An improved solvent-free synthesis of flunixin and 2-(arylamino) nicotinic acid derivatives using boric acid as catalyst

A simple solvent-free protocol for the preparation of flunixin, a potent non-narcotic, non-steroidal anti-inflammatory drugs is reported using boric acid as catalyst. Its salt, flunixin meglumine are then prepared under reflux in EtOH. This sustainable method are then extended for the synthesis of a series of 2-(arylamino) nicotinic acid derivatives. The present protocol combines non-hazardous neat conditions with associated benefits like excellent yield, straightforward workup, and use of readily available and safe catalyst in the absence of any solvent, which are important factors in the pharmaceutical industry. The pathway for catalytic activation of 2-chloronicotic acid with boric acid was also investigated using Gaussian 03 program package.

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Novel core-corona hybrid nanomaterials based on the conjugation of amphiphilic polymeric diblocks to the surface of multifunctional nanodiamond anchors

The poor aqueous solubility and the physicochemical instability of many marketed drugs and new chemical entities is one of the most challenging issues in pharmaceutical research and development. Polymeric micelles (PMs) are produced by the self-assembly of polymeric amphiphiles and they represent one of the most extensively investigated nanotechnology platforms for encapsulation, delivery and targeting of hydrophobic drugs. However, a main challenge is preventing their disassembly under extreme dilution in the body fluids, which leads to uncontrolled release of the encapsulated cargo. In this work, we developed an amphiphilic nanomaterial that resembles the core-corona architecture of a PM with superior stability in the body fluids. Specifically, we utilized carboxylated nanodiamonds (cNDs) as particulate anchors to covalently link amphiphilic diblock copolymers consisting of poly(epsilon-caprolactone) (PCL) and poly(ethylene glycol) monomethyl ether (PEG) as hydrophobic and hydrophilic components, respectively. We confirmed a successful core-corona nanostructure using various characterization techniques. In addition, TEM revealed the presence of a thin polymeric layer. Then, the cell compatibility was evaluated in Caco2 cell monolayers, an in vitro model of the intestinal epithelium. Finally, the encapsulation of the hydrophobic anti-helmintic drug nitazoxanide was studied. Cargoes as high as 17.5% w/w were achieved and the sustained release of the cargo according to the Korsmeyer-Peppas model demonstrated in vitro. Overall, preliminary results highlight the potential of this novel approach to extend the applicability of PMs in drug delivery.     

Computing topological indices of Sudoku graphs

In QSAR/QSPR study, physico-chemical properties and topological indices such as Randi?, atom-bond connectivity (ABC) and geometric-arithmetic (GA) index are used to predict the bioactivity of chemical compounds. A topological index is actually designed by transforming a chemical structure into a numeric number. These topological indices correlate certain physico-chemical properties like boiling point, stability, strain energy etc. of chemical compounds. Graph theory has found a considerable use in this area of research. The topological indices of certain interconnection networks were studied recently by Imran et al. (Appl Math Comput 244:936–951, 2014). In this paper, we extend this study to \(n\times n\) Sudoku graphs and derive analytical closed results of general Randi? index \(R_{\alpha }(G)\) for different values of “\(\alpha \)” for Sudoku (SK). We also compute the general Randi?, first Zagreb, ABC, GA, \(ABC_{4}\) and \(GA_{5}\) indices and give closed formulae of these indices for Sudoku graphs.     

A hierarchical multiscale finite element approach for modelling the heat affected zone of welded joints

In the present work a hierarchical multiscale approach, based on finite element method, is applied in order to characterize the heat affected zone (HAZ) of a welded joint with parent material S460M. The metallurgical constituents of particular regions of the HAZ was determined experimentally and, regarding the multiscale approach, a first-order computational homogenization method was implemented. In this context, effective stress-strain-relations in particular spots of the HAZ are determined applying prescribed displacement boundary conditions. The obtained relations were considered in subsequent finite element calculations of butt-welded joints under tensile loading, allowing a comparison of the numerical strain states to experimental results. (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

On FBDF5 Method for Delay Differential Equations of Fractional Order with Periodic and Anti-Periodic Conditions

In this paper, we study the fractional backward differential formula (FBDF) for the numerical solution of fractional delay differential equations (FDDEs) of the following form: \(\lambda _n {}_0^C D_t^{\alpha _n } y(t - \tau ) + \lambda _{n - 1} {}_0^C D_t^{\alpha _{n - 1} } y(t - \tau ) + \cdots + \lambda _1 {}_0^C D_t^{\alpha _1 } y(t - \tau ) + \lambda _{n + 1} y(t) = f(t), t \in [0,T]\), where \( \lambda _i \in \) \(\mathbb {R}\,(i = 1,\ldots ,n + 1)\,,\,\lambda _{n + 1} \ne 0,\,\, 0 \leqslant \alpha _1< \alpha _2< \cdots< \alpha _n < 1,\,\,T > 0,\) in Caputo sense. We find the Green’s functions for this equation corresponding to periodic/anti-periodic conditions in term of the Mittag-Leffler type. Our investigation is focused on stability properties of the numerical methods and we determine stability regions for the FDDEs. Finally, some numerical examples are given to show the effectiveness of the numerical method and the results are in excellent agreement with the theoretical analysis     

Lie algebras with few centralizers

We will characterize all finite dimensional Lie algebras with at most |F|²+|F|+2 centralizers, where F is the underlying field of Lie algebras under consideration.     

Mathematical and numerical modeling of melting in metal-ceramic composite beds

Many of the ceramics used in the manufacture of the metal-ceramic composites are available as powders, which has encouraged investigators to develop tool less manufacturing techniques. Innovative processes like combustion synthesis and laser sintering processes offer great potential for specific material combinations. These processes involve heat and mass transfer in porous matrix with melting, solidification and may be chemical reaction. Since the resulting transport is relatively complex, there are few mathematical models available. In the present study, melting and transport of metal is demonstrated for a one-dimensional bed with uniform heat generation and convectively cooled boundaries. The effects of different Bond, Biot and Prandtl numbers are discussed using constant and temperature varying material properties. At low bond number the transport is controlled by capillary forces and temperature and saturation distribution is symmetric about the center of the bed. For Biot number larger than ten the process is internally controlled. Effect of Prandtl number is opposite of that of the Bond number. Use of constant properties overpredicts the process rate by 13%.     

Two-dimensional transient dynamic response of orthotropic layered media

In this study, two-dimensional transient dynamic response of orthotropic plane layered media is investigated. The plane multilayered media consist of N different generally orthotropic, homogeneous and linearly elastic layers with different ply angles. In the generally orthotropic layer, representing a ply reinforced by unidirectional fibers with an arbitrary orientation angle, the principal material directions do not coincide with body coordinate axes. The solution is obtained by employing a numerical technique which combines the use of Fourier transform with the method of characteristics. The numerical results are displayed in curves denoting the variations of stress and displacement components with time at different locations. These curves clearly reveal, in wave profiles, the scattering effects caused by the reflections and refractions of waves at the boundaries and at the interfaces of the layers, and also the effects of anisotropy caused by fiber orientation angle. The curves properly predict the sharp variations in the response at the neighborhood of the wave fronts, which shows the power of the numerical technique employed in the study. By suitably adjusting the elastic constants, the results for multilayered media with transversely isotropic layers, or layers with cubic symmetry, or isotropic layers can easily be obtained from the general formulation. Furthermore, solutions for some special cases, including Lamb’s problem for an elastic half-space, are obtained and compared with the available solutions in the literature and very good agreement is found. Preliminary version presented at the Second International Congress on Mechatronics (MECH2K3), Graz, Austria, July 14-17, 2003.     

Efficient Solvent‐Free Synthesis of Benzothiazine‐Fused Pyrrolo[3,4‐c]coumarins: Cycloaddition Reactions between Coumarin‐Based Dihydrobenzothiazoles and Isocyanides

A new and unusual synthesis of benzothiazine‐fused pyrrolo[3,4‐c]coumarins, involving the ring‐opening of coumarin‐based dihydrobenzothiazoles and subsequent [4+1] cycloaddition reaction with isocyanides, was described. Thus, simple heating of various 3‐(2,3‐dihydro‐2‐methylbenzo[d]thiazol‐2‐yl)coumarins with isocyanides produced the title compounds in good yields under solvent‐free conditions.