measure exists, in particular in unbounded domains. We also show the uniqueness of the invariant measure for an equation defined on the upper half space if \(A\) is the Shrödinger-type operator \(A = \frac{1}{\rho }(\text {div} \rho \nabla u)\) where \(\rho = \text {e}^{-|x|^2}\) is the Gaussian weight.     

Estimation Problems for Periodically Correlated Isotropic Random Fields

Spectral theory of isotropic random fields in Euclidean space developed by M. I. Yadrenko is exploited to find a solution to the problem of optimal linear estimation of the functional

$$ A\zeta ={\sum\limits_{t=0}^{\infty}}\,\,\,{\int_{S_n}} \,\,a(t,x)\zeta (t,x)\,m_n(dx) $$

which depends on unknown values of a periodically correlated (cyclostationary with period T) with respect to time isotropic on the sphere S _n in Euclidean space E ⁿ random field ζ(t, x), t?∈?Z, x?∈?S _n . Estimates are based on observations of the field ζ(t, x)?+?θ(t, x) at points (t, x), t?=???1,???2, ..., x?∈?S _n , where θ(t, x) is an uncorrelated with ζ(t, x) periodically correlated with respect to time isotropic on the sphere S _n random field. Formulas for computing the value of the mean-square error and the spectral characteristic of the optimal linear estimate of the functional Aζ are obtained. The least favourable spectral densities and the minimax (robust) spectral characteristics of the optimal estimates of the functional Aζ are determined for some special classes of spectral densities.

     

Projective functors for algebraic groups

We investigate the regular subquotient category introduced by Soergel in [W. Soergel, On the relation between intersection cohomology and representation theory in positive characteristic, J. Pure Appl. Algebra 152 (1–3) (2000) 311–335]. A detailed study of projective functors enables one to relate those categories for semi-simple algebraic group G and its subgroup schemata G_rT. As an application we derive some information about the characters of tilting modules for G.     

All-fiber Kerr cell

An all-fiber nanosecond Kerr light gate is described that was constructed using microstructured fibers. The switching voltage for a 20?cm long device is as low as Vπ～85 V at a 1.06?μm wavelength. The device is fully spliced. The active element is a three-hole fiber provided with internal electrodes in the side-holes and a liquid core of nitrobenzene, which is fully enclosed. This work allows the exploiting of electrically driven liquid-core fibers and demonstrated the removal of the major limitations of Kerr cells in the past, allowing for integration, safe use, and relatively low switching voltage.     

Saturated Boronic Acids,Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry

This review discusses recent advances in the chemistry of saturated boronic acids, boronates, and trifluoroborates. Applications of the title compounds in the design of boron-containing drugs are surveyed, with special emphasis on α-amino boronic derivatives. A general overview of saturated boronic compounds as modern tools to construct C(sp³)−C and C(sp³)-heteroatom bonds is given, including recent developments in the Suzuki-Miyaura and Chan-Lam cross-couplings, single-electron-transfer processes including metallo- and organocatalytic photoredox reactions, and transformations of boron “ate” complexes. Finally, an attempt to summarize the current state of the art in the synthesis of saturated boronic acids, boronates, and trifluoroborates is made, with a brief mention of the “classical” methods (transmetallation of organolithium/magnesium reagents with boron species, anti-Markovnikov hydroboration of alkenes, and the modification of alkenyl boron compounds) and a special focus on recent methodologies (boronation of alkyl (pseudo)halides, derivatives of carboxylic acids, alcohols, and primary amines, boronative C−H activation, novel approaches to alkene hydroboration, and 1,2-metallate-type rearrangements).     

Synthesis of azachromones and azachromanones

Chemistry of Heterocyclic Compounds - This minireview highlights known methods for the synthesis of azachromones and azachromanones, including the earliest and the latest examples of their...