It is demonstrated that the fluid-phase thermodynamics theory conductor-like screening model for real solvents (COSMO-RS) as implemented in the COSMOtherm software can be used for accurate and ...efficient screening of coformers for active pharmaceutical ingredient (API) cocrystallization. The excess enthalpy, Hex, between an API–coformer mixture relative to the pure components reflects the tendency of those two compounds to cocrystallize. Thus, predictive calculations may be performed with decent effort on a large set of molecular data in order to identify potentially new cocrystal systems. In addition, it is demonstrated that COSMO-RS theory allows reasonable ranking of coformers for API solubility improvement. As a result, experiments may be focused on those coformers, which have an increased probability of cocrystallization, leading to the largest improvement of the API solubility. In a similar way as potential coformers are identified for cocrystallization, solvents that do not tend to form solvates may be determined based on the highest Hexs with the API. The approach was successfully tested on tyrosine kinase inhibitor axitinib, which has a propensity to form relatively stable solvated structures with the majority of common solvents, as well as on thiophanate-methyl and thiophanate-ethyl benzimidazole fungicides, which form channel solvates.
The reactions between catechol (H
cat) and niobium(V) or tantalum(V) precursors in basic aqueous solutions lead to the formation of catecholate complexes of different natures. The following complexes ...were isolated and characterized by single-crystal X-ray diffraction (SCXRD): (
) (NH
)
NbO(cat)
∙4H
O; (
) K
Nb(cat)
(Hcat)·2H
cat·2H
O; (
) Cs
NbO(cat)
·H
O; (
) (NH
)
Ta
O(cat)
·3H
O; (
) Cs
Ta(cat)
(Hcat)·H
cat; (
) Cs
Ta
O(cat)
·7H
O. The isolated crystalline products were characterized by elemental analysis, X-ray powder diffraction (XRPD), FTIR, and TGA. The structural features of these complexes, such as {Ta
O} unit geometry, Cs-π interactions, and crystal packing effects, are discussed.
Devices for direct measurement of the plasma potential and floating potential in the gas discharge in a reactive ion–plasma etching system are presented. The action of the devices developed for this ...purpose is based on the creation of a local magnetic field that makes it possible to purposefully change the conditions of ambipolar diffusion of charged particles. This allows the contact of the probe with the body of the positive plasma column without the appearance of floating potential on it. The results of measuring the plasma potential by the proposed and alternative methods are compared.
The Pd(II) complexes Pd(Cp)(L)
BF
were synthesized via the reaction of cationic acetylacetonate complexes with cyclopentadiene in the presence of BF
∙OEt
(
= 2,
= 1: L = PPh
(
), P(
-Tol)
,
(
...-methoxyphenyl)phosphine (TOMPP),
-2-furylphosphine,
-2-thienylphosphine;
= 1,
= 1: L = dppf, dppp (
), dppb (
), 1,5-bis(diphenylphosphino)pentane;
= 1,
= 2 or 3: 1,6-bis(diphenylphosphino)hexane). Complexes
-
were characterized using X-ray diffractometry. The inspection of the crystal structures of the complexes enabled the recognition of (Cp
)⋯(Ph-group) and (Cp
)⋯(CH
-group) interactions, which are of C-H…π nature. The presence of these interactions was confirmed theoretically via DFT calculations using QTAIM analysis. The intermolecular interactions in the X-ray structures are non-covalent in origin with an estimated energy of 0.3-1.6 kcal/mol. The cationic palladium catalyst precursors with monophosphines were found to be active catalysts for the telomerization of 1,3-butadiene with methanol (
up to 2.4∙10
mol 1,3-butadiene per mol Pd with chemoselectivity of 82%). Complex Pd(Cp)(TOMPP)
BF
was found to be an efficient catalyst for the polymerization of phenylacetylene (PA) (catalyst activities up to 8.9 × 10
g
·(mol
·h)
were observed).
Reactive oxygen species in status epilepticus Shekh-Ahmad, T.; Kovac, S.; Abramov, A.Y. ...
Epilepsy & behavior,
December 2019, 2019-12-00, 20191201, Letnik:
101, Številka:
Pt B
Journal Article
Recenzirano
Odprti dostop
There has been growing evidence for a critical role of oxidative stress in neurodegenerative disease, providing novel targets for disease modifying treatments. Although antioxidants have been ...suggested and tried in the treatment of epilepsy, it is only recently that the pivotal role of oxidative stress in the pathophysiology of status epilepticus has been recognized. Although conventionally thought to be generated by mitochondria, reactive oxygen species during status epilepticus and prolonged seizure are generated mainly by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (stimulated by NMDA receptor activation). Excessive production of reactive oxygen species results in lipid peroxidation, DNA damage, enzyme inhibition, and mitochondrial damage, culminating in neuronal death. Antioxidant therapy has been hampered by poor CNS penetration and rapid consumption by oxidants. However, alternative approaches such as inhibiting NADPH oxidase or increasing endogenous antioxidant defenses through activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) could avoid these problems. Small molecules that increase Nrf2 activation have proven to be not only effective neuroprotectants following status epilepticus, but also potently antiepileptogenic. There are “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures”.
•There is substantial evidence that reactive oxygen species are generated during and after status epilepticus.•There is growing evidence that the main source of reactive oxygen species in status epilepticus is not mitochondria but rather a plasma membrane-bound enzyme, NAPH oxidase.•Reactive oxygen species significantly contribute to mitochondrial failure and neuronal death during and following status epilepticus.•Promoting the production of endogenous antioxidants through activation of the transcription factor, Nrf2, not only neuroprotects, but also potently decreases the frequency of spontaneous seizures following status epilepticus.
This article considers a method for measuring the surface microrelief parameters of machine parts via optoelectronic and computer means, which is an integral part of the technological process of ...manufacturing machine parts with precision surfaces. This method is based on the computer processing of images of studied microreliefs, considered as a set of implementations of a stationary random process. The number of implementations of this process is assumed to be equal to the number of lines in the analyzed microrelief image. The microrelief image is considered a matrix of random numbers. For this matrix, mathematical expectations, variances, standard deviations, correlation moments, and the normalized autocorrelation coefficient for the matrix columns were calculated. To evaluate the proposed method, an optical-electronic complex was used, comprising an instrumental microscope with a video camera and a computer for digital processing of the obtained microrelief images of reference samples with different roughness. The surface roughness
Ra
was estimated using standard methods on a profilometer ranging from 0.025 µm to 0.13 µm. For correlation-spectral image processing, software was created in C++ using OpenCV tools. The results established that the parameters of the studied microreliefs largely determine the nature of the correlation functions. To identify the studied microreliefs, we determined the analytical dependencies of
Ra
on the average value of the variable component of the autocorrelation function and on its spectral density values. It has been established that the most promising optoelectronic approach to measuring the
Ra
of microrelief is to use the spectral density of its autocorrelation function, calculated from its halftone image. The results for the surface microrelief parameters of the inner ring raceways of instrument bearings are presented. These results are relevant for noncontact measurements of the roughness of industrial products in various branches of mechanical engineering.
Thermal state of permafrost in Russia Romanovsky, V. E.; Drozdov, D. S.; Oberman, N. G. ...
Permafrost and periglacial processes,
April/June 2010, Letnik:
21, Številka:
2
Journal Article
One of the most popular strategies of the optimization of drug properties in the pharmaceutical industry appears to be a solid form changing into a cocrystalline form. A number of virtual screening ...approaches have been previously developed to allow a selection of the most promising cocrystal formers (coformers) for an experimental follow-up. A significant drawback of those methods is related to the lack of accounting for the crystallinity contribution to cocrystal formation. To address this issue, we propose in this study two virtual coformer screening approaches based on a modern cloud-computing crystal structure prediction (CSP) technology at a dispersion-corrected density functional theory (DFT-D) level. The CSP-based methods were for the first time validated on challenging cases of indomethacin and paracetamol cocrystallization, for which the previously developed approaches provided poor predictions. The calculations demonstrated a dramatic improvement of the virtual coformer screening performance relative to the other methods. It is demonstrated that the crystallinity contribution to the formation of paracetamol and indomethacin cocrystals is a dominant one and, therefore, should not be ignored in the virtual screening calculations. Our results encourage a broad utilization of the proposed CSP-based technology in the pharmaceutical industry as the only virtual coformer screening method that directly accounts for the crystallinity contribution.
Drug formulations of anhydrous solid forms are generally preferred over hydrated forms. This is due to the risks of low exposure and unacceptable physical and chemical stability in comparison with ...anhydrous formulations. The purpose of the current study was to determine which descriptors can be most efficiently applied to virtual screening in order to provide answers to the following questions: 1) what is the propensity to form a solid state hydrate of a pharmaceutical compound, and 2) in regards to cocrystalline formulation, which coformer would provide for the highest stability with respect to relative humidity (RH) conditions? A number of properties of different complexity were tested to provide answers to these questions, including COSMO-RS excess free energy
G
ex
and enthalpy
H
ex
of hydration of the compound in amorphous state; octanol-water partition coefficient
c
log
P
; polar surface area TPSA; different combinations of molecular H-bond donor and acceptor counts; an excess enthalpy of API (active pharmaceutical ingredient)-coformer mixing; and coformer solubilities. It was demonstrated that the
G
ex
property provides the most efficient way of virtual screening of hydration propensity of solid pharmaceutical compounds. It was also demonstrated that a virtual coformer screening based on the API coformer miscibility, as measured by the COSMO-RS
H
ex
property, may be efficiently used to guide the experimental selection of coformers which have an increased probability of cocrystallization and provide the highest RH stability.
The descriptors were determined, which can be most efficiently applied to virtual screening in order to provide answers to the following questions: 1) what is the propensity to form a solid state hydrate of a pharmaceutical compound, and 2) which coformer would provide for the highest stability with respect to relative humidity conditions?
The paper is devoted to the current state and development plans of the monitoring and control system of the National Research Computer Network of Russia (NIKS). Some aspects of industry standards, ...best practice-based procedures and methodologies for network management, including FCAPS, eTOM, ITIL are briefly discussed. An overview of collaborative National Research and Education Networks (NRENs) experience in network monitoring and management is given, key functions of Network Operations Centers and examples of commercial and free program solutions used in real practice are provided. A general architecture and individual components of the monitoring and control system of NIKS taking into account the planned modernization are presented.
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