Synthesis and evaluation of polystyrene based soluble polymeric supports for organic synthesis

Several copolymers of linear polystyrene were prepared for evaluation as soluble polymeric supports for organic synthesis. These polymers were utilized for the synthesis of ?2-isoxazoline compounds. The target compounds were synthesized via 1,3-dipolar cycloaddition reactions between polymer bound alkenes and nitrile oxides generated in situ from their corresponding aldoximes. The cleaved ?2-isoxazoline compounds were tested for biological activity against Mycobacterium fortuitum. To compare the success of these linear polystyrene copolymers, some of the ?2-isoxazoline compounds synthesized on soluble polymeric supports were also prepared via traditional crosslinked polymer supports. The polymer-bound ?2-isoxazolines were also tested for antimicrobial activity. In addition attempts were made to prepare polymers containing the ?2-isoxazolines but anchored by non-hydrolysable bonds. Although the copolymers of polystyrene gave good loading capacity in mmol/g, and being soluble in chlorinated solvents it was possible to monitor the reactions by 1H NMR spectroscopy, the cleavage of the polymer bound products proved to be quite troublesome. Product purification was not as straightforward as it was anticipated. Isolation of the cleaved target compounds proved to be time consuming and laborious when compared to the traditional organic synthesis and solid phase organic synthesis (SPOS). Polymer-bound ?2-isoxazolines close to the polymer backbone exhibited some biological activity against Staphylococcus aureus. Polymers with substitution at the para-position of the aryl substituent at position 3 of isoxazoline ring showed antimicrobial activity.

Studies of the effects of molecular encounters on N.M.R. spin-lattice relaxation times

This thesis is concerned with investigations of the effects of molecular encounters on nuclear magnetic resonance spin-lattice relaxation times, with particular reference to mesitylene in mixtures with cyclohexane and TMS. The purpose of the work was to establish the best theoretical description of T1 and assess whether a recently identified mechanism (buffeting), that influences n.m.r. chemical shifts, governs Tl also. A set of experimental conditions are presented that allow reliable measurements of Tl and the N. O. E. for 1H and 13C using both C. W. and F.T. n.m.r. spectroscopy. Literature data for benzene, cyclohexane and chlorobenzene diluted by CC14 and CS2 are used to show that the Hill theory affords the best estimation of their correlation times but appears to be mass dependent. Evaluation of the T1 of the mesitylene protons indicates that a combined Hill-Bloembergen-Purcell-Pound model gives an accurate estimation of T1; subsequently this was shown to be due to cancellation of errors in the calculated intra and intemolecular components. Three experimental methods for the separation of the intra and intermolecular relaxation times are described. The relaxation times of the 13C proton satellite of neat bezene, 1,4 dioxane and mesitylene were measured. Theoretical analyses of the data allow the calculation of Tl intra. Studies of intermolecular NOE's were found to afford a general method of separating observed T1's into their intra and intermolecular components. The aryl 1H and corresponding 13C T1 values and the NOE for the ring carbon of mesitylene in CC14 and C6H12-TMS have been used in combination to determine T1intra and T1inter. The Hill and B.P.P. models are shown to predict similarly inaccurate values for T1linter. A buffeting contribution to T1inter is proposed which when applied to the BPP model and to the Gutowsky-Woessner expression for T1inter gives an inaccuracy of 12% and 6% respectively with respect to theexperimentally based T1inter.

Lipophilic antifolates as potential antipsoriatic agents

The lipophilic dihydrofolate reductase (DHFR) inhibitor m-azidopyrimethamine (MZP) was investigated for suitability for development as a topical antipsoriatic agent. The clinical features and treatments for psoriasis were reviewed. High performance liquid chromatography (HPLC) was employed as the main analytical method, with UV spectroscopy being used in some cases. Reduction of the azido-group was proposed as a potential detoxification mechanism for MZP. The rates of reduction of a series of substituted phenyl azide compounds by dithiothreitol were investigated and found to depend on the substitution pattern of the aryl azide molecular, with electron deficient azides exhibiting faster rates of reduction in the system studied. The rates of reduction of MZP and analogous compounds were also studied using this model. The skin penetration of MZP was assessed using an in vitro hairless mouse skin model. The rate of permeation (flux) of MZP across hairless mouse skin was found to be dependent on the quantity of propylene glycol used as cosolvent in the vehicle and the pH. The use of a pretreatment regime of oleic acid in propylene glycol was shown to greatly increase the penetration of MZP through the hairless mouse skin as compared to application without pretreatment, or pretreatment with other penetration enhancers. The metabolism of MZP was studied in in vitro models comprising skin homogenates, SV-K14 human keratinocyte cell cultures and skin commensal bacterial cultures. No conversion of MZP to the corresponding amine was detected in any of the models. The growth inhibitory properties of MZP were investigated in an in vitro SV-K14 human keratinocyte cell culture model and compared with those of other DHFR inhibitors. [14C]-pyrimethamine was shown to be taken up by the SV-K14 keratinocytes.

Delivery of phosphonoformate prodrugs

AIDS dementia complex is a common neurological syndrome thought to result from the invasion of the CNS by HIV. Phosphonoformate has anti-HIV activity but due to its charged nature is excluded from the CNS by the blood-brain barrier. Lipophilic triesters of phosphonoformate designed to improve transport properties are unsuitable prodrugs due to their rapid and complicated hydrolysis, involving competitive P-O and P-C bond cleavage. Diesters, though hydrolytically stable, are considered too polar to passively diffuse into the CNS. Hydrophilic drugs mimicking endogenous nutrients are known to be actively transported across the blood-brain barrier. In this thesis the possibility that diesters of phosphonoformate may be actively transported is investigated. Triesters of phosphonoformate with labile aryl carboxyl esterrs were synthesised and their hydrolysis followed by 31P NMR spectroscopy. The triesters were found to undergo rapid hydrolysis via P-C bond cleavage to the phosphite. Phosphonoformate diesters designed to be analogues of actively transported -keto acids have been synthesised and fully characterised. Tyrosine-phosphonoformate and lipid-phosphonoformate conjugates have also been synthesised and characterised. An in vitro model of the blood-brain barrier utilising confluent monolayers of porcine brain microvessel endothelial cells grown on a permeable support has been established. The presence of enzyme and antigen markers specific to the blood-brain barrier has been demonstrated for the endothelial cells and the diffusional properties of the model investigated with hydrophilic and lipophilic compounds. Active transport systems for -keto acids and large amino acids have been identified in the endothelial cell monolayers using 14C-pyruvate and 3H-L-tyrosine respectively. Temperature and concentration dependence of the two systems have been demonstrated and transport constants calculated. Competition with 14C-pyruvate transport was shown with other monocarboxylic acids including the anti-epileptic drug valproate. Stereospecificity was shown in that L-lactate inhibited pyruvate transport while D-lactate did not. Sodium methyl methoxycarbonylphosphonate, a phosphonoformate diester was shown not to compete for 14C-pyruvate transport indicating that this compound has no affinity for the carrier. Competition with 3H-L-tyrosine transport was shown with other large amino acids, including the anti-Parkinsonian agent L-dopa. Stereospecificity was shown using L- and D-tyrosine and L- and D-dopa. The tyrosine-phosphonoformate conjugate, which was stable under the experimental conditions, was shown to compete with 3H-Ltyrosine transport indicating that it may be actively transported at the blood-brain barrier. Thirty two triesters, diesters and monoesters of phosphonoformate, showed no activity in an anti-HIV screen above that attributable to hydrolysis to the parent compound.

Non-classical inhibitors of dihydrofolate reductase

This thesis comprises two main objectives. The first objective involved the stereochemical studies of chiral 4,6-diamino-1-aryl-1,2-dihydro-s-triazines and an investigation on how the different conformations of these stereoisomers may affect their binding affinity to the enzyme dihydrofolate reductase (DHFR). The ortho-substituted 1-aryl-1,2-dihydro-s-triazines were synthesised by the three component method. An ortho-substitution at the C6' position was observed when meta-azidocycloguanil was decomposed in acid. The ortho-substituent restricts free rotation and this gives rise to atropisomerism. Ortho-substituted 4,6-diamino-1-aryl-2-ethyl-1,2-dihydro-2-methyl-s-triazine contains two elements of chirality and therefore exists as four stereoisomers: (S,aR), (R,aS), (R,aR) and (S,aS). The energy barriers to rotation of these compounds were calculated by a semi-empirical molecular orbital program called MOPAC and they were found to be in excess of 23 kcal/mol. The diastereoisomers were resolved and enriched by C18 reversed phase h.p.l.c. Nuclear overhauser effect experiments revealed that (S,aR) and (R,aS) were the more stable pair of stereoisomers and therefore existed as the major component. The minor diastereoisomers showed greater binding affinity for the rat liver DHFR in in vitro assay. The second objective entailed the investigation into the possibility of retaining DHFR inhibitory activity by replacing the classical diamino heterocyclic moiety with an amidinyl group. 4-Benzylamino-3-nitro-N,N-dimethyl-phenylamidine was synthesised in two steps. One of the two phenylamidines indicated weak inhibition against the rat liver DHFR. This weak activity may be due to the failure of the inhibitor molecule to form strong hydrogen bonds with residue Glu-30 at the active site of the enzyme.

Dielectric studies of molecules and intramolecular relaxation processes

A new bridge technique for the measurement of the dielectric absorption of liquids and solutions at microwave frequencies has been described and its accuracy assessed. 'l'he dielectric data of the systems studied is discussed in terms of the relaxation processes contributing to the dielectric absorption and the apparent dipole moments. Pyridine, thiophen and furan in solution have a distribution of relaxation times which may be attributed to the small size of the solute molecules relative to the solvent. Larger rigid molecules in solution were characterized by a single relaxation time as would be anticipated from theory. The dielectric data of toluene, ethyl-, isopropyl- and t-butylbenzene as pure liquids and in solution were described by two relaxation times, one identified with molecular re-orientation and a shorter relaxation time.· The subsequent work was investigation of the possible explanations of this short relaxation process. Comparable short relaxation times were obtained from the analysis of the dielectric data of solutions of p-chloro- and p-bromotoluene below 40°C, o- and m-xylene at 25°C and 1-methyl- and 2 methylnaphthalene at 50 C. Rigid molecules of similar shapes and sizes were characterized by a single relaxation time identified with molecular re-orientation. Contributions from a long relaxation process attributed to dipolar origins were reported for solutions of nitrobenzene, benzonitrile and p-nitrotoluene. A short relaxation process of possible dipolar origins contributed to the dielectric absorption of 4-methyl- and 4-t-butylpyridine in cyclohexane at 25°C. It was concluded that the most plausible explanation of the short relaxation process of the alkyl-aryl hydrocarbons studied appears to be intramolecular relaxation about the alkyl-aryl bond. Finally the mean relaxation times of some phenylsubstituted compounds were investigated to evaluate any shortening due to contributions from the process of relaxation about the phenyl-central atom bond. The relaxation times of triphenylsilane and phenyltrimethylsilane were significantly short.

Site-selective direct arylation of unprotected adenine nucleosides mediated by palladium and copper:insights into the reaction mechanism

Reaction conditions facilitating the site-selective direct aryl functionalisation at the C-8 position of adenine nucleosides have been identified. Many different aromatic components may be effectively cross-coupled to provide a diverse array of arylated adenine nucleoside products without the need for ribose or adenine protecting groups. The optimal palladium catalyst loading lies between 0.5 and 5 mol %. Addition of excess mercury to the reaction had a negligible affect on catalysis, suggesting the involvement of a homogeneous catalytic species. A study by transmission electron microscopy (TEM) shows that metal containing nanoparticles, ca. 3 nm with good uniformity, are formed during the latter stages of the reaction. Stabilised PVP palladium colloids (PVP=N-polyvinylpyrrolidone) are catalytically active in the direct arylation process, releasing homogenous palladium into solution. The effect of various substituted 2-pyridine ligand additives has been investigated. A mechanism for the site-selective arylation of adenosine is proposed. © 2008 Elsevier Ltd. All rights reserved.

I.~Synthesis, isolation, and characterization of 1-(2-anthryl)-2-cyclopropylethylene and 1-(2-naphthyl)-2-cyclopropylethylene. II.~Titanium dioxide photocatalysis of haloethers: A mechanistic study

I. The target molecules are classified as 1-aryl 2-cyclopropyl substituted ethylene. In the ground state, these molecules have a number of conformers, which are in equilibrium through rotation about single bonds. Once excited, the conformers have fixed conformation and are no longer in equilibrium and can be distinguished by their UV-vis as well as fluorescence spectra. The synthetic strategy involves standard steps. Both 2-methylanthracene and 2-methylnaphthalene were brominated using N-bromosuccinimide to give the bromomethyl adduct, which then was reacted with triphenylphosphine to form the phosphonium salt. This was followed by the formation of the phosphorus ylide, which upon treatment with cyclopropanecarboxaldehyde gave the product.^ II. The degradation of three aliphatic haloethers: bis-(2-chloroethyl) ether, bis-(2-chloroisopropyl) ether, and bis-(2-chloroethoxy)methane and two aromatic haloethers: 4-chlorodiphenyl ether and 4-bromodiphenyl ether was studied. Product studies have been conducted on the titanium dioxide photocatalysis of these compounds including mass balance, monitoring and identifying intermediates to establish the reaction pathways to deduce a mechanism for their degradation. The extent of mineralization was determined from the measurement of halogen anion (Cl$\sp-$/Br$\sp-$) as well as total organic carbon. The relative rates of disappearance of the individual haloethers appear to be related to the hydrophobic character of the given compound. Reaction mechanisms involving hydroxyl radical are proposed to explain the observed results. ^

The study of silicates and refractory materials at high pressures and temperatures

To better understand high pressure behavior of solids, both silicates and oxides have been investigated to clarify the high pressure melting, phase transformations and thermal parameters as well as their size dependences, both theoretically and experimentally. ^ To judge the precision of data determined experimentally, the reliabilities of different high pressure techniques have been discussed. A thermodynamic model has been developed and demonstrated to be able to closely reproduce the melting of solids by comparison between results calculated and data obtained experimentally, including metals (Al, Ni and Pt), Silicates (Mg3Al 2Si3O12 and CaMgSi2O6), Halides (NaCl, CsCl and LiF) and Oxides (MgO, FeO and Al2O3). The melting data obtained have been discussed to address the dynamics of the Earth's interior. ^ Results obtained with Raman spectroscopy and x-ray diffraction show that solids including silicates (andradite and pyrope) and oxides (CeO2 and TiO2) undergo a series of pressure-induced phase transformations. The effects of particle size under high pressures have been investigated. The results obtained indicate that the reduction of particle size leads to the enhancement of the bulk modulus and a significant decrease of transition pressure in TiO2 (rutile) and CeO2. The pressure-induced amorphization in anatase also results from the size effects. ^ Combining the data obtained with global seismic tomography, the physics and chemistry of the Earth's mantle and the dynamics of the core-mantle interaction have been discussed. The high pressure phases of Al3+- and Fe3+-bearing minerals play important roles in the dynamics of the lower mantle. ^

New organogermanium substrates for palladium-catalyzed cross-coupling reactions. Application of organogermanes towards the synthesis of carbon-5 modified uridine analogues

The diverse biological properties exhibited by uridine analogues modified at carbon-5 of the uracil base have attracted special interest to the development of efficient methodologies for their synthesis. This study aimed to evaluate the possible application of vinyl tris(trimethylsilyl)germanes in the synthesis of conjugated 5-modified uridine analogues via Pd-catalyzed cross-coupling reactions. The stereoselective synthesis of 5-[(2-tris(trimethylsilyl)germyl)ethenyl]uridine derivatives was achieved by the radical-mediated hydrogermylation of the protected 5-alkynyluridine precursors with tris(trimethylsilyl)germane [(TMS)3GeH]. The hydrogermylation with Ph3GeH afforded in addition to the expected 5-vinylgermane, novel 5-(2-triphenylgermyl)acetyl derivatives. Also, the treatment with Me3GeH provided access to 5-vinylgermane uridine analogues with potential biological applications. Since the Pd-catalyzed cross-coupling of organogermanes has received much less attention than the couplings involving organostannanes and organosilanes, we were prompted to develop novel organogermane precursors suitable for transfer of aryl and/or alkenyl groups. The allyl(phenyl)germanes were found to transfer allyl groups to aryl iodides in the presence of sodium hydroxide or tetrabutylammonium fluoride (TBAF) via a Heck arylation mechanism. On the other hand, the treatment of allyl(phenyl)germanes with tetracyanoethylene (TCNE) effectively cleaved the Ge-C(allyl) bonds and promoted the transfer of the phenyl groups upon fluoride activation in toluene. It was discovered that the trichlorophenyl,- dichlorodiphenyl,- and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of TBAF in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two or three phenyl groups from the organogermane precursors. The methodology shows that organogermanes can render a coupling efficiency comparable to the more established stannane and silane counterparts. Our coupling methodology (TBAF/moist toluene) was also found to promote the transfer of multiple phenyl groups from analogous chloro(phenyl)silanes and stannanes.

Developing of Germyldesulonylation and Thiodesulfonylation Reactions for the Synthesis of Novel Nucleoside Analogues. Efficient Synthesis of Novel (α-Fluoro)vinyl Sulfides

S-adenosyl-L-homocysteine (AdoHcy) hydrolase effects hydrolytic cleavage of AdoHcy to produce both adenosine and L-homocysteine and is a feedback inhibitor of S-adenosyl- L-methionine (SAM). Nucleoside analogues bearing an alkenyl or fluoroalkenyl chain between sulfur and C5' utilizing Negishi coupling reactions were synthesized. Palladium-catalyzed cross-coupling between the 5'-deoxy-5'-(iodomethylene) nucleosides and alkylzinc bromides gives analogues with the alkenyl unit. Palladium-catalyzed selective monoalkylation of 5'-(bromofluoromethylene)-5'-deoxy-adenosine with alkylzinc bromide afford adenosylhomocysteine analogues with a 6'-(fluoro)vinyl motif. The vinylic adenine nucleosides produced time-dependent inactivation of the S-adenosyl-L-homocysteine hydrolases. Stannydesulfonylation reaction is a critical step in the synthesis of E-fluorovinyl cytidine (Tezacitabine) a ribonucleoside reductase inhibitor with a potent anticancer activity. The synthesis involves the removal of the sulfonyl group by a radical-mediated stannyldesulfonylation reaction using tributyltin hydride. In order to eliminate the toxicity of tin, I developed a radical-mediated germyldesulonylation utilizing less toxic germane hydrides. Treatment of the protected (E)-5'-deoxy-5'-[(p-toluenesulfonyl)-methylene]uridine and adenosine derivatives with tributyl- or triphenylgermane hydride effected radical-mediated germyldesulfonylations to give 5'-(tributyl- or triphenylgermyl)methylene-5'-deoxynucleoside derivatives as single (E)-isomers. Analogous treatment of 2'-deoxy-2'-[(phenylsulfonyl)methylene]uridine with Ph3GeH afforded the corresponding vinyl triphenylgermane product. Stereoselective halodegermylation of the (E)-5'-(tributylgermyl)-methylene-5'-deoxy nucleosides with NIS or NBS provided the Wittig-type (E)-5'-deoxy-5'-(halomethylene) nucleosides quantitatively. Radical-mediated thiodesulfonylation of the readily available vinyl and (α-fluoro) vinyl sulfones with aryl thiols in organic or aqueous medium to provide a bench and environmentally friendly protocol to access (α-fluoro)vinyl sulfides were developed. Methylation of the vinyl or (α-fluoro)vinyl phenyl sulfide gave access to the corresponding vinyl or (α-fluoro)vinyl sulfonium salts. These sulfonium ions were tested as possible methyl group donors during reactions with thiols, phenols or amino groups which are commonly present in natural amino acids.

Design and synthesis of S-ribosylhomocysteine analogues

Bacteria are known to release a large variety of small molecules known as autoinducers (AI) which effect quorum sensing (QS) initiation. The interruption of QS effects bacterial communication, growth and virulence. ^ Three novel classes of S-ribosylhomocysteine (SRH) analogues as potential inhibitors of S-ribosylhomocysteinase (LuxS enzyme) and AI-2 modulators of QS were developed. The synthesis of 2-deoxy-2-bromo-SRH analogues was attempted by coupling of the corresponding 2-bromo-2-deoxypentafuranosyl precursors with the homocysteinate anion. The displacement of the bromide from C2 rather than the expected substitution of the mesylate from C5 was observed. The synthesis of 4-C-alkyl/aryl-S-ribosylhomocysteine analogues involved the following steps: (i) conversion of the D-ribose to the ribitol-4-ulose; (ii) diastereoselective addition of various alkyl or aryl or vinyl Grignard reagents to 4-ketone intermediate; (iii) oxidation of the primary hydroxyl group at C1 followed by the intramolecular ring closure to the corresponding 4-C-alkyl/aryl-substituted ribono-1,4-lactones; (iv) displacement of the activated 5-hydroxyl group with the protected homocysteinate. Treatment of the 4-C-alkyl/aryl-substituted SRH analogues with lithium triethylborohydride effected reduction of the ribonolactone to the ribose (hemiacetal) and subsequent global deprotection with trifluoroacetic acid provided 4-C-alkyl/aryl-SRHs. ^ The 4-[thia]-SRH were prepared from the 1-deoxy-4-thioribose through the coupling of the &agr;-fluoro thioethers (thioribosyl fluorides) with homocysteinate anion. The 4-[thia]-SRH analogues showed concentration dependent effect on the growth on las (50% inhibitory effect at 200 µg/mL). The most active was 1-deoxy-4-[thia]-SRH analogue with sufur atom in the ring oxidized to sulfoxide decreasing las gene activity to approximately 35% without affecting rhl gene. Neither of the tested compounds had effect on bioluminescence nor on total growth of V. harveyi, but had however slight inhibition of the QS.^

New Organogermanium Substrates for Palladium-Catalyzed Cross-Coupling Reactions. Application of Organogermanes towards the Synthesis of Carbon-5 Modified Uridine Analogues

The diverse biological properties exhibited by uridine analogues modified at carbon-5 of the uracil base have attracted special interest to the development of efficient methodologies for their synthesis. This study aimed to evaluate the possible application of vinyl tris(trimethylsilyl)germanes in the synthesis of conjugated 5-modified uridine analogues via Pd-catalyzed cross-coupling reactions. The stereoselective synthesis of 5-[(2-tris(trimethylsilyl)germyl)ethenyl]uridine derivatives was achieved by the radical-mediated hydrogermylation of the protected 5-alkynyluridine precursors with tris(trimethylsilyl)germane [(TMS)3GeH]. The hydrogermylation with Ph3GeH afforded in addition to the expected 5-vinylgermane, novel 5-(2-triphenylgermyl)acetyl derivatives. Also, the treatment with Me3GeH provided access to 5-vinylgermane uridine analogues with potential biological applications. Since the Pd-catalyzed cross-coupling of organogermanes has received much less attention than the couplings involving organostannanes and organosilanes, we were prompted to develop novel organogermane precursors suitable for transfer of aryl and/or alkenyl groups. The allyl(phenyl)germanes were found to transfer allyl groups to aryl iodides in the presence of sodium hydroxide or tetrabutylammonium fluoride (TBAF) via a Heck arylation mechanism. On the other hand, the treatment of allyl(phenyl)germanes with tetracyanoethylene (TCNE) effectively cleaved the Ge-C(allyl) bonds and promoted the transfer of the phenyl groups upon fluoride activation in toluene. It was discovered that the trichlorophenyl,- dichlorodiphenyl,- and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of TBAF in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two or three phenyl groups from the organogermane precursors. The methodology shows that organogermanes can render a coupling efficiency comparable to the more established stannane and silane counterparts. Our coupling methodology (TBAF/moist toluene) was also found to promote the transfer of multiple phenyl groups from analogous chloro(phenyl)silanes and stannanes.

Asymmetric oxidation of sulfides

This review discusses synthesis of enantiopure sulfoxides through the asymmetric oxidation of prochiral sulfides. The use of metal complexes to promote asymmetric sulfoxidation is described in detail, with a particular emphasis on the synthesis of biologically active sulfoxides. The use of non-metal-based systems, such as oxaziridines, chiral hydroperoxides and peracids, as well as enzyme-catalyzed sulfoxidations is also examined.

Développement et caractérisation de dérivés dipyrrométhène pour des applications dans le domaine du photovoltaïque

Ce projet de recherche mené en collaboration industrielle avec St-Jean Photochimie Inc. / PCAS Canada vise le développement et la caractérisation de dérivés dipyrrométhène pour des applications dans le domaine du photovoltaïque. La quête du récoltage des photons se situant dans le proche-infrarouge a été au centre des modifications structurales explorées afin d’augmenter l’efficacité de conversion des cellules solaires de type organique et à pigments photosensibles. Trois familles de composés intégrant le motif dipyrrométhène ont été synthétisées et caractérisées du point de vue spectroscopique, électrochimique, structural ainsi que par modélisation moléculaire afin d’établir des relations structures-propriétés. La première famille comporte six azadipyrrométhènes au potentiel de coordination tétradentate sur des centres métalliques. Le développement d’une nouvelle voie synthétique asymétrique combinée à l’utilisation d’une voie symétrique classique ont permis d’obtenir l’ensemble des combinaisons de substituants possibles sur les aryles proximaux incluant les noyaux 2-hydroxyphényle, 2-méthoxyphényle et 2- pyridyle. La modulation du maximum d’absorption dans le rouge a pu être faite entre 598 et 619 nm. De même, la présence de groupements méthoxyle ou hydroxyle augmente l’absorption dans le violet (~410 nm) tel que démontré par modélisation. La caractérisation électrochimique a montré que les dérivés tétradentates étaient en général moins stables aux processus redox que leur contre-parti bidentate. La deuxième famille comporte dix dérivés BODIPY fusionnés de façon asymétrique en position [b]. L’aryle proximal a été modifié de façon systématique afin de mieux comprendre l’impact des substituents riches en électron et de la fusion de cycles aromatiques. De plus, ces dérivés ont été mis en relation avec une vaste série de composés analogues. Les résultats empiriques ont montré que les propriétés optoélectroniques de la plateforme sont régies par le degré de communication électronique entre l’aryle proximal, le pyrrole sur lequel il est attaché et le noyau indolique adjacent à ce dernier. Les maximums d’absorption dans le rouge sont modulables entre 547 et 628 nm et la fluorescence des composés se situe dans le proche- infrarouge. L’un des composé s’est révélé souhaitable pour une utilisation en photovoltaïque ainsi qu’à titre de sonde à pH. La troisième famille comporte cinq complexes neutres de RuII basés sur des polypyridines et portant un ligand azadipyrrométhène cyclométalé. Les composés ont montré une forte absorption de photons dans la région de 600 à 800 nm (rouge à proche- infrarouge) et qui a pu être étendue au-delà de 1100 nm dans le cas des dérivés portant un ligand terpyridine. L’analyse des propriétés optoélectroniques de façon empirique et théorique a montré un impact significatif de la cyclométalation et ouvert la voie pour leur étude en tant que photosensibilisateurs en OPV et en DSSC. La capacité d’un des complexes à photo-injecter un électron dans la bande de conduction du semi-conducteur TiO2 a été démontré en collaboration avec le groupe du Pr Gerald J. Meyer à University of North Carolina at Chapel Hill, premier pas vers une utilisation dans les cellules solaires à pigments photosensibles. La stabilité des complexes en solution s’est toutefois avérée problématique et des pistes de solutions sont suggérées basées sur les connaissances acquises dans le cadre de cette thèse.