Síntese, caracterização e estudo da ação antituberculose e citotóxica de hidrazonas derivadas de isoniazida e de seus complexos de cobre(II) e gálio(III)

No presente trabalho é descrita a obtenção de hidrazonas derivadas de isoniazida e de seus complexos de cobre(II) e gálio(III) candidatos a protótipos de fármacos antituberculose e antitumoral. Para investigar o efeito da modificação química sobre as bioatividades do fármaco isoniazida, foram preparados cinco derivados hidrazônicos: 2-piridinocarboxaldeído isonicotinoil hidrazona (HPCIH, 1), 2-acetilpiridina isonicotinoil hidrazona (HAPIH, 2), 2-benzoilpiridina isonicotinoil hidrazona (HBPIH, 3), 2-piridinoformamida isonicotinoil hidrazona (HPAmIH, 4) e 2-pirazinoformamida isonicotinoil hidrazona (HPzAmIH, 5), sendo o composto HPAmIH (4) inédito. Análises de ponto de fusão, espectroscopia de infravermelho (IV), espectrometria de massas, ressonância magnética nuclear (RMN), análise elementar e termogravimetria confirmaram a obtenção e pureza das hidrazonas. Foi determinada ainda a estrutura de HPCIH (1) por difração de raios X de monocristal. Essas moléculas foram efetivas em inibir o crescimento de cepas de micobactérias Mycobacterium tuberculosis H37Rv (ATCC 27294) nas concentrações testadas, com exceção de HPzAmIH (5). As hidrazonas HAPIH (2) e HBPIH (3) foram os compostos orgânicos mais ativos (concentração inibitória mínima, CIM = 0,625 g/mL), apresentando atividade antimicobacteriana apenas duas vezes inferior à do fármaco isoniazida.Quanto à ação contra células tumorais, as hidrazonas HAPIH (2) e HBPIH (3) foram as mais potentes contra as linhagens OVCAR-8 (tumor de ovário - humano), HCT-116 (tumor de cólon - humano) e SF-295 (glioblastoma humano), com inibições de 34,98 a 98,63% do crescimento celular, na concentração de 5 g/mL, enquanto que a isoniazida não foi efetiva contra as linhagens estudadas. Para avaliar o efeito da coordenação a metais sobre a atividade farmacológica das hidrazonas, foram sintetizados os complexos de cobre(II) e gálio(III), sendo todos inéditos: [Cu(HPCIH)Cl2]∙H2O (6), [Cu(HAPIH)Cl2]∙H2O (7), [Cu2(HBPIH)2Cl2]Cl2∙4H2O(8), [Cu(HPAmIH)Cl2]∙H2O (9), [Cu(HPzAmIH)Cl2]∙H2O (10), [Ga(HPCIH)2](NO3)32H2O (11), [Ga(HAPIH)(APIH)](NO3)22H2O (12), [Ga(HPAmIH)(PAmIH)](NO3)22H2O(13) e [Ga(HPzAmIH)(PzAmIH)](NO3)2H2O (14). Os complexos foram caracterizados por espectroscopia de IV, análise elementar, condutivimetria, RMN e espectroscopia eletrônica. Em geral, os complexos também demonstraram ação contra M. tuberculosis, sendo que apenas para 6, 9, 10 e 14 foi verificada melhor atividade em relação às hidrazonas livres. Os complexos metálicos foram tanto quanto ou mais ativos contra as células tumorais OVCAR-8, HCT-116 e SF-295 do que as hidrazonas livres. Merecem destaque os complexos 79 e 12, que apresentaram inibição de crescimento celular de 72,2100%, na concentração de 5 g/mL. Os resultados demonstram portanto que em geral os compostos 114 são menos ativos do que a isoniazida contra M. tuberculosis, enquanto que a modificação química do fármaco, formando-se hidrazonas com posterior complexação cobre(II) e gálio(III) constituíram uma estratégia interessante na obtenção de compostos mais potentes contra células tumorais

Focused ion beam etching of GaN

We have investigated the use of focused ion beam (FIB) etching for the fabrication of GaN-based devices. Although work has shown that conventional reactive ion etching (RIE) is in most cases appropriate for the GaN device fabrication, the direct write facility of FIB etching - a well-established technique for optical mask repair and for IC failure analysis and repair - without the requirement for depositing an etch mask is invaluable. A gallium ion beam of about 20nm diameter was used to sputter GaN material. The etching rate depends linearly on the ion dose per area with a slope of 3.5×10 -4μm3/pC. At a current of 3nA, for example, this corresponds to an etch rate of 1.05μm3/s. Good etching qualities have been achieved with a side wall roughness significantly below 0.1μm. Changes in the roughness of the etched surface plane stay below 8nm.

Occurrence of particle debris field during focused Ga ion beam milling of glassy carbon

To explore the machining characteristics of glassy carbon by focused ion beam (FIB), particles induced by FIB milling on glassy carbon have been studied in the current work. Nano-sized particles in the range of tens of nanometers up to 400 nm can often be found around the area subject to FIB milling. Two ion beam scanning modes - slow single scan and fast repetitive scan - have been tested. Fewer particles are found in single patterns milled in fast repetitive scan mode. For a group of test patterns milled in a sequence, it was found that a greater number of particles were deposited around sites machined early in the sequence. In situ EDX analysis of the particles showed that they were composed of C and Ga. The formation of particles is related to the debris generated at the surrounding areas, the low melting point of gallium used as FIB ion source and the high contact angle of gallium on glassy carbon induces de-wetting of Ga and the subsequent formation of Ga particles. Ultrasonic cleaning can remove over 98% of visible particles. The surface roughness (Ra) of FIB milled areas after cleaning is less than 2 nm. © 2010.

Gaussian Approximation Potential: an interatomic potential derived from first principles Quantum Mechanics

Simulation of materials at the atomistic level is an important tool in studying microscopic structure and processes. The atomic interactions necessary for the simulation are correctly described by Quantum Mechanics. However, the computational resources required to solve the quantum mechanical equations limits the use of Quantum Mechanics at most to a few hundreds of atoms and only to a small fraction of the available configurational space. This thesis presents the results of my research on the development of a new interatomic potential generation scheme, which we refer to as Gaussian Approximation Potentials. In our framework, the quantum mechanical potential energy surface is interpolated between a set of predetermined values at different points in atomic configurational space by a non-linear, non-parametric regression method, the Gaussian Process. To perform the fitting, we represent the atomic environments by the bispectrum, which is invariant to permutations of the atoms in the neighbourhood and to global rotations. The result is a general scheme, that allows one to generate interatomic potentials based on arbitrary quantum mechanical data. We built a series of Gaussian Approximation Potentials using data obtained from Density Functional Theory and tested the capabilities of the method. We showed that our models reproduce the quantum mechanical potential energy surface remarkably well for the group IV semiconductors, iron and gallium nitride. Our potentials, while maintaining quantum mechanical accuracy, are several orders of magnitude faster than Quantum Mechanical methods.

A novel hydraulic microactuator sealed by surface tension

In order to improve the power density of microactuators, recent research focuses on the applicability of fluidic power at microscale. The main encountered difficulties in the development of small fluidic actuators are related to production tolerances and assembly requirements. Furthermore, these actuators tend to comprise highly three-dimensional parts, which are incompatible with traditional microproduction technologies. This paper presents accurate production and novel assembly techniques for the development of a hydraulic microactuator. In addition, a scalable low friction seal, relying on surface tension forces, is presented. A prototype piston-type microactuator with a bore of 1 mm and a length of 13 mm is developed. Using a gallium-based surface tension seal, pressures of more than 90 kPa have been sealed without leakage. © 2005 Elsevier B.V. All rights reserved.

Noncontact measurement of charge carrier lifetime and mobility in GaN nanowires

The first noncontact photoconductivity measurements of gallium nitride nanowires (NWs) are presented, revealing a high crystallographic and optoelectronic quality achieved by use of catalyst-free molecular beam epitaxy. In comparison with bulk material, the NWs exhibit a long conductivity lifetime (>2 ns) and a high mobility (820 ± 120 cm 2/(V s)). This is due to the weak influence of surface traps with respect to other III-V semiconducting NWs and to the favorable crystalline structure of the NWs achieved via strain-relieved growth. © 2012 American Chemical Society.

Nanoscale-accuracy transfer printing of ultra-thin AlInGaN light-emitting diodes onto mechanically flexible substrates

The transfer printing of 2 μm-thick aluminum indium gallium nitride (AlInGaN) micron-size light-emitting diodes with 150 nm (±14 nm) minimum spacing is reported. The thin AlInGaN structures were assembled onto mechanically flexible polyethyleneterephthalate/polydimethylsiloxane substrates in a representative 16 × 16 array format using a modified dip-pen nano-patterning system. Devices in the array were positioned using a pre-calculated set of coordinates to demonstrate an automated transfer printing process. Individual printed array elements showed blue emission centered at 486 nm with a forward-directed optical output power up to 80 μW (355 mW/cm 2) when operated at a current density of 20 A/cm2. © 2013 AIP Publishing LLC.

On the variation of the 2DEG charge density with the density of the surface donor traps in AiGaN/GaN transistors

Gallium nitride (GaN) has a bright future in high voltage device owing to its remarkable physical properties and the possibility of growing heterostructures on silicon substrates. GaN High Electron Mobility Transistors (HEMTs) are expected to make a strong impact in off line applications and LED drives. However, unlike in silicon-based power devices, the on-state resistance of HEMT devices is hugely influenced by donor and acceptor traps at interfaces and in the bulk. This study focuses on the influence of donor traps located at the top interface between the semiconductor layer and the silicon nitride on the 2DEG density. It is shown through TCAD simulations and analytical study that the 2DEG charge density has an 'S' shape variation with two distinctive 'flat' regions, wherein it is not affected by the donor concentration, and one linear region. wherein the channel density increases proportionally with the donor concentration. We also show that the upper threshold value of the donor concentration within this 'S' shape increases significantly with the AIGaN thickness and the Al mole fraction and is highly affected by the presence of a thin GaN cap layer. © 2013 IEEE.

Optimising the dynamic performance of an all-wide-bandgap cascode switch

A SPICE simulation model of a novel cascode switch that combines a high voltage normally-on silicon carbide (SiC) junction field effect transistor (JFET) with a low voltage enhancement-mode gallium nitride field effect transistor (eGaN FET) has been developed, with the aim of optimising cascode switching performance. The effect of gate resistance on stability and switching losses is investigated and optimum values chosen. The effects of stray inductance on cascode switching performance are considered and the benefits of low inductance packaging discussed. The use of a positive JFET gate bias in a cascode switch is shown to reduce switching losses as well as reducing on-state losses. The findings of the simulation are used to produce a list of priorities for the design and layout of wide-bandgap cascode switches, relevant to both SiC and GaN high voltage devices. © 2013 IEEE.

Multimode resonances in metallically confined square-resonator microlasers

Directional emission InP/AlGaInAs square-resonator microlasers with a side length of 20 mu m are fabricated by standard photolithography and inductively coupled-plasma etching technique. Multimode resonances with about seven distinct mode peaks in a free-spectral range are observed from 1460 to 1560 nm with the free-spectral range of 12.1 nm near the wavelength of 1510 nm, and the mode refractive index versus the photon energy E (eV) as 3.07152+0.18304E are obtained by fitting the laser spectra with an analytical mode wavelength formula derived by light ray method. In addition, mode field pattern is simulated for cold cavity by two dimensional finite-difference time-domain technique.

Co doping enhanced giant magnetocaloric effect in Mn1-xCoxAs films epitaxied on GaAs (001)

A giant magnetocaloric effect was found in series of Mn1-xCoxAs films epitaxied on GaAs (001). The maximum magnetic entropy change caused by a magnetic field of 4 T is as large as 25 J/kg K around room temperature, which is about twice the value of pure MnAs film. The observed small thermal hysteresis is more suitable for practical application. Growing of layered Mn1-xCoxAs films with Co concentration changing gradually may draw layered active magnetic regenerator refrigerators closer to practical application. Our experimental result may provide the possibility for the combination of magnetocaloric effect and microelectronic circuitry.

Cathodoluminescence study on in composition inhomogeneity of thick InGaN layer

We have investigated the optical properties of thick InGaN film grown on GaN by cathodeluminescence (CL) spectroscopy. It is found that there is obvious In composition variation in both growth and lateral direction of InGaN film. The depth distribution of In composition is closely related to the strain relaxation process of InGaN film. Accompanied with the relaxation of compressive strain, the In composition of InGaN layer increases and the CL peak energy shifts towards red. Moreover, a rather apparent In composition fluctuation is found in the relaxed upper part of InGaN layer as confirmed by CL imaging.

Microstructure and strain analysis of GaN epitaxial films using in-plane grazing incidence x-ray diffraction

This paper investigates the major structural parameters, such as crystal quality and strain state of (001)-oriented GaN thin films grown on sapphire substrates by metalorganic chemical vapour deposition, using an in-plane grazing incidence x-ray diffraction technique. The results are analysed and compared with a complementary out-of-plane x-ray diffraction technique. The twist of the GaN mosaic structure is determined through the direct grazing incidence measurement of (100) reflection which agrees well with the result obtained by extrapolation method. The method for directly determining the in-plane lattice parameters of the GaN layers is also presented. Combined with the biaxial strain model, it derives the lattice parameters corresponding to fully relaxed GaN films. The GaN epilayers show an increasing residual compressive stress with increasing layer thickness when the two dimensional growth stage is established, reaching to a maximum level of -0.89 GPa.

Dislocation scattering in AlxGa1-xN/GaN heterostructures

The theoretical electron mobility limited by dislocation scattering of a two-dimensional electron gas confined near the interface of AlxGa1-xN/GaN heterostructures was calculated. Based on the model of treating dislocation as a charged line, an exponentially varied potential was adopted to calculate the mobility. The estimated mobility suggests that such a choice can simplify the calculation without introducing significant deviation from experimental data, and we obtained a good fitting between the calculated and experimental results. It was found that the measured mobility is dominated by interface roughness and dislocation scattering at low temperatures if dislocation density is relatively high (>10(9) cm(-2)), and accounts for the nearly flattening-out behavior with increasing temperature.

Low threshold lasing of GaN-based vertical cavity surface emitting lasers with an asymmetric coupled quantum well active region

We have fabricated and characterized GaN-based vertical cavity surface emitting lasers (VCSELs) with a unique active region structure, in which three sets of InGaN asymmetric coupled quantum wells are placed in a half-wavelength (0.5 lambda) length. Lasing action was achieved under optical pumping at room temperature with a threshold pumping energy density of about 6.5 mJ/cm(2). The laser emitted a blue light at 449.5 nm with a narrow linewidth below 0.1 nm and had a high spontaneous emission factor of about 3.0x10(-2). The results indicate that this active region structure is useful in reducing the process difficulties and improving the threshold characteristics of GaN-based VCSELs.