Chloroperoxidase (CPO) is one of the most versatile heme enzyme isolated from the marine fungus, Caldariomyces fumago. Functionally, CPO can catalyze four types of reactions: peroxidation (peroxidase-like), dismutation (catalase-like), halogenation (halogenase-like), and peroxygenation (P450-like). Structurally, CPO has a distal and proximal pockets that can be best described as a hybrid of classical peroxidase and P450s. As a heme-thiolate protein, CPO contains the conserved proximal Pro28-Cys29-Pro30 stretch found in other members of the family. However, the structural and functional roles of these proline residues remain poorly understood. Site-directed mutagenesis was undertaken to generates three CPO mutants, P28A-, P30A-, P28A/P30A-CPO. The replacement of the rigid proline with a more flexible alanine residue, freed up the back bone amide for the formation of additional amide-sulfur hydrogen bond, allowing the investigation of the importance of these residues in CPO catalysis. The three CPO mutants displayed dramatic difference in ligand binding affinity and catalytic activities relative to WT-CPO. Any mutations on the proline resides within the proximal loop eliminated the halogenation and dismutation activities but enhanced the vii epoxidation and peroxidation activities by 4-14 fold. As the binding affinity for cyanide, the CPO mutants displayed significantly higher dissociation constant relative to WT-CPO. Our results revealed that Pro28 and Pro30 play important roles in maintaining the versatility of CPO. As a versatile enzyme, CPO has great application potential in pharmaceutical and chemical industry due to its ability to catalyze the formation of chiral epoxides. Phe103 and Phe186 located on the distal pocket have been proposed to guard the access of substrates to the ferryl oxygen of the heme center. The interactions of these two phenylalanine residues restricted the size of substrates and regulates CPO’s enantioselectivity. F186A- and F103A/F186A-CPO were generated and characterized where the rate of peroxidation and epoxidation were significantly enhanced at the expense of halogenation and dismutation activities. Our results demonstrated that Phe186 played a subtler role relative to Phe103 in terms of substrate specificity and product enantioselectivity of CPO.

Cette thèse présente la synthèse et la caractérisation de complexes moléculaires bio-inspirés àliaison métal-thiol avec l'objectif de modéliser le site actif de certaines métalloenzymes. Enparticulier, notre but était d'améliorer notre compréhension sur le rôle que joue cette liaisonmétal-thiol dans les métalloenzymes, notamment au niveau de ses propriétés structurales etélectroniques ainsi que sur la réactivité des sites actifs associés. Le thiol lié à un métal peut êtresujet à deux types de réaction dans métalloenzymes : les réaction de S- alkylation ou de Soxygénation.Il a été montré que la réactivité de ces ligands thiols dépend fortement de la naturede l'ion métallique. Dans ce contexte, différents complexes thiolate Mn+ ont été synthétisés (VIII,VIV, VV, NiII, NiIII, CoII et CoIII), soit avec un ligand LN2S2 tétradentate ou LNS2 tridentate. Ces deuxligands sont constitués d'un ou deux azote(s) aromatique(s) (bipyridine ou pyridine) et de deuxthiols aliphatiques encombrants.Nous avons montré que le CoII ion représente un substitut structural satisfaisant pour lesmétalloenzymes contenant du zinc. Cependant, il n'est pas approprié comme substitutfonctionnel dans le cas particulier de la réaction de S- alkylation. En outre, nous avons pumodéliser l'étape d'activation de nitrile hydratase à cobalt, avec l'incorporation de trois atomesd'oxygène sur un complexe bis-thiolate de CoIII présentant la même dissymétrie que dansl’enzyme lors de la réaction de S- oxygénation. En revanche, avec le vanadium et le nickel, desespèces métal-peroxo ont pu être générées sans réaction intramoléculaire de S- oxygénation.Nos travaux ont ainsi conduit à l’obtention des premiers exemples de complexes peroxos dunickel et du vanadium possédant des liaisons métal-thiol.Nous avons également tenté de modéliser des réactions réalisées par des métalloenzymes dontle site actif est riche en soufre, dont l'activation et la réduction du diazote en ammoniac, réactionréalisée par les nitrogénases. Pour modéliser ces enzymes, un complexe thiolate du VIII a étésynthétisé et sa réactivité étudiée. Nos résultats préliminaires suggèrent que l’espèce réduite deVII correspondante est capable d'activer et de réduire l’hydrazine en ammoniac, réactioncorrespondant à la dernière étape de la réduction du diazote. / This thesis presents the synthesis and characterisation of bio-inspired molecular complexescontaining metal alkyl thiolate bonds with the goal of modelling metalloenzymes. In particular,we have attempted to improve our knowledge on the role that the bound alkyl thiolate plays inmetalloenzymes, including, structural features, electronic properties and also reactivity of theassociated active sites. The bound alkyl thiolate undergoes two main reactions inmetalloenzymes; S-alkylation and S-oxygenation. From the isolation and characterisation of thecorresponding active sites, it can be seen that the reactivity of the bound alkyl thiolate dependsgreatly on the metallic ion. In this context, different Mn+-thiolate complexes have beensynthesized (VIII, VIV, VV, NiII, NiIII, CoII and CoIII), with either a tetradentate LN2S2 or a tridentateLNS2 ligand. Both ligands consist of aromatic nitrogen (bipyridine or pyridine) donor atom(s)and also two bulky S-thiolate donor atoms.We have shown that the CoII ion is a suitable structural substitute for Zn-containingmetalloenzymes, however, it is inappropriate as a functional substitute in the particular case ofS-alkylation. Furthermore, we have been able to structurally model the activation step of cobaltnitrile hydratase, with the incorporation of three oxygen atoms on a CoIII bis alkyl thiolatecomplex evidencing dissymmetrical S-oxygenation. In contrast, using vanadium and nickel,metal-peroxo species have been generated, without intramolecular S-oxygenation. This researchhas led to some of the first examples of active oxygen nickel and vanadium complexes usingalkyl thiolate ligands.We have also attempted to model very difficult reactions carried out by sulfur richmetalloenzymes, especially the activation and reduction of dinitrogen realised by nitrogenases.To model this enzyme, a VIII alkyl thiolate complex has been synthesised and its reactivityinvestigated. Preliminary results suggest that the reduced VII species has the ability to activateand reduce hydrazine into ammonia, which is proposed to be the final stage of dinitrogenreduction.

Ce projet concerne la synthèse et caractérisation de nouveaux matériaux composites à base de nanoclusteurs de thiolates d’or Au25(SR)18 (tGNCs), supportés sur divers polymères de coordination (MOFs), ainsi que sur ZrO2. L’activité catalytique de ces matériaux a été évaluée sur la transformation de différents substrats. Les tGNCs sont des matériaux atomiquement bien définis et connus pour être actifs dans des réactions d’oxydation. Les nanoparticules de MOFs sont des matériaux pouvant servir de support pour des tGNCs avec de bonnes dispersions. Certains MOFs sont connus pour avoir des propriétés acides et peuvent être actifs en catalyse. Parmi eux, MIL-101 (Cr), UiO-66 (Zr) et ZIF-8 (Zn) on été choisis en raison de leur propriétés acides et/ou de stabilité thermique. La synergie entre les tGNCs et les MOFs a été évaluée à travers la conversion catalytique de différents substrats tels le glucose, le fructose, l’alcool benzylique et le furfural, impliquant des étapes nécessitant un caractère acide et/ou oxydant. Globalement, il n’a pas été observé d’impact de la présence d’or sur la réactivité de ces substrats, et les tendences catalytiques sont celles obtenues avec les MOFs seuls. Cela est certainement dû à la stabilité thermique non suffisante des MOFs qui prévient une calcination efficace des tNGCs. Lorsque ces clusters sont déposés sur ZrO2, il a été possible de les calciner à différentes températures pour étudier l’effet du ligand et de la taille de particules, pour des réactions d’oxydation en phase liquide. Ainsi, il a été montré par exemple que la température de calcination a un impact significatif sur le comportement catalytique de ces composites, qui ont donné de bonnes activités pour l’oxydation de l’alcool benzylique en benzaldéhyde dans le toluène et en conditions douces, et pour l’esterification oxydante du furfural en furoate de méthyle / This research project reports the synthesis and characterization of new composite materials based on Au25(SR)18 thiolate gold nanoclusters (tGNCs), supported over a range of metal organic frameworks (MOFs), and ZrO2. The synthesized composite materials were tested for catalytic transformations of various substrates. tGNCs are atomically well defined materials known to be active in oxidation reactions. MOFs nanoparticles are materials suitable for high dispersion of tGNCs. Some MOFs are known to have acidity and can be active as catalysts. Among them, MIL-101 (Cr), UiO-66 (Zr) and ZIF-8 (Zn) were chosen due to their acidic and/or thermal stability properties. The synergy between tGNCs and MOFs has been tested through catalytic conversions of different substrates like glucose, fructose, benzylalcohol and furfural, involving steps requiring acidic and oxidative features. Globally, no impact of the presence of Au clusters was observed, and the composite materials showed the same catalytic trends as those obtained with the MOFs alone. This is mainly due to the not sufficient thermal stability of the MOFs that prevents efficient calcination of the tGNCs. In contrast, when deposited on ZrO2 it was possible to calcine Au25(SG)18 nanoclusters at different temperatures to study the ligand and particle size effects in liquid phase oxidation reactions. For example, the calcination temperature had a significant impact on the catalytic behaviour of this composite materials, which showed good activity for the oxidation of benzyl alcohol into benzaldehyde in toluene under mild conditions, and of furfural oxidative esterification into methyl-2-furoate

Hauptziel dieser Arbeit ist die Synthese und Charakterisierung neuer Organosilicium-Chalcogen-Verbindungen (Chalcogen: Schwefel, Selen, Tellur), sowohl mit acyclischen, als auch mono- und polycyclischen Strukturen. Dabei konnten in vielen Fällen auch isostrukturelle Verbindungen mit Germanium- oder Zinnatomen anstelle von Silicium aufgebaut werden. Insgesamt wurden 42 der dargestellten Verbindungen auch durch Röntgenkristallstrukturanalysen charakterisiert. In cyclischen und polycyclischen Verbindungen war es damit auch möglich, die auftretenden Konformationen der Ringe- bzw. Ringsysteme zu bestimmen und die Resultate mit den Ergebnissen von DFT-Berechnungen zu vergleichen. Die NMR-Spektroskopie war parallel zu Kristallstrukturanalysen und GC/MS Messungen die Methode der Wahl zur Charakterisierung der dargestellten Verbindungen. Dabei boten sich neben der 1H und 13C NMR auch die 29Si, 119Sn, 207Pb, 77Se, und 125Te NMR Spektroskopie an, da man direkt die Elemente analysiert, die die Ringsysteme aufbauen, was zu einer weit höheren Strukturempfindlichkeit führt. Vor allem beim Vergleich von 77Se und 125Te NMR Daten analoger Selen- und Tellurverbindungen ergaben sich lineare Korrelationen sowohl der chemischen Verschiebungen als auch der Kopplungskonstanten 1JSiE bzw. 1JSnE mit Faktoren von ca. 2.5. Ähnliche Korrelationen konnten auch zwischen 29Si und 119Sn bzw. 119Sn und 207Pb NMR chemischen Verschiebungen gezogen werden. Von einigen Verbindungen konnten durch 29Si MAS NMR Spektroskopie auch die Tensorhauptwerte der chemischen Verschiebung ermittelt werden. Parallel dazu wurden mittels GIAO und IGLO Verfahren die 29Si NMR chemischen Verschiebungen ausgehend von den aus den Kristallstrukturanalysen zugänglichen Geometrien berechnet. Neben cyclischen Verbindungen konnten unter Verwendung des sperrigen Hypersilylrestes auch eine Reihe acyclischer Verbindungen mit der Sequenz Si–E–Si bzw. Si–E–Sn dargestellt und z. T. auch strukturell charakterisiert werden.

Two unspecific peroxygenases (UPO, EC 1.11.2.1) from the basidiomycetous fungi Marasmius rotula and Marasmius wettsteinii oxidized steroids with hydroxyacetyl and hydroxyl functionalities at C17 - such as cortisone, Reichstein's substance S and prednisone - via stepwise oxygenation and final fission of the side chain. The sequential oxidation started with the hydroxylation of the terminal carbon (C21) leading to a stable geminal alcohol (e.g. cortisone 21-gem-diol) and proceeded via a second oxygenation resulting in the corresponding α-ketocarboxylic acid (e.g. cortisone 21-oic acid). The latter decomposed under formation of adrenosterone (4-androstene-3,11,17-trione) as well as formic acid and carbonic acid (that is in equilibrium with carbon dioxide); fission products comprising two carbon atoms such as glycolic acid or glyoxylic acid were not detected. Protein models based on the crystal structure data of MroUPO (Marasmius rotula unspecific peroxygenase) revealed that the bulky cortisone molecule suitably fits into the enzyme's access channel, which enables the heme iron to come in close contact to the carbons (C21, C20) of the steroidal side chain. ICP-MS analysis of purified MroUPO confirmed the presence of magnesium supposedly stabilizing the porphyrin ring system.

Submitted by Maike Costa (maiksebas@gmail.com) on 2017-06-20T11:50:06Z No. of bitstreams: 1 arquivototal.pdf: 10487656 bytes, checksum: 9f874336a1873756d7bc4d26e57ee76d (MD5) / Made available in DSpace on 2017-06-20T11:50:06Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 10487656 bytes, checksum: 9f874336a1873756d7bc4d26e57ee76d (MD5) Previous issue date: 2016-05-13 / This work describes the synthesis, characterization and antifungal potential of twelve mesoionic derivatives from the 1,3-thiazolium-5-thiolate system. The compounds, totally unprecedented, were divided in two classes: one class derived from the mesoionic 2-(4-chlorophenyl)-3-methyl-4-(4-isopropylphenyl)-1,3-thyazolium-5- thiolate with ten substituted acetamides and other class derived from the mesoionic 2- (4-chlorophenyl)-3-methyl-4-(4-methylphenyl)-1,3-thyazolium-5-thiolate also with ten substituted acetamides. This compounds synthesis, which presented satisfactory yields (85 to 95 %), occurred in four stages: first the intermediary N-methyl-Carylglicine was synthesized via Strecker reaction with p-substituted aldehydes, followed by its aroylation to obtain N-methyl-N-aroyl-C-arylglicine, the next step was its cyclodehydration with acetic anhydride, 1,3-dipolar cycloaddition and cyclorevertion induced by CS2 to obtain the mesoionic compounds from the 1,3- thiazolium-5-thyolate as free base. Lastly, the mesoionic compounds were converted into his respective salts by the treatment with ten substituted acetamides. All compounds were characterized by spectroscopic techniques IR, NMR 1H and NMR 13C, and their antifungal potential against five strains of Candida albicans were evaluated. Only four compounds exhibited efficient activity (MI-1-A3, MI-1-A4, MI- 1-A6 and MI-1-A7) with MIC between 256 – 512 μg mL-1. An in silico investigation of the mesoionic compounds, the substituted acetamides and the mesoionic derivatives was also made and the results showed that both mesoionic compounds and his derivatives are good candidates to be a drug while all substituted acetamides should present high toxicity. / Neste trabalho descreve-se a síntese, caracterização e potencial antifúngico de vinte derivados mesoiônicos do sistema 1,3-tiazólio-5-tiolato. Os compostos, inéditos, foram divididos em duas classes: uma classe de compostos derivados do mesoiônico 2-(4-clorofenil)-3-metil-4-(4-isopropilfenil)-1,3-tiazólio-5-tiolato com dez acetamidas substituídas e outra classe de compostos derivados do mesoiônico 2-(4-clorofenil)-3- metil-4-(4-metilfenil)-1,3-tiazólio-5-tiolato e também com dez acetamidas substituídas. A síntese desses compostos, que apresentou rendimentos satisfatórios (85 a 95 %), ocorreu em quatro etapas: primeiramente o intermediário N-metil-Carilglicina foi sintetizado via reação de Strecker com aldeídos p-substituídos, seguido de sua aroilação para obter o N-metil-N-aroil-C-arilglicina, seguida da ciclo desidratação com anidrido acético, cicloadição e cicloreversão 1,3-dipolar induzida por CS2 para obter os mesoiônicos do sistema 1,3-tiazólio-5-tiolato na forma de base livre. Por fim os mesoiônicos foram convertidos em seus respectivos sais através do tratamento com dez acetamidas substituídas. Todos os compostos, intermediários, mesoiônicos, acetamidas e derivados mesoiônicos, foram caracterizados por técnicas espectroscópicas de IV, RMN de 1H e 13C e avaliou-se o potencial antifúngico dos derivados mesoiônicos contra cinco cepas de Candida albicans. Dentre os vinte derivados mesoiônicos investigados, apenas quatro, MI-1-A3, MI-1-A4, MI-1-A6 e MI-1-A7, exibiram eficiente atividade com concentrações inibitórias mínimas entre 256 – 512 μg mL-1. Neste trabalho realizou-se ainda uma investigação in silico dos compostos mesoiônicos, das acetamidas substituídas e dos derivados mesoiônicos e os resultados indicaram que tanto os compostos mesoiônicos quanto seus derivados são bons candidatos a fármacos enquanto que as dez acetamidas substituídas investigadas devem apresentar elevada toxicidade.

Hauptziel dieser Arbeit ist die Synthese und Charakterisierung neuer Organosilicium-Chalcogen-Verbindungen (Chalcogen: Schwefel, Selen, Tellur), sowohl mit acyclischen, als auch mono- und polycyclischen Strukturen. Dabei konnten in vielen Fällen auch isostrukturelle Verbindungen mit Germanium- oder Zinnatomen anstelle von Silicium aufgebaut werden. Insgesamt wurden 42 der dargestellten Verbindungen auch durch Röntgenkristallstrukturanalysen charakterisiert. In cyclischen und polycyclischen Verbindungen war es damit auch möglich, die auftretenden Konformationen der Ringe- bzw. Ringsysteme zu bestimmen und die Resultate mit den Ergebnissen von DFT-Berechnungen zu vergleichen. Die NMR-Spektroskopie war parallel zu Kristallstrukturanalysen und GC/MS Messungen die Methode der Wahl zur Charakterisierung der dargestellten Verbindungen. Dabei boten sich neben der 1H und 13C NMR auch die 29Si, 119Sn, 207Pb, 77Se, und 125Te NMR Spektroskopie an, da man direkt die Elemente analysiert, die die Ringsysteme aufbauen, was zu einer weit höheren Strukturempfindlichkeit führt. Vor allem beim Vergleich von 77Se und 125Te NMR Daten analoger Selen- und Tellurverbindungen ergaben sich lineare Korrelationen sowohl der chemischen Verschiebungen als auch der Kopplungskonstanten 1JSiE bzw. 1JSnE mit Faktoren von ca. 2.5. Ähnliche Korrelationen konnten auch zwischen 29Si und 119Sn bzw. 119Sn und 207Pb NMR chemischen Verschiebungen gezogen werden. Von einigen Verbindungen konnten durch 29Si MAS NMR Spektroskopie auch die Tensorhauptwerte der chemischen Verschiebung ermittelt werden. Parallel dazu wurden mittels GIAO und IGLO Verfahren die 29Si NMR chemischen Verschiebungen ausgehend von den aus den Kristallstrukturanalysen zugänglichen Geometrien berechnet. Neben cyclischen Verbindungen konnten unter Verwendung des sperrigen Hypersilylrestes auch eine Reihe acyclischer Verbindungen mit der Sequenz Si–E–Si bzw. Si–E–Sn dargestellt und z. T. auch strukturell charakterisiert werden.

A material to function as a molecular electronic device should have a strong coupling with electrodes through appropriate and well-defined anchoring groups and have to support an effective traveling of charges via a conjugated molecular backbone. Oligo(3-hexylthiophene)s are π-conjugated molecules having large applicability in several areas of organic electronics owing interesting semiconducting properties and they also hold great promises in the field of single-molecule electronics. Polymerization methods, in principle, allow construction of long conjugated systems in a single synthetic step, however, most of them lack precision. This work uses externally initiated chain-growth Kumada Catalyst - Transfer Polycondensation (KCTP) for the synthesis of semiconductive oligo(3-hexylthiophene) wires with controllable molecular weights, low polydispersities, high regioregularities as well as with well-defined starting and end groups. In such a way, the synthetic efforts were compromised to obtain relatively easy a series of very complex molecular wires with a reasonable structural precision. To modulate the electronic function of oligomer backbones, specific charge-transfer moieties (DMA-TCBD and Fc-TCBD) were inserted as side chains or end groups. In-situ termination of KCTP with ZnCl-functionalized electron rich alkynes followed by Diederich-type click reaction resulted in the synthesis of asymmetrical oligo(3-hexylthiophene)s having thiolate-functionalized starting groups and donor-functionalized end-groups with a high degree of end-group functionalizations. Side chains of double-thiolate functionalized oligo(3-hexylthiophene)s, on the other hand, were further modified with the insertion of charge-transfer groups by post-polymerization functionalization. While the facile synthesis and modification of oligo(3-hexylthiophene)s enable the control over the molecular backbone, the specific starting and end anchoring groups allow the control over the electrode oligomer interface. To assure the formation of alligator clips between oligomer backbone and Au electrode, the optimizations including proper end-group conversion into mild counterparts followed by in-situ deprotection into thiolates and the binding abilities on gold were investigated. Finally, the conductance of bis-end functionalized oligo(3-hexylthiophene)s was preliminarily studied through oligomer backbone by Mechanically Controllable Break Junctions (MCBJs) setup and through oligomer-attached DNA origami-templated gold nanowires by individual electrical contacts. The developed KCTP-based synthetic route, at the end, presents new opportunities for the facile synthesis, the ease of modification and the feasibility of asymmetrical and side chain functionalized oligo(3-hexylthiophene) wires for needs of molecular electronics.

Les polymères de coordination (PCs) à base de thiolates de métaux monétaires sont bien connus pour leurs propriétés luminescentes. Cependant, leurs structures sont sous-explorées. Dans cette thèse, nous présentons une étude pionnière visant la compréhension de la formation de la structure et de la corrélation ‘structure-propriétés’ des PCs homoleptiques neutres, [M(SR)]n, M = Cu(I), Ag(I), Au(I). Les composés avec les dérivés du thiophénolate étudiés dans ce travail, illustrent comment l'utilisation de certains ligands organiques fonctionnalisés conduit à la formation de réseaux 2D étendus ou de colonnes 1D par l'addition d'un encombrement stérique. De plus, la première étude structurelle comparative des PCs thiolées amorphes a été réalisée par analyse PDF. Les études photophysiques ont montré la diversité des propriétés luminescentes des PCs à base de thiolates de métaux monétaires. Des pics d'émission doubles ou multiples, un rendement quantique élevé, des émetteurs orange à proche infrarouge, des variations significatives de durée de vie en fonction de la température... toutes ces propriétés intrinsèques révèlent le potentiel élevé de ces composés pour diverses applications optiques / The coordination polymers (CPs) based on thiolates of coinage metals are well known for their luminescence properties. However, their structures stayed underexplored. In the thesis we present a pioneering study targeting the understanding of the structure formation and the ‘structure-properties’ correlation for neutral homoleptic CPs, [M(SR)]n, M = Cu(I), Ag(I), Au(I). The compounds with thiophenolate derivatives studied in the work, illustrate how the use of some functionalized organic ligands leads to the formation of extended 2D networks or 1D columns by addition of some steric hindrance. The first comparative structural study of amorphous thiolated CPs was performed by PDF analysis. The photophysical studies showed the diversity of luminescent properties of the CPs based on thiolates of coinage metals. Double or multiple emission peaks, high quantum yield of orange-toinfrared emitters, significant lifetime variation with temperature… all of these intrinsic properties reveal the high potential of these compounds for diverse optical applications

A material to function as a molecular electronic device should have a strong coupling with electrodes through appropriate and well-defined anchoring groups and have to support an effective traveling of charges via a conjugated molecular backbone. Oligo(3-hexylthiophene)s are π-conjugated molecules having large applicability in several areas of organic electronics owing interesting semiconducting properties and they also hold great promises in the field of single-molecule electronics. Polymerization methods, in principle, allow construction of long conjugated systems in a single synthetic step, however, most of them lack precision. This work uses externally initiated chain-growth Kumada Catalyst - Transfer Polycondensation (KCTP) for the synthesis of semiconductive oligo(3-hexylthiophene) wires with controllable molecular weights, low polydispersities, high regioregularities as well as with well-defined starting and end groups. In such a way, the synthetic efforts were compromised to obtain relatively easy a series of very complex molecular wires with a reasonable structural precision. To modulate the electronic function of oligomer backbones, specific charge-transfer moieties (DMA-TCBD and Fc-TCBD) were inserted as side chains or end groups. In-situ termination of KCTP with ZnCl-functionalized electron rich alkynes followed by Diederich-type click reaction resulted in the synthesis of asymmetrical oligo(3-hexylthiophene)s having thiolate-functionalized starting groups and donor-functionalized end-groups with a high degree of end-group functionalizations. Side chains of double-thiolate functionalized oligo(3-hexylthiophene)s, on the other hand, were further modified with the insertion of charge-transfer groups by post-polymerization functionalization. While the facile synthesis and modification of oligo(3-hexylthiophene)s enable the control over the molecular backbone, the specific starting and end anchoring groups allow the control over the electrode oligomer interface. To assure the formation of alligator clips between oligomer backbone and Au electrode, the optimizations including proper end-group conversion into mild counterparts followed by in-situ deprotection into thiolates and the binding abilities on gold were investigated. Finally, the conductance of bis-end functionalized oligo(3-hexylthiophene)s was preliminarily studied through oligomer backbone by Mechanically Controllable Break Junctions (MCBJs) setup and through oligomer-attached DNA origami-templated gold nanowires by individual electrical contacts. The developed KCTP-based synthetic route, at the end, presents new opportunities for the facile synthesis, the ease of modification and the feasibility of asymmetrical and side chain functionalized oligo(3-hexylthiophene) wires for needs of molecular electronics.