Phosphorescent organic light emitting diodes (PHOLEDs) based on efficient electrophosphorescent dopant, platinum(II)-pyridyltriazolate complex, bis[3,5-bis(2-pyridyl)-1,2,4-triazolato]platinum(II) (Pt(ptp)2) have been studied and improved with respect to power efficiency, external efficiency, chromacity and efficiency roll-off. By studying the electrical and optical behavior of the doped devices and functionality of the various constituent layers, devices with a maximum EQE of 20.8±0.2 % and power efficiency of 45.1±0.9 lm/W (77lm/W with luminaries) have been engineered. This improvement compares to devices whose emission initially could only be detected by a photomultiplier tube in a darkened environment. These devices consisted of a 65 % bis[3,5-bis(2-pyridyl)-1,2,4-triazolato]platinum(II) (Pt(ptp)2) doped into 4,4'-bis(carbazol-9-yl)triphenylamine (CBP) an EML layer, a hole transporting layer/electron blocker of 1,1-bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC), an electron transport layer of 1,3,5-tris(phenyl-2-benzimidazolyl)-benzene (TPBI), and a LiF/Al cathode. These devices show the acceptable range for warm white light quadrants and qualify to be called "warm white" even w/o adding another emissive layer. Dual EML devices composed of neat Pt(ptp)2 films emitting orange and CBP: Pt(ptp)2 film emitting blue-green produced a color rendering index (CRI) of 59 and color coordinates (CIE) of (0.47,0.49) at 1000Cd/m² with power efficiency of 12.6±0.2 lm/W and EQE of 10.8±0.2 %. Devices with two blue fluorescent emission layers as singlet filters and one broad yellow emission layer from CBP: Pt(ptp)2 displayed a CRI of 78 and CIE of (0.28,0.31) at 100Cd/m² with maximum power efficiency of 6.7±0.3 lm/W and EQE of 5.7±0.2 %.

<p><p>The wide-spread occurrence of biologically active nitrogen-containing heterocycles and allylic amines inspired us to develop atom-economical methods for their syntheses.</p></p><p><p>A cationic gold(I) <italic>N</italic>-heterocyclic carbene complex catalyzed the intermolecular hydroarylation of allenes with indoles to form (<italic>E</italic>)-allylic indoles in modest to good yield at room temperature. The protocol was effective for monosubstituted, 1,3-disubstituted, and tetrasubstituted allenes and various indoles.</p> </p><p><p>Platinum(II) bis(phosphine) complexes catalyzed the intermolecular hydroamination of monosubstituted allenes with secondary alkylamines in good yield with selective formation of (<italic>E</italic>)-allylic amines. The scope of the protocol included aryl and alkyl monosubstituted allenes as well as a variety of both cyclic and acyclic secondary alkylamines.</p></p><p><p>The scope of gold(I)-catalyzed intermolecular hydroamination of 1-alkenes with 1-methyl-2-imidazolidinone was expanded to include additional 1-alkenes functionalized with carboxylic acid derivatives. However, a nucleophile screen failed to identify nucleophiles other than cyclic ureas and 2-oxazolidinone that efficiently undergo hydroamination with 1-alkenes. Various carbamates, arylamines, amide derivatives, sulfur-containing amide derivatives, and &alpha;-heteroatom compounds failed to react with 1-octene under gold(I)-catalyzed conditions.</p></p><p><p>A chiral bis(gold) phosphine complex catalyzed the stereoconvergent, intermolecular enantioselective hydroamination of chiral, racemic 1,3-disubstituted allenes with carbamates to form <italic>N</italic>-allylic carbamates in good to high yield with up to 92% <italic>ee</italic>. In addition, enantiopurity experiments suggested the nature of the catalytically active species changes with increasing concentration of <italic>N</italic>-allylic carbamate.</p></p> / Dissertation

Mixed-metal Ru(II)-Pt(II) supramolecular complexes having the [(Ph₂phen)₂Ru(BL)PtCl₂]₂+ (Ph₂phen = 4,7-diphenyl-1,10-phenanthroline, and BL (bridging ligand) = dpp = 2,3-bis(2-pyridyl)pyrazine, or dpq = 2,3-bis(2-pyridyl)quinoxaline) structural motif were synthesized and their redox, photophysical, and photochemical properties studied. Subsequently the application of the Ru(II)-Pt(II) bimetallic complexes in light activated DNA modification and cytotoxicity were evaluated. The supramolecular design entails covalently coupling an efficient Ru(II) chromophore for photodynamic therapy (PDT) activity through a polyazine bridging ligand (dpp or dpq) to a cis-PtCl₂ bioactive site for covalent binding to biological substrates. The bioactive site is comparable to the first generation Pt-based chemotherapy agent cisplatin, cis-[PtCl₂(NH₃)₂]. The Ph₂phen ligand is known in [Ru(Ph₂phen)₃]²+ to provide enhanced excited state lifetime and increase quantum efficiency for singlet oxygen generation in comparison to the phen analog (Φ₁₀₂ = 0.97, Ph₂phen and Φ₁₀₂ = 0.54, phen). The redox and photophysical properties were analyzed at each synthetic step providing systematic evaluation of the complex properties. The [(Ph₂phen₂2Ru(BL)PtCl₂](PF₆)₂ complexes display reversible RuII/III oxidations at +1.61 (dpp) and +1.63 (dpq) V vs. Ag/AgCl with an irreversible PtII/IV oxidation occurring prior at +1.51 V vs. Ag/AgCl. Four reversible ligand reductions occur at -0.45 (dpp0/-), -1.15 (dpp-/2-), -1.33 (Ph₂phen0/-), and -1.52 (Ph₂phen0/-) V vs. Ag/AgCl. For the [(Ph₂phen)₂Ru(dpq)PtCl₂](PF₆)₂ complex, the first two reductions shift to more positive potentials at -0.19 and -0.95 V vs. Ag/AgCl, while the TL reductions remain generally unperturbed. The electronic absorption spectroscopy for the [(Ph₂phen)₂Ru(dpq)PtCl₂](PF₆)₂, BL = dpp or dpq, complexes is dominated in the UV region by Ph₂phen (274 nm) and BL-based (310-320 nm) π⟶ π* transitions and in the visible region by metal-to-ligand charge transfer (MLCT) transitions at 424 nm (Ru(dπ)→ Ph₂phen(π*) 1CT) and 517 nm (Ru(dπ)→ dpp(π*) 1CT) or 600 nm (Ru(dπ)→ dpq(π*) 1CT). Steady-state and time-resolved emission spectroscopy shows that upon attaching Pt to the Ru monometallic precursor the λmaxem shifts from 664 nm for [(Ph₂phen)2Ru(dpp)](PF₆)₂ to 740 nm for [(Ph₂phen)₂Ru(dpp)PtCl₂](PF₆)₂ and the excited state lifetime is reduced from 820 ns to 44 ns in accordance with the energy gap law. The τ = 44 ns for the Ru(dπ)→ dpp(π*) 3CT excited state was somewhat unexpected upon TL variation given the lack of formal involvement of Ph₂phen in the emissive state. This likely results from the Ph₂phen contribution to the formally Ru(dπ) donor orbital. Although not typically done, given the complexity of the study the Φ₁₀₂ was quantified for the [(Ph₂phen)₂Ru(BL)PtC₂]Cl₂ (BL = dpp, Φ₁₀₂ = 0.07 or dpq, Φ₁₀₂ = 0.03) complexes supporting 1O2 generation via energy transfer from the 3MLCT excited state. The thermal and photochemical interactions of the [(Ph₂phen₂2Ru(BL)PtCl₂]Cl₂ (BL = dpp or dpq) supramolecular complexes were studied in the presence of DNA and U87MG cancer cells. Thermal binding at the cis-PtCl₂ BAS in the Ru(II)-Pt(II) architecture was compared to cisplatin displaying similar reduced migration through the gel attributed to covalent binding to DNA. DNA photocleavage studies provided evidence of efficient strand cleavage when excited at 455 nm likely enhanced by producing 1O2 locally at the DNA target. DNA photobinding by the [(Ph₂phen)₂Ru(dpp)PtCl₂]Cl₂ complex was observed utilizing low energy light where typical Pt(II) agents do not absorb. This is the first example of MLCT excitation of a Ru(II)-Pt(II) complex to induce a photobinding event. MLCT excitation enhances electron density on the dpp making the Pt(II) a weaker Lewis acid and promoting halide loss. In addition, this system is photoactivated with low energy red light in the therapeutic window. These studies validate the supramolecular design and show that coupling a Ru(II) chromophore for PDT activity and a cis- PtCl₂ binding moiety for covalent DNA targeting affords a complex applicable in photochemotherapies. Analysis of cytotoxicity in the dark for [(Ph₂phen)₂Ru(dpp)PtCl₂]Cl₂ and cisplatin afforded LC50 values of 100 μM, which are confirmed by previous reports for cisplatin and the currently used chemotherapy, TMZ in U87MG cells. Photolysis of the [(Ph₂phen)₂Ru(dpp)PtCl₂]Cl₂ resulted in substantial reduction in the observed LC50 values to approximately 5 μM. The enhanced cytotoxicity via excitation into the formally Ru(dπ)→ BL(π*) CT excited state of [(Ph₂phen)2Ru(dpp)PtCl2]Cl2 indicates that the bimetallic complex undergoes an efficient light activated mechanism of action. The Ru(II)-Pt(II) complex displays substantially lower LC50 values through PDT action than currently used clinical treatments with LC50 values of 100 μM. The [(Ph₂phen)₂Ru(BL)PtCl₂]₂+ (BL = dpp or dpq) mixed-metal supramolecules utilizing the Ph₂phen TL have displayed surprising results. The direct coupling of the cis-PtCl₂ moiety to the (Ph₂phen)₂Ru(BL) chromophore display dramatically enhanced photophysical properties, relative to the bpy and phen systems with a longer excited state lifetime and improved light activated interactions with DNA, which was not previously observed for directly coupled Ru(II)- Pt(II) systems. The Ph₂phen TL positively influence the bioactivity compared to the typical deactivation observed in the bpy and phen systems. Probing the [(Ph₂phen)₂Ru(BL)PtCl₂]₂+ (BL = dpp or dpq) biological interactions confirms the importance of coupling an efficient light absorbing and 1O2 generating PDT-type unit with a cis-PtCl2 DNA binding unit for applications in covalent DNA photomodification, DNA photocleavage, and photocytotoxicity. It is proposed that excitation using visible light into the formally Ru(dπ)→ BL(π*) CT excited state leads to enhanced electron density on the BL and weakened Lewis acidity at the Pt(II) center, which facilitates halide loss for efficient biological substrate modification. Upon coordination of the Ru(II)-Pt(II) complexes at the biological substrate, 1O2 is localized providing effective targeting of the highly reactive oxygen species. The visible light induced activity of the [(Ph₂phen)₂Ru(BL)PtCl₂]₂+ (BL = dpp or dpq) supramolecules suggests a new mode of action in relation to cisplatin, which was further supported by the enhanced photocytotoxicity observed in the presence of U87MG cells. The results indicate that the Ru(II)-Pt(II) supramolecular structural motif hold great promise as a future photochemotherapy agent. / Ph. D.

The thesis work delineates the rational design and successful syntheses of platinum (II) complexes for achieving light promoted dual action anticancer properties. The research work focuses on the syntheses, elaborate characterization including crystallization and mechanistic aspects of photodegradation processes. Theoretical studies were done to elucidate the properties of the excited states. The interaction of active Pt (II) species with DNA is also explored. The cellular studies include evaluation of the photo-induced cytotoxicities, mode of cell death, nature of reactive oxygen species (ROS), quantification of cellular Pt content and cellular and sub-cellular localization of the complexes. Chapter I provides an overview of the hallmarks of cancer and the current anticancer treatment modalities. It outlines the evolution of platinum based chemotherapeutic drugs, their mechanism of action and associated disadvantages. It also depicts the resurgence of metal complexes as photosensitizers for photoactivated chemotherapy, a selective tripartite strategy which permits light induced tumor destruction. Detailed literature reports of potential transition metal complexes showing light induced generation of ROS and controlled delivery of multiple drugs in tumor microenvironment are presented. The key challenges are the delivery and controlled activation of the clinically approved platinum (II) drugs. These prime objectives of the present investigation are depicted as a concluding segment of this introductory chapter. Chapter II includes the syntheses, characterization, evaluation of visible light induced cytotoxicity and interaction with DNA of novel ferrocenyl terpyridine appended platinum (II) complexes. Detailed mechanistic investigations revealed the important role of ferrocene in light triggered generation of reactive oxygen species. The effect of extensive conjugation on the photophysical properties of the complexes were also rationalized from theoretical calculations. The alteration in DNA binding affinities of the complexes on incorporation of a ferrocene unit in the platinum (II)terpyridines is also reflected. The work is the first report of the remarkable photocytotoxicity of platinum(II) complexes in visible light with nominal dark toxicity. Chapter III deals with novel ferrocenyl terpyridyl platinum(II) complexes having tumor targeting biotinylated acetylides which were synthesized for achieving selective photocytotoxicity only in cancer cells. An interesting observation was the red light promoted release of biotinylated acetylide ligands from platinum centre thereby generating mono-functional Pt(II) species. The possible covalent interactions of these platinum(II) species with DNA were also explored. These biotin complexes exhibit preferential cellular uptake in BT474 breast cancer cells over HBL-100 breast normal cells resulting in targeted photocytotoxicity in visible light. Chapter IV rationalizes design, syntheses and extensive characterization of 2-(phenylazo)pyridine based platinum(II) catecholates containing photosensitizers. The O^O donor ligand was chosen to release the more cytotoxic bi-functional platinum(II) species based on the prior knowledge of the labile Pt-O bonds. Interestingly, we observed glutathione triggered release of the catecholates imparting dual action anticancer properties to the molecules. Detailed mechanistic aspects indicated a possible reduction of the metal coordinated azo bond by cellular glutathione. The excellent photocytotoxicity in HaCaT and MCF-7 cells, cellular ROS generation and apoptosis, cellular Pt content and localization of these complexes are discussed. Chapter V addresses the advantages of navigating the platinum(II) complexes to mitochondrial DNA instead of genomic DNA. BODIPY appended platinum(II) catecholates were synthesized and the BODIPY core was modified to fine-tune the photophysical properties. The visible light induced growth inhibitory effects of the complexes and the mechanism of cell death in light exposed cells are explored. The novelty of this work is the mitochondria targeted remarkable photocytotoxicity as well as cellular imaging properties of the complexes making them ideal candidates for developing platinum based theranostic agents. Chapter VI presents the syntheses, characterization of unprecedented platinum(II) complexes of curcumin for dual action DNA crosslinking and photochemotherapeutic activities. The important feature of these Pt(II) prodrugs is the photorelease of curcumin from Pt(II) centre which results in controlled delivery of two potential anticancer agents. The visible light induced cytotoxicities of the complexes in HaCaT, BT474, T47D, Hep3B and HPL1D cells, their effect on the various cellular events, the interaction of the complexes with DNA and their cellular distribution in light and dark are explored. The appropriate references are provided at the end of each chapter and allocated as superscripts in the main text. The synthesized complexes are denoted by bold-faced numbers. Crystallography data of the complexes that are structurally characterized by single crystal X-ray crystallography are given in CIF format in the enclosed CD (Appendix-I). Due acknowledgements are provided for mentioned literature reports. Any omission is purely unintentional and is deeply regretted. INDEX WORDS: Platinum(II) complexes • Crystal structure • Visible light induced cytotoxicity • Cellular imaging • Photochemotherapeutic agents • DNA crosslink.

The FDA-approved platinum compound, cisplatin, is commonly used as a chemotherapy drug to treat many forms of cancer. However, this compound also has several associated side-effects, including ototoxicity. This has made the development of novel platinum compounds that reduce cancer cell viability, while causing fewer and milder side-effects, an area of significant research interest. In the present study, we examined the apoptotic effects that four monofunctional platinum compounds, pyriplatin, phenanthriplatin, Pt(diethylenetriamine)Cl, and Pt(N,Ndiethyldiethylenetriamine) Cl, had on zebrafish inner ear auditory epithelial cells. We then compared the apoptotic effects of these compounds to those of cisplatin, which is a bifunctional platinum compound. Our hypothesis was that the four monofunctional platinum compounds would cause reduced inner ear apoptosis compared to cisplatin. Zebrafish were injected with either vehicle solution, cisplatin or with one of the monofunctional compounds. Later, at 24-hour and 48-hour time points, the zebrafish were euthanized, and two of their auditory inner ear endorgans, the utricle and saccule, were dissected out. A terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay was then used to label apoptotic cells, and the inner ear organs were viewed under a microscope. The number of apoptotic cells on each sample was quantified and the data were analyzed for significant differences between treatments. We found that with the exception of pyriplatin in the saccules, and with the exception of pyriplatin, Pt(N,N-diethyldiethylenetriamine)Cl, and phenanthriplatin in the utricles, the monofunctional compounds and cisplatin did not induce apoptosis in the inner ear of zebrafish at either time point. Based on these results we conclude that the monofunctional platinum compounds largely do not induce zebrafish inner ear apoptosis and if they were to produce ototoxicity, it would not be through an apoptotic mechanism.

Ce travail de thèse décrit l'utilisation de complexes de platine(II) dans les diodes électroluminescentes organiques (OLEDs). Ces complexes ([Pt(II) (tetra-tert-butylSalophen)] et [Pt(II) Salophen]) ont été caractérisés par les méthodes usuelles (1H RMN, spectroscopie UV-visible, électrochimie, diffraction des rayons X pour le [Pt(II) (tetra-tert-butylSalophen)]). Des calculs DFT ont corroboré les données expérimentales qui ont guidé le choix du Tris(8-hydroxyquinolinato) aluminum (Alq3) en tant que matrice. Des dispositifs bistables, susceptibles d'être utilisés en tant que mémoires, ont été obtenus lors du dopage, à 5%, d'OLEDs monocouches. La modulation de ce phénomène par l'ajout d'une couche de N,N'-Di(1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine (NPD) d'épaisseur contrôlée, a été mis en évidence. Des OLEDs bicouches (NPD/Alq3:Pt) émettant dans la gamme spectrale 640-750 nm (rouge profond), et présentant des rendements supérieurs à 20 %, ont ainsi été réalisées. En dopant la couche de NPD, des OLED jaunes présentant un comportement électro-chromatique ont été élaborées. Sous l'effet du dopage par ces complexes, l'augmentation de la durée de vie des OLEDs a aussi été démontrée. / This thesis describes the integration of platinum(II) complexes within organic light emitting diodes (OLEDs). These complexes ([Pt(II) (tetra-tert-butylSalophen)] and [Pt(II) Salophen]) were characterized by the usual methods ( 1H NMR, UV-Vis spectroscopy, electrochemistry and X-ray diffraction for [Pt(II) (tetra-tert-butylSalophen)]). DFT calculations support the experimental data which guided the selection of Tris(8-hydroxyquinolinato) aluminum (Alq3)as host. 5% doping in monolayer OLEDs gave bistable devices which may be used as memory. Modulation of this phenomenon was allowed by adding a controlled layer of N,N'-Di(1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine (NPD). Bilayer OLEDs (NPD/Alq3:Pt) were shown to emit in the deep-red range between 640-750nm with efficiencies higher than 20%. Upon doping with complexes, an enhancement in the lifetime of OLEDs was highlighted.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-07-12T17:59:56Z No. of bitstreams: 1 williantassiogomesnovato.pdf: 7712650 bytes, checksum: adfa7e3f6c5e2987d6257a1273717217 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-13T16:53:43Z (GMT) No. of bitstreams: 1 williantassiogomesnovato.pdf: 7712650 bytes, checksum: adfa7e3f6c5e2987d6257a1273717217 (MD5) / Made available in DSpace on 2016-07-13T16:53:43Z (GMT). No. of bitstreams: 1 williantassiogomesnovato.pdf: 7712650 bytes, checksum: adfa7e3f6c5e2987d6257a1273717217 (MD5) Previous issue date: 2012-08-02 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / No presente trabalho, metodologias teóricas foram utilizadas para análise de propriedades estruturais, termodinâmicas e cinéticas de agregados do peptídeo β- amilóide Aβ(1-42) e seus adutos formados com complexos de platina(II) derivados da 1,10-fenantrolina (ortofenantrolina), os quais são considerados potenciais agentes reguladores do Mal de Alzheimer (MA). Através de técnicas de modelagem molecular propomos um modelo de estrutura/reatividade/estabilidade para esta classe de compostos metálicos com resíduo de histidinas (His). Utilizando simulações de Dinâmica Molecular (DM) foi possível propor o perfil aglomerativo entre os peptídeos, no qual resíduos de His foram mapeados de forma topológica e identificados como responsáveis pela estabilidade dos aglomerados. Os resultados obtidos concordam com os indícios experimentais os quais sugerem que o bloqueio dos sítios de His favorece a diminuição da formação de aglomerados Aβ(1-42). Na segunda parte do trabalho, a cinética da reação entre complexos de Pt(II) com Aβ(1-42) foi investigada utilizando métodos quânticos (QM) e híbridos (QM/MM). O alvo biológico foi dividido em 3 níveis contendo 1, 10 e 42 resíduos de aminoácidos (AA) respectivamente, de tal forma que pudéssemos perceber a resposta desaglomerativa induzida por esta classe de compostos de Pt(II) nos adutos formados, sendo viável para o desenvolvimento de possíveis futuras novas drogas anti-MA. / In the present work, theoretical methods were used to analyze the structural, thermodynamic and kinetic properties of β-amyloid peptide aggregates and its adducts formed with phenanthroline derivatives platinum(II) complex, which are considered potentials regulators of Alzheimer’s disease. Through molecular modeling techniques, we propose a model of structure/reactivity/stability to this class of metal compounds with hitidine (His) residues. Using Molecular Dynamic (MD) simulations was possible to propose the agglomerative profile among the peptides in which His residues of were mapped in a topological and identified as the responsible for the clusters’s stability. The obtained results are in agreement with the experimental evidences, which suggests that blocking the His sites, favors the decrease of formation of the Aβ(1-42) agglomerates. In the second part of the work, the reaction kinetics between Pt(II) complexes with Aβ(1-42) was investigated using quantum methods (QM) and hybrid (QM/MM). The biological target was divided into 3 parts containing 1, 10 and 42 amino acids residues (AA) respectively, so that it was possible to note the deagglomerative response induced by this class of metal compounds in the formed adducts, being feasible the development of possible new drugs against Alzheimer disease.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-05-09T17:32:07Z No. of bitstreams: 1 carolinamauadlopes.pdf: 3121763 bytes, checksum: 9c9d315487de2459b697ebfde962011b (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-17T14:28:10Z (GMT) No. of bitstreams: 1 carolinamauadlopes.pdf: 3121763 bytes, checksum: 9c9d315487de2459b697ebfde962011b (MD5) / Made available in DSpace on 2017-05-17T14:28:10Z (GMT). No. of bitstreams: 1 carolinamauadlopes.pdf: 3121763 bytes, checksum: 9c9d315487de2459b697ebfde962011b (MD5) Previous issue date: 2014-08-29 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O câncer é uma das principais causas de morte no mundo, sendo cada vez maior a busca pela cura desta doença. Atualmente, destacam-se três principais formas de tratamento, sendo elas a cirurgia, a radioterapia e a quimioterapia. A quimioterapia tem sido uma alternativa extremamente valiosa no tratamento do câncer, no entanto, é bastante agressiva aos pacientes. Diversos estudos vêm sendo desenvolvidos na tentativa de encontrar novos compostos ativos e menos tóxicos. Mais da metade das drogas disponíveis para o tratamento do câncer são compostos naturais ou derivados deles. Por outro lado, complexos de platina atraem grande atenção dos pesquisadores em decorrência à eficácia da cisplatina e análogos como agentes antitumorais já bem estabelecidos no uso clínico. No presente trabalho é apresentada a síntese e caracterização de 15 novos complexos de platina com ligantes sintéticos obtidos de produtos naturais da classe dos terpenos. Os complexos foram caracterizados por espectroscopia vibracional, RMN de 1H, de 13C e 195Pt, análise térmica e análise elementar. Foram testadas ainda a atividade antibacteriana dos compostos e a citotoxicidade em células tumorais e células normais. Nenhum dos compostos analisados mostrou-se ativo contra o crescimento bacteriano nas cepas testadas, no entanto, com relação à citotoxicidade foram obtidos resultados interessantes no que tange a seletividade celular. Destaca-se o composto 9 que apresentou elevado valor de índice se seletividade para melanoma metastático e valor IC50 não tão distante ao composto de referência, a cisplatina. / Cancer is a leading cause of death worldwide, and there is an ongoing search for treatments or cure for this disease. At the present, there are three main forms of treatment: surgery, radiotherapy and chemotherapy. Chemotherapy has been an extremely valuable alternative in the treatment of cancer, however, is quite aggressive to the patients. Many studies have been conducted in an attempt to find more active and less toxic compounds. More than half of the available anti-cancer drugs are natural compounds or derived from them. On the other hand, platinum complexes attract attention from researchers due to the efficacy of cisplatin and analogues as antitumor agents which are already well established in clinical use. The present work comprehends the synthesis and characterization of 15 novel platinum complexes derived from modified ligands obtained from natural terpene. The complexes were characterized by vibrational, 1H , 13C and 195Pt NMR spectroscopies, thermal and elemental analyses. The antibacterial activity and cytotoxicity of the compounds in tumor and normal cells were tested. None of the compounds examined were active against bacterial growth for the tested strains, however, regarding cytotoxicity interesting results were obtained in relation to the selectivity index. For instance, compound 9 exhibited high selectivity index for metastatic melanoma cells and IC50 value close to the reference drug, cisplatin.

Substitution of the 1,5-cyclooctadiene (cod) ligand in PtCl2(cod) (1) by the diphosphine ligand 4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (bpcd) yields PtCl2(bpcd) (2). Knoevenagel condensation of 2 with 9-anthracenecarboxaldehyde leads to the functionalization of the bpcd ligand and formation of the corresponding 2-(9-anthracenylidene)-4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (abpcd) substituted compound PtCl2(abpcd) (3), which is also obtained from the direct reaction of 1 with the abpcd ligand in near quantitative yield. The reaction of 3 with disodium maleonitriledithiolate (Na2mnt) affords the chelating dithiolate compound Pt(mnt)(abpcd) (4). The reaction of PtCl2(bpcd) (2) with 4-methyl-1,2-benzene dithiol under basic conditions affords Pt(tdt)(bpcd) (5). Compounds 2-5 have been fully characterized in solution by IR and NMR spectroscopies (1H and 31P), and their molecular structures established by X-ray crystallography. The electrochemical properties of 2&#8209;5 have examined by cyclic voltammetry, and the nature of the HOMO and LUMO levels in systems 2-4 has been established by MO calculations at the extended Hückel level, the results of which are discussed with respect to electrochemical data and related diphosphine derivatives. In addition the new compounds 2-5 have been isolated by column chromatography and characterized by IR, UV-Vis spectroscopy.

No description available.