L'objet de cette étude est d'utiliser la technique des micelles inverses pour synthétiser des nanoparticules à transition de spin, de taille et de forme contrôlées afin d'en permettre l'utilisation en électronique moléculaire. Dans la première partie, nous avons déterminé les paramètres de synthèse influençant la taille et la forme des particules d'un complexe à transition de spin à fort potentiel d'application. Dans un deuxième temps, nous avons utilisé ces paramètres sur trois autres complexes afin de comprendre la relation entre les paramètres de la synthèse et la morphologie des particules. Les nanoparticules ainsi synthétisées constituent la base d'une discussion sur l'existence d'un lien entre la taille/forme des particules et les propriétés de transition de spin. Enfin, la dernière partie de ce travail est consacrée à l'utilisation de ces matériaux en électronique moléculaire, et l'observation des propriétés de photoconductivité et photovoltaïque à l'échelle des nanoparticules.

La protéine farnésyltransférase (FTase) est une métalloenzyme à zinc catalysant le transfert d'une chaîne farnésyle provenant du pyrophosphate de farnésyle (FPP) sur le résidu cystéine de certaines protéines possédant un motif CaaX C-terminal où C est la cystéine farnésylée, a est un acide aminé aliphatique et X est Ser, Ala, Gln ou Met. Une fois additionné, le groupement farnésyle fait office de point d'ancrage rendant possible la fixation des protéines à la membrane cellulaire et de guide moléculaire facilitant la liaison de ces protéines prénylées à d'autres protéines. D'abord étudiée en oncologie, la FTase constitue aujourd'hui une cible potentielle pour la thérapie antiparasitaire qui manque cruellement de médicaments suite à l'apparition de phénomènes de résistance. La nécessité d'améliorer les thérapies existantes ouvre la voie de recherches innovantes pour trouver de nouvelles molécules bioactives.Lors de ces travaux de thèse, les deux stratégies de recherche pratiquées en chimie médicinale ont été utilisées.La première approche a consisté à synthétiser des analogues bisubstrats 1,2,3-triazoles pouvant se lier à la fois sur le site de liaison de la protéine et sur celui du FPP. Cette approche rationnelle a aussi permis d'ébaucher une synthèse monotope de triazoles 1,5-disubstitués à partir d'amines primaires. L'approche par criblage constitue la deuxième méthode de recherche de nouveaux inhibiteurs. Dans ce contexte, la chimiothèque de l'ICSN a été criblée et deux composés de type 3-arylthiophène ont révélé de bonnes activités et une structure originale dans l'inhibition de la FTase. Ainsi, des travaux de relations structure-activité ont été réalisés pour moduler les différentes positions du thiophène et la nature de l'hétérocycle central.Ce travail nous a permis d'élaborer une librairie de plus d'une centaine de composés. L'évaluation biologique de ces analogues sur FTases isolées humaine et de T. brucei et sur parasites T. brucei et P. falciparum a révélé des molécules particulièrement intéressantes et prometteuses.

In der vorliegenden Arbeit wird die Darstellung neuer organischer Polyazide dokumentiert, die durch einfache nucleophile Substitution mittels NaN3 dargestellt werden können. Organische Azide mit der Formel RN3 können sich unter Stickstoff-Abspaltung in exothermen, teilweise explosionsartigen Reaktionen zersetzen. Sie sind daher prinzipiell als energiereiche Materialien (HEDM) für entsprechende Anwendungen geeignet. Die als Treibladungsmaterialien potentiell geeignetsten, handhabungssicheren, dendritischen Polyazide werden unter anderem mittels Thermogravimetrie und Differenzkalorimetrie analysiert. In einer neuen Synthesemethode können die wenig bekannten Heteroazidomethane aus Tris(azidomethyl)amin erzeugt werden. Von besonderem Interesse ist dabei die Synthese neuartiger Azidohalogenmethane. Diese können durch analytische Gas-Chromatographie charakterisiert und mittels präparativer Gas-Chromatographie isoliert werden. Durch die 1,3-dipolare Cycloaddition mit Cyclooctin konnten einige Heteroazidomethane zu Triazolen abgefangen und so einer Einkristall-Röntgen-Strukturanalyse zugeführt werden. Als letztes in der homologen Reihe der Azidomethane noch fehlendes Azid konnte Tetraazidomethan synthetisiert werden. Das Perazidomethan besitzt mit 93.3% den für organische Azide höchstmöglichen Stickstoffgehalt. Seine Existenz wurde bislang lediglich durch molekültheoretische Berechnungen nahegelegt. Die Synthese dieses homoleptischen Kohlenstoffazides gelang durch die Behandlung von Trichloracetonitril mit Natriumazid. Es ließ sich durch präparative GC als extrem explosive, farblose Flüssigkeit isolieren. Mit Hilfe der analytischen GC konnten sowohl der Siedepunkt als auch die Polarität von C(N3)4 abgeschätzt werden. C(N3)4 wird desweiteren durch IR, MS, 13C-NMR und 15N-NMR-Spektroskopie sowie durch Einkristall-Röntgen-Strukturanalysen seiner Abfangprodukte mit Cyclooctin charakterisiert. Mit Wasser zeigt C(N3)4 eine quantitative Hydrolyse unter Bildung von Carbonyldiazid. Durch Austauschprozesse mit Na15N3 konnte die mögliche Dissoziation von C(N3)4 nachgewiesen werden. Reaktionen von C(N3)4 mit Phosphinen führen zu Cyanamidderivaten, mit Norbornen sowie Norbornadien wurden über vielstufige Reaktionsmechanismen Aminotetraazole erhalten.

Polymer electrolyte membrane fuel cells (PEMFCs) have been looked as potential alternative energy conversion devices to conventional energy conversion systems such as combustion engines. Proton conducting membranes (PEMs) are one critical component of PEMFCs. The development of novel electrolyte membranes with dense structure, good mechanical flexibility, and high proton conductivity, but with little or no dependence on humidity at temperatures above 100¡ãC remains an important challenge to the realization of practical PEM fuel cells. In this thesis, to solve the technical difficulties existing in current high temperature PEM systems based on phosphoric acid and imidazole, a new type of proton conducting species 1H-1,2,3-triazole has been explored, and proved to have high proton conductivity and also enough electrochemical stability for fuel cell applications. In further experiments, effective methods have been developed to synthesize triazole derivatives and polymers. The properties of the synthesized polymers have studied and reported in this thesis. Preliminary computational simulations have also been performed to study the proton conducting mechanism to provide intrinsic information of the proton conducting process in 1H-1,2,3-triazole. In the final part, research works on other proton conducting species including H3PO4 and other heterocycles have been reported.

Submitted by JANAINE DO ROCIO IVASSECHEN null (janaine_jri@yahoo.com.br) on 2016-02-23T23:37:58Z No. of bitstreams: 1 dissertação Janaíne.pdf: 2608394 bytes, checksum: 89d6d43b306c92a291cb379448dd11de (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-02-24T14:58:59Z (GMT) No. of bitstreams: 1 ivassechen_jr_me_araiq.pdf: 2608394 bytes, checksum: 89d6d43b306c92a291cb379448dd11de (MD5) / Made available in DSpace on 2016-02-24T14:58:59Z (GMT). No. of bitstreams: 1 ivassechen_jr_me_araiq.pdf: 2608394 bytes, checksum: 89d6d43b306c92a291cb379448dd11de (MD5) Previous issue date: 2016-01-07 / A determinação direta de metais presentes em baixas concentrações em amostras de águas naturais é geralmente dificultada devido à presença de espécies interferentes. Os metais que foram estudados, Cu (II), Pb(II), Co (II), Ni (II) e Cd (II) são de interesse ambiental em razão de seu uso intensivo, distribuição e por serem absolutamente não-degradáveis podem acumular-se em matrizes ambientais manifestando toxicidade. Neste projeto desenvolveu-se a sílica como suporte sólido para o ancoramento da molécula 4-amino-3-hidrazino-5-mercapto-1,2,4-triazole e sua aplicação na adsorção/remoção de íons em solução aquosa. O material foi caracterizado por espectroscopia na região do infravermelho (FTIR), o qual apresentou bandas em 1690- 1649 e 790 cm-1 , característica de ligações N-H de aminas primárias do ligante. A ressonância magnética nuclear de 13C e 29Si (RMN) comprovam o ancoramento do ligante. As medidas de área de superfície específica pelo método de BET e diâmetro de poro resultaram em uma área de 795,51 ± 1,14 m2 g-1 e poros numa gama de 1,1 a 7,1 nm. A Microscopia Eletrônica de Varredura (MEV) mostrou que o material tem formato esférico com tamanhos aproximadamente de 10 μm e a Análise por Energia Dispersiva de Raios X (EDX) mostrou uma distribuição homogênea do sililante por toda a superfície do material. Com isso, confirmou-se a ocorrência da reação de modificação. O material foi aplicado em estudos de adsorção para determinação da sua capacidade máxima, bem como estudos da influência do pH e estudos cinéticos no processo de equilíbrio Os experimentos foram realizados pelo método de batelada. O primeiro teste foi o pHPZC, que indica a melhor faixa de pH (5-9) para a adsorção. Os estudos de adsorção dos metais em solução apresentaram o melhor resultado quando o pH era igual a 6, o equilíbrio de adsorção foi atingido depois de 50 minutos de agitação. Para todas as espécies investigadas o processo de adsorção é melhor descrito pelo modelo de pseudo- segunda ordem. Com esses parâmetros estabelecidos os valores de capacidade máxima de adsorção foram encontrados, sendo 0,129; 0,102; 0,105; 0,113; e 0,076 mmol g-1 para o Cu, Ni, Pb, Co e Cd, respectivamente. A sílica modificada foi aplicada na pré-concentração de Cu (II) em amostras aquosas. Com um fator de enriquecimento de 20 vezes, a coluna provou ser estável ao longo de 24 ciclos de adsorção/dessorção. / The direct determination of metals present at trace levels in natural water samples is generally difficult due to the presence of interfering species. Metals that were studied, Cu(II), Pb(II), Co(II), Ni(II) and Cd(II) are of environmental interest because of its intensive use, distribution, and as a consequence of its non-degradability can be accumulated in environmental matrices manifesting toxicity. In this project was developed a mesoporous silica as solid support for the anchoring of 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole molecule to be applied in the adsorption/removal of metals from aqueous solution. The material was characterized by infrared spectroscopy (FTIR), which showed bands at 1649 and 1690- 790 cm-1, characteristic of NH bonds of primary amines, existing in molecule ligand. The nuclear magnetic resonance 13C and 29Si (NMR) confirm the anchoring of the ligand. Measurements of specific surface area by the BET method and pore diameter resulted in an area of 795.51 ± 1.14 m2 g-1 and pores in a range from 1.1 to 7.1 nm. Scanning Electron Microscopy (SEM) showed that the material has spherical shape with sizes of approximately 10 μm and the analysis by Energy Dispersive X-ray (EDX) showed a homogeneous distribution of silylant over material surface. Thus, it was confirmed the occurrence of the modification reaction. The material was applied in adsorption studies to determine its maximum adsorption capacity, as well as studies of the influence of pH and kinetic studies on the balance process. The experiments were performed by the batch method. The first test was the pHPZC which indicates the best pH range (5-9) for the adsorption. Adsorption studies showed the best results when pH was near 6 and the adsorption equilibrium was attained after 50 minutes of stirring time. For all species investigated the adsorption process is better described by the pseudo- second order kinetic model. With these parameters established the maximum adsorption capacity values found were 0.129, 0.102, 0.105, 0.113 and 0.076 mmol g-1 for Cu(II), Ni(II), Pb(II), Co(II) and Cd(II), respectively. Modified silica was also applied in the preconcentration of Cu(II) from aqueous samples with 20 fold enrichment factor and the packed column proved to be stable over 24 cycles of adsorption/desorption.

No capítulo 1 apresentamos uma síntese eficiente de compostos 5-organoteluro-1H- 1,2,3-triazóis realizada via reação de cicloadição [3+2] entre azidas orgânicas e alquinos substituídos com organotelúrio. Além disso, os 5-organoteluro-1H-1,2,3-triazóis foram funcionalizados na posição 5 do anel triazólico por reação de acoplamento cruzado de Sonogashira. A regioquímica dos produtos de cicloadição foram descritas com base em experimentos de RMN, cálculos teóricos e cristalografia de raio-x. Apresentamos uma proposta mecanística para a cicloadição mediada por cobre, baseada em experimentos de espectrometria de massas de alta resolução. No capítulo 2, investigamos a eficiência de reações one-pot com indol, cloreto de oxalila e diferentes nucleófilos para obtermos derivados do indol-3-glioxila em condições adequadas. Do mesmo modo, envolvendo a adição de azidas orgânicas, levando à síntese de indol-3-glioxil-1,2,3-triazóis, os produtos foram obtidos com rendimentos que variaram de 59 a 85%. / In chapter 1 we present an efficient synthesis of 5-organotelluro-1H-1,2,3-triazole compounds that was accomplished via the [3+2]-cycloaddition reaction of organoazides and organotelluro alkynes. Additionally, 5-organotelluro-1H-1,2,3-triazoles were readily functionalized at the 5-position via the Sonogashira cross-coupling reaction, leading to highly functionalised triazoles. The regiochemistry of the products was assessed by bidimensional NMR experiments, theoretical calculations and x-ray crystallography. We presented a mechanistic proposal for the cycloaddition mediated by copper, based on high resolution mass spectrometry experiments. In chapter 2 we investigated a general and efficient reaction of indole with oxalyl chloride and nucleophiles providing indole-3-glyoxyl derivatives which has been developed in mild conditions. In the same fashion, the other reaction involved the addition of organic azides leading to the synthesis of indole-3-glyoxyl-1,2,3-triazoles, which proceeds smoothly generating the products in moderate to high yields.

O tratamento de sementes tem como objetivo tradicional erradicar ou reduzir os fungos associados às sementes, além de protegê-las de patógenos presentes no solo. Algumas doenças que ocorrem na parte área das plantas podem ser manejadas através do tratamento das sementes com produtos sistêmicos. Essa forma de controle tem sido utilizada há muitos anos, visando o controle de fungos biotróficos em arroz e trigo. A ferrugem asiática da soja é a principal doença que ataca a cultura, a qual necessita de ferramentas eficientes para seu manejo. O objetivo desta dissertação foi verificar a contribuição do tratamento de sementes de soja com produtos fitossanitários no manejo da ferrugem asiática. Desta forma, produtos fitossanitários foram aplicados às sementes de soja em diferentes doses, a fim de se verificar os efeitos fitotóxicos sobre sementes e plântulas que eventualmente fossem causados pelos mesmos. As maiores doses não fitotóxicas de cada tratamento foram selecionadas, novamente aplicadas às sementes e distribuídas em campo experimental, onde se verificou o efeito do tratamento das sementes isoladamente ou com a aplicação foliar de fungicidas foliares, no manejo da ferrugem asiática da soja. Ciproconazol + azoxistrobina (10,0 + 25,0g i.a./100kg de sementes), difenoconazol (50,0), epoxiconazol (2,5), fluquinconazol (50,0), flutriafol (10,0), flutriafol TS (5,0), flutriafol + tiofanato metílico (10,0 + 50,0), tebuconazol (10,0), tebuconazol + trifloxistrobina (10,0 + 5,0), tetraconazol (10,0), triticonazol (25,0), acibenzolar-S-methyl (50,0) e pó de rocha (2,0) não apresentaram fitotoxicidade e foram comparados em campo. Ciproconazol + azoxistrobina (25,0 + 10,0g i.a./100kg de sementes) e epoxiconazol (2,5) diminuíram a emergência das plântulas de soja em campo. No ensaio somente com tratamento de sementes, sem aplicação de fungicida foliar, tebuconazol e tebuconazol + trifloxistrobina diminuíram a ferrugem asiática em plantas de soja. Quando se integrou a pulverização foliar de fungicidas, fluquinconazol, tebuconazol e tebuconazol + trifloxistrobina, diminuíram a severidade da ferrugem asiática da soja. Apesar de não aumentar o rendimento da cultura, o tratamento de sementes pode contribuir no manejo da ferrugem asiática da soja, mantendo a segurança e o rendimento do produtor. / Seed treatment has as traditional objective to eradicate or to reduce fungi associated with seeds and to protect them from soilborne pathogens. Some diseases that occur in the aerial part of plants may be managed through seed treatment with systemic products. This kind of control has been used for many years, aiming the control of biotrophic fungi in rice and wheat. Soybean\'s asian rust is the main disease that attacks the culture, which needs efficient tools for its management. The objective of this study was to verify the contribution of soybean seed treatment with phytosanitary products in the management of asian rust. In this case, phytosanitary products were applied to soybean seeds in different doses, aiming to verify the phytotoxicity effects onto seeds and seedlings that eventually would be caused by these products. The highest non phytotoxic doses of each treatment were selected, applied again to seeds and these were distributed on experimental field, where it was verified the effect of each seed treatment with and without foliar application of fungicides, in the management of soybean\'s asian rust. Ciproconazol + azoxystrobin (10,0 + 25,0g a.i./100kg of seeds), difenoconazol (50,0), epoxiconazol (2,5), fluquinconazole (50,0), flutriafol (10,0), flutriafol TS (5,0), flutriafol + thiophanate-methyl (10,0 + 50,0), tebuconazole (10,0), tebuconazole + trifloxystrobin (10,0 + 5,0), tetraconazole (10,0), triticonazole (25,0), acibenzolar-S-methyl (50,0) and rock powder (2,0) did not present phytotoxicity and were compared in field. Ciproconazol + azoxystrobin (25,0 + 10,0g a.i./100kg of seeds) and epoxiconazol (2,5) decreased the seedling\'s emergency in field. In the experiment with only seed treatment, with no foliar fungicide application, tebuconazole and tebuconazole + trifloxystrobin decreased asian rust in soybean plants. When the application of foliar fungicide was integrated, fluquinconazole, tebuconazole and tebuconazole + trifloxystrobin the asian rust severity decreased. Despite there was no increase in the culture yield, seed treatment can contribute in asian rust´s management, increasing the safety an the revenue of the producer.

Among the different pulmonary fungal infections, aspergillosis, and in particular invasive pulmonary aspergillosis (IPA), are becoming the most worrying diseases in immunocompromised patients. This is due to their high incidence and mortality. Indeed, invasive aspergillosis manifests as invasive pulmonary disease accounting for 50/60% of all cases, with a mortality of 50-90% in severely immunocompromised patients. Triazoles act by inhibiting 14-α demethylase, a fungal cytochrome P450 enzyme implicated in the synthesis of ergosterol, an essential constituent of fungal cell walls. Moreover, they interact with the same cytochrome present in large quantities in the human liver, inducing possible drug-drug interactions in IPA patients. Consequently, interactions resulting from inhibitors, inductors, or substrates of cytochromes can modify the plasmatic concentrations of triazoles or other drugs administered concomitantly. To overcome these important issues, pulmonary delivery of triazoles could be an interesting alternative to conventional routes.The aim of this work was to develop triazole-based dry powders for inhalation able to be deposited adequately in the lungs, with a release of drug and a lung retention that can optimize its pharmacological action. This work focused on two active pharmaceutical ingredients (API): itraconazole (ITZ), for which improved solubility was needed, and voriconazole (VCZ), for which slow release was required.Concerning ITZ, solid dispersions for inhalation (SDIs) comprising ITZ and mannitol were previously developed in our laboratory. The selected SDI showed interesting results in terms of improved dissolution and lung retention in vivo in mice during a pharmacokinetic study. Therefore, this SDI was tested in a murine preclinical model of IPA and showed promising results in terms of prophylaxis efficacy. One aim of this work was to continue the pharmaceutical development of this promising SDI by making a scaling-up study. These methods were intended to improve the SDI’s ecological footprint and productivity by increasing the production yield and decreasing the amount of solvents and time used in its manufacture. During the first step of this study, the obtained SDI showed interesting results obtaining similar powder characteristics (i.e. amorphous content, aerodynamic performance, and dissolution profiles) from concentrated solutions using a laboratory-scale spray-dryer B-290 (Büchi, Switzerland) before using a pilot-scale spray-dryer (GEA Niro, Denmark). Then, the upscaling was performed on the pilot spray-dryer allowing the production of SDIs with increased productivity (yield and process duration). These SDIs had similar powder characteristics than the optimized lab-scale SDIs. During the second part of this work we developed VCZ based dry powder for inhalation. The aim was to slow down the release of this highly permeable and very slightly soluble API and to prolong its lung residence. To this end, various lipidic excipients were chosen. The selection took into account the potential good pulmonary tolerance of the lipids and their hydrophobicity to evaluate their ability to slow down the VCZ release (FPFs 20-25%, slowed release up to 24h, burst effect of ± 58% of VCZ dissolved within 30min). Immediate-release SDIs were also developed to have a comparator reference for the pharmacokinetic and efficacy studies (FPFs of 40%).Then, a pharmacokinetic study in mice was performed following the pulmonary administration of one immediate-release and two sustained-release SDIs (with or without PEG excipient). With an 80-fold higher pulmonary exposure over 24 hours, the slow-release SDIs presented a real interest compared to the immediate-release SDI. Moreover, in accordance with these results, VCZ plasma exposure following the administration of the SDI with PL90-H was more than 1.5-fold higher than its pulmonary exposure (AUC0-24 of 8.70 µg.h/g in the lungs and 14.70 µg.h/mL in the plasma). The slow-release formulations presented plasma exposures at least 15 times lower than their pulmonary exposures (AUC0-24 in lung of 741.40 and 686.85 µg.h/g vs plasmatic AUC0-24 of 37.44 and 42.81 µg.h.mL, respectively with and without PEG excipient). Moreover, the presence of PEG excipient did not influence the residence time and the exposure of the VCZ within the lungs. Finally, the sustained-release SDIs administration by inhalation led to VCZ lung and plasma concentrations higher than the minimal inhibitory concentration (MIC) of VCZ against Aspergillus fumigatus (1 μg/mL) over 24 h. Finally, a murine model of IPA was developed in our lab. The immunosuppression model was fixed and performed by the intraperitoneal (IP) injection of corticosteroids to induce a neutropenia state. Then, different doses of spores (from 1.10^4 to 5.10^6 spores) were inoculated to the neutropenic mice via an endotracheal instillation and the survival rate of each group was observed. Unfortunately, the survival rate resulting from the different infections were not reproducible. Therefore, these models were not suitable to conduct the efficacy study. This underlined the link between the immunosuppressive model and the infection. Indeed, the IPA murine model should be developed according to the immune state of the animal, the Aspergillus conidia species and its concentration to be used. / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished

<p><i>Chemistry of Complex High-Nitrogen Materials</i> begins with a brief background on a few high explosive materials and their applications, followed by synthesis routes and characterization methods of energetic materials. Several new complex high-nitrogen materials where synthesized and presented in the following chapters. These novel energetics include several nitrilimines, triazoles, tetrazoles, methyl sydnone imines, azasydnones, and an annulated heterocycle. Their energetic properties are discussed and compared with other well-known explosive materials.</p>

A thesis submitted to the school of graduate studies in the partial fulfillment of the requirements for the degree doctor of philosophy. / Fungal populations occupy a vast number of ecological niches across many geographic areas around the planet. Fungi act as essential nutrient recyclers, playing key roles as saprophytes, mutualists, and pathogens. As humans, we use these broad properties of fungi in biochemical and pharmaceutical industries, creating a plethora of products ranging from antimicrobials to food products. However, certain fungal species have become a devastating burden on human public health. Of these fungal species, my PhD thesis has focused on the critically important mold Aspergillus fumigatus. This mold is an opportunistic human pathogen, being the leading etiological cause of the spectrum of diseases termed aspergillosis that yearly affects over 8,000,000 people worldwide. In addition, the rising number of antifungal resistant strains around the world, especially within environmental populations, is of critical concern. Given that almost all aspergillosis infections result from environmental strains, and that soil is a major ecological niche for A. fumigatus, my thesis focused on characterizing genetic and phenotypic aspects of soil isolates of A. fumigatus obtained from many geographic and climatic regions around the world. My analyses revealed extensive allelic and genotypic diversity within and among populations. These A. fumigatus populations were defined by both historical differentiations, high gene flow, non-random recombination, and high susceptibility to triazole antifungals. Additionally, I tested the sexual fecundity of a subset of these global strains and found that geographic and genetic distance between the pairs of parental strains had little effect on sexual fecundity. Lastly, my research found broad variations in growth of a global sample of A. fumigatus strains at different temperatures. Again, no relationship of either geographic or genetic distance on strain growth was observed. Overall, my research highlights the extraordinary nature of A. fumigatus populations to quickly spread and adapt across diverse and complex environments. / Thesis / Doctor of Philosophy (PhD) / Aspergillus fumigatus is a cosmopolitan mold that causes opportunistic infections in humans termed aspergillosis. To better understand the environmental reservoirs of aspergillosis infection, I investigated soil populations of this fungus, as soil is likely the largest reservoir of A. fumigatus. I isolated A. fumigatus strains from 11 countries across 6 continents and genetically compared these soil populations to each other and to clinical A. fumigatus populations. I found extensive genetic diversity within most local soil populations, along with different relationships among geographic populations. When a sample of these global strains were sexually crossed, I uncovered high variation in their sexual fecundity, which lowered at higher geographic distances. Lastly, strains exhibited high variations in growth at different temperatures regardless of climatic, genetic, and geographic factors from where they were isolated. My thesis highlights the extraordinary phenotypic variations and complex population structure of A. fumigatus populations isolated from soil across the globe.