Os objetivos do presente trabalho foram: i) aprimorar o procedimento alternativo de mediação por íons metálicos da alcoólise da ligação peptidil-resina com vistas à obtenção de ésteres metílicos de peptídeos protegidos (Nα-acil-peptídeo protegido-OMe) em condição reacional branda e com alta eficiência; ii) investigar a aplicabilidade do procedimento para a preparação de Nα-acil-peptídeo protegido-SR e de Nα-acil-aminoácido-OR; iii) verificar se os Nα-acil-peptídeo-OMe obtidos atuariam como doadores de acila em reações de formação de ligação peptídica catalisadas por lipases. Para tanto, na busca da melhor condição de metanólise e comparação com os procedimentos usuais de alcoólise de ligação peptidil-resina, foram usados: o fragmento 22-24 da colecistocinina-33 humana (tripeptídeo modelo), Ca2+, Zn+2, Co+2 e Cu+2 (mediadores), as resinas oxima de Kaiser (KOR), p-hidroximetilfenil acetamidometil, ácido p-hidroximetilbenzóico e álcool p-benziloxibenzil (suportes poliméricos), misturas de MeOH com DCM, DMSO, NMP, THF ou DMF (solventes) e 25, 37, 50 ou 60°C. A condição ótima encontrada [KOR, Ca+2 (1 eq./eq. de peptídeo), 50% MeOH/DMF, 50°C] foi empregada com sucesso na preparação do Nα--acil-heptapeptídeo protegido-OMe, fragmento do peptídeo quimiotático M de Vespa mandarinia. Variações dessa condição foram usadas com sucesso nas preparações dos Nα-acil-tripeptídeo protegido-S(CH2)2COOEt e Nα-acil-Ala-OR (R: Me; Bzl), pois eles foram gerados com boas qualidades e rendimentos similares ou superiores aos obtidos via procedimentos usuais. Após desproteção de cadeias laterais, os Nα-acil-tripeptídeo-OMe e Nα-acil-heptapeptídeo-OMe foram usados em reações de acoplamento com Gly-NH2 em presença de preparações lipásicas comerciais. Estes ensaios inéditos também foram bem sucedidos, pois após adequação das condições reacionais, os Nα-acil-tetrapeptídeo-NH2 e Nα-acil-octapeptídeo-NH2 foram obtidos com boas qualidades e rendimentos de 65% (1 h) e 55% (24 h), respectivamente. / The present work aimed to: i) improve the alternative procedure based on mediation by metal ions of peptide-resin linkage alcoholysis to obtain fully protected peptide methyl esters (Nα-acyl-protected peptide-OMe) under mild reaction condition and with high efficiency; ii) investigate the usefulness of the alternative procedure for preparing Nα-acyl-protected peptide-SR and Nα-acyl-amino acid-OR; iii) verify whether the resulting Nα-acyl-peptide-OMe would act as acyl donors in peptide bond formation catalyzed by lipases. Thus, in the search for the best methanolysis condition and comparison with the usual procedures for that, we used: fragment 22-24 of human cholecystokinin-33 (model tripeptide), Ca+2, Zn+2, Co+2 and Cu+2 (mediators), Kaiser oxime resin (KOR), p-hydroxymethylphenylacetamido methyl resin, p-hydroxymethylbenzoic acid resin and p-benzyloxy benzyl alcohol resin (polymeric supports), mixtures of MeOH and DCM, DMSO, NMP, THF or DMF (solvents) and 25, 37, 50 or 60°C. The optimal condition found [KOR, Ca+2 (1 eq./eq. of peptide), 50% MeOH/DMF, 50°C] was used successfully for preparing Nα-acyl-protected heptapeptide-OMe, fragment 1-7 of the chemotactic peptide M produced by Vespa mandarinia. Variations of this condition were employed successfully for preparing Nα-acyl-protected tripeptide-SR and Nα-acyl-Ala-OR (R: Me, Bzl): indeed, these compounds were obtained in good quality and with similar or superior yields than those provided by usual procedures. After side chain deprotections, the Nα-acyl-tripeptide and Nα-acyl-heptapeptide methyl esters obtained were used in coupling reactions with Gly-NH2 in the presence of commercial lipase preparations. Those pioneer reactions were also successful, since after optimizing the conditions, Nalfa-acyl-tetrapeptide-NH2 and Nα-acyl-octapeptide-NH2 were obtained in good qualities with yields of 65% (1 h) and 55% (24 h), respectively.

This thesis describes the development of new synthetic methodologies for preparation of bioactive interesting compounds, e.g. substituted pyridines, piperidines or piparazines. Thesecompounds are synthesized from commercially available, cheap and easily prepared reagents, videlicet the reaction between Grignard reagents and heterocyclic N-oxides.  The first part of this thesis deals with an improvement for synthesis of dienal-oximes and substituted pyridines. This was accomplished by a rapid addition of Grignard reagents to pyridine N-oxides at rt. yielding a diverse set of substituted dienal-oximes. During these studies, it was observed that the obtained dienal-oxmies are prone to ring-close upon heating. By taking advantage of this, a practical synthesis of substituted pyridines was developed. In the second part, an ortho-metalation of pyridine N-oxides using Grignard reagents is discussed. The method can be used for incorporation of a range of different electrophiles, including aldehydes, ketones and halogens. Furthermore, the importance for incorporation of halogens are exemplified through a Suzuki–Miyaura coupling reaction of 2-iodo pyridine N-oxides and different boronic acids. Later it was discovered that if the reaction temperature is kept below -20 °C, the undesired ringopening can be avoided. Thus, the synthesis of 2,3-dihydropyridine N-oxide, by reacting Grignard reagents with pyridine N-oxides at -40 °C followed by sequential addition of aldehyde or ketone, was accomplished. The reaction provides complete regio- and stereoselectivity yielding trans-2,3-dihydropyridine N-oxides in good yields. These intermediate products could then be used for synthesis of either substituted piperidines, by reduction, or reacted in a Diels–Alder cycloaddtion to give the aza-bicyclo compound. In the last part of this thesis, the discovered reactivity for pyridine N-oxides, is applied on pyrazine N-oxides in effort to synthesize substituted piperazines. These substances are obtained by the reaction of Grignard reagents and pyrazine N-oxides at -78 °C followed by reduction and protection, using a one-pot procedure. The product, a protected piperazine, that easily can be orthogonally deprotected, allowing synthetic modifications at either nitrogens in a fast and step efficient manner. Finally, an enantioselective procedure using a combination of PhMgCl and (-)-sparteine is discussed, giving opportunity for a stereoselective synthesis of substituted piperazines.

Die vorliegende Arbeit befasst sich mit der Synthese, dem Reaktionsverhalten, den Festkörperstukturen und den elektronischen Eigenschaften von neuartigen Übergansmetall-komplexen der Gruppen 4, 8 und 10 des Peridoensystems der Elemente. Die Arbeit befasst sich unter anderem mit der Darstellung von Alkyloxy- und Aryloxy-substituierten Titanocenverbindungen des Typs [Ti](Cl)(OR) {[Ti] = (C5H5SiMe3)2Ti; R = organischer Rest). Mittels cyclovoltammetrischer Experimente und anhand von Festkörpestrukturen wird der elektronische Einfluss der organischen Reste auf das Metallzentrum untersucht. Weiterhin befasst sich die Arbeit mit der Synthese von in para-Position substituierten NCN-Pincerverbindungen. Durch die Wahl des Substituenten in para-Postition sowie des Übergangsmetalls der Gruppe 10 des Periodensystems der Elemente ist es möglich, verschiedenartig gerichtete polymere Strukturen zu bilden. Ein weiterer Schwerpunkt der vorliegenden Arbeit liegt in der Synthese und Untersuchung der elektronischen Eigenschaften von NCN-Pincer-substituierten Ferrocenen. Der Einfluss der NCN-Pincer auf die Elektronendichte des Ferrocens wird bestimmt sowie die Eignung derartiger Systeme als elektrochemische Sensoren zur molekularen Erkennung von Schwefeldioxid wird untersucht.

A facile method for the direct conversion of oximes into carbonyl compounds by treatment with manganese triacetate is described. Manganese triacetate can be used for an effective and mild oxidizing agent for the regeneration of carbonyl compounds in good yield. Many functional groups are tolerated under reaction conditions.

Os objetivos do presente trabalho foram: i) aprimorar o procedimento alternativo de mediação por íons metálicos da alcoólise da ligação peptidil-resina com vistas à obtenção de ésteres metílicos de peptídeos protegidos (Nα-acil-peptídeo protegido-OMe) em condição reacional branda e com alta eficiência; ii) investigar a aplicabilidade do procedimento para a preparação de Nα-acil-peptídeo protegido-SR e de Nα-acil-aminoácido-OR; iii) verificar se os Nα-acil-peptídeo-OMe obtidos atuariam como doadores de acila em reações de formação de ligação peptídica catalisadas por lipases. Para tanto, na busca da melhor condição de metanólise e comparação com os procedimentos usuais de alcoólise de ligação peptidil-resina, foram usados: o fragmento 22-24 da colecistocinina-33 humana (tripeptídeo modelo), Ca2+, Zn+2, Co+2 e Cu+2 (mediadores), as resinas oxima de Kaiser (KOR), p-hidroximetilfenil acetamidometil, ácido p-hidroximetilbenzóico e álcool p-benziloxibenzil (suportes poliméricos), misturas de MeOH com DCM, DMSO, NMP, THF ou DMF (solventes) e 25, 37, 50 ou 60°C. A condição ótima encontrada [KOR, Ca+2 (1 eq./eq. de peptídeo), 50% MeOH/DMF, 50°C] foi empregada com sucesso na preparação do Nα--acil-heptapeptídeo protegido-OMe, fragmento do peptídeo quimiotático M de Vespa mandarinia. Variações dessa condição foram usadas com sucesso nas preparações dos Nα-acil-tripeptídeo protegido-S(CH2)2COOEt e Nα-acil-Ala-OR (R: Me; Bzl), pois eles foram gerados com boas qualidades e rendimentos similares ou superiores aos obtidos via procedimentos usuais. Após desproteção de cadeias laterais, os Nα-acil-tripeptídeo-OMe e Nα-acil-heptapeptídeo-OMe foram usados em reações de acoplamento com Gly-NH2 em presença de preparações lipásicas comerciais. Estes ensaios inéditos também foram bem sucedidos, pois após adequação das condições reacionais, os Nα-acil-tetrapeptídeo-NH2 e Nα-acil-octapeptídeo-NH2 foram obtidos com boas qualidades e rendimentos de 65% (1 h) e 55% (24 h), respectivamente. / The present work aimed to: i) improve the alternative procedure based on mediation by metal ions of peptide-resin linkage alcoholysis to obtain fully protected peptide methyl esters (Nα-acyl-protected peptide-OMe) under mild reaction condition and with high efficiency; ii) investigate the usefulness of the alternative procedure for preparing Nα-acyl-protected peptide-SR and Nα-acyl-amino acid-OR; iii) verify whether the resulting Nα-acyl-peptide-OMe would act as acyl donors in peptide bond formation catalyzed by lipases. Thus, in the search for the best methanolysis condition and comparison with the usual procedures for that, we used: fragment 22-24 of human cholecystokinin-33 (model tripeptide), Ca+2, Zn+2, Co+2 and Cu+2 (mediators), Kaiser oxime resin (KOR), p-hydroxymethylphenylacetamido methyl resin, p-hydroxymethylbenzoic acid resin and p-benzyloxy benzyl alcohol resin (polymeric supports), mixtures of MeOH and DCM, DMSO, NMP, THF or DMF (solvents) and 25, 37, 50 or 60°C. The optimal condition found [KOR, Ca+2 (1 eq./eq. of peptide), 50% MeOH/DMF, 50°C] was used successfully for preparing Nα-acyl-protected heptapeptide-OMe, fragment 1-7 of the chemotactic peptide M produced by Vespa mandarinia. Variations of this condition were employed successfully for preparing Nα-acyl-protected tripeptide-SR and Nα-acyl-Ala-OR (R: Me, Bzl): indeed, these compounds were obtained in good quality and with similar or superior yields than those provided by usual procedures. After side chain deprotections, the Nα-acyl-tripeptide and Nα-acyl-heptapeptide methyl esters obtained were used in coupling reactions with Gly-NH2 in the presence of commercial lipase preparations. Those pioneer reactions were also successful, since after optimizing the conditions, Nalfa-acyl-tetrapeptide-NH2 and Nα-acyl-octapeptide-NH2 were obtained in good qualities with yields of 65% (1 h) and 55% (24 h), respectively.

Une des principales limites de la chimiothérapie du cancer est le manque de sélectivité des agents cytotoxiques vis-à-vis des cellules tumorales, entrainant de nombreux effets secondaires. L’intérêt de la vectorisation est d’administrer l’agent cytotoxique sélectivement aux cellules cancéreuses et ainsi d’éviter de faire subir l’action du médicament aux cellules saines. Cette thèse a pour but de synthétiser des prodrogues multivalentes qui utilisent la sous unité B de la toxine de Shiga (STxB) comme agent de vectorisation, ciblant préférentiellement les cellules cancéreuses Gb3-positives. Les deux agents cytotoxiques choisis, un dérivé de la camptothécine et de l’auristatine, ont été liés de façon covalente auvecteur via un espaceur bifonctionnel clivable par le glutathion. L’espaceur a également été remplacé par un répartiteur multivalent susceptible de délivrer une quantité plus importante d’agent cytotoxique à l’intérieur des cellules tumorales.Parallèlement à ce projet de vectorisation d’un agent thérapeutique, des sondes IRM capables de marquer in vivo les tumeurs possédant à leur surface le récepteur Gb3 ont été synthétisées. L’IRM a une très bonne définition spatiale, mais souffre d’un manque de sensibilité. Pour augmenter le contraste, nous avons utilisé une stratégie reposant sur lamultivalence des espaceurs liés à des molécules de DOTA-Gd, un agent de contraste classiquement utilisé en IRM. Ces dernières ont été fixées à STxB via un répartiteur multivalent (des nano-bâtonnets d’or). Le signal IRM est plus intense et donc plus facile à détecter. Enfin, nous avons développé une nouvelle méthode chimique basée sur la ligationoxime pour optimiser la création de conjugués entre STxB et des antigènes comme outils de vaccination. Le conjugué STxB-ovalbumine a permis une meilleure présentation de l’antigène par les cellules dendritiques, conduisant chez la souris à une induction efficace de lymphocytes T. / Pas de résumé en anglais

La recherche actuelle sur le cancer se tourne vers des « stratégies ciblées » afin de développer de nouvelles méthodes diagnostiques plus sensibles et performantes, ainsi que de nouvelles thérapies plus efficaces mais aussi mieux tolérées. Dans ce contexte, nos travaux sont consacrés à la conception de vecteurs synthétiques ciblant un récepteur cellulaire surexprimé par les tumeurs, l'intégrine alphaVbeta3. Ce ciblage permet de concentrer les drogues ou les éléments de détection au niveau tumoral. L'outil utilisé pour la construction chimique de nos vecteurs est un châssis décapeptidique cyclique RAFT (Regioselectively Addressable Functionalized Template) présentant deux domaines indépendants permettant de séparer les deux fonctions du vecteur. Sur un domaine, la fonction de ciblage est assurée par la présentation multivalente de ligands -RGD- spécifiques du récepteur. L'autre domaine du vecteur supporte les molécules d'intérêt à vectoriser : agents thérapeutiques pour limiter la prolifération du foyer malin ou agents de détection pour l'imagerie médicale.

Récemment, de nombreux efforts ont été consacrés au développement d'oligonucléotides synthétiques pour des applications thérapeutiques et de diagnostique variées. Les oligonucléotides modifiés peuvent inhiber sélectivement l'expression des gènes en se liant spécifiquement à des séquences d'ADN et/ou d'ARN ciblées à travers les stratégies antigène, antisens ou d'ARN interférent. Les aminoxy peptides forment facilement des structures secondaires bien définies comme des alpha-, béta-, gamma-turns ou des hélices, ce qui nous a inspiré pour concevoir de nouveaux oligonucléotides modifiés dans le but d'étudier leurs propriétés physico-chimiques et biologiques. Au cours de ce travail, la synthèse de nucléosides aminoxy acides et de leurs oligomères a été entreprise en séries ribose et désoxyribose. Dans la première partie, les fonctions aminoxyle, acide carboxylique et aldéhyde ont été introduites sur la partie osidique de la thymidine. Différents nucléosides monofonctionnalisés ont été synthétisés à l'aide notamment des réactions de Mitsunobu, d'O-allylation et d'oxydation. Les nucléosides monomères ont ensuite été couplés entre eux conduisant aux nouveaux dinucléosides liés par liaison N-oxy amide, oxime et aminoxy. Dans la seconde partie, la synthèse de différentes uridines aminoxy acides a été étudiée à partir de l'uridine, des 2,2'-anhydro et 2,3'-anhydro uridines. Une uridine aminoxy ester a pu être obtenue en passant par la 3'-oxo uridine via une homologation (réaction de Wittig) et l'introduction de la fonction oxyamine en position 5' par une substitution nucléophile du dérivé iodé. En parallèle, dans la continuité des travaux réalisés au laboratoire sur la synthèse des glycoamino acides, nous avons synthétisé des C-glycosyl aminoxy acides jamais décrits dans la littérature, dans le but de générer de nouveaux mimes de glycopeptides. A partir du C-allyl glucopyranoside perbenzylé, deux C-glucosyl aminoxy acides diastéréoisomères ont été préparés.

Made available in DSpace on 2015-05-14T12:59:37Z (GMT). No. of bitstreams: 1 parte1.pdf: 2125844 bytes, checksum: f5e0174d3679c5bce4f74af8ed1b3d4f (MD5) Previous issue date: 2009-08-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Decreased availability of NO in the vasculature promotes the progression of cardiovascular diseases and oximes represents a NO-donor group capable of to restore this defictIn rat superior mesenteric arterial rings, as non-aromatic oximes: diacetylmonoxime and dimetylglycone-oxime, as aromatic oximes: benzofenone-oxime, 4-Cl-benzofenone and cinnamaldheyde-oxime isomeric mixture were markedly less potent than tans-E-cinnamaldheyde-oxime (E CAOx) whose relaxation was concentration-dependent in denuded-endothelum pre-contracted rings with PHE (pD2 = 5,11 ± 0,05), or U46619 (pD2 = 5,03 ± 0,06), an tromboxanic agonist TP, or with A23187 (pD2 = 4,70 ± 0,06), an Ca2+ ionophore, beyond KCl 60mM (pD2 = 4,50 ± 0,06). The relaxation was not modified by endothelium or L-NAME (100 μM, NOS inhibitor), proadifen (30 M; inibidor do citocromos P450), ou de N-acetyl-L-Cysteyn (1 mM e 3 mM; an NO- scavenger). However, was affected by cytochromos P4501A1 and NADPH-dependent reductases inhibitor, 7ethoxyresorufin (7 ER, 10 μM; pD2 = 4,82 ± 0,07), and NO scavenger, PTIO (300 M; pD2 = 4,68 ± 0,11). Demonstrating that E-CAOx induces independent-endothelium relaxation with a possible NO production, mediated by NADPH-dependent reductases. These results corroborate with E-CAOx action of to increase DAF-T fluorescence, in rat aorta smooth miocytes, abolished by 7-ER pre-incubation. Futhermore, the Emax decrease caused by (Rp)-8pCPT-cGMPS (10 M; PKG inhibitor), plus potency reduction by ODQ presence (0,1 M; pD2 = 4,65 ± 0,07 e 10 M; pD2 = 4,41 ± 0,04), a soluble guanylyl-cyclase inhibitor, reforce the pathway NO/cGC/cGMP/PKG participation. On the other hand, the presences of KCl 20mM and TEA (1 mM; pD2 = 4,62 ± 0,04), a BKCa blocker, were capable of the interfering in response, but not 4-AP (1 mM; Kv blocker) and Glibenclamide (10 M; a KATP blocker). In ODQ (10 M) combinations, only KCl 20mM, interpose on Emax, suggesting that K+ channels contribution, majorly BKCa, is sGC-activation dependent. Due relaxing pre-contracted rings: with S(-)BayK 8644 (pD2 = 4,95 ± 0,05), a direct activator of dihydropiridine-sensitive Cav, and rings pre-contracted with PHE in the presence of Niphedipine (1 M), E-CAOx can also to be acting by inhibits Ca2+ influx through dihydropiridine-sensitive Cav or to interfere in contract mechanisms ulterior to Ca2+ entry, as is the case of Na+/Ca2+ exchanger. This hypothesis is justified by reduction in response due the Ni+2 presence (Na+/Ca2+ inhibitor). In conclusion, the data shown that E-CAOx was the more potent oxime investigated with NO production thougth NADPH-dependent reductases action and subsequentely pathway CGs/GMPc/PKG activation associated to BKCa activation, Cav inhibition and exchalenger Na+/Ca2+activation. / Uma diminuição da disponibilidade do NO na vasculatura promove a progressão de doenças vasculares e as oximas representam um grupo de doadores de NO capaz de reestabelecer tal deficiência. Em anéis de artéria mesentérica superior isolada de rato, tanto as oximas não aromáticas: diacetilmonoxima e dimetilglioxima, quanto as oximas aromáticas: benzofenona-oxima, 4 Cl benzofenona-oxima e a mistura isômera de cinamaldeído-oximas foram menos potentes que trans-cinamaldeído-oxima (E-CAOx) cujo relaxamento foi dependente de concentração em anéis pré-contraídos com: FEN (pD2 = 5,11 ± 0,05), um agonista adrenérgico, ou com U46619 (pD2 = 5,03 ± 0,06), um agonista tromboxânico TP, ou com A23187 (pD2 = 4,70 ± 0,06), um ionóforo de íons Ca2+, além de KCl 60mM (pD2 = 4,50 ± 0,06). O relaxamento não foi modificado pela presença do endotélio ou de L-NAME (100 M; inibidor das sintases de NO), proadifeno (30 M; inibidor do citocromos P450), ou de N-acetil-L-cisteína (1 mM e 3 mM; seqüestrador de NO-). Entretanto, foi afetado pela presença do inibidor de citocromos P4501A1 e de redutases dependentes de NADPH, 7-Etoxi-resurofino (7-ER, 10 M; pD2 = 4,82 ± 0,07), e do sequestrador de NO, PTIO (300 M; pD2 = 4,68 ± 0,11). Demonstrando que E-CAOx causa um relaxamento independente de endotélio com possível produção de NO , mediado por redutases dependentes de NADPH. Tais resultados corroboram com a ação de E-CAOx em aumentar a fluorescência emitida por DAF-T, em mióciotos de aorta de rato, abolida pela presença de 7-ER (10 M). Além disso, a diminuição do efeito máximo de E-CAOx causada pela presença de (Rp)-8pCPT-cGMPS (10 M; inibidor da PKG), somada à diminuição da potência causada pelo ODQ (0,1M; pD2 = 4,65 ± 0,07 e 10M; pD2 = 4,41 ± 0,04), um inibidor da ciclase de guanilil solúvel (CGs), reforçam a participação da via NO/CGs/GMPc/PKG. Por outro lado, as presenças de KCl 20mM (pD2 = 4,78 ± 0,04) e de TEA (1 mM; pD2 = 4,62 ± 0,04), um bloqueador de BKCa, foram capazes de interferir na resposta, mas 4-aminopiridina (1 mM; bloqueador de Kv) e Glibenclamida (10 M; bloqueador de KATP) não. Em combinações com ODQ (10M), apenas KCl 20 mM, interferiu no Emax, sugerindo que a contribuição dos canais para K+, principalmente dos BKCa, é dependente da ativação da CGs. Por relaxar anéis pré-contraídos com S(-)BayK 8644 (pD2 = 4,95 ± 0,05), um ativador direto dos Cav sensíveis à diidropiridinas, e anéis pré-contraídos com FEN na presença de nifedipino (1 M; inibidor dos Cav), E-CAOx pode também estar atuando por inibir o influxo de íons Ca2+ ou interferir em mecanismos contráteis posteriores à entrada de Ca2+, como é o caso do trocador Na+/Ca2+. Tal hipótese é justificada pela redução da resposta provocada pela presença do Ni+2 (inibidor do trocador Na+/Ca2+). Em conclusão, os dados demonstram que E-CAOx foi a oxima investigada mais potente e que produz NO via ação das redutases dependentes de NADPH com subseqüente ativação da via CGs/GMPc/PKG associada à ativação dos BKCa, inibição dos Cav e ativação do trocador Na+/Ca2+.

Die vorliegende Arbeit befasst sich mit der Synthese, dem Reaktionsverhalten, den Festkörperstukturen und den elektronischen Eigenschaften von neuartigen Übergansmetall-komplexen der Gruppen 4, 8 und 10 des Peridoensystems der Elemente. Die Arbeit befasst sich unter anderem mit der Darstellung von Alkyloxy- und Aryloxy-substituierten Titanocenverbindungen des Typs [Ti](Cl)(OR) {[Ti] = (C5H5SiMe3)2Ti; R = organischer Rest). Mittels cyclovoltammetrischer Experimente und anhand von Festkörpestrukturen wird der elektronische Einfluss der organischen Reste auf das Metallzentrum untersucht. Weiterhin befasst sich die Arbeit mit der Synthese von in para-Position substituierten NCN-Pincerverbindungen. Durch die Wahl des Substituenten in para-Postition sowie des Übergangsmetalls der Gruppe 10 des Periodensystems der Elemente ist es möglich, verschiedenartig gerichtete polymere Strukturen zu bilden. Ein weiterer Schwerpunkt der vorliegenden Arbeit liegt in der Synthese und Untersuchung der elektronischen Eigenschaften von NCN-Pincer-substituierten Ferrocenen. Der Einfluss der NCN-Pincer auf die Elektronendichte des Ferrocens wird bestimmt sowie die Eignung derartiger Systeme als elektrochemische Sensoren zur molekularen Erkennung von Schwefeldioxid wird untersucht.