Maleate salts of bedaquiline

Bedaquiline is one of two important new drugs for the treatment of drug-resistant tuberculosis (TB). It is marketed in the US as its fumarate salt, but only a few salts of bedaquiline have been structurally described so far. We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-methoxyquinolin-3-yl)-3-hydroxy-3-(naphthalen-1-yl)-4-phenylbutyl]dimethylazanium 3-carboxyprop-2-enoate}, C32H32BrN2O2 +·C4H3O4 −, namely, a hemihydrate, a tetrahydrofuran (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by in situ single-crystal-to-single-crystal desolvation. All salts exhibit a 1:1 cation-to-anion ratio, with the anion present as monoanionic hydromaleate and a singly protonated bedaquilinium cation. The maleate exhibits the strong intramolecular hydrogen bond typical for cis-dicarboxylic acid anions. The conformations of the cations and packing interactions in the maleate salts are compared to those of free base bedaquiline and other bedaquilinium salts.

Download Full-text

Structure of Palladium Single-Crystal Films Prepared by Flash Evaporation onto (001) NaCl Substrates

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100069272 ◽

1970 ◽

Vol 28 ◽

pp. 456-457

Author(s):

L. E. Murr ◽

G. Wong

Keyword(s):

Single Crystal ◽

High Vacuum ◽

Ultra High Vacuum ◽

High Rate ◽

Flash Evaporation ◽

Optimum Load ◽

Single Crystal Films ◽

Crystal Films ◽

A Current

Palladium single-crystal films have been prepared by Matthews in ultra-high vacuum by evaporation onto (001) NaCl substrates cleaved in-situ, and maintained at ∼ 350° C. Murr has also produced large-grained and single-crystal Pd films by high-rate evaporation onto (001) NaCl air-cleaved substrates at 350°C. In the present work, very large (∼ 3cm2), continuous single-crystal films of Pd have been prepared by flash evaporation onto air-cleaved (001) NaCl substrates at temperatures at or below 250°C. Evaporation rates estimated to be ≧ 2000 Å/sec, were obtained by effectively short-circuiting 1 mil tungsten evaporation boats in a self-regulating system which maintained an optimum load current of approximately 90 amperes; corresponding to a current density through the boat of ∼ 4 × 104 amperes/cm2.

Download Full-text

Single Crystal Growth of High-Pressure Phases of Ice and Salt Hydrate Far Below the Original Melting Point by Mixing Alcohol: Crystal Structure Determination of Magnesium Chloride Heptahydrate

10.26434/chemrxiv.11345063.v2 ◽

2020 ◽

Author(s):

Keishiro Yamashita ◽

Kazuki Komatsu ◽

Hiroyuki Kagi

Keyword(s):

Crystal Structure ◽

High Pressure ◽

Crystal Growth ◽

Single Crystal ◽

Room Temperature ◽

Growth Technique ◽

Salt Hydrate ◽

X Ray

An crystal-growth technique for single crystal x-ray structure analysis of high-pressure forms of hydrogen-bonded crystals is proposed. We used alcohol mixture (methanol: ethanol = 4:1 in volumetric ratio), which is a widely used pressure transmitting medium, inhibiting the nucleation and growth of unwanted crystals. In this paper, two kinds of single crystals which have not been obtained using a conventional experimental technique were obtained using this technique: ice VI at 1.99 GPa and MgCl<sub>2</sub>·7H<sub>2</sub>O at 2.50 GPa at room temperature. Here we first report the crystal structure of MgCl2·7H2O. This technique simultaneously meets the requirement of hydrostaticity for high-pressure experiments and has feasibility for further in-situ measurements.

Download Full-text

Laser damage mechanism and in-situ observation of stacking fault relaxation in β-Ga2O3 single crystal by EFG method

CrystEngComm ◽

10.1039/d1ce00131k ◽

2021 ◽

Author(s):

Bo Fu ◽

Gaohang He ◽

Wenxiang Mu ◽

Yang Li ◽

Boyuan Feng ◽

...

Keyword(s):

Single Crystal ◽

Light Field ◽

Damage Mechanism ◽

Stacking Fault ◽

High Light ◽

Laser Damage ◽

In Situ Observation ◽

Structure Destruction

We designed an original and effective method to study the laser damage mechanism of β-Ga2O3 single crystal grown by edge-defined film-fed growth (EFG). The structure destruction under high light field...

Download Full-text

Manipulating the Conformation of 3,2′:6′,3″-Terpyridine in [Cu2(μ-OAc)4(3,2′:6′,3″-tpy)]n 1D-Polymers

Chemistry ◽

10.3390/chemistry3010015 ◽

2021 ◽

Vol 3 (1) ◽

pp. 182-198

Author(s):

Dalila Rocco ◽

Samantha Novak ◽

Alessandro Prescimone ◽

Edwin C. Constable ◽

Catherine E. Housecroft

Keyword(s):

Single Crystal ◽

Crystal Structures ◽

Metal Binding ◽

Polymer Chains ◽

X Ray Diffraction ◽

Face To Face ◽

Single Crystal Structures ◽

Π Stacking ◽

Metal Binding Domain ◽

Packing Interactions

We report the preparation and characterization of 4′-([1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (1), 4′-(4′-fluoro-[1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (2), 4′-(4′-chloro-[1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (3), 4′-(4′-bromo-[1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (4), and 4′-(4′-methyl-[1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (5), and their reactions with copper(II) acetate. Single-crystal structures of the [Cu2(μ-OAc)4L]n 1D-coordination polymers with L = 1–5 have been determined, and powder X-ray diffraction confirms that the single crystal structures are representative of the bulk samples. [Cu2(μ-OAc)4(1)]n and [Cu2(μ-OAc)4(2)]n are isostructural, and zigzag polymer chains are present which engage in π-stacking interactions between [1,1′-biphenyl]pyridine units. 1D-chains nest into one another to give 2D-sheets; replacing the peripheral H in 1 by an F substituent in 2 has no effect on the solid-state structure, indicating that bifurcated contacts (H...H for 1 or H...F for 2) are only secondary packing interactions. Upon going from [Cu2(μ-OAc)4(1)]n and [Cu2(μ-OAc)4(2)]n to [Cu2(μ-OAc)4(3)]n, [Cu2(μ-OAc)4(4)]n, and [Cu2(μ-OAc)4(5)]n·nMeOH, the increased steric demands of the Cl, Br, or Me substituent induces a switch in the conformation of the 3,2′:6′,3″-tpy metal-binding domain, and a concomitant change in dominant packing interactions to py–py and py–biphenyl face-to-face π-stacking. The study underlines how the 3,2′:6′,3″-tpy domain can adapt to different steric demands of substituents through its conformational flexibility.

Download Full-text

In-situ X-ray tomography investigation of pore damage effects during a tensile test of a Ni-based single crystal superalloy

Materials Characterization ◽

10.1016/j.matchar.2021.111180 ◽

2021 ◽

pp. 111180

Author(s):

Keli Liu ◽

Junsheng Wang ◽

Bing Wang ◽

Pengcheng Mao ◽

Yanhong Yang ◽

...

Keyword(s):

Tensile Test ◽

Single Crystal ◽

Single Crystal Superalloy ◽

X Ray

Download Full-text

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies

Acta Haematologica ◽

10.1159/000500229 ◽

2019 ◽

Vol 143 (1) ◽

pp. 73-77

Author(s):

Anat Gafter-Gvili ◽

Ariadna Tibau ◽

Pia Raanani ◽

Daniel Shepshelovich

Keyword(s):

Hematological Malignancies ◽

New Drugs ◽

Priority Review ◽

Regulatory Review ◽

Regulatory Pathways ◽

The Us ◽

Black Box Warnings ◽

Accelerated Approval ◽

Drug Approvals ◽

Approved Drugs

The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115–316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.

Download Full-text

Crack Propagation Behavior of a Ni-Based Single-Crystal Superalloy during In Situ SEM Tensile Test at 1000 °C

Crystals ◽

10.3390/cryst10111047 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1047

Author(s):

Wenxiang Jiang ◽

Xiaoyi Ren ◽

Jinghao Zhao ◽

Jianli Zhou ◽

Jinyao Ma ◽

...

Keyword(s):

Crack Propagation ◽

Tensile Test ◽

Single Crystal ◽

Crack Propagation Rate ◽

Propagation Rate ◽

Single Crystal Superalloy ◽

Propagation Path ◽

Propagation Behavior ◽

Crack Propagation Behavior

An in situ scanning electron microscope (SEM) tensile test for Ni-based single-crystal superalloy was carried out at 1000 °C. The stress displacement was obtained, and the yield strength and tensile strength of the superalloy were 699 MPa and 826 MPa, respectively. The crack propagation process, consisting of Model I crack and crystallographic shearing crack, was determined. More interestingly, the crack propagation path and rate affected by eutectics was directly observed and counted. Results show that the coalescence of the primary crack and second microcrack at the interface of a γ/γ′ matrix and eutectics would make the crack propagation rate increase from 0.3 μm/s to 0.4 μm/s. On the other hand, crack deflection decreased the rate to 0.05 μm/s. Moreover, movement of dislocations in front of the crack was also analyzed to explain the different crack propagation behavior in the superalloy.

Download Full-text

On The Optimized Nucleation of Near-Single-Crystal Cvd Diamond Film

MRS Proceedings ◽

10.1557/proc-416-81 ◽

1995 ◽

Vol 416 ◽

Cited By ~ 2

Author(s):

L. C. Chen ◽

C. C. Juan ◽

J. Y. Wu ◽

K. H. Chen ◽

J. W. Teng

Keyword(s):

Single Crystal ◽

Photoelectron Spectroscopy ◽

Morphological Evolution ◽

Present Report ◽

Ex Situ ◽

Nucleation Density ◽

Induced Current ◽

Current Time ◽

Single Crystal Diamond

ABSTRACTNear-single-crystal diamond films have been obtained in a number of laboratories recently. The optimization of nucleation density by using a bias-enhanced nucleation (BEN) method is believed to be a critical step. However, the condition of optimized nucleation has never been clearly delineated. In the present report, a novel quantitative technique was established to monitor the nucleation of diamond in-situ. Specifically, the induced current was measured as a function of nucleation time during BEN. The timedependence of induced current was studied under various methane concentrations as well as substrate temperatures. The optimized nucleation condition can be unambiguously determined from the current-time plot. Besides the in-situ current probe, ex-situ x-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were also used to investigate the chemical and morphological evolution. Characteristic XPS and AFM features of optimized nucleation is discussed.

Download Full-text

Cellulose organic solvents: V. Conformational aspects of N,N-dimethyl ethanolamine N-oxide in its crystalline and diluted states

Canadian Journal of Chemistry ◽

10.1139/v84-002 ◽

1984 ◽

Vol 62 (1) ◽

pp. 6-10 ◽

Cited By ~ 7

Author(s):

E. R. Maia ◽

A. Péguy ◽

S. Pérez

Keyword(s):

Tertiary Amine ◽

Amine Oxide ◽

Direct Methods ◽

Monoclinic Space Group ◽

Cyclic Form ◽

Asymmetric Unit ◽

Ir And Nmr Spectroscopy ◽

Conformational Investigation ◽

Intramolecular Hydrogen ◽

Strong Intramolecular Hydrogen Bond

N,N-Dimethyl ethanolamine N-oxide (DMEAO) belongs to the class of tertiary amine oxide molecules that are good solvents for cellulose, although not being cyclic. Crystallographic investigation shows that anhydrous DMEAO is monoclinic, space group Cc, a = 25.725(9), b = 7.023(4), c = 9.483(5) Å, β = 101.16(10)°, Z = 12. The crystal structure has been solved by direct methods and refined to a final R value of 0.063 for 575 observed reflexions. Three independent molecules are found within the asymmetric unit; one of these displays a pseudo-cyclic form dictated by the occurrence of a strong intramolecular hydrogen bond. Conformational investigation of DMEAO in solution, using ir and nmr spectroscopy shows that this pseudo-cyclic form is more likely to occur in diluted states. These findings are related to the ability of this tertiary amine oxide to act as a good solvent, up to a water content of one water molecule per DMEAO molecule.

Download Full-text