PONTES, D. L.; MOREIRA, I. S. Estudo de complexos de ferro-cyclam com ligantes carboxilados e polinitrilados. 2008. 162 f. Tese (Doutorado em Química Orgânica) - Centro de Ciências, Universidade Federal do Ceará, 2008. / Submitted by José Jairo Viana de Sousa (jairo@ufc.br) on 2014-10-13T17:44:37Z No. of bitstreams: 1 2008_tese_dlpontes.pdf: 1451677 bytes, checksum: 33babff92184cef9a5bc083765e8a3d6 (MD5) / Approved for entry into archive by José Jairo Viana de Sousa(jairo@ufc.br) on 2014-11-11T22:49:04Z (GMT) No. of bitstreams: 1 2008_tese_dlpontes.pdf: 1451677 bytes, checksum: 33babff92184cef9a5bc083765e8a3d6 (MD5) / Made available in DSpace on 2014-11-11T22:49:04Z (GMT). No. of bitstreams: 1 2008_tese_dlpontes.pdf: 1451677 bytes, checksum: 33babff92184cef9a5bc083765e8a3d6 (MD5) Previous issue date: 2008 / The main objective of this work is to contribute with the chemistry of the system Fe-Cyclam through the synthesis and characterization of complexes with carboxylate ligants, acetate and oxalate, and polinitrilate ligands, 7,7,8,8-tetracyanoquinodimethane (TCNQ) and tetracyanoethylene (TCNE). The infrared spectra of the cis-[Fe(cyclam)ox]PF6 complex allowed to identify the coordination of the oxalate ligand to the iron metal in a bidentate mode as well as to suggest the presence of the macrocycle in the coordination sphere of the metal. The redox potential of the complex was observed at –39mV vs Ag/AgCl. The potential is dislocated 240mV for more positive potential when compared to that observed for the precursor complex cis-[Fe(cyclamCl2]Cl. This effect can be attributed to the stronger σ effect of the oxalate ligand when compared to the chlorine. The UV-Vis spectra of the complex, presented three bands: 229nm, attributed to a cyclam intraligand transition and the bands 293nm and 357nm, referring to ligand to metal electronic transfer from π orbitals of the oxalate to dπ* of the metal. The photochemical experiments proved the great sensibility of the complex to the light presence, being observed the reactivity effect of the complex formed after the light exposition by the formation of the trans-[Fe(cyclam)acet2]PF6 complex. Through the Ray-X obtained of the crystal of the trans-[Fe(cyclam)acet2]PF6 complex was possible to identify the coordination of two molecules of acetate at the trans position, as well as to identify the disposition of the cyclam ligand on the plane in a trans-III arrange. The infrared spectrum of the complexes cis - [Fe(cyclam)(TCNX)Cl]Cl, where the TCNX represent the ligands TCNQ and TCNE, present a great number of bands referring to the νCN, when compared with the ligands not coordinated, confirming the symetry changed induced by the metal coordination. Through the wavenumber variation of these bands was possible to identify that the TCNQ and TCNE ligands are coordinated in your radical way, oxidation state –1, suggestion this way the occurrence of a electron transfer from the iron, previously reduced (Fe+2), to the TCNX ligands. The redox potentials of the iron metals in the complexes with the polinitrilate ligands TCNQ (693mV vs ENH) and TCNE (854mV vs ENH) were dislocated for more positive potentials, when compared to the cis-[Fe(cyclam)Cl2]Cl precursor complex (405mV vs ENH), indicating the occurrence of an electronic density transfer to the TCNX molecules. The two potentials of the ligands on the complexes were closer than the ligands not coordinated, this approximation of the potential indicate a decrease of the inner electron transfer. The electronic spectra of the complexes, showed bands in the low energy region, attributed to a charge transfer LMCT, from the TCNX pπ orbital to the metal dπ* orbital. In the cis-[Fe(cyclam)(TCNQ)Cl]Cl complex, the band was observed at 764nm while in the complex with the TCNE ligand this band was observed at 861nm. Also, the complexes presented bands at 557nm (TCNE complex) and 568nm (TCNQ complex)referring to the LMCT transitions from the chlorine atoms to the iron metal reinforcing the assignment of the (Fe+3) oxidation state for the metal center. / O objetivo deste trabalho é contribuir com o desenvolvimento da química do sistema Fe-cyclam, através da síntese e caracterização de novos complexos metálicos deste sistema com duas classes de ligantes: carboxilados (oxalato e acetato) e ligantes polinitrilados (7,7,8,8 –tetracianoquinodimetano e tetracianoetileno ). Através da caracterização do complexo cis-[Fe(cyclam)ox]PF6 por infravermelho foi possível identificar que o ligante oxalato encontra-se coordenado ao centro metálico de forma bidentada, bem como garantir que o ligante macrocíclico cyclam continua na esfera de coordenação do metal. O potencial formal de meia onda do processo redox Fe3+/2+ do complexo foi observado em –39mV vs Ag/AgCl. O potencial observado encontra-se deslocado 240mV para menores valores em relação ao complexo precursor, favorecendo ao estado de oxidação Fe3+ do metal, devido ao maior efeito σ doador do ligante oxalato frente aos cloretos. O espectro UV-Vis do complexo cis–[Fe(cyclam)ox]PF6, em meio aquoso, apresentou três bandas: 229nm, atribuída a uma transição intraligante do cyclam, 293nm e 357nm, atribuídas à transferência de carga de orbitais π do ligante para o orbitais dπ* do metal. Os experimentos fotoquímicos demonstraram a grande sensibilidade do complexo à luz, sendo observado a labilização do ligante oxalato da esfera de coordenação do metal, e a reatividade da espécie formada através da obtenção do complexo trans-[Fe(cyclam)acet2]PF6, Através do estudo de Raio-X, obtido a partir do cristal do complexo trans-[Fe(cyclam)acet2]PF6, foi possível comprovar o modo de coordenação das duas moléculas de acetato na posição trans, bem como a identificação da disposição do cyclam no plano da molécula através de um arranjo conformacional trans-III. Os espectros no infravermelho dos complexos cis - [Fe(cyclam)(TCNX)Cl]Cl, onde TCNX representa os ligantes TCNQ ou TCNE, apresentaram um maior número de bandas referentes aos estiramentos CN, comparativamente aos ligantes livres, confirmando a alteração da simetria do ligante causada pela coordenação do metal. Com base nos deslocamentos destas freqüências para menores valores, comparativamente ao ligante livre, foi possível identificar que os ligantes TCNQ e TCNE estão coordenados em sua forma radicalar, estado de oxidação –1, sugerindo assim a ocorrência de um processo de transferência de elétrons do centro metálico, previamente reduzido (Fe2+), para os ligantes TCNX. Os potenciais redox dos átomos de ferro, nos complexos com os ligantes polinitrialados TCNQ (693mV vs ENH) e TCNE (854mV vs ENH), foram deslocados para potenciais mais positivos, comparativamente ao observado no complexo precursor cis-[Fe(cyclam)Cl2]Cl (405mV vs ENH), indicando assim um forte deslocamento de densidade eletrônica dπ para os orbitais de simetria π dos ligantes TCNX. Os processos centrados nos ligantes coordenados ficaram mais próximos do que nos ligantes livres, indicando uma diminuição na barreira de transferência de elétrons, que segundos dados da literatura leva a uma melhor condução elétrica. Os espectros eletrônicos dos complexos, em meio aquoso, apresentaram uma banda localizada em baixa energia, atribuída a transferências de carga do tipo LMCT dos orbitais pπ das moléculas de TCNX, para os orbitais dπ* do íon Fe3+. No complexo com o ligante TCNQ, esta banda aparece em 764nm e no complexo com o ligante TCNE, em 861nm. Observa-se ainda nos dois complexos a presença das bandas referentes às transições LMCT dos cloretos para o íon Fe3+ em regiões muito próximas, em 557 no complexo com TCNE e em 568nm no complexo com TCNQ. A presença desta banda novamente sugere a presença do Ferro no estado oxidado (Fe+3).

Some bicyclam compounds are highly active as HIV inhibitor agents with high selectivity for the CXCR4 coreceptor, an important protein receptor for the human immunodeficiency virus. One particular bicyclam, AMD3100 (1,1’-(1,4-phenylenebismethylene)-bis-1,4,8,11-tetraazacyclotetra- decane, known as xylyl-bicyclam) reached Phase II clinical trials in 2001. More recently, it has been relaunched commercially as Mozobil, a stem cell mobiliser. The activity of this macrocycle and configurationally restricted analogues as antivirals against HIV, have been shown to increase on complexation with zinc. A range of metals has been studied with varying degrees of activity seen, but none show activity comparable with the zinc complexes. In order to investigate the chemistry of macrocycles in their role as anti-HIV agents, the syntheses of vanadium-cyclam, vanadium-bicyclam and zinc constrained cyclam complexes have been carried out. Of the many oxovanadium(IV) cyclam complexes synthesised, those with a sulfate or chloride axial ligand trans- to the V=O group were chosen for comparison purposes with oxovanadium(IV) bicyclam analogues for both solid state and solution analyses. X-ray crystallography showed that the oxovanadium(IV) cyclam complexes crystallised in the thermodynamically stable trans-III configuration. Aqueous solution studies using EPR spectroscopy revealed a different behaviour for the oxovanadium(IV) cyclam and bicyclam complexes studied. Results suggested that the 6th axial ligand trans- to the V=O group could undergo facile exchange in solution for the cyclam complexes but may be retained in the bicyclam complexes. Antiviral test results for oxovanadium(IV) cyclam complexes revealed these to be completely inactive against HIV. Xylyl-bicyclam was synthesised and complexed with vanadium, as oxovanadium(IV) sulfate and chloride structures. EPR spectroscopy results suggested that for the bicyclam chloride complex some displacement of the 6th axial ligand may occur, but the bicyclam sulfate appeared to retain both axial ligands. More importantly, these ligands also appear to have a significant effect on the hyperfine coupling constant, A. Antiviral test results for oxovanadium(IV) bicyclam sulfate and chloride complexes revealed these to be highly active against HIV, with the chloride structure showing similar activity to AMD3100. Possible interactions between the V=O group and the protein backbone of CXCR4 were studied using molecular modelling techniques, incorporating the X-ray crystal structure obtained for the oxovanadium(IV) cyclam sulfate complex. This revealed the possibility of a weak interaction between the oxygen of the V=O group and the proton of the alpha-carbon of a tryptophan residue, Trp195. No metal-carboxylate interaction was seen between the vanadium centre and aspartate residue Asp171 in the binding site investigated, possibly due to the distance between them being unfavourable for formation of a coordination bond (3.4 Å). Possible hydrogen bonding was seen between the carboxylate oxygens of Asp171 and the NH protons of the trans-III configured ring. These studies may demonstrate how oxo-metals interfere with the protein backbone in such a way as to distort the molecule from an optimum binding geometry. It may also indicate the importance of a second binding site known to support a cis-V configuration of the macrocycle, bearing in mind that vanadium bicyclam complexes do show activity as antivirals against HIV. It is possible that one ring of the vanadium bicyclam complexes interacts with the binding site for the trans-III configuration in a similar fashion to the cyclam complexes and the antiviral activity may result, in this case, from interactions formed through binding of the second ring. The aromatic linker is also thought to be important. Cyclams can be constrained by adding bulky substituents and/or additional rings to the structure and this has the effect of stabilising one configuration. NMR studies show how a zinc constrained cyclam retains the trans-III configuration in solution and also shows high activity against HIV, comparable with the vanadium bicyclam sulfate complex. This emphasises how the oxo-vanadium cyclams must be in an unfavourable position and unable to form crucial interactions known to be important for antiviral activity. A 4-coordinate zinc constrained macrocycle showed unusual binding to three ring nitrogens and may reveal an intermediate species in the uptake and release of metals by cyclams. Further complexation by exchange of the axial ligand revealed a 5-coordinate zinc bound to all four nitrogens on the ring. This thesis provides the first investigation into the role of oxo-vanadium complexes as antiviral agents against HIV looking at possible interactions of the oxo-metal group with the protein backbone of the CXCR4 receptor. An investigation into configurational change in solution for zinc constrained cyclams is also described.

This thesis involves reactions of cyclam with Mn(III), Ni(II) and Fe(II). The chemistry of each metal with cyclam will be presented in sections discussing each metal. The initial intent of this thesis was to examine and compare the structures and electronic spectra of a series of trans monomeric first row transition metal cyclam compounds. Both Mn(III) and Ni(II) form such trans monomeric complexes with cyclam and their structural and electronic characteristics are, indeed, examined in this thesis. However, in the course of our study, we found that Fe(II) and cyclam in acetonitrile in the presence of oxygen form a di-macrocycle shown here: [See PDF]

<p>Tetraazamacrocycles, such as cyclam (1,4,8,11-tetraazacyclotetradecane), are useful ancillary ligands in the formation of organometallic complexes. Coordination of a 3d metal can lead to the formation of square planar complexes, such as with Ni^II and Cu^II, or octahedral complexes upon coordination of additional ligands, such as with Co^II/III and Cr^II/III. Notably with Cr, a mixture of <i>cis-</i> and <i>trans-</i>octahedral complexes are formed, and the isomerism can be influenced through <i>C</i>-substitution of the cyclam macrocycle. Herein, Cr^III complexes featuring <i>C</i>-substituted cyclam derivatives and either redox-active ligands or alkynyl ligands are reported.</p> <p>Chapter 1 features an introduction to the photophysical processes of Cr(III), an overview of cyclam and its derivatives, and a brief review of Cr^III(cyclam/cyclam’) bis-alkynyl complexes for various applications. Chapter 2 discusses the structural, optical, electronic, and magnetic characterizations of <i>cis</i>-[Cr(HMC)catecholate]⁺ and <i>cis</i>-[Cr(HMC)semiquinonate]²⁺ complexes, which feature redox-active catecholate and semiquinonate ligands. Chapter 3 highlights a series of <i>trans</i>-[Cr(HMC)(C₂Ar)Cl]⁺ complexes, which expands upon prior research on bis-alkynyl complexes. Chapter 4 discusses how a different <i>C</i>-substituted cyclam derivative, MPC, is used to produce <i>trans</i>-[Cr(MPC)Cl₂]⁺ starting material in higher quantity than the HMC derivative. This allows for higher amounts of <i>trans</i>-[Cr(MPC)(C₂Ar)₂]⁺ complexes to be synthesized, making it a more practical macrocycle for the future pursuit of dissymmetric bis-alkynyl complexes.</p>

Neste trabalho são apresentados estudos referentes a dois grupos de sistemas contendo dióxido de enxofre como principal foco, tendo em vista a importância desta molécula em sistemas ambientais e sua caracteristicas químicas interessantes como seu caráter anfotérico e sua capacidade de interação com sistemas inorgânicos via oxigênio ou enxofre. Tendo como principais feramentas as espectroscopias vibracionais (espalhamento Raman e absorção no Infravermelho), eletrônica (UV-VIS) e Ressonância Magnética Nuclear (RMN) investigou-se as interações inter e intramoleculares dos sistemas de interesse. Primeiramente foi investigada a interação do SO2 com aminoálcoois, sendo que estes sistemas apresentam boa capacidade de absorção do SO2. Destaca-se a formação de zwitteríons pela interação do SO2 com o grupamento alcoólico da molécula, observado apenas quando da presença de grupo amino para estabilização da separação de cargas gerada, mostou-se que o poduto fomado é mais estavél quanto menor a separação das cargas e menor o impedimento estérico na amina. Este sistema foi investigado quanto a sua revesibilidade, que foi observada sempre acompanhada de degradação do aminoálcool. O segundo sistema refere-se a interação do dióxido de enxofre com complexos de níquel em dois estados de oxidação (II/III) com ligante macrocíclico cyclam (1,4,8,11- Tetraazaciclotetradecano); o diferencial deste estudo frente a outros apresentados na literatura é a análise das reações em meio anidro. Nos experimentos em meio livre de O2 obseva-se a redução do complexo de Ni (III) a Ni(II) e em meio contendo O2 observa-se a oxidação do complexo de Ni(II) a Ni(III), mostrando a importância do O2 para a manutenção de um ciclo catalítico capaz de oxidar SO2 a SO42-. Os resultados aqui apresentados indicam que os mecanismos em meio anidro são bastante semelhantes aos observados em meio aquoso. / In this work we focus on two sulfur dioxide containing systems due to the relevance of this molecule in environmental science and its interesting physico-chemical properties as its amphoteric characteristic and ability to interact with inorganic systems through oxygen or sulfur atoms. The main tools for investigation was vibrational spectroscopy (Raman scattering and Infrared absorption), electronic spectroscopy (UV-VIS) and Nuclear Magnetic Resonance (NMR), whereby the intra and intermolecular interactions were probed. The first subject of investigation was the study of interactions between SO2 and amino alcohol. This system shows great ability to capture SO2, highlighting the zwitterionic formation due to the bonding of SO2 via the alcoholic part of the amino alcohol molecule, what is only possible due to the presence of the amino group to stabilize the charge separation, the stability of the poduct depends on the steric hindrance and on the charge separation. The reversibility of the system was investigated and it was always accompanied by degradation of the amino alcohol. The second system consists in the investigation of interactions between SO2 and two nickel-cyclam (1,4,8,11-Tetraazacyclotetradecane) complexes, where the metal is in different oxidation states (II/III). This work is different from previous in the sense that the analyses are carried out in anhydrous environment. In O2 free environment we were able to see the reduction of Ni(III) to Ni(II) complex, and in presence of O2 the oxidation of Ni(II) to Ni(III) complex occurs, showing the relevance of O2 to catalytic cicle that is able to transform SO2 to SO42-. Our results suggest that the mechanisms in aqueous and nonaqueous environments are very similar.

Neste trabalho são apresentados estudos referentes a dois grupos de sistemas contendo dióxido de enxofre como principal foco, tendo em vista a importância desta molécula em sistemas ambientais e sua caracteristicas químicas interessantes como seu caráter anfotérico e sua capacidade de interação com sistemas inorgânicos via oxigênio ou enxofre. Tendo como principais feramentas as espectroscopias vibracionais (espalhamento Raman e absorção no Infravermelho), eletrônica (UV-VIS) e Ressonância Magnética Nuclear (RMN) investigou-se as interações inter e intramoleculares dos sistemas de interesse. Primeiramente foi investigada a interação do SO2 com aminoálcoois, sendo que estes sistemas apresentam boa capacidade de absorção do SO2. Destaca-se a formação de zwitteríons pela interação do SO2 com o grupamento alcoólico da molécula, observado apenas quando da presença de grupo amino para estabilização da separação de cargas gerada, mostou-se que o poduto fomado é mais estavél quanto menor a separação das cargas e menor o impedimento estérico na amina. Este sistema foi investigado quanto a sua revesibilidade, que foi observada sempre acompanhada de degradação do aminoálcool. O segundo sistema refere-se a interação do dióxido de enxofre com complexos de níquel em dois estados de oxidação (II/III) com ligante macrocíclico cyclam (1,4,8,11- Tetraazaciclotetradecano); o diferencial deste estudo frente a outros apresentados na literatura é a análise das reações em meio anidro. Nos experimentos em meio livre de O2 obseva-se a redução do complexo de Ni (III) a Ni(II) e em meio contendo O2 observa-se a oxidação do complexo de Ni(II) a Ni(III), mostrando a importância do O2 para a manutenção de um ciclo catalítico capaz de oxidar SO2 a SO42-. Os resultados aqui apresentados indicam que os mecanismos em meio anidro são bastante semelhantes aos observados em meio aquoso. / In this work we focus on two sulfur dioxide containing systems due to the relevance of this molecule in environmental science and its interesting physico-chemical properties as its amphoteric characteristic and ability to interact with inorganic systems through oxygen or sulfur atoms. The main tools for investigation was vibrational spectroscopy (Raman scattering and Infrared absorption), electronic spectroscopy (UV-VIS) and Nuclear Magnetic Resonance (NMR), whereby the intra and intermolecular interactions were probed. The first subject of investigation was the study of interactions between SO2 and amino alcohol. This system shows great ability to capture SO2, highlighting the zwitterionic formation due to the bonding of SO2 via the alcoholic part of the amino alcohol molecule, what is only possible due to the presence of the amino group to stabilize the charge separation, the stability of the poduct depends on the steric hindrance and on the charge separation. The reversibility of the system was investigated and it was always accompanied by degradation of the amino alcohol. The second system consists in the investigation of interactions between SO2 and two nickel-cyclam (1,4,8,11-Tetraazacyclotetradecane) complexes, where the metal is in different oxidation states (II/III). This work is different from previous in the sense that the analyses are carried out in anhydrous environment. In O2 free environment we were able to see the reduction of Ni(III) to Ni(II) complex, and in presence of O2 the oxidation of Ni(II) to Ni(III) complex occurs, showing the relevance of O2 to catalytic cicle that is able to transform SO2 to SO42-. Our results suggest that the mechanisms in aqueous and nonaqueous environments are very similar.

Verbindungen mit einer Vielzahl von Oberflächeneinheiten (Multimere) sind im Hinblick auf eine nuklearmedizinische Anwendung von besonderem Interesse, da durch definierte Strukturmodifizierung das Bindungsverhalten an bestimmte Zielstrukturen, die Löslichkeit und damit die Bioverteilung und Pharmakokinetik beeinflusst werden können. Baut man eine Verbindung so auf, dass sich im Inneren ein metallbindendes Zentrum befindet, ergibt sich einerseits die Möglichkeit, das Radiometall chemisch stabil zu binden, andererseits durch genannte Oberflächenfunktionalisierung eine spezifische Bindung im Zielgewebe zu erreichen. Im Rahmen dieser Arbeit wurden neuartige mehrfunktionale Verbindungen mit einer Cyclam-Kerneinheit synthetisiert. Cyclam bildet mit Cu(II)-Ionen äußerst stabile Komplexe, was im Hinblick auf eine radiopharmazeutische Anwendung der Radiometallkomplexe von 64Cu oder 67Cu für diagnostische und therapeutische Zwecke äußerst interessant ist. Für eine symmetrische Mehrfachfunktionalisierung wurde auf ein Tetraamin mit Cyclamkern zurückgegriffen. Die Kupplung von vier Dansylchlorid-Einheiten war erfolgreich. Über geschützte Glucosyl-Isothiocyanate wurden Derivate mit vier Zuckereinheiten gewonnen. Nach der Entfernung der Schutzgruppen wurde die Bindung an das kohlenhydratbindende Lektin Concanavalin A mittels isothermer Kalorimetrie bestimmt. Es war ein deutlicher Anstieg der Stabilitätskonstante K im Vergleich zu den monomeren Zuckern zu beobachten. Die Kinetik der Cu(II)-Komplexierung wurde UV/Vis-spektroskopisch bestimmt. Wegen der langsamen Cu-Komplexierungskinetik der Thioharnstoff-verbrückten Glycodendrimere wurde der Schwerpunkt bei den nachfolgenden Untersuchungen zur Kupplung von Peptiden über Amidbindungen gelegt. Nach zahlreichen erfolglosen Kupplungsversuchen von Peptiden mit einer freien Aminogruppe an Cyclamtetrapropionsäure im organischen Medium wurden im wässrigen Milieu Cyclamderivate mit ein bis zu drei Peptideinheiten durch Peptidkupplung erzeugt. Die Synthese kupplungsfähiger Peptidisothiocyanate blieb erfolglos. Schließlich führte eine Michael-Addition von Acrylamid-Arg-Tyr-OH und Acrylamid-Neurotensin(8-13)-OH an Cyclam zu den gewünschten tetrameren Verbindungen. Das Neurotensintetramer mit vier zielsuchenden Einheiten wurde für weiterführende radiochemische und radiopharmakologische Untersuchungen eingesetzt. Es kann unter milden Bedingungen sehr effizient mit 64Cu radiomarkiert werden, wobei eine spezifische Aktivität von 12 GBq pro µmol und Markierungsausbeuten von durchschnittlich 95-98% erzielt werden können. Erwartungsgemäß werden die Neurotensineinheiten unter diesen Bedingungen abgebaut, wobei im Vergleich zu freiem H-Neurotensin(8-13)-OH, welches innerhalb von zwei Minuten abgebaut wird, die In-vivo-Halbwertszeit des Tetramers 34 Minuten beträgt. Es konnte keine Transmetallierung beziehungsweise Transchelatisierung beobachtet werden, was die Stabilität des Komplexes zeigt. PET-Untersuchungen nach Applikation des 64Cu-markierten Neurotensin-Tetramers wiesen eine erhöhte Anreicherung von radioaktiver Substanz in Tumoren von LoVo- und HT29-Mäusen nach. Um zu unsymmetrischen Cyclamderivaten mit dem Ziel der gleichzeitigen Einführung zielsuchender, löslichkeitsvermittelnder und fluoreszierender Einheiten zu gelangen, wurden unterschiedliche Schutzgruppen eingesetzt. Die Blockierung primärer Aminogruppen eines Cyclam-Derivates mit MMTr-, Boc- und Z-Schutzgruppen lieferte Produkte, die sauber isoliert, aber nicht selektiv entschützt werden konnten. Daher wurden die Aminstickstoffatome des Cyclams direkt geschützt. Ausgehend von Cyclam-Boc3 konnten über Kupplungsreaktionen Aminosäure- und Dipeptidmethylester als unsymmetrische Cyclamderivate gewonnen werden. Damit ist ein Syntheseweg entwickelt worden, der die Darstellung unsymmetrischer Cyclamderivate mit einer definierten Anzahl von gewünschten biologisch aktiven Molekülen beziehungsweise löslichkeitsvermittelnder oder fluoreszierender Einheiten gestattet.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Os compostos trans-[Co(cyclam)(SO3)(NCS)]Â4H2O, trans-[Ru(NH3)4(NCS)(SO4)] e trans-[(SO3)(cyclam)Co&#8722;NCS&#8722;Ru(NH3)4(NCS)](BF4), onde cyclam = 1,4,8,11-tetraazaciclotetradecano, foram sintetizados e caracterizados por difraÃÃes de raios-X, espectroscopias vibracional na regiÃo do infravermelho e eletrÃnica nas regiÃes do ultravioleta e visÃvel (UV-Vis) e por tÃcnicas eletroquÃmicas. O grau de comunicaÃÃo eletrÃnica entre os Ãtomos de Co e Ru do complexo binuclear foi avaliado por eletroquÃmica e espectroscopia eletrÃnica na regiÃo do infravermelho prÃximo. Apenas para o complexo trans-[Co(cyclam)(SO3)(NCS)]Â4H2O foi possÃvel a obtenÃÃo de cristais que permitiram a determinaÃÃo estrutural. Os dados obtidos indicam estrutura monoclÃnica com o ligante cyclam no plano equatorial e os ligantes SO32&#8722; e NCS&#8722; ocupando posiÃÃes trans e coordenados ao Ãtomo de Co atravÃs, respectivamente, dos Ãtomos de S e N. Este resultado à reforÃado atravÃs da observaÃÃo, no espectro vibracional, de bandas tipicamente atribuÃdas ao ligante cyclam quando este se encontra em uma geometria trans. Os resultados de voltametria cÃclica deste composto indicam um mecanismo eletroquÃmico-quÃmico-eletroquÃmico. De fato, os experimentos de espectroeletroquÃmica (potencial controlado em -0,80 V vs Ag/AgCl) indicam que este composto experimenta, apÃs reduÃÃo, reaÃÃo de substituiÃÃo das molÃculas SO32&#8722; e NCS&#8722; por molÃculas do solvente (L), formando compostos do tipo [Co(cyclam)(L)2]2+. A observaÃÃo, no espectro vibracional do complexo trans-[Ru(NH3)4(NCS)(SO4)], das bandas em 2132, 887 e 478 cm-1, atribuÃdas aos modos de &#957;CN, &#957;CS e &#948;(NCS), respectivamente, do ligante NCS&#8722;, indica a coordenaÃÃo deste grupo atravÃs do Ãtomo de nitrogÃnio. Estudos eletroquÃmicos e de espectroscopia eletrÃnica deste composto em meio aquoso indicam que a reduÃÃo do centro metÃlico induz a reaÃÃo de substituiÃÃo do ligante SO42&#8722; por uma molÃcula de H2O. A reaÃÃo para formaÃÃo do composto binuclear, portanto, foi realizada em condiÃÃes redutoras a fim de induzir a formaÃÃo do aquo-complexo de rutÃnio e, em seguida, a reaÃÃo de substituiÃÃo da molÃcula de H2O por um sÃtio de coordenaÃÃo do monÃmero trans- [Co(cyclam)(SO3)(NCS)]Â4H2O. Os resultados obtidos para o material isolado indicam que hà a formaÃÃo do complexo binuclear com o ligante NCS&#8722; ocupando a posiÃÃo ponte. A curva voltamÃtrica obtida para este composto apresenta dois pares de ondas redox com potenciais formais de meia-onda (E1/2) em &#8722;0,27 e 0,13 V vs Ag|AgCl atribuÃdos, respectivamente, aos centros metÃlicos de Co e Ru. Comparativamente aos monÃmeros, hà a observaÃÃo de um deslocamento positivo de potencial o que reflete a estabilizaÃÃo do estado reduzido para o Ãtomo de rutÃnio, RuII, e desestabilizaÃÃo do estado oxidado para o Ãtomo de cobalto, CoIII. Este resultado à atribuÃdo a coordenaÃÃo a um centro oxidado, CoIII, cuja carga nuclear efetiva aumenta a deslocalizaÃÃo de densidade eletrÃnica aumentando o carÃter retirador do ligante ponte NCS&#8722;. O valor da constante de comproporcionamento, Kc = 5,78 x 106, calculada a partir da diferenÃa entre os valores de E1/2, indica um forte grau de comunicaÃÃo entre os centros metÃlicos e classifica este complexo como um sistema de valÃncia mista de classe II. / Trans-[Co(cyclam)(SO3)(NCS)]Â4H2O, trans-[Ru(NH3)4(NCS)(SO4)], and trans-[(SO3)(cyclam)Co&#8722;NCS&#8722;Ru(NH3)4(NCS)](BF4) complexes, where cyclam = 1,4,8,11-tetraazacyclotetradecane, were synthesized and characterized by X-ray difraction, vibrational and electronic (ultraviolet, visible and near infrared) spectroscopies, and electrochemical techniques. The electronic communication between Co and Ru metal centers of the binuclear complex was evaluated by electrochemistry and electronic spectrocopy in the near infrared region. Crystals suitable for X-ray studies were only isolated for the trans-[Co(cyclam)(SO3)(NCS)]Â4H2O complex. The obtained results indicate a monoclic structure with cyclam ligand at the equatorial plane and SO32&#8722; and NCS&#8722; moieties occupying the axial positions being coordinated through, respectively, sulfur and nitrogen atoms. This result is reinforced by the observation, in the vibrational spectrum, of bands typically assigned to the cyclam ligand in a trans configuration. The cyclic voltammograms obtained for this compound indicate as Electrochemical-Chemical-Electrochemical mechanism. In fact, the spectroelectrochemical experiments obtained at -0.80 V vs Ag/AgCl show that this compound, upon reduction, suffers a substitution reaction in which the SO32&#8722; and NCS&#8722; moieties are replaced by solvent molecules (L) thus forming [Co(cyclam)(L)2]2+ type complexes. The observation in the vibrational spectrum of the trans-[Ru(NH3)4(NCS)(SO4)] complex of the 2132, 887 e 478 cm-1 bands assigned, respectively, to the &#957;CN, &#957;CS e &#948;(NCS) vibrational modes of the NCS&#8722; ligand indicates that this moiety is coordinated through the nitrogen atom. Electrochemical and spectroscopic studies of this compound in aqueous medium indicate that the reduction of the metal center induces the replacement of SO42&#8722; ligand by a water molecule. The synthesis of the binuclear compound, therefore, was made under reductive conditions aiming to produce the aquo-complex and, then, replace the water molecule by a coordination site of the trans-[Co(cyclam)(SO3)(NCS)]Â4H2O complex. The results obtained for the isolated material hints that the binuclear complex is formed with the NCS&#8722; fragment as the bridge ligand. The acquired cyclic voltammogram presents two redox process with the half-wave formal potentials (E1/2) observed at &#8722;0.27 and 0.13 V vs Ag|AgCl and being assigned to the Co and Ru metal centers, respectively. In comparison to the monomers, the positive potential shift reflects the stabilization of the reduced state of the ruthenium metal atom (RuII) and the destabilization of the cobalt metal center (CoIII). This result is assigned to the coordination to an oxidated metal center, CoIII, whose effective nuclear charge increased the electronic delocalization increasing the withdrawing character of the NCS&#8722; bridge ligand. The comproportionation constant, Kc = 5.78 x 106, was calculated from the difference between the E1/2 values. The Kc value indicates a strong electronic communication between the metal atoms and classifies this binuclear complex as a mixed valence system of class II.

Doctor of Philosophy / Department of Chemistry / Stefan Kraft / Highly toxic aromatic halogenated compounds such as PCB’s, PCDF’s and PCDD’s act as persistent organic pollutants and can bio-accumulate. These compounds are highly stable to oxidation, reduction and thermal degradation. Current remediation technologies are expensive and can cause the formation of even more toxic byproducts. It is clear that an environmentally friendly and inexpensive remediation technology is required. Our goal was the synthesis of dehalogenation catalysts incorporating aromatic side arms for the pre-concentration of the substrates to the catalysts. We envisioned that aromatic side arms would allow the aggregation of catalyst and substrate to form a pre-complex that would enhance rates of dehalogenation. Rapid and stereochemically predictable synthesis of N and C functionalized nickel cyclam complexes were a priority for this project. Synthesis of N-functionalized cyclam molecules and subsequent metal incorporation proceeds smoothly to form trans(III) nickel cyclam complexes. However longer reaction times, initiation periods and short catalyst lifetimes made these complexes unsuitable for long-term study. Cyclization of dipeptides and tetrapeptides using a metal template in basic conditions led to the formation of cyclopeptide nickel complexes with stereochemistry retained from the peptide precursors. Free cyclopeptides could be isolated from the nickel complexes by treatment with HCl. Cyclopeptides are reduced to the cyclam molecules via a LAH reduction in low to moderate yields. Nickel incorporation into the cyclam molecules produced C-functionalized nickel catalysts with stereochemical integrity maintained throughout the synthesis. Intermolecular CH-π interactions can be seen in the solid state for the nickel cyclam complexes with aromatic side arms. Reduction data show that the C-functionalized catalysts do not show improved rates of reduction for several aromatic substrates but small rate enhancements are observed for the reduction of chloronaphthalene over the unfunctionalized catalyst.

<p>Obtaining a greater understanding of photo-induced electron-transfer (PET) processes is key to synthesizing photovoltaic materials with enhanced efficiency. Gaining knowledge about the structure property relationship in photo-active donor-bridge-acceptor (<i>D-B-A</i>) dyads will help to optimize electronic and photoelectronic materials. Metal acetylide complexes have attracted increasing interest for their potential applications as building blocks for electronic and photoelectronic materials. Their unique υ(C≡C) (2000-2100 cm^-1) allows for selective excitation, making them an appealing target for attenuating PET processes across a metal acetylide backbone. The following topics will be discussed: i.) an overview of M(cyclam′) alkynyl chemistry, where M = Cr, Fe, Co, or Ni, with a focus on reactivity and spectroscopy, ii.) selective synthesis of dissymmetric species, utilizing a Co^III(cyclam) (1,4,8,11-tetraazacyclotetradecane) alkynyl bridge, iii) synthesis and characterization of metal alkynyl <i>D-B-A</i> dyads <i>trans- </i>[R'₂N-4-C₆H₄C₂-Co^III(cyclam)-C_n-NAP^R]⁺(n = 2 or 4), where the chromophore acceptor is NAP^iPr (<i>N</i>-isopropyl-1,8-napthalimide) and the putative donor is -C₆H₄-4-NR'₂ (R' = Me or Ph-4-OMe), iv.) design and synthesis of <i>D-B-A</i> derivatives, alter NAP^R (R = mesityl, methyl, 1-ethylpropyl, 2-ethylhexyl, or octyl) to tune reactivity and crystallinity, v.) electronic and spectroscopic influence the bridging center on <i>A</i>, and vi.) effect of η² coordination of MX₂ (MX₂ = CuCl₂ or Ag(NO₃)₂) to the alkyne bridge on electron transfer. </p>