Investigating interactions between proteins and small molecules at an atomic scale is fundamental towards understanding biological processes and designing novel candidates during the pre-clinical stages of drug discovery. By optimizing the methods used to study these interactions in terms of accuracy and computational cost, we can accelerate this aspect of biological research and contribute more readily to therapeutic design. While biological assays and other experimental techniques are invaluable in quantitatively determining in vitro and in vivo inhibition activity, as well as validating computational predictions, there is an inherent benefit in the possible throughput provided by molecular dynamics (MD) simulations and related computational methods. These calculations provide researchers with unparalleled access to large amounts of all-atom sampling of biological systems, including non-physical pathways and other enhanced sampling methods. This dissertation presents research into advancing the application of expanded ensemble and other simulation-based methods of ligand design towards reliable and efficient absolute free energy of binding calculations on the scale of hundreds to thousands of small molecule ligands. This culminates in a combined workflow that allows for an automated approach to the force-field parameterization of custom systems, simulation preparation, optimization of the restraint and sampling protocols, production free energy simulations, and analysis that has facilitated the computation of absolute binding free energy predictions. Specifically highlighted is our ongoing effort to discover novel inhibitors of the main protease (Mpro) of SARS-CoV-2 as well as participation in the SAMPL9 Host-Guest Challenge. / Chemistry

Mono- and dinuclear chromiumtricarbonyl and manganesetricarbonyl complexes of dibenzo[a,e]cyclooctatetraene (DBCOT) were synthesized and characterized. In the bis(chromiumtricarbonyl)DBCOT synthesis, the main product was the syn,anti isomer where the two Cr(CO)3 moieties coordinate to opposite faces of the DBCOT backbone. This complex exhibits three dynamic processes in solution. A ring inversion of the organic skeleton occurs while the two chromiumtricarbonyl moieties undergo tripod rotation. This is the first study where eight-membered ring inversion is studied for a pi-coordinated metallic system. The rate of inversion at various temperatures was determined by 1H NMR line shape analysis at two different field strengths (300 and 600 MHz). Compared with other cyclooctatetraene compounds reported, there is a large positive entropy of activation and a relatively high enthalpy of activation in this system. DFT calculations, using the B3LYP/6-31G** basis set, were performed to gain a better understanding of the experimental results. It is proposed that free rotation of both Cr(CO)3 groups in the planar transition state are responsible for the large entropy of activation for ring inversion in hexahapto,hexahapto-dibenzo[a,e]cyclooctatetraene-syn,anti-bis(tricarbonylchromium). The relatively large enthalpy of activation is due to a stabilizing interaction between the endo carbonyl groups on the syn-Cr(CO)3 and the remote arene. In the monometallic DBCOT complexes, the metal can either be inside or outside the tub conformation. Interestingly, the crystal structures show opposite orientations for the isoelectronic chromium and manganese systems. The Cr(CO)3 group is positioned anti relative to the DBCOT backbone while the Mn(CO)3+ is syn. It should be noted that the optimized gas phase geometries obtained through DFT calculations agree with the crystallographic results. Electrochemical studies were performed to investigate the change in redox behavior associated with coordination of mono and bis-chromium units to the DBCOT backbone. Four new organometallic crystal structures are reported in this dissertation. Different tripod orientations, DBCOT backbone angles, and metal orientation relative to the interior of the organic skeleton are found. C-H...O, C-H...pi, and charge assisted C-H...F hydrogen bonding interactions were observed in the solid state packing. The structural motifs found suggest these complexes could serve as organometallic synthons in supramolecular chemistry.

När det handlar om ROT-projekt (renovering, om- och tillbyggnad) är det viktigt för entreprenören att uppnå långsiktig lönsamhet. För att säkerhetsställa detta är det av stor vikt att upprätta noggranna kalkyler som håller under hela byggprojektet. I dagsläget finns små marginaler för eventuella kostnadsökningar därmed ytterst lite utrymme för misstag. Eftersom förutsättningarna vid ROT-projekt ständigt varierar beroende på typ av badrum och skadeorsak är det därför väldigt svårt att uppskatta och beräkna kostnader utifrån rådande förutsättningar.  Utifrån detta finns det ett behov hos entreprenören att förstå varför kalkylerna avviker och hur man kan undvika detta i framtida projekt. Examensarbetet innehåller både en analys av kalkylerade kostnader och dess verkliga utfall samt en analys av kalkylverktyget Meps. Då ROT-sektorn är stor och omfattande har vi valt att avgränsa oss till badrumsrenoveringar som en följd utav vattenskador. Utifrån analys av kalkyler och kalkylverktyget samt intervjuer med parter både från entreprenör och från beställarsidan har vi kommit fram till en rad slutsatser om hur företaget kan ta fram noggrannare kalkyler i framtiden. Framförallt anser vi att företaget ska föra en tätare dialog med försäkringsbolagen för att vara en del i utvecklingen av kalkylverktyget. Vi anser även att man bör avsätta resurser för att utveckla erfarenhetsåterföringen inom företaget. / It is important for the contractor to have an accurate calculation throughout the whole project, especially when it comes to ”ROT”-projects (renovation and reconstruction).There is very little room for mistakes since the budget is very tight. Since the conditions always differ from one project to another it’s very important to take this into account. Due to this there is a great need for the contractor to understand why the calculations do not add up in the end so they can avoid income losses in the future. This report contains both an analysis of the calculated costs and the outcome for five different projects and also an analysis of the program used for calculating the costs, Meps. Since the ROT-sector is big and comprehensive we have decided only to analyse bathroom renovations due to water damages. From the analysis of the calculations and Meps together with interviews with contractors and clients we have come to the following conclusions: First of all we suggest that the entrepreneur should have a closer dialogue with the insurance company to be a part of the development of Meps. We also suggest that they should devote more resources for feedback in the company.

This thesis deals with the study of skill sets which the students acquired prior to attending the Faculty of Education at Charles University, specifically the Department of Chemistry and Chemistry Education, and how their knowledge of the subject improved after attending the Chemistry Calculations course, specifically in the 2020/2021 winter semester. In the first part of this thesis, where the theoretical standpoints are established, the thesis deals with the research of chemistry calculations wherein, for example, the students' issues regarding these calculations are outlined. Additionally, this part includes the includes the position of chemical calculations inside curriculum documents (RVP ZV, RVP G and RVP SOV) and how they are accepted and used directly in elementary and high schools. The second, practical, part studies the students' ability to solve chemical calculations after attending high school. The study was carried out by entrance exams. Not only was the success rate observed, but also the reasons of success or failure were examined. In the subsequent section of the study, a similar entrance exam was given out to students who have attended the Chemistry Calculations course, which delivered insight into whether the course improved the knowledge of the students on this subject. All...

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<p>Radical polymers bearing open-shell moieties at their pendant sites offer potential advantages in processing, stability, and optoelectronic properties compared to conventional doped conjugated polymers. The rapid development of radical-containing polymers has occurred across various applications in energy storage devices and electronic systems. However, significant gaps still exist in understanding the key structure-property-function relationships governing charge transport phenomena in these materials. Most reported radical conductors primarily rely on (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) radicals, which raises fundamental questions about the ultimate limits of charge transport capabilities and the impact of radical chemistry choice on material deficiencies. Moreover, an understanding gap persists when it comes to connecting the computable electronic features of individual units and the charge transport behavior of these materials in condensed phases. This dissertation seeks to address these gaps by developing a molecular understanding of charge transport in radical-bearing materials through a combined computational and experimental approach.</p> <p><br></p> <p>The initial stage of this dissertation investigated the impact of dimeric orientations and interactions on charge transport by conducting a density functional theory (DFT) study on a diverse set of open-shell chemistries relevant to radical conductors. The results revealed the anomalously high reorganization energies of the TEMPO radical due to strong spin-localization, which may result in inefficient charge transfer. Additionally, a significant mismatch was identified between dimeric conformations favored by intermolecular interactions and those maximizing charge transfer. This study provided new insights into the impact of steric hindrance and spin delocalization on elementary charge transfer steps and suggests opportunities for exploiting directing interactions to enhance charge transport in these materials.</p> <p><br></p> <p>Building upon these findings, we established a direct relationship between the molecular architecture and intrinsic charge transport properties. To accomplish this, single-molecule characterization methods (i.e., break junction techniques) were implemented to study the nanoscale charge transport properties of radical-containing oligomeric nonconjugated molecules. Temperature-dependent measurements and molecular modeling revealed that the presence of radicals improves tunneling at the nanoscale. Integrating open-shell moieties into nonconjugated molecular structures significantly enhances charge transport, thereby characterizing charge transport through radicals at the individual level and opening new avenues for implementing molecular engineering in the field of nanoelectronics.</p> <p><br></p> <p>To further connect the electronic properties of repeat units with the condensed-phase charge transport behavior of radical polymers, a quantum chemical study was carried out to explicitly evaluate the interplay between polymer design, open-shell chemistries, and intramolecular charge transport. After comprehensive conformational sampling of the configurational space of radical polymers, we determined their anticipated intrachain charge transport values by utilizing graph-based transport metrics. We show that charge transport in radical polymers primarily hinges on the choice of radical chemistry, which in turn affects the optimal selection of backbone chemistry and spacer group to ensure proper radical alignment and prevent undesired trap states. These findings highlight the potential for a substantial synthetic exploration in radical polymers for radical conductors.</p> <p><br></p> <p>In summary, this dissertation provides compelling evidence of radical-mediated charge transport and suggests potential design guidelines to enhance the charge transfer behavior of radical-containing polymer materials. Furthermore, these findings inform future research directions in fine-tuning molecular engineering and modular design to enable the development of radical-based materials and their end-use applications in organic electronics.</p>

This project has dealt with the developing a new technology for a renewable energy source, the wave energy, which is considered as one of the renewable resources with a potential to contribute to an energy production corresponding to about 10% of the world’s energy consumption nowadays. A point absorber concept that is using a Power Take-off (PTO) unit converts the sea surface wave motion into electricity thanks to a buoy at the sea surface which is moved by the waves. Due to harsh working conditions, the maintenance would cause too many issues, and a mooring system needs to be developed. The aim in this paper is to design a durable mooring system for at least 20 years of operation even working in a harsh sea environment. A geometry model of the mooring system has been built since the dimensioning of its components was performed. Several concepts were generated and evaluated with a Pugh matrix. An analysis of the different stresses affecting the performance of the system was made to validate the design. In addition, the detail design of the different parts of the system has made to allow their manufacture in future work. / Projektet har behandlat utvecklingen av en ny teknik för en förnybar energikälla, vågenergin, som anses vara en av de mest lovande förnybara resurserna med potential att bidra till en energiproduktion som motsvarar cirka 10 procent av världens energiförbrukning . Ett punktabsorberande koncept som använder en kraftuttagsenhet (PTO) omvandlar havsytans vågsrörelser till elektricitet. På grund av hårda arbetsförhållanden ger underhållsarbete stora problem och ett förtöjningssystem behöver utvecklas. Syftet med detta projekt är att utforma ett hållbart förtöjningssystem för minst 20 års drift, även i en hård havsmiljö. En geometrisk modell av förtöjningssystemet har skapats baserad på dimensionering av dess komponenter. Flera koncept genererades och utvärderades med en Pugh-matris. En simulering av de olika spänningar som påverkar systemets prestanda gjordes för att validera designen. Dessutom har detaljkonstruktion av de olika delarna av systemet gjorts, så att de kan tillverkas i ett framtida arbete.

I Sverige står bygg- och fastighetssektorn för nära en femtedel av koldioxidutsläppen och en tredjedel av energianvändningen varav en stor del kommer från uppvärmning av byggnader. Ett tillvägagångssätt för att minska energibehovet i bostäder är genom krav på energieffektivitet. Där spelar isoleringsmaterial stor roll för att minska värmeförlusterna i byggnaden. Ett problem med för tjock isolering är att isoleringsmaterialen i sig har viss kvantifierbar miljöpåverkan. I denna studie bestäms livscykelpåverkan från olika isoleringsmaterial med avseende på primärenergianvändning, växthuspotential, kostnad samt övrig miljöpåverkan. Studien undersöker även hur tjockleken av olika isoleringsmaterial påverkar driftenergin i byggnaden Backåkra 2, belägen i centrala Stockholm. Syftet är att bestämma den optimala tjockleken för varje isoleringsmaterial i byggnaden med avseende att minimera primärenergianvändningen, växthuspotentialen samt kostnaderna under en tidsperiod på 50 år. Övrig miljöpåverkan fastställs även. Materialen som utvärderats är glasull, cellulosaisolering, polyuretan/polyisocyanurat, vakuumisolering, aerogel, grafitcellplast, samt fenolbaserad isolering. Två olika avfallsscenarier implementeras varav ett scenario har hög materialåtervinning och ett annat har hög energiåtervinning. I en känslighetsanalys studeras inverkan av primärenergifaktorn, isoleringsmaterialens livslängd, koldioxidfaktorn, U-värden i byggnadens fönster samt andra värden för livscykelpåverkan. Resultaten visar att vald tjocklek av isoleringsmaterial i byggnaden i dag ligger nära den optimala tjockleken med avseende på minimal primärenergianvändning. Om isoleringsmaterialet har lägre koldioxidutsläpp under sin livscykel hamnar tjockleken i dagsläget nära den optimala tjockleken med avseende att minimera växthuspotentialen. Materialet aerogel har högst värden i alla påverkanskategorier i båda avfallsscenarierna. Lägst primärenergianvändning har vakuum- och cellulosaisolering vid optimala tjockleka på . Cellulosaisolering ger även upphov till lägst växthuspotential medan grafitcellplast har lägst kostnad för de optimala tjocklekarna i båda avfallsscenarier. Hög material-återvinningsgrad ger upphov till tjockare isolering och högre värden för påverkansfaktorerna. En hög energiåtervinningsgrad leder däremot till tunnare isolering och lägre värden. Att optimera isoleringsmaterialens tjocklek utifrån alla tre kriterier (primärenergianvändning, växthuspotential och kostnad) kan innebära svårigheter eftersom skillnaden mellan optimala tjocklekar är stor. Resultatet är känsligast för förändringar av livslängden och denna bör utvärderas noggrannare i framtida studier för att i högre utsträckning likna den verkliga byggnaden. Framtida studier kan även kretsa kring mer generell tillämpning av liknande analys för olika typer av byggnader i olika geografiska regioner. I vissa typer av byggnader är isoleringsmaterialens påverkan gällande primärenergianvändning och växthuspotential i förhållande till den totala byggnaden signifikant. I sådana fall har optimering av isoleringstjocklek stor betydelse för byggnadens totala prestanda och kan bidra till att minska byggnadens miljöpåverkan. Avslutningsvis kan denna studie bidra till en minskning av primärenergianvändningen, miljöpåverkan och kostnaderna i en energieffektiv byggnad. Därmed erhålls ett hållbarhetsperspektiv under hela livscykeln. / In Sweden, the construction and real estate sector accounts for approximately one fifth of the carbon dioxide emissions and one third of the total energy use, mainly due to heating. In order to reduce both energy requirement and environmental impact, energy efficient measures are of great importance. Insulation materials play a major role in reducing heat losses. However, manufacturing of insulation materials is an energy-intensive process with impact on the environment. In this study, the life cycle impact of seven different insulation materials was determined. The study considers the energy efficient building “Backåkra 2” in Sweden, planned to be completed next year, as a case study for evaluating lifecycle environmental and economic performances. It is investigated how the operating energy in “Backåkra 2” is affected by the choice of different insulation materials and their thicknesses. The optimal thickness of each insulation material in the building was determined in order to minimize primary energy use, global warming potential and cost over a period of 50 years. For the determined thicknesses, other environmental impacts were also investigated. The evaluated insulation materials are glass wool, cellulose insulation, polyuretan/polyisocyanurat, vacuum insulation, aerogel, graphite foam insulation, and phenolic based insulation. In the lifecycle analysis, two different waste scenarios are also implemented, of which one has high material recycling and the other has high energy recovery. A sensitivity analysis examines the impact of the primary energy factor, the lifespan of the insulation materials, the carbon dioxide factor, the U-values in the building's windows and other values for the life cycle impact. The results show that the selected thickness of insulation material in the building today of 19 cm is close to the optimal thickness with respect to minimal primary energy use. If the insulation material has lower carbon dioxide emissions during its lifecycle, the thickness is at present close to the optimal thickness in terms of minimizing the global warming potential. Aerogel has the highest values in all impact categories in both waste scenarios. Vacuum insulation will achieve the lowest primary energy use at its optimal thicknesses of 11,26 cm for waste scenario 0 while cellulose will achieve the lowest primary energy use of all materials at a thickness of 64,5 cm for waste scenario 50. Cellulose insulation also has the lowest global warming potential, while graphite foam insulation has the lowest cost for the optimal thicknesses in both waste scenarios. Higher material recovery rates give optimum at larger thicknesses, while high energy recovery rates lead to thinner insulation thickness. Optimizing the thickness of insulation materials based on all three criteria (primary energy use, global warming potential and cost) can cause difficulties due to a high difference in results. The result in the analysis is sensitive to changes in lifespan, and this should be more carefully evaluated in future studies to resemble the real building. Future studies can also revolve around more general application of similar analysis for different types of buildings in different geographic regions. In some types of buildings, the impact of insulation materials on primary energy use and global warming potential compared to the total building is significant. In such cases, optimization of insulation thickness has a significant impact on the overall performance and can reduce the environmental impact generated by the building. In conclusion, this study can contribute to a reduction of the primary energy use, the environmental impact and the costs in an energy efficient building throughout the whole life cycle.

Despite not being a tangible substance, light is becoming an increasingly valuable tool in numerous areas of science and technology: the use of laser excitation of a fluorescent probe can generate incredibly detailed images of cellular structures without the need for large amounts of dissection; new types of solar cells are being produced using organic dyes to harvest light; computer data can be stored by inducing a chemical change in a compound through irradiation with light. However, before any of these materials can be applied in such a way, their properties must first be analyzed for them to be deemed viable. The focus of this dissertation is the photophysical characterization, linear and nonlinear, of a several novel organic compounds, and a europium complex, as well as using quantum chemical calculation techniques to understand some of the phenomena that are witnessed and begin to develop predictive capability. The nonlinear characterization of compounds utilizes wavelengths outside of their linear absorption range, where a focused beam can achieve the same excitation as one at half the wavelength, though this effect has a quadratic dependence on power. The potential for nonlinear excitation, or two-photon absorption (2PA), is becoming of increasing interest and importance for organic chromophores. Exciting only a small volume of material at a focal point makes it possible to nondestructively image samples in 3-dimensions, record data in multiple layers, and fabricate intricate structures through photopolymerization reactions. Lanthanides such as europium are known to exhibit sharp emission bands when excited, typically through an antenna effect due to the low probability of achieving direct excitation. This emission is long-lived, and through gating systems can readily be separated from background noise and autofluorescence (often observed in biological samples) that have much shorter lifetimes. Thus, one of the foci of this dissertation is the photophysical investigation of a series of novel lanthanide complexes, with particular attention to a europium complex.