Polymer mechanochemistry, wherein exogenous forces are harnessed to drive chemical processes within polymeric matrices, has afforded access to an astounding array of otherwise kinetically prohibitive reactivity. These multifarious mechanochemical transformations include formally symmetry forbidden electrocyclic processes, thermodynamically disfavored isomerizations, and thermally inaccessible cycloreversions of both carbocyclic and heterocyclic functionalities. The fundamental principles that govern mechanochemistry, however, remain elusive. To address this deficiency, we report a series of experimental and computational efforts that probe chemical reactivity under the action of mechanical force. Specifically, we have explored the formal 1,3-dipolar cycloreversion of 1,2,3-triazole moieties in an effort to understand the interplay between kinetic stability and mechanical perturbation. Briefly, 1,4-disubstituted 1,2,3-triazoles were embedded within high molecular weight poly(methyl acrylate) chains and reverted into their azide and terminal alkyne precursors sonochemically. The liberated azide and alkyne moieties were identified by orthogonal chemical ligation to chromophores, and the reactive azido- and alkynyl-polymer fragments could be recoupled through a copper-mediated cycloaddition. Inspired by this result, we developed a computational model to rapidly discover qualitative trends in mechanochemical reactivity. Application of this model to the cycloreversion of 1,2,3-triazoles revealed an intriguing result: the 1,5-disubstitued regioisomer was predicted to exhibit enhanced susceptibility to mechanical cycloreversion in comparison to the 1,4-disubstituted congener. This trend was experimentally verified upon embedding 1,5-disubstituted 1,2,3-triazoles into high molecular weight poly(methyl acrylate) chains and subjecting them to ultrasonication. Specifically, the observed rate constant for chain scission of a poly(methyl acrylate) material containing the 1,5-disubstituted isomer was 20% larger than that of an analogous material containing the 1,4-disubstituted congener. Having established confidence in the predictive capabilities of our model, we undertook an exhaustive evaluation of regiochemical effects on the activation of six previously reported mechanically labile scaffolds. Our theoretical work suggested that all of the evaluated scaffolds could exhibit suppressed reactivity under stress (an underexplored phenomenon), and this result was supported by experimental investigation. Moreover, our theoretical considerations predicted that anti-Hammond effects (i.e., increased structural dissimilarity between reactant and transition state geometries as the two approach energetically) could be predominant in mechanochemical processes. Finally, we endeavored to expand the scope of polymer mechanochemistry beyond traditional chemical systems to biologically relevant species. We found that the photophysical properties of fluorescent protein variants could be modulated by embedding the proteins within poly(methyl methacrylate) matrices and compressing the resulting composites. / text

Made available in DSpace on 2015-05-14T13:21:13Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2559856 bytes, checksum: 50fe82b4059b56d6e01eb8e3cf66ea70 (MD5) Previous issue date: 2012-10-20 / Financiadora de Estudos e Projetos - Finep / Mesoionic compounds are notable heterocyclic for having the most diverse biological properties, physical and chemical properties. Are defined as flat and non-aromatic heterocyclic Betaines stabilized by electron delocalization. Through an in situ cycloaddition/cicloreversion 1,3-dipolar were obtained two mesoionic, MI-1.1 and MI-1.2 through of the interconversion system 1,3-oxazólio-5-olato (Munchnonas) for 1,3-tiazólio-5-tiolato. A nucleophilic substitution reaction with excess methyl iodide, CH3I, promoted the first modification to the mesoionic system were changed of free base to iodates salts, S-methylated forming derivatives mesoionic, MI-2.1 e MI-2.2. These underwent a cyclodehydration reaction in the presence of acetic anhydride yielding two mesoionic system 1,3-diazolium-5-thiolate, MI-3.1 and MI-3.2, which in turn were alkylated again and originated two derived in the form of iodates salts S-methylated, MI-4.1 and MI-4.2. As the mesoionic and its derivatives: MI-2.1, MI-2.2, MI-3.1, MI-3.2, MI-4.1 and MI-4.2 and unpublished literature. Their structures were elucidated by spectroscopic techniques for RMN 1H and 13C and infrared light through a comparative analysis with existing structures. / Os compostos mesoiônicos são heterocíclicos notáveis por apresentar as mais diversas propriedades biológicas, físicas e químicas. São definidos como betaínas heterocíclicas planas e não aromáticas estabilizadas por deslocalização de elétrons. Através de uma reação in situ de cicloadição/cicloreversão 1,3-dipolar obtiveram-se dois mesoiônicos, MI-1.1 e MI-1.2, através da interconversão do sistema 1,3-oxazólio-5-olato (Munchnonas) para 1,3-tiazólio-5-tiolato. Uma reação de substituição nucleofílica com excesso de iodeto de metila, CH3I, promoveu a primeira modificação no sistema mesoiônico sendo transformados de base livre para sais iodatos S-metilados formando os derivados mesoiônicos, MI-2.1 e MI-2.2. Estes sofreram uma reação de ciclodesidratação na presença de anidrido acético obtendo-se dois mesoiônicos do sistema 1,3-diazólio-5-tiolato, MI-3.1 e MI-3.2, que por sua vez foram alquilados novamente e originaram dois derivados em forma de sais iodatos S-metilados, MI-4.1 e MI-4.2. Sendo os mesoiônicos e seus derivados: MI-2.1, MI-2.2, MI-3.1, MI-3.2, MI-4.1 e MI-4.2 inéditos na literatura. Suas estruturas foram elucidadas por meio de técnicas espectroscópicas de RMN 1H e 13C e infravermelho através de uma análise comparativa com estruturas já existentes.

4,5-Dihydro-1,2,3-oxadiazoles are postulated to be key intermediates in the synthesis of ketones from alkenes on an industrial scale, alkylation of DNA in vivo, decomposition of N-nitrosoureas (potent carcinogens), and are also a subject of great interest for theoretical chemists. In this thesis, formation of the parent compound and decay into secondary products has been studied by NMR monitoring analysis. The elusive properties and the intermediacy of the parent compound, 4,5-dihydro-1,2,3-oxadiazole, in the decomposition of suitably substituted N-nitrosoureas using Tl(I) alkoxides as bases, have been confirmed by the characterisation of its decay products viz., ethylene oxide, acetaldehyde, and especially diazomethane, at very low temperatures by 1H NMR, 13C NMR, 15N NMR, and relevant 2D NMR methods. Moreover, it has been shown that the methylation of nucleophilic molecules by 3-methyl-4,5-dihydro-1,2,3-oxadiazolium salts, which are considered to be activated forms of β−hydroxyalkylnitrosamines, does not involve 4,5-dihydro-1,2,3-oxadiazole as an intermediate, as has been reported in literature; instead, nucleophilic substitution leading to synthesis of open-chain products dominates the reaction. / 4,5-Dihydro-1,2,3-oxadiazole wurden als Schlüsselintermediate in der industriellen Synthese von Ketonen aus Alkenen, der in vivo Alkylierung von DNA und der Zersetzung von N-Nitrosoharnstoffen (potente Karzinogene) postuliert. Sie sind ebenso von großem Interesse in der theoretischen Chemie. Im Rahmen dieser Arbeit wurde die Bildung der Stammverbindung und deren Zersetzung in sekundäre Produkte mittels NMR-Verfolgung studiert. Die ausgesprochene Kurzlebigkeit der Stammverbindung 4,5-Dihydro-1,2,3-oxadiazol wurde durch die Charakterisierung der Produkte bei der Zersetzung geeignet substituierter N-Nitrosoharnstoffe mit Tl(I)-Alkoxiden bestätigt. Die Zersetzungsprodukte Ethylenoxid, Acetaldehyd und besonders Diazomethan wurden bei sehr niedrigen Temperaturen mittels 1H-NMR, 13C-NMR, 15N-NMR und relevanten 2D-NMR-Methoden charakterisiert. Des Weiteren konnte gezeigt werden, dass die Methylierung nucleophiler Spezies mit 3-Methyl-4,5-dihydro-1,2,3-oxadiazoliumsalzen, welchen als aktivierte Äquivalente der β−Hydroxyalkylnitrosamine verstanden werden, nicht zur Bildung von 4,5-Dihydro-1,2,3-oxadiazol als Intermediat führt, so wie dies in der Literatur berichtet wurde. Stattdessen wird die Bildung offenkettiger Produkte durch nukleophile Substitution bevorzugt.

4,5-Dihydro-1,2,3-oxadiazoles are postulated to be key intermediates in the synthesis of ketones from alkenes on an industrial scale, alkylation of DNA in vivo, decomposition of N-nitrosoureas (potent carcinogens), and are also a subject of great interest for theoretical chemists. In this thesis, formation of the parent compound and decay into secondary products has been studied by NMR monitoring analysis. The elusive properties and the intermediacy of the parent compound, 4,5-dihydro-1,2,3-oxadiazole, in the decomposition of suitably substituted N-nitrosoureas using Tl(I) alkoxides as bases, have been confirmed by the characterisation of its decay products viz., ethylene oxide, acetaldehyde, and especially diazomethane, at very low temperatures by 1H NMR, 13C NMR, 15N NMR, and relevant 2D NMR methods. Moreover, it has been shown that the methylation of nucleophilic molecules by 3-methyl-4,5-dihydro-1,2,3-oxadiazolium salts, which are considered to be activated forms of β−hydroxyalkylnitrosamines, does not involve 4,5-dihydro-1,2,3-oxadiazole as an intermediate, as has been reported in literature; instead, nucleophilic substitution leading to synthesis of open-chain products dominates the reaction. / 4,5-Dihydro-1,2,3-oxadiazole wurden als Schlüsselintermediate in der industriellen Synthese von Ketonen aus Alkenen, der in vivo Alkylierung von DNA und der Zersetzung von N-Nitrosoharnstoffen (potente Karzinogene) postuliert. Sie sind ebenso von großem Interesse in der theoretischen Chemie. Im Rahmen dieser Arbeit wurde die Bildung der Stammverbindung und deren Zersetzung in sekundäre Produkte mittels NMR-Verfolgung studiert. Die ausgesprochene Kurzlebigkeit der Stammverbindung 4,5-Dihydro-1,2,3-oxadiazol wurde durch die Charakterisierung der Produkte bei der Zersetzung geeignet substituierter N-Nitrosoharnstoffe mit Tl(I)-Alkoxiden bestätigt. Die Zersetzungsprodukte Ethylenoxid, Acetaldehyd und besonders Diazomethan wurden bei sehr niedrigen Temperaturen mittels 1H-NMR, 13C-NMR, 15N-NMR und relevanten 2D-NMR-Methoden charakterisiert. Des Weiteren konnte gezeigt werden, dass die Methylierung nucleophiler Spezies mit 3-Methyl-4,5-dihydro-1,2,3-oxadiazoliumsalzen, welchen als aktivierte Äquivalente der β−Hydroxyalkylnitrosamine verstanden werden, nicht zur Bildung von 4,5-Dihydro-1,2,3-oxadiazol als Intermediat führt, so wie dies in der Literatur berichtet wurde. Stattdessen wird die Bildung offenkettiger Produkte durch nukleophile Substitution bevorzugt.