Expanding crystal structure prediction to larger and more flexible molecules of pharmaceutical interest

The use of Crystal Structure Prediction (CSP) studies in the pharmaceutical industry is currently limited by computational cost, which scales badly with molecular size and flexibility. This thesis seeks to develop new methods that would allow to perform CSP studies on larger, more flexible pharmaceutical-like molecules. First, a full CSP workflow was successfully used to predict the crystal structure of a large flexible molecule for the 6th Blind Test and in a joint computational-experimental study of the antihelminthic drug mebendazole. These CSP studies were integrated with three previously published computational analyses of flexible pharmaceuticals and used to benchmark the development of new methods. Successively, knowledge-based conformational information retrieved from the Cambridge Structural Database (CSD) was used to facilitate the generation of candidate crystal structures of these five molecules. Millions of crystal structures were generated at a reduced computational cost, but with an equally effective coverage of the conformational search space, compared to the original CSP efforts. The importance of treating conformational flexibility when optimising search-generated crystal structures was then assessed. This led to using dispersion-corrected density functional tight-binding (DFTB-D) as an intermediate step to minimise all intra- and intermolecular degrees of freedom of several thousands of search-generated crystal structures. DFTB-D reduced the cost of the final lattice energy evaluations by providing better starting points, and results of similar quality to the original CSP studies were obtained after optimising only the intermolecular interactions with a higher quality wave-function. Finally, a CSD survey was performed to determine thresholds that can discriminate the great majority of polymorphs from duplicate determinations. These thresholds and comparison methods were implemented in a Python programme that can be used in CSP studies to perform clustering and to interpret the results more effectively. The prospects for expanding the use of CSP to pharmaceutical development are discussed

Towards the cryogenic sliding mechanism for MOONS-ESO

The Multi-Object Optical and Near-Infrared Spectrograph (MOONS) shall be installed at one of the Very Large Telescopes (VLT) at the European Southern Observatory (ESO) in Paranal Chile. The instrument is being designed and built by an international consortium on behalf of ESO. The design is based on a three arms configuration, RI, YJ and H band, where RI and H have two possible resolutions. To achieve this goal it will be necessary to implement a sliding mechanism changing the dispersers, the filters and the cross dispersion prisms. This article describes the cryogenic exchanger mechanism that is under realization and the preliminary mechanical and optical tests that we have done at the cryogenic facility of Arcetri observatory of Florence. Parts of these test are based on interferometric measurements of the optics to study the behaviour of the mechanical supporting structure, and part are based on the cryogenic sliding system that will be used to move approximately 200 Kg of mass for 350 mm of travel range. The cryogenic sliding system, rails, screws, motors, is based on commercial components as the position measurement device that is based on commercial potentiometers. The results of the tests and performances at cryogenic temperature are reported in this paper

GIANO and HARPS-N together: towards an Earth-mass detection instrument

This article describes the works we are doing for modifying the interface between the high resolution infrared spectrograph GIANO (0.97-2.4 micron) and the TNG telescope, passing from a fiber feed configuration to the original design of a direct light-feeding from the telescope to the spectrograph. So doing the IR spectrograph, GIANO, will work in parallel to HARPS-N spectrometer (0.38-0.70 micron), the visible high resolution spectrograph, thanks to a new telescope interface based on a dichroic window that simultaneously feeds the two instrumentes: this is GIARPS (GIAno and haRPS). The scientific aims of this project are to improve the radial velocity accuracy achievable with GIANO, down to a goal of 1 m/s, the value necessary to detect Earth-mass planets on habitable orbits around late-M stars, to implement simultaneous observations with Harps-N and GIANO optimizing the study of planets around cool stars. The very broad wavelengths range is particularly important to discriminate false radial velocity signals caused by stellar activity. We therefore include several absorption cells with different mixtures of gases and a stabilized Fabry Perot cavity, necessary to have absorption lines over the 0.97-2.4 microns range covered by GIANO. The commissioning of GIARPS is scheduled by the end of 2016

The detector control unit of the fine guidance sensor instrument on-board the ARIEL mission: design status

ARIEL is an ESA mission whose scientific goal is to investigate exoplanetary atmospheres. The payload is composed by two instruments: AIRS (ARIEL IR Spectrometer) and FGS (Fine Guidance System). The FGS detection chain is composed by two HgCdTe detectors and by the cold Front End Electronics (SIDECAR), kept at cryogenic temperatures, interfacing with the F-DCU (FGS Detector Control Unit) boards that we will describe thoroughly in this paper. The F-DCU are situated in the warm side of the payload in a box called FCU (FGS Control Unit) and contribute to the FGS VIS/NIR imaging and NIR spectroscopy. The F-DCU performs several tasks: drives the detectors, processes science data and housekeeping telemetries, manages the commands exchange between the FGS/DPU (Data Processing Unit) and the SIDECARs and provides high quality voltages to the detectors. This paper reports the F-DCU status, describing its architecture, the operation and the activities, past and future necessary for its development

The instrument control unit of the ARIEL payload: design evolution following the unit and payload subsystems SRR (system requirements review)

ARIEL (Atmospheric Remote-sensing InfraRed Large-survey) is a medium-class mission of the European Space Agency, part of the Cosmic Vision program, whose launch is foreseen by early 2029. ARIEL aims to study the composition of exoplanet atmospheres, their formation and evolution. The ARIEL’s target will be a sample of about 1000 planets observed with one or more of the following methods: transit, eclipse and phase-curve spectroscopy, at both visible and infrared wavelengths simultaneously. The scientific payload is composed by a reflective telescope having a 1m-class elliptical primary mirror, built in solid Aluminium, and two focal-plane instruments: FGS and AIRS. FGS (Fine Guidance System)1 has the double purpose, as suggested by its name, of performing photometry (0.50-0.55 µm) and low resolution spectrometry over three bands (from 0.8 to 1.95 µm) and, simultaneously, to provide data to the spacecraft AOCS (Attitude and Orbit Control System) with a cadence of 10 Hz and contributing to reach a 0.02 arcsec pointing accuracy for bright targets. AIRS (ARIEL InfraRed Spectrometer) instrument will perform IR spectrometry in two wavelength ranges: between 1.95 and 3.9 µm (with a spectral resolution R > 100) and between 3.9 and 7.8 µm with a spectral resolution R > 30. This paper provides the status of the ICU (Instrument Control Unit), an electronic box whose purpose is to command and supply power to AIRS (as well as acquire science data from its two channels) and to command and control the TCU (Telescope Control Unit)

GIARPS: the unique VIS-NIR high precision radial velocity facility in this world

GIARPS (GIAno & haRPS) is a project devoted to have on the same focal station of the Telescopio Nazionale Galileo (TNG) both the high resolution spectrographs HARPS-N (VIS) and GIANO (NIR) working simultaneously. This could be considered the first and unique worldwide instrument providing cross-dispersed echelle spectroscopy at a high resolution (R=115,000 in the visual and R=50,000 in the IR) and over in a wide spectral range (0.383 - 2.45 micron) in a single exposure. The science case is very broad, given the versatility of such an instrument and the large wavelength range. A number of outstanding science cases encompassing mainly extra-solar planet science starting from rocky planet search and hot Jupiters, atmosphere characterization can be considered. Furthermore both instrument can measure high precision radial velocity by means the simultaneous thorium technique (HARPS - N) and absorbing cell technique (GIANO) in a single exposure. Other science cases are also possible. Young stars and proto-planetary disks, cool stars and stellar populations, moving minor bodies in the solar system, bursting young stellar objects, cataclysmic variables and X-ray binary transients in our Galaxy, supernovae up to gamma-ray bursts in the very distant and young Universe, can take advantage of the unicity of this facility both in terms of contemporaneous wide wavelength range and high resolution spectroscopy.Comment: 8 pages, 5 figures, SPIE Conference Proceeding

Heat treatment procedure of the Aluminium 6061-T651 for the Ariel Telescope mirrors

The Atmospheric Remote-Sensing Infrared Exoplanet Large Survey (Ariel) is the M4 mission adopted by ESA’s ”Cosmic Vision” program. Its launch is scheduled for 2029. The purpose of the mission is the study of exoplanetary atmospheres on a target of ∼ 1000 exoplanets. Ariel scientific payload consists of an off-axis, unobscured Cassegrain telescope. The light is directed towards a set of photometers and spectrometers with wavebands between 0.5 and 7.8 µm and operating at cryogenic temperatures. The Ariel Space Telescope consists of a primary parabolic mirror with an elliptical aperture of 1.1· 0.7 m, followed by a hyperbolic secondary, a parabolic collimating tertiary and a flat-folding mirror directing the output beam parallel to the optical bench; all in bare aluminium. The choice of bare aluminium for the realization of the mirrors is dictated by several factors: maximizing the heat exchange, reducing the costs of materials and technological advancement. To date, an aluminium mirror the size of Ariel’s primary has never been made. The greatest challenge is finding a heat treatment procedure that stabilizes the aluminium, particularly the Al6061T651 Laminated alloy. This paper describes the study and testing of the heat treatment procedure developed on aluminium samples of different sizes (from 50mm to 150mm diameter), on 0.7m diameter mirror, and discusses future steps

FEA testing the pre-flight Ariel primary mirror

Ariel (Atmospheric Remote-sensing Infrared Exoplanet Large-survey) is an ESA M class mission aimed at the study of exoplanets. The satellite will orbit in the lagrangian point L2 and will survey a sample of 1000 exoplanets simultaneously in visible and infrared wavelengths. The challenging scientific goal of Ariel implies unprecedented engineering efforts to satisfy the severe requirements coming from the science in terms of accuracy. The most important specification – an all-Aluminum telescope – requires very accurate design of the primary mirror (M1), a novel, off-set paraboloid honeycomb mirror with ribs, edge, and reflective surface. To validate such a mirror, some tests were carried out on a prototype – namely Pathfinder Telescope Mirror (PTM) – built specifically for this purpose. These tests, carried out at the Centre Spatial de Liège in Belgium – revealed an unexpected deformation of the reflecting surface exceeding a peek-to-valley of 1µm. Consequently, the test had to be re-run, to identify systematic errors and correct the setting for future tests on the final prototype M1. To avoid the very expensive procedure of developing a new prototype and testing it both at room and cryogenic temperatures, it was decided to carry out some numerical simulations. These analyses allowed first to recognize and understand the reasoning behind the faults occurred during the testing phase, and later to apply the obtained knowledge to a new M1 design to set a defined guideline for future testing campaigns

GIANO-TNG spectroscopy of red supergiants in the young star cluster RSGC3

Aims: The Scutum complex in the inner disk of the Galaxy has a number of young star clusters dominated by red supergiants that are heavily obscured by dust extinction and observable only at infrared wavelengths. These clusters are important tracers of the recent star formation and chemical enrichment history in the inner Galaxy. Methods: During the technical commissioning and as a first science verification of the GIANO spectrograph at the Telescopio Nazionale Galileo, we secured high-resolution (R ≃ 50 000) near-infrared spectra of five red supergiants in the young Scutum cluster RSGC3. Results: Taking advantage of the full YJHK spectral coverage of GIANO in a single exposure, we were able to measure several tens of atomic and molecular lines that were suitable for determining chemical abundances. By means of spectral synthesis and line equivalent width measurements, we obtained abundances of Fe and iron-peak elements such as Ni, Cr, and Cu, alpha (O, Mg, Si, Ca, Ti), other light elements (C, N, F, Na, Al, and Sc), and some s-process elements (Y, Sr). We found average half-solar iron abundances and solar-scaled [X/Fe] abundance patterns for most of the elements, consistent with a thin-disk chemistry. We found depletion of [C/Fe] and enhancement of [N/Fe], consistent with standard CN burning, and low 12C /13C abundance ratios (between 9 and 11), which require extra-mixing processes in the stellar interiors during the post-main sequence evolution. We also found local standard of rest VLSR = 106 km s-1 and heliocentric Vhel = 90 km s-1 radial velocities with a dispersion of 2.3 km s-1. Conclusions: The inferred radial velocities, abundances, and abundance patterns of RSGC3 are very similar to those previously measured in the other two young clusters of the Scutum complex, RSGC1 and RSGC2, suggesting a common kinematics and chemistry within the Scutum complex