Analysis of the conformational profiles of fenamates shows route towards novel, higher accuracy, force-fields for pharmaceuticals

In traditional molecular mechanics force fields, intramolecular non-bonded interactions are modelled as intermolecular interactions, and the form of the torsion potential is based on the conformational profiles of small organic molecules. We investigate how a separate model for the intramolecular forces in pharmaceuticals could be more realistic by analysing the low barrier to rotation of the phenyl ring in the fenamates (substituted N-phenyl-aminobenzoic acids), that results in a wide range of observed angles in the numerous fenamate crystal structures. Although the conformational energy changes by significantly less than 10 kJmol-1 for a complete rotation of the phenyl ring for fenamic acid, the barrier is only small because of small correlated changes in the other bond and torsion angles. The maxima for conformations where the two aromatic rings approach coplanarity arise from steric repulsion, but the maxima when the two rings are approximately perpendicular arise from a combination of an electronic effect and intramolecular dispersion. Representing the ab initio conformational energy profiles as a cosine series alone is ineffective; however, combining a cos2ξ term to represent the electronic barrier with an intramolecular atom-atom exp-6 term for all atom pairs separated by three or more bonds (1-4 interactions) provides a very effective representation. Thus we propose a new, physically motivated, generic analytical model of conformational energy, which could be combined with an intermolecular model to form more accurate force-fields for modelling the condensed phases of pharmaceutical-like organic molecules

Picking out polymorphs: H-bond prediction and crystal structure stability

A methodology has been developed to predict the propensity for hydrogen bonds to form in crystal structures, treating each potential H-bond as a binary response variable, and modelling its likelihood using a set of relevant chemical descriptors [1]. Modelling is tailored to a target using chemically similar known structures, from e.g. the Cambridge Structural Database [2], making it accessible to the complete spectrum of organic structures, including solvates, hydrates and cocrystals. Recent work has developed the approach to predicting interand intramolecular H-bonds when either type can occur. By way of a comparison between possible and observed H-bonds, the method has been applied to assess structural stability, which shows much promise in the domain of polymorph screening in the pharmaceutical industry. We will introduce the methodology and illustrate its application using a selection of pharmaceutical compounds, one of which will be Abbott’s wellpublicised anti-HIV medication ritonavir (Norvir™). Owing to a hidden, more stable form II with much lower bioavailability, ritonavir was temporarily withdrawn from the market with significant financial impact [3]. Our method quickly suggests a real threat of polymorphism in this compound, and strongly supports the relative stability of form II over form I. For all examples, the high predictivity of the method is emphasised

Modeling of Microwave Absorption Mechanisms in Metallic Powders

The microwave processing in powder metallurgy has only been under focus since the pioneering work of Roy and coworkers in 1999. The combination of the electromagnetic simulations using the Finite Integration Technique (FIT) and the extraction of effective properties can be used with success in the field of material science. The simulations over a wide range of frequency show a resonant behavior in the effective magnetic permeability of copper powders. The resonance frequency depends on the particle size and the conductivity of the material

The Application of Leadership in the Army of the Czech Republic

Předkládaná diplomová práce se zabývá aplikací koncepce leadershipu v Armádě České republiky. Vymezuje pojem vedení lidí a důležitost jeho implementace v prostředí Armády České republiky. Cílem diplomové práce je navrhnout změny ve vztazích a komunikaci nadřízený-podřízený v oblasti vedení lidí v Armádě České republiky. Ke splnění cíle je nutné zpracovat dostupnou zahraniční literaturu týkající se leadershipu v armádě. Dále dotazníkovým šetřením analyzovat současný stav leadershipu v Armádě České republiky.The following diploma thesis is dealing with the application of leadership in the Army of the Czech Republic. It defines the leadership and importance of its integration in the Czech Army environment. The diploma thesis contains employee’s current conditions evaluation and requirements in the field of HR Management. The questionnaire was used to acquire this information. Further, the diploma thesis suggests the changes in relationships and communication between superior and subordinates.

Zaangażowanie Sióstr Franciszkanek Misjonarek Maryi w ratowanie dzieci Zamojszczyzny przed zagładą w czasie okupacji niemieckiej

Wyższa Szkoła Zarządzania i Administracji w Zamościu9912

Traveling Poles Elimination Scheme And Calculations Of External Quality Factors Of HOMS In SC Cavities

The main scope of this work is the automation of the extraction procedure of the external quality factors Qext of Higher Order Modes HOMs in Superconducting SC radio frequency RF cavities. The HOMs are generated by charged particle beams traveling through a SC cavity at the speed of light amp; 8776; 1 . The HOMs decay very slowly, depending on localization inside the structure and cell to cell coupling, and may influence succeeding charged particle bunches. Thus it is important, at the SC cavity design optimization stage, to calculate the Qext of HOMs. Traveling Poles Elimination TPE scheme was used to automatically extract Qext from the transmission spectra and careful eigenmode analysis of the SC cavity was performed to confirm TPE results. The eigenmode analysis also delivers important information about band structure, cell to cell coupling and allows rapid identification of modes that could interact with the charged particle bunches

Photochemical study of a new bimolecular photoinitiating system for vat photopolymerization 3D printing techniques under visible light

In this work, we presented a new bimolecular photoinitiating system based on 2-amino-4,6-diphenylpyridine-3-carbonitrile derivatives as visible photosensitizers of diphenyliodonium salt. Real-time FTIR and photo-DSC photopolymerization experiments with a cycloaliphatic epoxide and vinyl monomers showed surprisingly good reactivity of the bimolecular photoinitiating systems under UV-A, as well as under visible light sources. Steady-state photolysis, fluorescence experiments, theoretical calculations of molecular orbitals, and electrochemical analysis demonstrated photo-redox behavior as well as the ability to form initiating species via photo-reduction or photo-oxidation pathways, respectively. Therefore, the 2-amino-4,6-diphenylpyridine-3-carbonitrile derivatives were also investigated as a type II free-radical photoinitiator with amine. It was confirmed that the 2-amino-4,6-diphenylpyridine-3-carbonitrile derivatives, in combination with different types of additives, e.g., amine as a co-initiator or the presence of onium salt, can act as bimolecular photoinitiating systems for cationic, free-radical, and thiol-ene photopolymerization processes by hydrogen abstraction and/or electron transfer reactions stimulated by either near-UV or visible light irradiation. Finally, the 2-amino-4,6-diphenylpyridine-3-carbonitrile derivatives were selected for 3D printing rapid prototyping experiments. Test objects were successfully printed using purely cationic photosensitive resin, created on a 3D printer with a visible LED light source

Microwave-assisted synthesis and spectroscopic properties of novel pyridine-based fluorescent molecular probes

[EN] Fluorescent molecular probes become interesting analytical tools in determination and labeling of chemical compounds and physical properties such as viscosity and polarity. Currently known fluorescent molecular probes can selectively and regardless of the environment detect only few molecules, and applicability in determination of micro- viscosity and micro-polarity are limited to narrow range and specific condition, therefore design and synthesis of novel molecular probes with extended range of operation are highly needed [1]. Traditional synthesis of 2-amino-4,6-diphenyl-pyridine-3-carbonitrile’s requires two step reaction with long heating time or and toxic solvent. By application of microwave irradiation, reaction time can be firmly shortened with the same or higher efficiency [2]. Derivatives of 2-amino-4,6-diphenyl-pyridine-3-carbonitrile can find application in different fields of science. Depending on the structure of fluorophore, those compounds exhibit high sensitivity to changes in polarity and viscosity of environment, also concentration of specific cations, and pH can be determined by measuring of fluorescence spectrum.The authors are grateful to the Foundation for Polish Science (Warsaw, Poland) - Project REINTEGRATION (Contract No. REINTEGRATION/2016-1/4 – “Synthesis and photochemistry/photophysics studies of the intelligent luminescent molecular sensors for selective detection in biochemistry and chemistry”) for financial support of the FPT research. The authors also acknowledge the support of the PROM programme no. PPI/PRO/2018/1/00013/U/001 which is co-financed by the European Social Fund under the Knowledge Education Development Operational Programme.http://ocs.editorial.upv.es/index.php/AMPERE2019/AMPERE2019Fiedor, P.; Ortyl, J.; Galek, M. (2019). Microwave-assisted synthesis and spectroscopic properties of novel pyridine-based fluorescent molecular probes. Editorial Universitat Politècnica de València. 394-400. https://doi.org/10.4995/AMPERE2019.2019.9829OCS39440