Features of Corporate Liability for Violation of Competition Law

The relevance of the study is determined by the need to establish corporate responsibility for breach of legislation. In this regard, this paper is aimed at identifying features of competition and corporate responsibility for breach of competition law. Particular attention is drawn to the case when corporations become monopolists and, in fact, dictate market rules. Consideration of the development aspect of competition law suggests that it largely limits the growth of corporate business and forces corporations to formulate strategies for splitting the business, thereby determining the conduct of business. In the modern world, where business is in many respects globalised, such measures can lead to a decrease in market indicators and form a dependence on the operations of certain corporations in the local market. The leading method to the study of this issue is the modelling method, which allows to consider this problem as a targeted and organised procedure related to the improvement and application of competition law, as well as the protection and development of competition. The novelty of the study lies in the possibility of limiting the activities of a corporation in a market that is occupied by it and where there is no practical competition. The authors consider the mechanism of self-regulation as a source of domestic competition law. The paper determines that self-regulation processes are also subject to state supervision and thus corporate self-regulation becomes an aspect of the regulation of competition enforcement by the state at large. The practical significance of the study is determined by the structural feature of the corporation as a quasi-state mechanism and the regulation of external relations between the state and corporations as tax residents on this basis

Donor-acceptor stacking arrangements in bulk and thin-film high-mobility conjugated polymers characterized using molecular modelling and MAS and surface-enhanced solid-state NMR spectroscopy

Conjugated polymers show promising properties as cheap, sustainable and solution-processable semiconductors. A key challenge in the development of these materials is to determine the polymer chain structure, conformation and packing in both the bulk polymer and in thin films typically used in devices. However, many characterisation techniques are unable to provide atomic-level structural information owing to the presence of disorder. Here, we use molecular modelling, magic-angle spinning (MAS) and dynamic nuclear polarisation surface-enhanced NMR spectroscopy (DNP SENS) to characterise the polymer backbone group conformations and packing arrangement in the high-mobility donor-acceptor copolymer diketopyrrolo-pyrrole-dithienylthieno[3,2-b] thiophene (DPP-DTT). Using conventional H-1 and C-13 solid-state MAS NMR coupled with density functional theory calculations and molecular dynamics simulations, we find that the bulk polymer adopts a highly planar backbone conformation with a laterally-shifted donor-on-acceptor stacking arrangement. DNP SENS enables acquisition of C-13 NMR data for polymer films, where sensitivity is limiting owing to small sample volumes. The DNP signal enhancement enables a two-dimensional H-1-C-13 HETCOR spectrum to be recorded for a drop-cast polymer film, and a C-13 CPMAS NMR spectrum to be recorded for a spin-coated thin-film with a thickness of only 400 nm. The results show that the same planar backbone structure and intermolecular stacking arrangement is preserved in the films following solution processing and annealing, thereby rationalizing the favourable device properties of DPP-DTT, and providing a protocol for the study of other thin film materials

Ітеративне використання великих хімічних просторів у пошуку лікарських засобів

Aim. To demonstrate the advantages of large-scale virtual libraries generated using chemical protocols previously validated in primary steps of the drug discovery process.Results and discussion. Two validated parallel chemistry protocols reported earlier were used to create the chemical space. It was then sampled based on diversity metric, and the sample was subjected to the virtual screening on BRD4 target. Hits of virtual screening were synthesized and tested in the thermal shift assay.Experimental part. The chemical space was generated using commercially available building blocks and synthetic protocols suitable for parallel chemistry and previously reported. After narrowing it down, using MedChem filters, the resulting sub-space was clustered based on diversity metrics. Centroids of the clusters were put to the virtual screening against the BRD4 active center. 29 Hits from the docking were synthesized and subjected to the thermal shift assay with BRD4, and 2 compounds showed noticeable dTm.Conclusions. A combination of cheminformatics and molecular docking was applied to find novel potential binders for BRD4 from a large chemical space. The selected set of predicted molecules was synthesized with a 72 % success rate and tested in a thermal shift assay to reveal a 6 % hit rate. The selection can be performed iteratively to fast support of the drug discovery.Мета. Продемонструвати переваги віртуальних бібліотек великого розміру, згенерованих за валідованими раніше хімічними протоколами, на перших етапах пошуку лікарських засобів.Результати та їх обговорення. На основі двох валідованих методів синтезу, придатних для паралельної хімії, описаних раніше, було створено хімічний простір. На основі різноманітності з одержаної віртуальної бібліотеки зроблено вибірку, яку було піддано віртуальному скринінгу щодо активного центру білка BRD4. Хіти віртуального скринінгу було синтезовано й перевірено за допомогою диференційної сканувальної калориметрії.Експериментальна частина. На основі комерційно доступних вихідних реагентів та раніше репрезентованих синтетичних протоколів, придатних для паралельної хімії, згенеровано хімічний простір. Простір було зменшено за рахунок застосування медхімічних фільтрів; результатний підпростір було кластеризовано за критерієм різноманітності. Центроїди кластерів було піддано молекулярному докінгу щодо активного центру білка BRD4. Базуючись на результатах проведеного докінгу, синтезовано 29 хітів, які було піддано диференційній сканувальній калориметрії з білком BRD4; з цим 2 сполуки продемонстрували помітний зсув точки топлення.Висновки. Для пошуку нових потенційних лігандів BRD4 у великому хімічному просторі було застосовано комбінацію хемоінформатики і молекулярного докінгу. Набір молекул, що мали високу передбачену активність, було синтезовано з успішністю 72 %. Серед синтезованих сполук виявлено первинні хіти (6 % сполук). Подібний процес можна повторювати ітеративно для швидкої підтримки розроблення ліків

When yield prediction does not yield prediction: an overview of the current challenges

Machine Learning techniques face significant challenges when predicting advanced chemical properties, such as yield, feasibility of chemical synthesis, and optimal reaction conditions. These challenges stem from the high-dimensional nature of the prediction task and the myriad essential variables involved, ranging from reactants and reagents to catalysts, temperature, and purification processes. Successfully developing a reliable predictive model not only holds potential for optimizing High-Throughput experiments but can also elevate existing retrosynthetic predictive approaches and bolster a plethora of applications within the field. In this review, we systematically evaluate the efficacy of current ML methodologies in chemoinformatics, shedding light on their milestones and inherent limitations. Additionally, a detailed examination of a representative case study provides insights into prevailing issues related to data availability and transferability in the discipline

An NMR crystallography DFT-D approach to analyse the role of intermolecular hydrogen bonding and π–π interactions in driving cocrystallisation of indomethacin and nicotinamide

Density functional theory (DFT) calculations using the Perdew–Burke–Ernzerhof (PBE) exchange-correlation functional are presented for a 1 : 1 cocrystal formed by indomethacin and nicotinamide (IND-NIC) as well as for crystal structures of the individual components. DFT-D approaches which correct the DFT energy for dispersion effects, specifically the Grimme (G06) and Tkatchenko–Scheffler (TS) schemes, are investigated: for geometry optimisation starting with crystal structures determined experimentally by diffraction and allowing the atomic positions and the unit cell to vary, closest agreement with the experimental unit cell parameters is achieved with the PBE-TS approach (calculated volumes are less than 4% smaller than in experiment). Calculations of solid-state NMR chemical shifts using the GIPAW (gauge including projector augmented wave) approach are presented. Closest agreement between NMR chemical shifts calculated with variable and fixed (experimental) unit cell parameters is also observed for the PBE-TS approach: the root mean squared standard deviation difference is 0.15 ppm (1H) and 0.29 ppm (13C) for PBE-TS, as compared to 0.45 ppm (1H) and 0.68 ppm (13C) with standard PBE. Differences in 1H chemical shifts calculated for the full periodic crystal structure and for isolated molecules extracted from the geometry-optimised crystal structure are presented in conjunction with NICS (nucleus independent chemical shift) maps, so as to separately quantify intermolecular hydrogen bonding and π–π interactions. This analysis is complemented by total energy calculations, including also at the B97D/6-311+G* level of theory with basis set superposition error correction, in order to understand the interactions that drive cocrystallisation

Topological behavior mimicking ethylene–hexene copolymers using branched lactones and macrolactones

A new approach towards polyolefin-like copolyesters is introduced based on a single set of reaction conditions. The delicate balance between steric hindrance and monomer reactivity determines whether random or block copolymers are formed

Unraveling Unprecedented Charge Carrier Mobility through Structure Property Relationship of Four Isomers of C12-BTBT

info:eu-repo/semantics/nonPublishe

Virtual Screening in Search for a Chemical Probe for Angiotensin-Converting Enzyme 2 (ACE2)

We elaborate new models for ACE and ACE2 receptors with an excellent prediction power compared to previous models. We propose promising workflows for working with huge compound collections, thereby enabling us to discover optimized protocols for virtual screening management. The efficacy of elaborated roadmaps is demonstrated through the cost-effective molecular docking of 1.4 billion compounds. Savings of up to 10-fold in CPU time are demonstrated. These developments allowed us to evaluate ACE2/ACE selectivity in silico, which is a crucial checkpoint for developing chemical probes for ACE2

Rotator side chains trigger cooperative transition for shape and function memory effect in organic semiconductors

Martensitic transition is commonly seen in steel and shape memory alloys but rarely in organic materials. Chung et al. discover martensitic transitions in organic electronics and utilize it in designing field-effect transistors, leading to shape memory effect that in return modifies charge transport properties