Mitigating UVA light induced reactivity of 6-thioguanine through formation of a Ru(II) half-sandwich complex

The organometallic complex of (eta(6)-cymene)Ru(II)Br with 6-thioguanine (6-TG) shows better photostability than the biologically active 6-thioguanine which is used as an immunosuppressant and as an anticancer agent.

Substitution-Modulated Anticancer Activity of Half-Sandwich Ruthenium(II) Complexes with Heterocyclic Ancillary Ligands

Ten new organometallic half-sandwich ruthenium complexes with heterocyclic ligands have been synthesized (H1-H10). The substituents on the ancillary heterocyclic ligands were varied to understand the effect of substitution on anticancer activity. The crystallographic characterization of five complexes confirms that they adopt three-legged piano-stool structures and are stabilized by intramolecular hydrogen bonding. Complexes H2 and H3 also exhibit halogen bonding in the solid state. In aqueous media, the complexes form dinuclear ruthenium species. Complex H1 with a noncytotoxic heterocycle, 6-fluoro-2-mercaptobenzothiazole, and complex H11 with the unsubstituted 2-mercaptobenzothiazole are the most active against A2780 and KB cell lines. The substitution of the H atoms on the ancillary ligand with Cl or Br atoms leads to a decrease in the anticancer activity. With the exception of fluorine-substituted H5, the complexes with mercaptobenzoxazole (H6-H9) are inactive against all of the tested cell lines. Ruthenium complexes with mercaptonaphthimidazole (H10) and mercaptobenzimidazole (H13) do not show any anticancer activity. The active complexes show a biphasic melting curve when incubated with calf thymus (CT) DNA. These complexes only inhibit thioredoxin reductase (TrxR) enzyme activity to a small extent. The substitution of hydrogen atoms with fluorine atoms in the aromatic heterocyclic ligands on organometallic half-sandwich ruthenium complexes has the most beneficial effect on their anticancer activity.

New physics in e(+)e(-) -> Z(gamma) at the ILC with polarized beams: explorations beyond conventional anomalous triple gauge boson couplings

One of the most-studied signals for physics beyond the standard model in the production of gauge bosons in electron-positron collisions is due to the anomalous triple gauge boson couplings in the Z(gamma) final state. In this work, we study the implications of this at the ILC with polarized beams for signals that go beyond traditional anomalous triple neutral gauge boson couplings. Here we report a dimension-8 CP-conserving Z(gamma)Z vertex that has not found mention in the literature. We carry out a systematic study of the anomalous couplings in general terms and arrive at a classification. We then obtain linear-order distributions with and without CP violation. Furthermore, we place the study in the context of general BSM interactions represented by e(+)e(-)Z(gamma) contact interactions. We set up a correspondence between the triple gauge boson couplings and the four-point contact interactions. We also present sensitivities on these anomalous couplings, which will be achievable at the ILC with realistic polarization and luminosity.

Modal tailoring and closed-form solutions for rotating non-uniform Euler-Bernoulli beams

In this paper, the free vibration of a rotating Euler-Bernoulli beam is studied using an inverse problem approach. We assume a polynomial mode shape function for a particular mode, which satisfies all the four boundary conditions of a rotating beam, along with the internal nodes. Using this assumed mode shape function, we determine the linear mass and fifth order stiffness variations of the beam which are typical of helicopter blades. Thus, it is found that an infinite number of such beams exist whose fourth order governing differential equation possess a closed form solution for certain polynomial variations of the mass and stiffness, for both cantilever and pinned-free boundary conditions corresponding to hingeless and articulated rotors, respectively. A detailed study is conducted for the first, second and third modes of a rotating cantilever beam and the first and second elastic modes of a rotating pinned-free beam, and on how to pre-select the internal nodes such that the closed-form solutions exist for these cases. The derived results can be used as benchmark solutions for the validation of rotating beam numerical methods and may also guide nodal tailoring. (C) 2014 Elsevier Ltd. All rights reserved.

Tailoring the second mode of Euler-Bernoulli beams: an analytical approach

In this paper, we study the inverse mode shape problem for an Euler-Bernoulli beam, using an analytical approach. The mass and stiffness variations are determined for a beam, having various boundary conditions, which has a prescribed polynomial second mode shape with an internal node. It is found that physically feasible rectangular cross-section beams which satisfy the inverse problem exist for a variety of boundary conditions. The effect of the location of the internal node on the mass and stiffness variations and on the deflection of the beam is studied. The derived functions are used to verify the p-version finite element code, for the cantilever boundary condition. The paper also presents the bounds on the location of the internal node, for a valid mass and stiffness variation, for any given boundary condition. The derived property variations, corresponding to a given mode shape and boundary condition, also provides a simple closed-form solution for a class of non-uniform Euler-Bernoulli beams. These closed-form solutions can also be used to check optimization algorithms proposed for modal tailoring.

Seleno-Nucleobases and Their Water-Soluble Ruthenium-Arene Half-Sandwich Complexes: Chemistry and Biological Activity

Half-sandwich organometallic ruthenium complexes of seleno-nucleobases, 3 and 4, were synthesized and characterized. The structures of both complexes were determined by X-ray crystallography and are the first crystal structures of ruthenium complexes with seleno-nucleobases. Interestingly, 3 self-assembles aided by adventitious water in DMF to give a tetranuclear square 3a center dot 6H(2)O. Complex 4 is active against Jurkat and Molt-4 cell lines but inactive against the K562 cell line, whereas 3 is completely inactive against all three cell lines. The free ligand 6-selenopurine (1) and 6-selenoguanine (2) are highly active against these cell lines. Compound 2, like its thio analogue, is unstable under UVA light, whereas 4 is stable under similar conditions, which suggests that the ruthenium complex could reduce problems associated with the instability of the free ligand, 2, under irradiation.

Stress Engineering using Si3N4 for stiction free release of SOI beams

We report on the effect of thin silicon nitride (Si3N4) induced tensile stress on the structural release of 200nm thick SOI beam, in the surface micro-machining process. A thin (20nm / 100nm) LPCVD grown Si3N4 is shown to significantly enhance the yield of released beam in wet release technique. This is especially prominent with increase in beam length, where the beams have higher tendency for stiction. We attribute this yield enhancement to the nitride induced tensile stress, as verified by buckling tendency and resonance frequency data obtained from optical profilometry and laser doppler vibrometry.

Non-uniform beams and stiff strings isospectral to axially loaded uniform beams and piano strings

In this paper, we derive analytical expressions for mass and stiffness functions of transversely vibrating clamped-clamped non-uniform beams under no axial loads, which are isospectral to a given uniform axially loaded beam. Examples of such axially loaded beams are beam columns (compressive axial load) and piano strings (tensile axial load). The Barcilon-Gottlieb transformation is invoked to transform the non-uniform beam equation into the axially loaded uniform beam equation. The coupled ODEs involved in this transformation are solved for two specific cases (pq (z) = k (0) and q = q (0)), and analytical solutions for mass and stiffness are obtained. Examples of beams having a rectangular cross section are shown as a practical application of the analysis. Some non-uniform beams are found whose frequencies are known exactly since uniform axially loaded beams with clamped ends have closed-form solutions. In addition, we show that the tension required in a stiff piano string with hinged ends can be adjusted by changing the mass and stiffness functions of a stiff string, retaining its natural frequencies.

First hyperpolarizability of Ru-half-sandwich complexes: The effect of halogen atom substitution on the ancillary ligand

The first hyperpolarizability (beta) of a series of half-sandwich Ru complexes with a mercaptobenzothiazole ligand bearing a halogen atom substitution in the para-position has been investigated by hyper-Rayleigh scattering and quantum chemical calculations. The heterocyclic ligand with a bromine atom in the para position makes it a very good donor and charge flows to the Ru center enhancing the beta value of the complex by a factor of 2 compared to the complex with the ligand without the halogen substitution. The resonance (+R) and the inductive (-I) effects exerted by the halogen atom in the para position push electrons in opposing directions in the complex. For the Br and Cl atoms the resonance effect dominates which enables the ligand to donate electrons to the metal center thereby increasing the hyperpolarizability whereas for the fluorine atom, the inductive effect is dominant which reduces the charge flow to the metal and the hyperpolarizability drops even below that of the unsubstituted ligand. This unprecedented halogen atom effect on beta of metal complexes is reported. (C) 2015 Elsevier By. All rights reserved.

A spectral element for wave propagation in honeycomb sandwich construction considering core flexibility

Spectral elements are found to be extremely resourceful to study the wave propagation characteristics of structures at high frequencies. Most of the aerospace structures use honeycomb sandwich constructions. The existing spectral elements use single layer theories for a sandwich construction wherein the two face sheets vibrate together and this model is sufficient for low frequency excitations. At high frequencies, the two face sheets vibrate independently. The Extended Higher order SAndwich Plate theory (EHSaPT) is suitable for representing the independent motion of the face sheets. A 1D spectral element based on EHSaPT is developed in this work. The wave number and the wave speed characteristics are obtained using the developed spectral element. It is shown that the developed spectral element is capable of representing independent wave motions of the face sheets. The propagation speeds of a high frequency modulated pulse in the face sheets and the core of a honeycomb sandwich are demonstrated. Responses of a typical honeycomb sandwich beam to high frequency shock loads are obtained using the developed spectral element and the response match very well with the finite element results. It is shown that the developed spectral element is able to represent the flexibility of the core resulting into independent wave motions in the face sheets, for which a finite element method needs huge degrees of freedom. (C) 2015 Elsevier Ltd. All rights reserved.

CROSS-SECTIONAL ANALYSIS OF PRE-TWISTED THICK BEAMS USING VARIATIONAL ASYMPTOTIC METHOD

An asymptotically-exact methodology is presented for obtaining the cross-sectional stiffness matrix of a pre-twisted moderately-thick beam having rectangular cross sections and made of transversely isotropic materials. The anisotropic beam is modeled from 3-D elasticity, without any further assumptions. The beam is allowed to have large displacements and rotations, but small strain is assumed. The strain energy of the beam is computed making use of the constitutive law and the kinematical relations derived with the inclusion of geometrical nonlinearities and initial twist. Large displacements and rotations are allowed, but small strain is assumed. The Variational Asymptotic Method is used to minimize the energy functional, thereby reducing the cross section to a point on the reference line with appropriate properties, yielding a 1-D constitutive law. In this method as applied herein, the 2-D cross-sectional analysis is performed asymptotically by taking advantage of a material small parameter and two geometric small parameters. 3-D strain components are derived using kinematics and arranged as orders of the small parameters. Warping functions are obtained by the minimization of strain energy subject to certain set of constraints that renders the 1-D strain measures well-defined. Closed-form expressions are derived for the 3-D non-linear warping and stress fields. The model is capable of predicting interlaminar and transverse shear stresses accurately up to first order.

Analysis of Transverse Shear Strains in Pre-Twisted Thick Beams using Variational Asymptotic Method

The cross-sectional stiffness matrix is derived for a pre-twisted, moderately thick beam made of transversely isotropic materials and having rectangular cross sections. An asymptotically-exact methodology is used to model the anisotropic beam from 3-D elasticity, without any further assumptions. The beam is allowed to have large displacements and rotations, but small strain is assumed. The strain energy is computed making use of the beam constitutive law and kinematical relations derived with the inclusion of geometrical nonlinearities and an initial twist. The energy functional is minimized making use of the Variational Asymptotic Method (VAM), thereby reducing the cross section to a point on the beam reference line with appropriate properties, forming a 1-D constitutive law. VAM is a mathematical technique employed in the current problem to rigorously split the 3-D analysis of beams into two: a 2-D analysis over the beam cross-sectional domain, which provides a compact semi-analytical form of the properties of the cross sections, and a nonlinear 1-D analysis of the beam reference curve. In this method, as applied herein, the cross-sectional analysis is performed asymptotically by taking advantage of a material small parameter and two geometric small parameters. 3-D strain components are derived using kinematics and arranged in orders of the small parameters. Closed-form expressions are derived for the 3-D non-linear warping and stress fields. Warping functions are obtained by the minimization of strain energy subject to certain set of constraints that render the 1-D strain measures well-defined. The zeroth-order 3-D warping field thus yielded is then used to integrate the 3-D strain energy density over the cross section, resulting in the 1-D strain energy density, which in turn helps identify the corresponding cross-sectional stiffness matrix. The model is capable of predicting interlaminar and transverse shear stresses accurately up to first order.

Exploring isospectral cantilever beams using electromagnetism inspired optimization technique

Isospectral beams have identical free vibration frequency spectrum for a specific boundary condition. The problem of finding non-uniform beams which are isospectral to a given uniform beam, with fixed-free boundary condition, leads to a multimodal optimization problem. The first Q natural frequencies of the given uniform Euler-Bernoulli beam are determined using analytical solution. The first Q natural frequencies of a non-uniform beam are obtained with the help of finite element modeling. In order to obtain the non-uniform beams isospectral to a given uniform beam, an error function is designed, which calculates the difference between the spectra of the given uniform beam and the non-uniform beam. In our study, this error function is minimized using electromagnetism inspired optimization technique, a population based iterative algorithm inspired by the attraction-repulsion physics of electromagnetism. Numerical results show the existence of the isospectral non-uniform beams for a given uniform beam, which occur as local minima. Non-uniform beams isospectral to a damaged beam, are also explored using the proposed methodology to illustrate the fact that accurate structural damage identification is difficult by just frequency measurements. (C) 2012 Elsevier B.V. All rights reserved.

Contrasting Electronic Requirements for C-H Binding and C-H Activation in d(6) Half-Sandwich Complexes of Rhenium and Tungsten

A computational study of the interaction half-sandwich metal fragments (metal=Re/W, electron count=d(6)), containing linear nitrosyl (NO+), carbon monoxide (CO), trifluorophosphine (PF3), N-heterocyclic carbene (NHC) ligands with alkanes are conducted using density functional theory employing the hybrid meta-GGA functional (M06). Electron deficiency on the metal increases with the ligand in the order NHC < CO < PF3 < NO+. Electron-withdrawing ligands like NO+ lead to more stable alkane complexes than NHC, a strong electron donor. Energy decomposition analysis shows that stabilization is due to orbital interaction involving charge transfer from the alkane to the metal. Reactivity and dynamics of the alkane fragment are facilitated by electron donors on the metal. These results match most of the experimental results known for CO and PF3 complexes. The study suggests activation of alkane in metal complexes to be facile with strong donor ligands like NHC. (C) 2015 Wiley Periodicals, Inc.

A Disulfide Stabilized beta-Sandwich Defines the Structure of a New Cysteine Framework M-Superfamily Conotoxin

The structure of a new cysteine framework (-C-CC-C-C-C) ``M''-superfamily conotoxin, Mo3964, shows it to have a beta-sandwich structure that is stabilized by inter-sheet cross disulfide bonds. Mo3964 decreases outward K+ currents in rat dorsal root ganglion neurons and increases the reversal potential of the Na(V)1.2 channels. The structure of Mo3964 (PDB ID: 2MW7) is constructed from the disulfide connectivity pattern, i.e., 1-3, 2-5, and 4-6, that is hitherto undescribed for the ``M''-superfamily conotoxins. The tertiary structural fold has not been described for any of the known conus peptides. NOE (549), dihedral angle (84), and hydrogen bond (28) restraints, obtained by measurement of (h3)J(NC') scalar couplings, were used as input for structure calculation. The ensemble of structures showed a backbone root mean square deviation of 0.68 +/- 0.18 angstrom, with 87% and 13% of the backbone dihedral (phi, psi) angles lying in the most favored and additional allowed regions of the Ramachandran map. The conotoxin Mo3964 represents a new bioactive peptide fold that is stabilized by disulfide bonds and adds to the existing repertoire of scaffolds that can be used to design stable bioactive peptide molecules.