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Данная работа предполагает разработку методики анализа остаточных органических растворителей (ООР) в субстанциях натрия 3,8-диэтоксикарбонил-4-оксо-4Н-пиразоло[5,1-c][1,2,4]триазинид моногидрата (AB-19) и натрия 7-метилтио-4-оксо-3-циано-4Н-[1,2,4]триазоло[5,1-c][1,2,4]триазинида тригидрата (MNR-857). Анализ литературных данных показал, что наиболее предпочтительным методом определения ООР является метод газожидкостной хроматографии с парофазным вводом пробы. Для определения целевых аналитов в исследуемых субстанциях рассмотрены схемы синтеза и строение соединений, и определено, что образцы могут содержать органические растворители II (гексан, пиридин, метанол) и III (этанол, этилацетат, 2-пропанол) классов опасности. Однако опытные данные показали наличие в образцах субстанций только этанола и пропан-2-ола. В связи с этим проводили количественное определение только указанных растворителей. На основе литературных данных были определены исходные условия проведения хроматографического анализа. На практике исходная методика была скорректирована: изменение массы навески, разведения образца, времени выдерживания виалы, установление диапазона концентраций применения методики и метода количественного определения. Разработанную методику анализа подвергали испытаниям на пригодность по таким показателям как специфичность, линейность, предел количественного определения, сходимость, промежуточная прецизионность и правильность. Согласно проведенным исследованиям была доказана достоверность и надежность получаемых с использованием данной методики результатов. Количественное определение ООР с помощью разработанной методики в образцах субстанций AB-19 (3 партии синтеза) и MNR-857 (5 партий синтеза) подтвердило их соответствие требованиям ОФС.1.1.0008.15 по показателю остаточные органические растворители (не более 0,5 % для растворителей III класса опасности). / This paper discusses the development of a method for assay of residual organic solvents in substances in substances such as sodium 3,8-diethoxycarbonyl-4-oxo-4H-pyrazolo[5,1-c][1,2,4]triazinide monohydrate (AB-19) and sodium 7-methylthio-4-oxo-3-cyano-4H-[1,2,4]triazolo[5,1-c][1,2,4]triazinide trihydrate (MNR-857). An analysis of the literature data showed that the most preferred method for determining residual organic solvents is headspace gas-liquid chromatography. To determine the target analytes in the studied substances, synthesis schemes and the structure of compounds are considered. Thanks to this, it was decided that the samples might contain organic solvents of hazard classes II and III. Class II includes hexane, pyridine, methanol, and сlass III includes ethanol, ethyl acetate, 2-propanol. However, experimental data showed the presence of only ethanol and propan-2-ol in the samples of substances. In this regard, an assay was carried out only for these two solvents. Based on literature data, the initial conditions for the chromatographic analysis were determined. The original method was adjusted by changing the test portion of sample, diluting the samples, the holdup time of the vial, as well as by establishing ranges of concentrations and the method of quantitative measurement. The developed analysis method was tested for suitability by such indicators as specificity, linearity, limit of quantification, repeatability, intermediate precision, and accuracy. According to the research, it was demonstrated that the analytical technique is acceptable for solving the task. The residual organic solvents were quantified using the developed procedure for three batches of synthesis of substance AB-19 and for five batches of synthesis of substance MNR-857. The percentage of residual organic solvents in all samples was less than 0.5%. Thus, the results obtained satisfy the requirements of the article OFS.1.1.0008.15 of the State Pharmacopoeia of the Russian Federation in terms of residual organic solvents.

The method of using stimulated reductive dechlorination when remediating sites contaminated with chlorinated solvents is not unusual, but not many studies have been done on the overall process outside of a controlled environment. In order to investigate the process, principal component analysis (PCA) and partial least square (PLS) regression was used to identify the most important parameters for the degradation of the chlorinated solvents. The most important parameter for all chlorinated compounds turned out to be oxygen, with levels of degradation products increasing with decreasing levels of dissolved oxygen. Dissolved oxygen was deemed the most important variable to measure during a control program on the site. The degradation dynamics of the process were investigated to examine the behaviour of the chlorinated solvents and their degradation products. The degradation products of the main contaminant TCE were found in all observation points, which indicates an ongoing reductive dechlorination all over the site. A large amount of the mother product, TCE, was found in two observation points, which were believed to be situated close to the sources of the TCE contamination. Over the observation period of 2,5 years the levels of TCE in the source areas decreased significantly to below the remediation goal. However, the levels of TCE increased in another observation point further downstream, with concentrations still increasing at the end of this study. The levels in this point were lower than those measured initially in the source area, but still much higher than the accepted values. Possible reasons for this appearance of TCE could be an isolated sheet of contaminants being pushed into the observation point from a nearby location or transport of the contaminants from the source area in units of higher conductivity such as sand lenses or fractures in the clayey soil. / Att använda stimulerad reduktiv deklorering som metod för att sanera fastigheter förorenade med klorerade lösningsmedel är inte ovanligt, men få studier har undersökt det övergripande saneringsförloppet utanför de kontrollerade förhållanden i en labbmiljö. För att undersöka nedbrytningsprocessen användes principalkomponentsanalys (PCA) och partial least square (PLS) regression i syfte att identifiera de parametrar som hade störst påverkan på nedbrytningen av de klorerade föroreningarna. Den enskilt viktigaste parametern visade sig vara halten löst syre i grundvattnet, då halterna av nedbrytningsprodukter ökade med minskande syrehalt. Därför ses syre som den viktigaste parametern för att följa förloppet och är den parameter som bör mätas i kontrollprogram över nedbrytningsprocessen.   Nedbrytningsdynamiken analyserades under en observationsperiod på 2,5 år för att studera hur de klorerade föroreningarna betedde sig under nedbrytningsförloppet. Nedbrytningsprodukter hittades i provtagningspunkter över hela fastigheten vilket visar på en pågående reduktiv deklorering. En stor mängd av moderprodukten TCE hittades i två punkter som bedömdes vara källor till TCE-spridningen. Under observationsperioden sjönk halterna av TCE i dessa två punkter till under gränsen för åtgärdsmålet, dock ökade koncentrationen av TCE i en annan provpunkt längre nedströms källområdet. Halterna i provpunkten var inte lika höga som de initiala halterna i källområdet, men de var långt högre än det fastställda åtgärdsmålen och ökade fortfarande när undersökningen avslutades. Möjliga förklaringar till varför halterna ökade i denna provpunkt är att ett sjok av TCE från omkringliggande sediment har transporterats till provpunkten, eller att en föroreningstransport har skett från källområdet via områden med högre konduktivitet i till exempel sandlinser eller sprickor.

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No / The purpose of this work was to explore NIR spectroscopy as a PAT tool to monitor the formation of ibuprofen and nicotinamide cocrystals during extrusion based solvent free continuous cocrystallization (SFCC). Drug and co-former were gravimetrically fed into a heated co-rotating twin screw extruder to form cocrystals. Real-time process monitoring was performed using a high temperature NIR probe in the extruder die to assess cocrystal content and subsequently compared to off-line powder X-ray diffraction measurements. The effect of processing variables, such as temperature and mixing intensity, on the extent of cocrystal formation was investigated. NIR spectroscopy was sensitive to cocrystal formation with the appearance of new peaks and peak shifts, particularly in the 4800-5200 cm(-1) wave-number region. PXRD confirmed an increased conversion of the mixture into cocrystal with increase in barrel temperature and screw mixing intensity. A decrease in screw rotation speed also provided improved cocrystal yield due to the material experiencing longer residence times within the process. A partial least squares analysis in this region of NIR spectrum correlated well with PXRD data, providing a best fit with cocrystal conversion when a limited range of process conditions were considered, for example a single set temperature. The study suggests that NIR spectroscopy could be used to monitor cocrystal purity on an industrial scale using this continuous, solvent-free process.

Brittleness of a polymeric material has a direct relationship with the material's performance and furthermore shares an inverse relationship with that material's flexibility. The concept of flexibility of materials has been understood but merely explained with a hand-waving manner. Thus, it has never been defined by a calculation, thereby lacking the ability to determine a definite quantitative value for this characteristic. Herein, an equation is presented and proven which makes determining the value of flexibility possible. Such an equation could be used to predict a material's flexibility prior to testing it, thus saving money and valuable time for those in research and in industry. Substantiating evidence showing the relationship between flexibility of polymers and their respective mechanical properties is presented. Further relating the known tensile properties of a given polymer to its flexibility is expanded upon by proving its relationship to the linear coefficient of thermal expansion for each polymer. Additionally, determining flexibility for polymers whose chemical structures have been compromised by respective solvents has also been investigated to predict a solvent's impact on a polymer after exposure. Polymers examined through literature include polycarbonate (PC), polystyrene (PS), teflon (PTFE), styrene acrylonitrile (SAN), acrylonitrile butadiene styrene (ABS), poly(ethersulfone) (PES), low density polyethylene (LDPE), polypropylene (PP), poly(methyl methacrylate) (PMMA), and poly(vinylidene fluoride) (PVDF). Further testing and confirmation was made using PC, PS, ABS, LDPE, PP, and PMMA.

The insertion of carbon dioxide into the Si–N bonds of aminodisilanes ((RR′N)nMe3–nSi)2 affords carbamoyloxydisilanes ((RR′NC(O)O)nMe3–nSi)2. Some of the obtained insertion products feature pentacoordinate silicon atoms in the solid state and in solution, with two carbamoyloxy moieties bridging the Si–Si bond. The aminodisilanes and their insertion products were extensively analyzed, including single-crystal X-ray structure analyses. The temperature dependence of the higher coordination was investigated using variable temperature NMR experiments.

<p>U slučajevima neuspe&scaron;ne endodontske terapije, neophodno je ponovno lečenje kanala korena. Ortogradni endodontski retretman podrazumeva uklanjanje postojećeg materijala za punjenje iz kanala uz dodatno či&scaron;ćenje, dezinfekciju i ponovnu finalnu opturaciju kanala. Važan korak u toku retretmana je &scaron;to potpunije uklanjanje postojećeg kanalnog punjenja kako bi se pristupilo svim delovima kanalnog sistema. Cilj doktorske teze bio je da se ispita kvalitet čis&scaron;ćenja zidova kanala korena nakon endodontskog retretmana pomoću skening elektronske mikroskopije (SEM). Posmatran je uticaj vrste materijala za opturaciju, uticaj upotrebe rastvarača i uticaj ručnih i ma&scaron;inskih instrumenata na količinu zaostalog materijala na zidovima kanala. Takođe, ispitan je uticaj ovih faktora na apikalnu transportaciju materijala i na vreme potrebno za retretman, a utvrđena je i učestalost o&scaron;tećenja kori&scaron;ćenih instrumenata. Materijal i metode: Ukupan uzorak činilo je 125 ekstrahovanih, humanih jednokorenih zuba. Nakon preparacije kanala korena, 120 zuba je podeljeno u dve grupe i napunjeno pomoću dva različita materijala za opturaciju (gutaperkom i resilonom). U zavisnosti od tehnike uklanjanja ovih materijala, grupe su dalje podeljene u odnosu na kori&scaron;ćene instrumente (Hedstrom, ProTaper i Twisted File) i u odnosu na upotrebu rastvarača (sa i bez hloroforma). Preostalih 5 zuba, bez kanalnog punjenja, kori&scaron;ćeni su kao kontrolna grupa. Nakon zavr&scaron;enog retretmana, korenovi su uzdužnim cepanjem razdvojeni, a odabrane polovine posmatrane na SEM-u. Mikrofotografije svake trećine kanala načinjene su pri uveličanju od 500x. Količina preostalog materijala za punjenje ocenjivana je pomoću skale. Otvoreni dentinski kanalići prebrojavani su na mikrofotografijama načinjenim pri uveličanju od 1000x, u odnosu na uvek konstantnu povr&scaron;inu. Rezultati: Analiza rezultata ukazala je na postojanje statistički značajne razlike u kvalitetu či&scaron;ćenja zidova kanala u zavisnosti od uklanjanog materijala za opturaciju. Kvalitet či&scaron;ćenja zidova kanala bio je veći nakon uklanjanja gutaperke nego nakon uklanjanja resilona. Rotirajućim, ma&scaron;inskim instrumentima je efikasnije uklanjana gutaperka, a ručnim Hedstrom turpijama je bolje uklanjan resilon. Posmatrajući ceo uzorak, ProTaper instrumenti ostavljali su velike količine materijala na zidovima kanala nakon endodontskog retretmana. Međutim, uklanjanje materijala pomoću ovih instrumenata bilo je najbrže. Primena rastvarača značajno je doprinela bržem uklanjanju materijala, dok uticaj na kvalitet či&scaron;ćenja zidova kanala nije bio značajan. Posmatrajući kanal korena po trećinama, najveća količina materijala nalazila se u apikalnoj trećini, bez obzira na vrstu uklanjanog materijala i kori&scaron;ćenih instrumenata, i bez obzira na upotrebu rastvarača tokom retretmana. Učestalost o&scaron;tećenja instrumenata bila je značajno veća prilikom upotrebe Twisted File instrumenata. Apikalna transportacija materijala je bila veća tokom uklanjanja resilon materijala i kada su kori&scaron;ćene ručne Hedstrom turpije. Zaključak: Kvalitet či&scaron;ćenja zidova kanala nakon uklanjanja gutaperke je veći nego nakon uklanjanja resilona. Dizajn i vrsta instrumenata utiče na kvalitet či&scaron;ćenja zidova kanala korena. Upotreba rastvarača tokom retretmana ne utiče značajno na smanjenje količine materijala zaostalog na zidovima kanala. Ma&scaron;inski pokretani instrumenti i upotreba rastvarača značajno skraćuju vreme potrebno za endodontski retretman.</p> / <p>In cases when endodontic treatment fails, it is necessary to retreat the root canal. Orthograde endodontic retreatment requires the removal of the existing root filling material with additional cleaning, disinfection and refilling of the canal. An important step during retreatment is complete removal of existing filling materials, to regain access to all parts of the canal system. The aim of the doctoral thesis was to investigate the cleanliness of root canal walls after removal of two different obturation material. The retreatment efficacy was observed depending on the usage of solvent and different hand or rotary instruments. The amount of residual material on the canal walls was assessed using scanning electron microscopy (SEM). Also, apical transportation of the obturation material, working time and frequency of instrument damage during retreatment was recorded. Materials and Methods: The total sample consisted of 125 extracted, single-rooted human teeth. After root canal preparation, 120 teeth were divided in two groups and filled using two different obturation materials (gutta-percha and resilon). Depending on the technique of removing these materials, the groups were further divided, in relation to the used instruments (Hedstrom, ProTaper and Twisted File), as well as in relation to the use of solvent (with or without chloroform). The remaining 5 tooth without canal filling were used as a control group. After root canal desopturation, the longitudinaly splitted root halves were observed on SEM. Microphotography of each third were made at magnification of 500x. The amount of remaining filling material was evaluated by using a scale. Open dentinal tubules were counted on microphotographies made at a magnificiation of 1000x, on a surface that was always constant. Results: Analysis of the results indicated a significant difference in the cleanliness of the canal walls depending on the used obturation material. Cleanliness of the canal walls was higher after gutta-percha removal than after the removal of resilon.&nbsp; Rotary instruments were more effective in removing gutta-percha and Hedstrom hand files better removed resilon. ProTaper instruments left more residual material on canal walls, however endodontic retreatment with these instruments was the fastest. The application of solvent significantly contributed to faster material removal, while the impact on the increase of canal cleanliness was not significant. The largest amount of material remained in the apical third, regardless of the type of material removed and instruments used, and also regardless whether solvent was used for retreatment. The frequency of instrument deformation and fracture was significantly higher when Twisted File instruments were used. Apical transportation of material had a significantly higher occurrence during resilon removal and when manual Hedstrom files were used. Conclusion: Cleanliness of the canal walls was higher after the removal of gutta-percha than after the removal of resilon. The use of solvent is not significant on the increase of canal wall cleanliness, but significantly shortens the time needed for retreatment. There is a difference in the cleanliness of root canal walls depending on the used instruments. Engine-driven rotary instruments and the use of a solvent significantly shortens the time needed for endodontic retreatment.</p>

Durant ma thèse, j’ai recherché des conditions pour l'activation / fonctionnalisation de liaisons C-H pour l’arylation d’hétérocycles viables pour l’industrie. Par rapport aux protocoles de couplage classiques tels que les réactions de Suzuki, Stille ou Negishi, la fonctionalisation de liaisons C-H fournit des procédures moins coûteuses et plus écologiques si elle tolère des groupements utiles en synthèse et si elle utilise des solvants peu ou non toxiques. Nous avons observé que le thiophène peut être arylé en C2 avec de nombreux bromures d'aryle en présence de seulement 0.2 mol% de Pd(OAc)2. Ensuite, nous avons démontré que des solvants de type alcool tels que le pentan-1-ol permet le couplage de thiazoles ou d’imidazoles avec des bromures d’aryle. Ce type de solvant est certainement plus viable pour l’industrie que les solvants usuellement utilisés pour ces couplages tels que le DMF ou le DMAc. Nous avons ensuite montré que certains de ces couplages peuvent même être effectués sans aucun solvant. Finalement, nous avons démontré que de nombreuses fonctions sur des bromopyridines sont tolérées lors de ces couplages, permettant l’accès à des pyridines arylées fonctionnelles utiles pour l’industrie pharmaceutique en une étape. / During my PhD, I searched for industrially viable conditions for activation / functionalization of CH bonds for the arylation of heterocycles. Compared to conventional coupling protocols such as Suzuki, Stille or Negishi reactions, the functionalization of CH bonds provides less costly and more environmentally friendly procedures if it tolerates synthetically useful functional groups and if it uses solvents with little or no toxicity. We observed that thiophene can be arylated at C2 with a wide scope of aryl bromides in the presence of only 0.2 mol% of Pd(OAc)2. Then, we demonstrated that alcoholic solvents such as pentan-1-ol allow the coupling of thiazoles or imidazoles with aryl bromides. This type of solvent is certainly more viable for the industry as the solvents commonly used for these couplings such as DMF or DMAc. We then showed that some of these couplings can even be performed without any solvent. Finally, we have shown that many functions on bromopyridines are tolerated in these couplings, enabling access to arylated functionalized pyridines useful for the pharmaceutical industry in one step.