•Co-crystals provide a versatile approach to enhancing drug properties, such as solubility, dissolution and bioavailability – optimizing formulations and addressing challenges associated with APIs, ...thereby offering numerous benefits in drug development, formulation and patent protection.•Machine learning, crystal structure prediction and a combination thereof have the potential to facilitate design and discovery of co-crystals.•Machine learning approaches require large and balanced datasets that are not yet available, based on literature sources.•Network-based recommendation models can be an alternative to machine learning approaches for imbalanced datasets.•Kinetic effects are also taken into consideration in crystal structure prediction methodologies.
Pharmaceutical co-crystals represent a growing class of crystal forms in the context of pharmaceutical science. They are attractive to pharmaceutical scientists because they significantly expand the number of crystal forms that exist for an active pharmaceutical ingredient and can lead to improvements in physicochemical properties of clinical relevance. At the same time, machine learning is finding its way into all areas of drug discovery and delivers impressive results. In this review, we attempt to provide an overview of machine learning, deep learning and network-based recommendation approaches applied to pharmaceutical co-crystallization. We also present crystal structure prediction as an alternative to machine learning approaches.
The first copper‐catalyzed highly chemo‐, regio‐, diastereo‐, and enantioselective Kinugasa/Michael domino reaction for the desymmetrization of prochiral cyclohexadienones is described. In the ...presence of a chiral copper catalyst, alkyne‐tethered cyclohexadienones couple with nitrones to generate the chiral spirocyclic lactams with excellent stereoselectivity (up to 97 % ee, >20:1 dr). The new method provides direct access to versatile highly functionalized spirocyclic β‐lactams possessing four contiguous stereocenters, including one quaternary and one tetra‐substituted stereocenter.
Spiro staircase: Copper‐catalyzed asymmetric Kinugasa/Michael domino reactions of alkyne‐tethered cyclohexadienones and nitrones provide a direct stereoselective approach to spirocyclic β‐lactams possessing four contiguous stereocenters.
A key legacy of the recently launched the Transiting Exoplanet Survey Satellite (TESS) mission will be to provide the astronomical community with many of the best transiting exoplanet targets for ...atmospheric characterization. However, time is of the essence to take full advantage of this opportunity. The James Webb Space Telescope (JWST), although delayed, will still complete its nominal five year mission on a timeline that motivates rapid identification, confirmation, and mass measurement of the top atmospheric characterization targets from TESS. Beyond JWST, future dedicated missions for atmospheric studies such as the Atmospheric Remote-sensing Infrared Exoplanet Large-survey (ARIEL) require the discovery and confirmation of several hundred additional sub-Jovian size planets (Rp < 10 R⊕) orbiting bright stars, beyond those known today, to ensure a successful statistical census of exoplanet atmospheres. Ground-based extremely large telescopes (ELTs) will also contribute to surveying the atmospheres of the transiting planets discovered by TESS. Here we present a set of two straightforward analytic metrics, quantifying the expected signal-to-noise in transmission and thermal emission spectroscopy for a given planet, that will allow the top atmospheric characterization targets to be readily identified among the TESS planet candidates. Targets that meet our proposed threshold values for these metrics would be encouraged for rapid follow-up and confirmation via radial velocity mass measurements. Based on the catalog of simulated TESS detections by Sullivan et al., we determine appropriate cutoff values of the metrics, such that the TESS mission will ultimately yield a sample of ∼300 high-quality atmospheric characterization targets across a range of planet size bins, extending down to Earth-size, potentially habitable worlds.
A strategy to control the switch between a non‐cycloaddition reaction and a cycloaddition reaction of enals, using N‐heterocyclic carbene (NHC) catalyisis, has been developed. The new scalable ...protocol leads to γ‐amino‐acid esters bearing a tetrasubstituted stereocenter in good yields and high stereoselectivities by homo‐Mannich reactions of enals and isatin‐derived ketimines. By simply changing the N‐ketimine substituent to an ortho‐hydroxy phenyl group, the corresponding spirocyclic oxindolo‐γ‐lactams are obtained.
Switcheroo: An NHC‐catalyzed homo‐Mannich reaction between enals and isatin‐derived ketimines opens a novel, efficient, and highly stereoselective entry to oxindole‐γ‐amino esters. A simple change of the N‐ketimine substituent allows a switch to the formation of the corresponding spirocyclic γ‐lactams. NHC=N‐heterocyclic carbene.
The potassium absorption on HD189733b and HD209458b Keles, Engin; Mallonn, Matthias; von Essen, Carolina ...
Monthly notices of the Royal Astronomical Society. Letters,
10/2019, Letnik:
489, Številka:
1
Journal Article
Recenzirano
Odprti dostop
ABSTRACT In this work, we investigate the potassium excess absorption around 7699 Å of the exoplanets HD189733b and HD209458b. For this purpose, we used high-spectral resolution transit observations ...acquired with the 2 × 8.4 m Large Binocular Telescope (LBT) and the Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI). For a bandwidth of 0.8 Å, we present a detection >7σ with an absorption level of 0.18 per cent for HD189733b. Applying the same analysis to HD209458b, we can set 3σ upper limit of 0.09 per cent, even though we do not detect a K-excess absorption. The investigation suggests that the K feature is less present in the atmosphere of HD209458b than in the one of HD189733b. This comparison confirms previous claims that the atmospheres of these two planets must have fundamentally different properties.
Halogen bonding in self‐complementary 1:2 metal–ligand complexes obtained from copper(II) bromide (CuBr2) and seven 2,5‐dihalopyridines were analyzed using single‐crystal X‐ray diffraction. All ...presented discrete complexes form 1D polymeric chains connected with C–X···Br–Cu halogen bonds (XB). In (2‐chloro‐5‐X‐pyridine)2·CuBr2 (X = Cl, Br, and I) only the C5‐halogen and in (2‐bromo‐5‐X‐pyridine)2·CuBr2 (X = Cl, Br, and I) both C2‐ and C5‐halogens form C–X···Br–Cu halogen bonds with the X acting as the XB donor and copper‐coordinated bromide as the XB acceptor. The electron‐withdrawing C2‐chloride in (2‐chloro‐5‐X‐pyridine)2·CuBr2 complexes has only a minor effect on the C5–X5···Br–Cu XBs, and the X5···Br distances follow the expected order I5 < Br5 < Cl5 with RXB values of 0.91, 0.94, and 0.99, respectively. In (2‐bromo‐5‐X‐pyridine)2·CuBr2 complexes, due to the polarization of both halogens, the C2–X2···Br–Cu and C5–X5···Br–Cu RXB values are very similar 0.92–0.99 as a result of the competition between C2‐ and C5‐halogens for XB formation. In addition to the classical halogen bonds, the square‐planar CuII complexes exhibit C2–X2···Cu (X = Cl and Br) contacts perpendicular to the Br–Cu–Br plane with shorter C2–Br2···Cu than C2–Cl2···Cu contacts. These interactions induce a pseudo‐octahedral geometry for CuII ions. Notably, C2–X2···Br–Cu halogen bonds and the additional C2–X2···Cu contacts are slightly enhanced by the C5‐halogen electronegativity.
2,5‐Dihalopyridine–copper(II) bromide complexes were investigated to understand the mutual polarization of X2 on X5 and vice versa, as well as their effect on C–X2/X5···Br–Cu halogen bond lengths in solid‐state X‐ray crystal structures. The change in C–X2/X5···Br–Cu halogen bond lengths due to X2‐/X5‐substituent effects were evaluated by comparing with C–X2/X3···Br–Cu halogen bonds in (2‐X‐pyridine)2·CuBr2 (X = Cl and Br) and (3‐X‐pyridine)2·CuBr2 (X = Cl, Br, and I) complexes, respectively.
Abstract
The Transiting Exoplanet Survey Satellite (TESS) is NASA's latest space telescope dedicated to the discovery of transiting exoplanets around nearby stars. Besides the main goal of the ...mission, asteroseismology is an important secondary goal and very relevant for the high-quality time series that TESS will make during its two-year all-sky survey. Using TESS for asteroseismology introduces strong timing requirements, especially for coherent oscillators. Although the internal clock on board TESS is precise in its own time, it might have a constant drift. Thus, it will need calibration, or else offsets might inadvertently be introduced. Here, we present simultaneous ground- and space-based observations of primary eclipses of several binary systems in the Southern ecliptic hemisphere, used to verify the reliability of the TESS timestamps. From 12 contemporaneous TESS/ground observations, we determined a time offset equal to 5.8 ± 2.5 s, in the sense that the barycentric time measured by TESS is ahead of real time. The offset is consistent with zero at the 2.3
σ
level. In addition, we used 405 individually measured mid-eclipse times of 26 eclipsing binary stars observed solely by TESS in order to test the existence of a potential drift with a monotonic growth (or decay) affecting the observations of all stars. We find a drift corresponding to
σ
drift
= 0.009 ± 0.015 s day
−1
. We find that the measured offset is of a size that will not become an issue for comparing ground-based and space data for coherent oscillations for most of the targets observed with TESS.
Abstract
High-resolution spectroscopic visible data were obtained with the Ultraviolet and Visible Echelle Spectrograph on the Very Large Telescope. Our goal was to analyze the data in an effort to ...detect the presence of sodium in the atmosphere of hot Jupiter exoplanet KELT-10b, as well as characterize the orbit of the planet via the Rossiter-McLaughlin effect. Eighty spectra were collected during a single transit of KELT-10b. After standard spectroscopic calibration using ESO-Reflex, the synthetic telluric modeling software
molecfit
was applied to remove terrestrial atmospheric effects, and to refine the wavelength calibration. Sodium is recognized by its characteristic absorption doublet located at 5895.924 and 5889.951 Å, which can be seen in the planet atmosphere transmission spectrum and through excess absorption during the transit. The radial velocity of the host star was analyzed by measuring the average shift of absorption features from spectrum to spectrum. Our results indicate a sodium detection in the planet transmission spectrum with a line contrast of 0.66% and 0.43% ± 0.09% for the sodium DII and DI lines, respectively. Excess absorption measurements agree to within one half combined standard deviation between the planet transmission spectrum (0.143% ± 0.020%, a 7
σ
detection) and during the time series (0.124% ± 0.034%, a 3.6
σ
detection) in a band 1.25 Å wide. The wavelength grid corrections provided by
molecfit
were insufficient to determine radial velocities and measure the Rossiter-McLaughlin effect.
A novel short entry to 3,4‐disubstituted adipic acids has been developed by employing an asymmetric NHC‐catalyzed 3+2 cycloaddition of enals with masked cinnammates in moderate to good yields and ...high stereoselectivities. The synthetic utility of the protocol was demonstrated by the basic conversion of the masked cyclopentanone intermediates to 3S,4S‐disubstituted adipic acid precursors of pharmaceutically important gababutins.
One‐pot to adipic acids: The NHC‐catalyzed asymmetric 3+2 cycloaddition of enals with masked cinnamates opens a new short entry to adipic acid derivatives in moderate to good yields and high stereoselectivities. The utility of the protocol is showcased by the one‐pot asymmetric synthesis of 3S,4S‐disubstituted adipic acids, precursors for the synthesis of 3,4‐disubstituted gababutins, which are used for the treatment of various diseases.