Latently-reactive conjugated polymer-coated single-walled carbon nanotubes / Single-walled carbon nanotubes (SWNTs) are intensely investigated nanomaterials that exhibit intriguing physical and optoelectronic properties. Although SWNTs are highly regarded in terms of their potential societal impact, commercialization of SWNT applications has been dampened by the difficulty in SWNT processability and purification. Current commercially viable carbon nanotube syntheses produce complex mixtures of metallic and semiconducting SWNTs, as well as amorphous carbon and metal catalyst particles. Furthermore, the ability to decorate carbon nanotube surfaces to modulate their properties is non-trivial, especially if concurrent preservation of optoelectronic properties is desired. To date, the issues of SWNT solubilization, sorting, and functionalization have been approached in a piecemeal fashion. Conjugated polymers, which are macromolecules that possess extended π-systems, have the potential to address all of these issues simultaneously. In my Thesis, I explore conjugated polymer structures to investigate (i) factors that influence dispersion selectivity, and (ii) the decoration of polymer-SWNT complexes by incorporating reactive moieties into the polymer structure. The work presented in this Thesis begins by examining the ability of conjugated polymers to sort SWNTs. To date, the selective dispersion of metallic SWNTs is unrealized. In Chapter 2, I examine the effect of the electronic nature of the conjugated backbone on the selective dispersion of SWNTs by preparing SWNT dispersions pre- and post-methylation of a pyridine-containing conjugated polymer. In doing so, I prepare a series of polymers with identical degrees of polymerization and dispersity (to minimize extraneous selectivity factors) and find that electron rich π-systems disperse only semiconducting SWNTs, while electron poor π-systems disperse relatively more metallic SWNTs. In Chapter 3, I challenge the conventional wisdom that complete backbone conjugation is required to selectively disperse semiconducting SWNTs by introducing non-conjugated linkers into the polymer backbone and demonstrating that nanotube sorting is still possible. I next examine conjugated polymers as tools that can simultaneously sort SWNTs and impart reactivity to the polymer-SWNT complex, while preserving SWNT optoelectronic properties. In Chapter 4, I incorporate azides into polyfluorene side chains and perform solution-phase Strain-Promoted Azide-Alkyne Cycloaddition (SPAAC). I show that the polymer-SWNT complex can be rapidly decorated with strained cyclooctyne derivatives, and that only pre-clicked polymer enables for sorting of semiconducting SWNTs. The sorted SWNT population can then be made water soluble post-SPAAC, enabling for the study of SWNT emission in solvents with very different polarity. In Chapter 5, I examine the reactivity of azide-containing polymer-SWNT thin films and show that thin film properties can be drastically altered. Interfacial chemistry enables for the spatially-resolved patterning of a Janus polymer-SWNT thin film containing both hydrophilic and hydrophobic regions. In Chapter 6, I devise a system to perform aqueous solution-phase chemistry on the polymer-SWNT complex. The water soluble polymer-SWNT complex allows for functionalization of the hydrophobic SWNT scaffold with polar and charged molecules. Clicking an acidochromic switch onto the polymer-SWNT surface enables for control over the SWNT emission properties. Lastly, in Chapter 7 I develop a conjugated polymer whose backbone can be functionalized using visible light. The visible-light mediated photoclick coupling of a conjugated polymer backbone enables for rapid polymer modification and is the first example of spatially-resolved conjugated polymer backbone functionalization. / Thesis / Doctor of Philosophy (PhD) / Carbon nanotubes are cylindrical shells of carbon that possess fascinating physical, optical, and electrical properties. Commercial syntheses of carbon nanotubes produce complex mixtures of impure material, and raw carbon nanotube samples further suffer from insolubility. A grand challenge preventing commercialization of carbon nanotube applications is simultaneously solubilizing, sorting, and functionalizing carbon nanotube structures while avoiding damage to the nanotube properties. To date, these issues have been tackled in a piecemeal fashion. In my Thesis, I explore conjugated polymer coatings as a solution to address these problems all at once. I investigate how modifying conjugated polymer structure can (i) influence carbon nanotube purification and (ii) produce latently-reactive polymer-nanotube complexes that can be used to decorate carbon nanotubes without damaging nanotube properties.

Yes / We report a simple temperature-responsive bioconjugate system comprising superfolder green fluorescent protein (sfGFP) decorated with poly[(oligo ethylene glycol) methyl ether methacrylate] (PEGMA) polymers. We used amber suppression to site-specifically incorporate the non-canonical azide-functional amino acid p-azidophenylalanine (pAzF) into sfGFP at different positions. The azide moiety on modified sfGFP was then coupled using copper-catalyzed “click” chemistry with the alkyne terminus of a PEGMA synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization. The protein in the resulting bioconjugate was found to remain functionally active (i.e., fluorescent) after conjugation. Turbidity measurements revealed that the point of attachment of the polymer onto the protein scaffold has an impact on the thermoresponsive behavior of the resultant bioconjugate. Furthermore, small-angle X-ray scattering analysis showed the wrapping of the polymer around the protein in a temperature-dependent fashion. Our work demonstrates that standard genetic manipulation combined with an expanded genetic code provides an easy way to construct functional hybrid biomaterials where the location of the conjugation site on the protein plays an important role in determining material properties. We anticipate that our approach could be generalized for the synthesis of complex functional materials with precisely defined domain orientation, connectivity, and composition. / Engineering and Physical Sciences Research Council (EPSRC), University of Warwick, National Science Foundation (U.S.) (NSF), United States. Defense Advanced Research Projects Agency (DARPA), Seventh Framework Programme (European Commission) (FP7), European Research Council (ERC)

Les interactions entre les sucres et les lectines sont généralement l'étape clé dans de nombreux phénomènes biologiques et pathologiques. Malgré leu r importance cruciale, ces interactions sont paradoxalement caractérisées par des constantes d'affinité faibles et nécessite une multiprésentation des motifs saccharidiques pour être significatives. Cette augmentation est appelée "effet cluster". En outre, les techniques d'analyse actuellement utilisées en laboratoire nécessitent des quantités importantes de produits, ce qui est difficilement compatible avec les méthodes de synthèse actuelle. Pour pallier ces difficultés, une approche originale basée sur l'utilisation conjointe de glycooligonucléotide et de puces à ADN a été proposée. Les glycoconjugués basés sur des squelettes phosphodiesters et couplés à des séquences d'ADN ont été synthétisés en utilisant la chimie des oligonucléotides, couplée à la "click chemistry". La séquence d'ADN quant à elle a permis l'ancrage sur une puce à ADN et donc la mesure de leur affinité vis-à-vis de différentes lectines. Ce manuscrit rapporte le développement des nouvelles méthodologies de synthèse des glycooligonucléotides ainsi que la préparation de nombreux glycoconjugués originaux, dont l'affinité pour différentes lectines a été mesurée via l'utilisation de la puce à ADN. L'influence de plusieurs paramètres a été étudiée: le nombre de résidus, l'arrangement spatial, la lipophilie etc. Il s'avère que l'arrangement spatial semble être l'un des points les plus importants dans la mise au point d'un glycoconjugué. / The interactions between carbohydrates and lectins are generally the "key step" in many biological and pathological phenomena. Despite their importance, these interactions are paradoxically characterized by low affinity constants and requires multipresence of saccharide to be significant. This increase is called "cluster effect". In addition, the analysis techniques currently used in the laboratory requires large quantities of products, which is hardly compatible with the current methods of synthesis. To circumvent these difficulties, a original approach based on the combined use of glycooligonucleotides and DNA microarrays has been proposed. Glycoconjugates based on phosphodiester skeletons linked to DNA sequences have been synthesized using the chemistry of oligonucleotides, coupled with the "click chemistry". The DNA sequence has allowed the anchoring on a DNA chip and therefore the measurement of their affinity versus different lectins.This manuscript reports the development of new synthetic methodologies for the glycooligonucleotides synthesis and the preparation of many original glycoconjugates, whose affinity for various lectins was measured through the use of DNA microarray. The influence of several parameters was studied: the number of residues, the spatial arrangement, etc. lipophilicity. The spatial arrangement appears to be one of the most important parameters in the development of a glycoconjugate.

Os Clusters de acetato de rutênio de fórmula geral [Ru3O(AcO)6L3]n proporcionam blocos de montagem interessantes para sistemas supramoleculares, exibindo características eletrocrômicas e redox reversível, cobrindo uma ampla faixa de potenciais em solventes aquosos e orgânicos. Nesta Tese, estas espécies foram combinadas com o ligante tridentado, 4\'-piridil-2,2\':6\',2\"-terpiridina (pytpy), produzindo complexos do tipo [Ru3O(AcO)6(pytpy)3]n e [Ru3O(AcO)6(py)2(pytpy)]n, que foram totalmente caracterizados em estado sólido e solução. Nestes complexos a terpiridina permanece disponível para ligar-se a íons metálicos como o Fe(II), gerando um complexo binuclear de baixo spin muito estável, do tipo {Fe[Ru3O(AcO)6(py)2(pytpy)]2}n. Este processo pode ser monitorado eletroquimicamente, partindo de íons Fe(III), que exibem uma baixa afinidade pela terpiridina central, e ciclando o potencial para gerar íons de Fe(II). Desta forma, pode-se executar um procedimento típico de click chemistry, que leva a uma estrutura estendida, Fe-cluster-pytpy na superfície do eletrodo. Este filme conserva a funcionalidade dos blocos de montagem, permitindo aplicações interessantes em dispositivos moleculares, tais como sensores e smart Windows. / Ruthenium acetate clusters of general formula [Ru3O(AcO)6L3]n provide interesting building blocks for assembling supramolecular systems, displaying reversible redox and electrochromic characteristics, over a wide range of potentials in aqueous and organic solvents. In this thesis, such species has been combined with the tritopic, 4\'-pyridil-2,2\':6\',2\"-terpiridine (pytpy) ligand, yielding complexes of the type [Ru3O(AcO)6(pytpy)3]n and [Ru3O(AcO)6(py)2(pytpy)]n, which have been fully characterized in solid state and solution. In these complexes, the terpyridine moiety remains available for binding metals ions, such as Fe(II), generating very stable, low spin binuclear complexes, of the type n. This process can be monitored electrochemically, starting from Fe(III) ions, which exhibits a much lower affinity for the terpyridine center, and cycling the potentials in order to generate Fe(II) ions. In this way, one can start a click chemistry, ending up with an extended structure of Fe-cluster-pytpy film at the electrode surface. This film preserves the functionality of the building block complexes, a llowing many possible applications in molecular devices, such as sensors and smart windows.

A tuberculose (TB) é uma doença infectocontagiosa causada principalmente pelo Mycobacterium tuberculosis (Mtb). A TB era uma doença considerada em vias de extinção, porém sua incidência voltou a aumentar devido a diversos fatores, como o fluxo migratório dos chamados \"Países Reservatórios\" e a pandemia da AIDS. Em 2013, a OMS estimou 9 milhões de novos casos de TB e 1,5 milhões de mortes. A multirresistência aos quimioterápicos disponíveis justifica a procura por novos tuberculostáticos. Face ao exposto, o trabalho objetivou a síntese de potenciais inibidores da maltosiltransferase (GlgE), um novo e promissor alvo contra o Mtb, utilizando Planejamento com base na Estrutura do Alvo Molecular -- Structure-Based Drug Design (SBDD). A comparação das simulações de dinâmica molecular do sistema apo da GlgE e em complexo com a maltose-1-fosfato (M1P) mostrou as mudanças estruturais, em nível atômico, decorrentes da ligação com seu substrato. Levando em consideração estes dados, as simulações de docking dos potenciais inibidores revelaram que análogos glicosídicos e maltosídicos triazólicos ligados a grupos aromáticos substituídos possuem melhores perfis de interação com o sítio ativo da GlgE e, por essa razão, foram escolhidos para síntese. Assim, sintetizaram-se análogos glicosídicos e maltosídicos através da click chemistry, obtendo-se rendimentos variados. Posteriormente, realizaram-se ensaios enzimáticos e microbiológicos no Institute for Tuberculosis Research (ITR), University of Illinois at Chicago, USA. Apesar de os ensaios enzimáticos estarem em andamento, os compostos ensaiados apresentaram atividades que variaram de moderada a fraca, frente à cepa H37Rv. Dois compostos glicosídicos exibiram valores de Concentração Inibitória Mínima (CIM) inferiores a 60 µM, sem efeito citotóxico em células VERO em concentrações superiores a 250 µM. Tais resultados indicam que o análogo glicosídico triazólico aromático, como o NDS 112, pode ser utilizado como protótipo interessante para o planejamento de novas séries de compostos capazes de atuar como tuberculostáticos / Tuberculosis (TB) is an contagious infectious disease mainly caused by Mycobacterium tuberculosis (Mtb). TB was a disease considered in extinction, but its incidence has risen again due to several factors, such as the migration from \"Reservatoir Countries\" and AIDS pandemic. In 2013, WHO estimated 9 million new TB cases and 1.5 million deaths. Multidrug resistance to drugs available in chemotherapy validates the search for new TB drugs. In this context, this work aimed to the design and synthesis of potential inhibitors of maltosyltransferase (GlgE), a new and promissor target against Mtb using Structure-Based Drug Design. Comparison between molecular dynamic simulations of GlgE apo system and in complex with maltose-1-phosphate (M1P) showed important structural changes at molecular level due to substrate binding. Considering these data, docking simulations of potential inhibitors revealed that glucoside and maltoside triazoles analogues bound to substituted aromatic groups have better interaction profiles with the GlgE active site and for this reason they were chosen for synthesis. Thus, glucoside and maltoside triazole analogues were synthetized through click chemistry with different yields. Then, enzymatic and microbiological assays were performed at Institute for Tuberculosis Research (ITR), University of Illinois at Chicago, USA. Although the enzymatic assays are ongoing, componds were tested against H37Rv strains and they have shown activity ranging from moderate to weak. Two compounds presented Minimal Inhibitory Concentration (MIC) values below 60 µM, without cytotoxic effect in VERO cells in concentrations higher than 250 µM. These results indicate that glucosidic aromatic triazoles analogues, such as NDS 112, can be used as a prototype for design new series of compounds capable of acting as antituberculosis agents

Neste trabalho promovemos a síntese de sulfóxidos vinílicos ?-substituídos através da reação de acoplamento cruzado de Suzuki-Miyaura. Também foi feita a síntese de sulfóxidos enínicos inéditos, pela adição do nucleófilo no carbono β-sulfóxido. Esses compostos eram passíveis de serem submetidos a reação de rearranjo de Pummerer aditivo e assim gerarem uma pequena biblioteca de compostos α-tioaldeídos. Um desses aldeídos sintetizados foi empregado na reação de formação de uma imina propargílica, com consequente reação de CuAAC formando iminas triazólicas. Outras iminas arílicas foram sintetizadas, passando por uma etapa de redução, com intuito de se obter a amina livre, para que fosse feita a reação de ciclização com auxílio de um agente eletrofílico. Outra classe de composto organoenxofre foi sintetizada, as N-sulfinil imina, que após a reação de acoplamento cruzado de Sonogashira, com consequente remoção de um grupo protetor e a formação do anel heterocíclico, foram obtidos compostos triazólicos N-sulfinil imínicos. / In this work we promote the synthesis of α-substituted vinylic sulfoxides through the Suzuki-Miyaura cross coupling reaction. Also the synthesis of unpublished enynic sulfoxides was made, by the addition of the nucleophile in the β-sulfoxide carbon. These compounds were susceptible to additive Pummerer rearragement reaction and thus generated a small library of compounds. One of these aldehydes synthesized was used in the formation reaction of a propargyl imine, with consequent CuAAC reaction, forming triazol imines. Other aryl imines were synthesized, undergoing a reduction step, in order to obtain the free amine, so that the cyclization reaction was carried out with the aid of an electrophilic agent. Another class of organosulfur compound was synthesized, the N-sulfinyl imine, which after the Sonogashira cross-coupling reaction, with consequent removal of a protecting group and formation of the heterocyclic ring, N-sulfinyl imine triazolic compounds were obtained.

A tuberculose (TB) é uma doença infectocontagiosa causada principalmente pelo Mycobacterium tuberculosis (Mtb). A TB era uma doença considerada em vias de extinção, porém sua incidência voltou a aumentar devido a diversos fatores, como o fluxo migratório dos chamados \"Países Reservatórios\" e a pandemia da AIDS. Em 2013, a OMS estimou 9 milhões de novos casos de TB e 1,5 milhões de mortes. A multirresistência aos quimioterápicos disponíveis justifica a procura por novos tuberculostáticos. Face ao exposto, o trabalho objetivou a síntese de potenciais inibidores da maltosiltransferase (GlgE), um novo e promissor alvo contra o Mtb, utilizando Planejamento com base na Estrutura do Alvo Molecular -- Structure-Based Drug Design (SBDD). A comparação das simulações de dinâmica molecular do sistema apo da GlgE e em complexo com a maltose-1-fosfato (M1P) mostrou as mudanças estruturais, em nível atômico, decorrentes da ligação com seu substrato. Levando em consideração estes dados, as simulações de docking dos potenciais inibidores revelaram que análogos glicosídicos e maltosídicos triazólicos ligados a grupos aromáticos substituídos possuem melhores perfis de interação com o sítio ativo da GlgE e, por essa razão, foram escolhidos para síntese. Assim, sintetizaram-se análogos glicosídicos e maltosídicos através da click chemistry, obtendo-se rendimentos variados. Posteriormente, realizaram-se ensaios enzimáticos e microbiológicos no Institute for Tuberculosis Research (ITR), University of Illinois at Chicago, USA. Apesar de os ensaios enzimáticos estarem em andamento, os compostos ensaiados apresentaram atividades que variaram de moderada a fraca, frente à cepa H37Rv. Dois compostos glicosídicos exibiram valores de Concentração Inibitória Mínima (CIM) inferiores a 60 µM, sem efeito citotóxico em células VERO em concentrações superiores a 250 µM. Tais resultados indicam que o análogo glicosídico triazólico aromático, como o NDS 112, pode ser utilizado como protótipo interessante para o planejamento de novas séries de compostos capazes de atuar como tuberculostáticos / Tuberculosis (TB) is an contagious infectious disease mainly caused by Mycobacterium tuberculosis (Mtb). TB was a disease considered in extinction, but its incidence has risen again due to several factors, such as the migration from \"Reservatoir Countries\" and AIDS pandemic. In 2013, WHO estimated 9 million new TB cases and 1.5 million deaths. Multidrug resistance to drugs available in chemotherapy validates the search for new TB drugs. In this context, this work aimed to the design and synthesis of potential inhibitors of maltosyltransferase (GlgE), a new and promissor target against Mtb using Structure-Based Drug Design. Comparison between molecular dynamic simulations of GlgE apo system and in complex with maltose-1-phosphate (M1P) showed important structural changes at molecular level due to substrate binding. Considering these data, docking simulations of potential inhibitors revealed that glucoside and maltoside triazoles analogues bound to substituted aromatic groups have better interaction profiles with the GlgE active site and for this reason they were chosen for synthesis. Thus, glucoside and maltoside triazole analogues were synthetized through click chemistry with different yields. Then, enzymatic and microbiological assays were performed at Institute for Tuberculosis Research (ITR), University of Illinois at Chicago, USA. Although the enzymatic assays are ongoing, componds were tested against H37Rv strains and they have shown activity ranging from moderate to weak. Two compounds presented Minimal Inhibitory Concentration (MIC) values below 60 µM, without cytotoxic effect in VERO cells in concentrations higher than 250 µM. These results indicate that glucosidic aromatic triazoles analogues, such as NDS 112, can be used as a prototype for design new series of compounds capable of acting as antituberculosis agents

Os Clusters de acetato de rutênio de fórmula geral [Ru3O(AcO)6L3]n proporcionam blocos de montagem interessantes para sistemas supramoleculares, exibindo características eletrocrômicas e redox reversível, cobrindo uma ampla faixa de potenciais em solventes aquosos e orgânicos. Nesta Tese, estas espécies foram combinadas com o ligante tridentado, 4\'-piridil-2,2\':6\',2\"-terpiridina (pytpy), produzindo complexos do tipo [Ru3O(AcO)6(pytpy)3]n e [Ru3O(AcO)6(py)2(pytpy)]n, que foram totalmente caracterizados em estado sólido e solução. Nestes complexos a terpiridina permanece disponível para ligar-se a íons metálicos como o Fe(II), gerando um complexo binuclear de baixo spin muito estável, do tipo {Fe[Ru3O(AcO)6(py)2(pytpy)]2}n. Este processo pode ser monitorado eletroquimicamente, partindo de íons Fe(III), que exibem uma baixa afinidade pela terpiridina central, e ciclando o potencial para gerar íons de Fe(II). Desta forma, pode-se executar um procedimento típico de click chemistry, que leva a uma estrutura estendida, Fe-cluster-pytpy na superfície do eletrodo. Este filme conserva a funcionalidade dos blocos de montagem, permitindo aplicações interessantes em dispositivos moleculares, tais como sensores e smart Windows. / Ruthenium acetate clusters of general formula [Ru3O(AcO)6L3]n provide interesting building blocks for assembling supramolecular systems, displaying reversible redox and electrochromic characteristics, over a wide range of potentials in aqueous and organic solvents. In this thesis, such species has been combined with the tritopic, 4\'-pyridil-2,2\':6\',2\"-terpiridine (pytpy) ligand, yielding complexes of the type [Ru3O(AcO)6(pytpy)3]n and [Ru3O(AcO)6(py)2(pytpy)]n, which have been fully characterized in solid state and solution. In these complexes, the terpyridine moiety remains available for binding metals ions, such as Fe(II), generating very stable, low spin binuclear complexes, of the type n. This process can be monitored electrochemically, starting from Fe(III) ions, which exhibits a much lower affinity for the terpyridine center, and cycling the potentials in order to generate Fe(II) ions. In this way, one can start a click chemistry, ending up with an extended structure of Fe-cluster-pytpy film at the electrode surface. This film preserves the functionality of the building block complexes, a llowing many possible applications in molecular devices, such as sensors and smart windows.

Neste trabalho promovemos a síntese de sulfóxidos vinílicos ?-substituídos através da reação de acoplamento cruzado de Suzuki-Miyaura. Também foi feita a síntese de sulfóxidos enínicos inéditos, pela adição do nucleófilo no carbono β-sulfóxido. Esses compostos eram passíveis de serem submetidos a reação de rearranjo de Pummerer aditivo e assim gerarem uma pequena biblioteca de compostos α-tioaldeídos. Um desses aldeídos sintetizados foi empregado na reação de formação de uma imina propargílica, com consequente reação de CuAAC formando iminas triazólicas. Outras iminas arílicas foram sintetizadas, passando por uma etapa de redução, com intuito de se obter a amina livre, para que fosse feita a reação de ciclização com auxílio de um agente eletrofílico. Outra classe de composto organoenxofre foi sintetizada, as N-sulfinil imina, que após a reação de acoplamento cruzado de Sonogashira, com consequente remoção de um grupo protetor e a formação do anel heterocíclico, foram obtidos compostos triazólicos N-sulfinil imínicos. / In this work we promote the synthesis of α-substituted vinylic sulfoxides through the Suzuki-Miyaura cross coupling reaction. Also the synthesis of unpublished enynic sulfoxides was made, by the addition of the nucleophile in the β-sulfoxide carbon. These compounds were susceptible to additive Pummerer rearragement reaction and thus generated a small library of compounds. One of these aldehydes synthesized was used in the formation reaction of a propargyl imine, with consequent CuAAC reaction, forming triazol imines. Other aryl imines were synthesized, undergoing a reduction step, in order to obtain the free amine, so that the cyclization reaction was carried out with the aid of an electrophilic agent. Another class of organosulfur compound was synthesized, the N-sulfinyl imine, which after the Sonogashira cross-coupling reaction, with consequent removal of a protecting group and formation of the heterocyclic ring, N-sulfinyl imine triazolic compounds were obtained.

Target-guided synthesis is an approach to drug discovery that uses the biological target as a template to direct synthesis of its own best inhibitors from small molecule fragments. The process bridges the gap between chemical synthesis of drug candidates and their biological binding assay, merging the two operations into a single process whereby the active site or a binding pocket within the structure of the biological target directly controls the assembly of the best inhibitor in situ. Two different approaches to target-guided synthesis, the thermodynamic approach, making use of reversible reactions, and the kinetic approach, which uses an irreversible reaction, have been employed to discover novel, isoform selective inhibitors of the glutathione transferase (GST) enzyme family – possible drug targets in cancer and parasitic disease treatments. The thermodynamic approach described in this thesis uses the aniline-catalysed reversible acyl hydrazone formation reaction to create a dynamic covalent library of bivalent ligands designed to bind the dimeric structure of GST. In the presence of GST one of the bivalent ligands was selectively amplified at the expense of the other library members. This ligand was shown, via biological assays, to be a specific inhibitor for one isoform of GST, the mu isoform mGSTM1-1. A kinetic approach has also been investigated as a way to identify novel bivalent GST inhibitors utilising the Huisgen 1, 3 dipolar cycloaddition reaction. An azide and alkyne fragment library was designed to bind across the dimeric GST structure. The inhibitor structures are therefore bivalent, containing two anchoring fragments known to bind to the GST active site, linked by a triazolopeptide spacer. The triazole provides the click chemistry disconnection, enabling rapid in situ screening of candidate alkyne and azide fragments for inhibitor discovery. Whilst the in situ reaction with GST yielded inconclusive results, a number of the triazole products were found to have low nanomolar inhibitory activity towards GST.