Дисертації з теми "Copper(II) Curcumin Complexes"

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO
Foram sintetizados 16 complexos de cobre(II) coordenados com seis aminoácidos presentes na placa b-amilóide, que está associada à Doença de Alzheimer - ácido aspártico, ácido glutâmico, metionina, glicina, serina e arginina, outros dois aminoácidos também encontrados no cérebro - cisteína e homocisteína, além da L-carnitina e acetil-L-carnitina que vêm sendo utilizados como suplemento alimentar em pacientes com doenças neurodegenerativas. Nosso objetivo foi verificar a afinidade do cobre(II) com estes aminoácidos, uma vez que o envelhecimento provoca aumento no cérebro tanto das concentrações de íons cobre como dos níveis de todos estes aminoácidos (que são consequência de fragmentações peptídicas). Por esta razão, procurou-se trabalhar in vitro com condições próximas ao meio biológico utilizando apenas água deionizada como solvente. Os complexos obtidos foram caracterizados pelas seguintes técnicas: análise elementar (espectrometria de absorção atômica e CHN), condutimetria, análise termogravimétrica, ressonância paramagnética eletrônica, voltametria cíclica e espectroscopia no infravermelho. Foi possível verificar que, exceto a acetil-L-carnitina, todos se comportam como ligantes bidentados e complexam facilmente ao cobre(II). Ácido aspártico, ácido glutâmico, serina, metionina, glicina e arginina se coordenaram através do átomo de oxigênio do grupo carboxilato e do átomo de nitrogênio do grupo amino, cisteína e homocistéina através do átomo de enxofre e do átomo de nitrogênio do grupo amino, L-caritina através do átomo de oxigênio do grupo carboxilato e do átomo de oxigênio alcoólico e acetil-L-carnitina se coordena monodentadamente através do átomo de oxigênio do grupo carboxilato.
Sixteen complexes of copper(II) with six amino acids that are present in the b-amyloid peptide, which is associated with Alzheimer’s disease - aspartic acid, glutamic acid, methionine, glycine, serine and arginine -, two amino acids also found in the brain - cysteine and homocysteine -, as well as L-carnitine and acetyl-L-carnitine, which have been used as food supplement in patients with neurodegenerative diseases, were studied. Our aim was to determine the affinity of copper(II) with these amino acids, since aging causes an increase in brain concentrations of copper ions as well as in the level of all of these amino acids, as a consequence of peptide fragmentation. For this reason, we decided to do an in vitro study in similar conditions as the biological environment, using only deionized water as solvent. These compounds were characterized through the following techniques: elementary analysis (atomic absorption spectrometry and CHN), conductimetry, thermogravimetric analysis, electron paramagnetic resonance, electrochemical analysis, and infrared spectroscopy. It was possible to verify that, except for acetyl-L-carnitine, all amino acids behaved as bidentate ligands. They all form complexes with copper(II) easily. Aspartic acid, glutamic acid, serine, methionine, glycine and arginine coordinate through the oxygen atom of the a-carboxylate group and the nitrogen atom of the amine group. Cysteine and homocysteine coordinate through the sulfur atom and the nitrogen atom of the amine group, L-Carnitine coordinates through one oxygen atom of the carboxylate group and one oxygen atom of the alcohol group, and acetyl-L -carnitine coordinates through the oxygen atom of the carboxylate group.

Cisplatin is one of the most active drugs in anticancer therapy, and it is currently used for the treatment of a wide range of cancers, in particular advanced ones. After its introduction in clinical therapy, the research in this field has focused on the preparation of new metal complexes with increased activity and lower side-effects. Besides, the use of drug combinations with synergistic effect, i.e. an effect greater than the sum of the effects of the single drugs, has been introduced. This thesis is focused on the preparation of Cu(II) and Pt(II) complexes and on the study of their cytotoxic properties, alone or in combination with cisplatin. Cu(II) complexes with 1,10-phenantroline (phen), 1,10-phenantrolin-5,6-dione and 1,10- phenantrolin-5,6-diol, with 1:1 or 1:2 metal:ligand stoichiometry, have been synthesized. In addition, mixed Cu(II) complexes with phen and thiophene derivatives of general formula [Cu(phen)2(T)](ClO4)2 (T=1-methylthio-thiophene-2-carboxylic acid, 2- methylthio-thiophene-1-carboxylic acid, 2-thiophenecarboxamide, 2- thiophenecarboxylate) have been prepared. A family of Pt(II) complexes of general formula [Pt(P)(D)2](ClO4)2, being P a derivative of phen and D a derivative of imidazolidin-2-thione, has been synthesized. In order to find the species present in solution in conditions similar to the physiological ones (37 °C and NaCl 0.1 M), the formation constants of the complexes have been determined through potentiometric titrations. The dipole moments of the platinum complexes have been determined through quantum mechanical calculations. The in vitro cytotoxic activity of ligands and metal complexes has been evaluated against a panel of human tumour cell lines, and it has been correlated to their structures. Finally, a new method, based on experimental design and artificial neural networks, has been proposed for the evaluation of the synergy in mixtures of two or more drugs. Exploiting this method, the cytotoxic activity of mixture of cisplatin and three Cu(II) complexes ([Cu(phen)(H2O)2(ClO4)2], [Cu(phen)2(H2O)](ClO4)2 e [Cu(phen)2(imidazolidin-2-thione)](ClO4)2) has been studied, and the combination with higher synergistic effect have been identified.

This study focuses on the antimicrobial activity of Cu(II) complexes of some orthohydroxybenzaldimines and its derivatives. Four different categories of Schiff base ligands were prepared by condensing salicylaldehyde, o-vanillin, p-vanillin and vanillin with p- and osubstituted anilines; 1-aminonaphthalene; 2- and 3-aminopyridine; 2- and 3- aminomethylpyridine as well as 2-aminobenzimidazole. The last category was prepared from ophenylenediamine and o-vanillin. The Schiff base ligands have been characterized by a combination of elemental analysis and spectral (¹H- and ¹³C-NMR, UV/Visible, infrared and Raman) data. The existence of strong intramolecular hydrogen bonding in the orthohydoxybenzaldimines was evident from the chemical shift values of the hydroxyl proton in the ¹H-NMR spectra of the Schiff base ligands. The hydroxyl proton resonates at high frequency and thus absorbed far downfield at 13.46-11.83 ppm, reflecting the presence of hydrogen bonding between the hydroxyl proton and the imine nitrogen. In the p-substituted aniline analogues of the Schiff base, a plot of the chemical shift values of the hydroxyl proton against the Hammett's substituent parameters gave a linear correlation between the electronegativities of the substituents and the chemical shift values. The nitro group with the highest electronegativity caused the least deshielding of the hydroxyl proton and thus absorbed upfield compared to the less electronegative substituents such as the CH3 and OCH3 analogues. Likewise, in the solid state infrared spectra of the ligands, the hydroxyl stretching band of the ortho-hydroxyl Schiff base ligands was observed as a very broad band and at much lower frequency, 3100-2100 cm⁻¹, indicating the existence of strong intramolecular hydrogen bonding. In the same vein, ¹H- and ¹³C-NMR spectral data for the Schiff base ligands indicated that the prepared compounds exist in the enol form in aprotic solvent, chloroform. The methine proton appeared as singlet and there was no carbonyl signal in the ¹³C-NMR spectra of the Schiff base ligands. This was supported by the infrared data having no vibrational band attributable to the carbonyl stretching of the keto-form of the Schiff base ligands in solid state. However, the UV/Visible study of the Schiff base ligands in protic solvent, methanol, suggested the existence of some of the Schiff base ligands in keto-enol form. A band at greater than 400 nm was observed in the UV/Visible spectra of the ligands and this has been attributed to the presence of the keto form of orthohydroxyl Schiff base ligands in solution. A plot of the molar absorptivity (ε) of the band at greater than 400 nm against Hammett substituent parameters revealed that the intensity of the bands increased with the electronegativity of the substituents. The Cu(II) complexes of salicylaldehyde, o-vanillin and a few p-vanillin based Schiff base ligands are reported in this work. It was observed that introduction of Cu(II) ions into the ligand system resulted in the hydrolysis of the imine band in few cases. All the isolated complexes have been characterized by elemental analysis, conductivity measurement, infrared and UV/Visible spectral data. The structures of three of the Cu(II) complexes were further confirmed by X-ray single crystal diffraction. The Schiff base ligands either coordinated as neutral base through the imine nitrogen or via the imine nitrogen and the phenolic oxygen atoms. In addition, the benzimidazole-based and ovan-2-pico analogues equally coordinated through the imidazole N-3 nitrogen and the azine nitrogen respectively; thus acted as tridentate. In general, the synthesized Cu(II) complexes fell into seven categories viz: [Cu(LH)Cl(H₂O)]Cl; [Cu(LH)₂Cl₂].xH₂O; [CuL₂]; [Cu₂L₂]; [Cu(LH)Cl(H₂O)]Cl; and [MLCl]. The Cu(II) complexes of the form, M(LH)₂Cl₂.xH₂O were either 1:1 or non-electrolyte in methanol and DMF. The third category, CuL₂, was however, non-electrolyte existing as neutral four coordinate Cu(II) complexes. X-ray single crystal structure of Cu(II) complexes derived from the ammonia-based Schiff bases revealed a square planar geometry for the complexes and this agreed with the planar geometry that has been reported for Cu(II) complexes of N-arylsalicylaldimines of the type studied in this work. The complexes, [Cu₂L₂], resulted from the ortho-hydroxyaniline analogues and were polymeric with the Schiff base ligands coordinating to the Cu(II) ions as tridentate dibasic via the imine nitrogen, phenolic oxygen and the aminophenolic oxygen atoms. Cu(II) complexes prepared from ovan-2-ampy and ovan-2-pico Schiff bases were of the forms [Cu(LH)Cl(H₂O)]Cl and [CuLCl] respectively. The X-ray crystal structure of [Cu(ovan-2- pico)Cl] revealed a four-coordinate square planar geometry for the complex. In the same vein, the o-phenylenediamine complexes were of the form [Cu(L)(H₂O)], with the X-ray crystal structure of [Cu(bis-ovanphen)(H₂O)] revealing a square pyramidal geometry. The Schiff base ligands and the isolated Cu(II) complexes have been evaluated for their antimicrobial activity against three bacterial strains (Escherichia coli ATCC® 8739™*, Staphylococcus aureus subsp. aureus ATCC® 6538™* and Bacillus subtilis subsp. spizizeni ATCC® 6633™*) and one fungal strain, Candida albicans ATCC® 2091™*, using agar disc diffusion and broth dilution techniques. It was observed that the presence of the methoxyl group at the ortho-position of the aldehyde moiety of the Schiff base ligands enhanced the activity of the ligand tremendously and thus the o-vanillin analogues showed the highest potency against the tested organisms. In addition, the hydroxyaniline analogues were equally the most promising of all the substituted aniline based Schiff bases. The o-vanillin analogues of the aminopyridines and aminomethylpyridines also exhibited significant activity against the tested organisms. All the 2-aminobenzimidazole series were active against the tested organisms. It should be noted that E. coli was the least susceptible of all the microorganisms while the highest potency was exhibited against the fungus of choice, Candida albicans. Lastly, chelation of the Schiff base ligands with Cu(II) ions did not have significant influence on the activity of the free ligands.

Alcacio, Tim. The Molecular Scale Nature of Copper(II) and Arsenate Bonding With Goethite-Humate Complexes. In soils, interactions between clay minerals and natural organic matter are known to affect the cycling of heavy metals and anions. Contaminant structures at mineral surfaces that contain adsorbed organic matter will have a significant influence on the bioavailability of the contaminant. The structure of copper(II) and arsenate complexes on goethite in the presence and absence of adsorbed humic acid were studied with extended x-ray absorption fine structure (EXAFS) spectroscopy and with x-ray absorption near edge structure (XANES) spectroscopy. The copper(II) and arsenate formed edge shared inner-sphere surface complexes with goethite. The copper(II) itself was present in a distorted octahedral configuration, and ternary complexes involving bonding with both the humic acid and the goethite (Type A complexes) or adsorbed humic acid (Type B complexes), occurred at pH 5.6. At pH 8, the copper(II) was found to display a stronger affinity for the goethite surface and the formation of ternary complexes did not occur. The EXAFS analyses demonstrated that arsenate was present in a tetrahedral configuration and was predominantly bonded to goethite surface sites. Regardless of the level of adsorbed humic acid, the arsenic coordination environment was similar and indicated that ternary complexes could not be distinguished.

Two diimine-diamine ligands derived from the [2+1] template condensation of 1,3-diaminopropane with 2,6-diformyl-4-R-phenol [R = Me, (L¹)-; R = tBu, (L⁸)-], have been isolated as their dicopper(II) hydroxo-bridged complex cations. The ring-closure condensation reaction of the dicopper complex cation of (L¹)- with 2,5-diformylfuran produced a new asymmetric tetraimine macrocycle, (L³)- as the methoxo-, hydroxo- and ethoxo-bridged dicopper(II) complexes. The hydroxo- and ethoxo-bridged dicopper(II) complexes of (L³)- were isolated from the recrystallisation of the methoxo-bridged analogue using N,N-dimethylformamide, in the absence or presence of ethanol, respectively. The structures of the dicopper(II) acyclic complexes of (L¹)- and of the ethoxo-bridged complex of (L³)- have been determined by X-ray crystallography. Two hexacopper(II) complexes of a new acyclic Schiff-base ligand, derived from the [3+2] condensation of 1,3-diamino-2-hydroxypropane with 4-t-butyl-2,6- diformylphenol, were isolated. Preliminary X-ray crystallographic investigations on these hexacopper(II) complexes revealed a CU₆ ring templating the ligand such that the primary amine groups are held in an appropriate orientation and separation for ring-closure with a dicarbonyl compound. Two tetracopper(II) macro cyclic complexes were obtained from the [2+2] template condensation of 1,5-diarnino-3-hydroxypentane and 2,6-diformyl-4- Methylphenol. One of the complexes was isolated as a tetrafluoroborate complex, while the other as a formate complex. The formate complex, whose crystal structure has been determined, is believed to have been generated by the hydrolysis of N,N-dimethylformamide at room temperature, promoted by the tetrafluoroborate complex. The tetrafluoroborate complex underwent dimerisation to give an octacopper(II) complex. Another tetracopper(II) complex was synthesised by the template condensation of 1,5-diamino-3-hydroxypentane and 2,6-diformyl-methylphenol. X-ray structure determination of this complex revealed that it is a dimer of two dinuclear macro cyclic complexes. The two copper(II) ions in one unit of the dimer are bound inside the macro cycle "laterally". In contrast, two copper(II) ions are found to be held "diagonally" within the cavity of another Schiff-base macrocycle, derived from the [2+2] template condensation of 2,6-diformyl-4-methylphenol with triethylenetetramine.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO
COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO
PROGRAMA DE SUPORTE À PÓS-GRADUAÇÃO DE INSTS. DE ENSINO
PROGRAMA DE EXCELENCIA ACADEMICA
Norfloxacina (NFX) é um antibiótico fluorescente de amplo espectro bacteriológico, membro da família das fluorquinolonas (FQs). A interação das FQs com íons metálicos pode incrementar a ação bactericida e agir contra a resistência das bactérias frente aos antibióticos. Diversos exemplos de complexos mistos de norfloxacina e Cu(II) podem ser encontrados na literatura. A compreensão dos mecanismos moleculares de interação desses antibióticos com os diferentes componentes das células e com nanopartículas de ouro, como transportadores do fármaco, é extremamente importante. Para entender essas interações, neste trabalho utilizamos diferentes técnicas espectroscópicas, como espectroscopia de fluorescência estacionária e resolvida no tempo, absorção de luz UV-Visível e ressonância paramagnética eletrônica (RPE). A interação de NFX e do complexo ternário Cu(II):L:NFX, onde o ligante L é a 1,10-fenantrolina (Phen) ou 2,2-bipiridina (Bipy), com micelas e lipossomas unilamelares pequenos de fosfatidilcolina de ovo (PC) foi estudada usando espectroscopia de fluorescência em estado estacionário e resolvida no tempo. Foi estudada a estabilidade dos complexos ternários formados em micelas. Foram obtidas constantes de estabilidade no interior de micelas de SDS, as quais mostraram valores muito maiores do que em tampão. Já os espectros de RPE deram maiores detalhes sobre a estrutura dos complexos e confirmaram a formação do complexo ternário dentro das micelas. Foram estudadas as interações de FQs e seus complexos de cobre com lipossomas de PC preparados com diferentes densidades superficiais de carga elétrica negativa. No estudo da interação de FQs com nanopartículas de ouro sintetizadas por ablação a laser (nanocompósitos, AuNCs), NFX mostrou maiores mudanças, tanto na absorbância como na fluorescência, do que as FQs ciprofloxacina (CFX) e levofloxacina (LFX). Os resultados sugerem mudanças no índice de refração na superfície dos AuNCs, por associação com o fármaco e/ou formação de aglomerados como resultado da interação. Observou-se também uma supressão lenta, porém significativa, na fluorescência da NFX, sem mudança na posição do pico, indicando que NFX mantém o seu estado inicial de protonação ligando-se à superfície dos AuNCs. Também foi observada a liberação de FQs ligadas à superfície de AuNPs mediante substituição por tióis, que ocasiona recuperação parcial da fluorescência da fluorquinolona. Por último, como o surfactante aniônico SDS se mostrou promissor na interação com NFX, em comparação com surfactantes catiônicos e neutros, e como os AuNCs são estáveis em SDS, estudamos a interação de NFX com AuNCs sintetizados em presença de SDS e, para comparação, com AuNCs colocados em solução de SDS após a síntese.
Norfloxacin (NFX) is a fluorescent antibiotic of broad bacteriological spectrum, member of the fluoroquinolone (FQ) family. The interaction of FQs with metal ions can increase the bactericidal action and act against antibiotics bacterial resistance. Several examples of mixed-ligand norfloxacin Cu (II) complexes can be found in the literature. Understanding the molecular mechanisms of interaction of these antibiotics with different cell components and with gold nanoparticles as drug transporters is extremely important. To clarify these interactions, we used different spectroscopic techniques, such as steady-state and time-resolved fluorescence spectroscopy, UV-Visible light absorption, and electron paramagnetic resonance (EPR). The interaction of NFX and the ternary complex Cu(II):L:NFX, where the L is the ligand 1,10-phenanthroline (Phen) or 2,2-bipyridine (Bipy), with micelles and small unilamellar liposomes of egg phosphatidylcholine (PC) was studied using steady-state and time-resolved fluorescence spectroscopy. The stability of the ternary complexes formed in micelles was studied, and stability constants were obtained inside SDS micelles, which showed values much larger than in buffer. The EPR spectra gave further details on the structure of the complexes, and confirmed the formation of the ternary complex inside the micelles. The interactions of FQs and their copper complexes with PC liposomes prepared with different surface densities of negative electrical charge were studied. In the study of the interaction of FQs with gold nanoparticles synthesized by laser ablation (nanocomposites, AuNCs), NFX showed greater changes than FQs ciprofloxacin (CFX) and levofloxacin (LFX) in both absorbance and fluorescence. The results suggest changes in the surface refractive index of the AuNCs and/or cluster formation, as result of the interaction with the drug. A slow but significant quenching of NFX fluorescence was also observed, with no change in peak position, indicating that NFX maintains its initial state of protonation by binding to the surface of the AuNCs. Release of FQs attached to the surface of AuNCs by thiols has also been observed, which causes partial recovery of FQ fluorescence. Finally, as the anionic surfactant SDS showed to be promising in the interaction with NFX, compared to cationic and neutral surfactants, and because the AuNCs are stable in SDS, we studied the interaction of NFX with AuNCs synthesized in the presence of SDS and, for comparison, with AuNCs placed in SDS solution after synthesis.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO
COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO
PROGRAMA DE SUPORTE À PÓS-GRADUAÇÃO DE INSTS. DE ENSINO
O câncer constitui patologia de grande importância, visto que já corresponde à segunda maior causa de mortes em todo o mundo, havendo perspectiva de crescimento em número de casos para os próximos anos. Os tratamentos quimioterápicos atuais caracterizam-se por um elevado custo e índice terapêutico relativamente reduzido, estando associados a diversos efeitos colaterais e de resistência do tumor. Diante disso, muitos esforços têm sido direcionados na busca por novas drogas com melhor perfil farmacológico e com atividade frente a linhagens resistentes de tumor, bem como na viabilização de novas vias de administração. Neste sentido, diferentes abordagens têm sido empregadas para o desenho de drogas anticâncer baseadas em metais, como o desenvolvimento de novos complexos análogos à cisplatina, assim como de complexos que se mostrem mais seletivos ao ambiente tumoral. Uma estratégia bastante promissora compreende a preparação de complexos de metais inertes em elevados estados de oxidação, que possam atuar como pró-drogas, atingindo o tumor alvo sem redução prévia nem grandes transformações. Apenas no interior da massa tumoral, devido à condição de hipóxia (baixa oxigenação), normalmente não encontrada em tecidos normais, estes compostos seriam reduzidos, originando então as espécies ativas, que atacariam o alvo mais facilmente. O cobre, por apresentar dois estados de oxidação cujo potencial de redução é acessível dentro da faixa do potencial redox celular, é um elemento promissor. Nesse contexto, foram sintetizados neste trabalho dois complexos de cobre(II) e dois complexos de platina(II) dos ligantes isoméricos 1- e 2-fenil-1,2,3-triazol-4-carboxaldeído-oxima, nunca antes explorados no contexto da Química de Coordenação, sendo que apenas os complexos de cobre poderiam, a princípio, atuar como pró-drogas biorredutíveis. Os complexos foram caracterizados por análise elementar (CHN e AAS), espectroscopia vibracional e termogravimetria. Estudos de EPR no estado sólido foram realizados para os complexos de cobre(II); já os complexos de platina(II) foram também caracterizados por RMN de 195Pt. A modelagem computacional foi utilizada como recurso complementar à proposição estrutural e atribuição das bandas vibracionais dos complexos, com exceção do composto [Cu2(mu-L1)2(HL1)(ClO4)2(OH2)]·2H2O (1), cuja estrutura foi determinada por difração de raios X em monocristal. O outro complexo de cobre(II) é mononuclear: cis-[Cu(HL2)2Cl2] (2). Já os compostos de platina(II) são mononucleares e, como esperado, quadráticos, obedecendo às fórmulas: cis-[Pt(HL1)2Cl2]1 H2O (3) e cis-[Pt(HL2)2Cl2] (4). Os complexos de cobre foram testados nas linhagens de células leucêmicas U937 e THP-1, sendo o complexo 1 e HL1 ainda testados em células normais do sangue do tipo PBMC. Nas linhagens tumorais testadas ambos os complexos reduziram a viabilidade celular de maneira concentração-dependente. O perfil de atividade frente às células U937 foi semelhante para 1 e 2. Entretanto, o composto 1 foi duas vezes mais ativo que 2 contra a linhagem celular THP-1. Cabe ressaltar que 1 foi 23 porcento mais tóxico para a linhagem leucêmica THP-1 do que para as células normais PBMC. HL1 foi capaz de reduzir a viabilidade celular das linhagens tumorais em aproximadamente 30 porcento, não se mostrando tóxico para as PBMC. Os complexos de platina, por sua vez, foram testados na linhagem K562, de leucemia mielóide crônica, tendo ambos demonstrando toxicidade similar e cerca de 5x maior que a droga carboplatina.
Cancer pathology is of great importance, since it is the second leading cause of death worldwide, with a prospect of growth in the number of cases for the next decades. Current chemotherapy treatments are characterized by high cost and a relatively low therapeutic index and are associated with several side effects and tumor resistance. Therefore, many efforts have been focused on the search for new drugs with an improved pharmacological profile and tumor-resistant lineage activity, as well as the feasibility of new administration routes. In this regard, different approaches have been employed for the design of metal-based anticancer drugs, such as the development of new cisplatin analogue complexes, as well as complexes that may be more selective to the tumor environment. A very promising strategy involves the preparation of high oxidation state inert metal complexes, which may act as prodrugs, reaching the tumor target without prior reduction or significant transformations. Only inside the tumor mass, due to hypoxia conditions (low oxygen) not normally found in normal tissues, these compounds would be reduced, originating the active species which would then attack the target more easily. Copper, by presenting two oxidation states whose reduction potential is accessible within the range of the cellular redox potential, is a promising element. In this context, two copper(II) complexes and two platinum(II) complexes with the isomeric ligands 1- and 2-phenyl-1,2,3-triazole-4-carboxaldehyde oxime were synthesized in the present study, which have never before been explored in the context of Coordination Chemistry, with only the copper complexes, in theory, demonstrating the potential to act as bioreductive prodrugs. The complexes were characterized by elemental analysis (CHN and AAS), vibrational spectroscopy and thermogravimetry. EPR studies in solid state were performed for the copper(II) complexes, while the platinum(II) complexes were also characterized by 195Pt NMR. Computer modeling was used as a complementary resource for structural propositions and assignment of the vibrational bands of the complexes, with the exception of coordination compound [Cu2(mu-L1)2(HL1)(ClO4)2(OH2)]·2H2O (1), whose structure was determined by single crystal X-ray diffraction. The other mononuclear copper(II) complex is cis-[Cu(HL2)2Cl2] (2). On the other hand, the platinum(II) compounds are mononuclear and as expected, quadratic, according to the formulae cis-[Pt(HL1)2Cl2]1 H2O (3) and cis-[Pt(HL2)2Cl2] (4). The copper complexes were tested against the leukemic cell lines U937 and THP-1, with complex 1 and HL1 also being tested on normal PBMC blood cells. Both complexes reduced cell viability in a concentration-dependent manner in the tested tumor lines; The activity profile towards U937 cells was similar for 1 and 2. However, compound 1 was twice as active as 2 against cell line THP-1. It is worth noting that 1 was 23 percent more toxic against the leukemic cell line THP-1 when compared to normal PBMC cells. The platinum complexes, alternatively, were tested against the K562 cell line, chronic myeloid leukemia, and both demonstrated similar toxicity, approximately 5x higher than carboplatin.

Abstract According to Horizon 2020, Europe's photonics industry is strong (e.g. in laser-based manufacturing, medical photonics, sensing, lighting) and has the possibility to exploit new emerging market opportunities. Advanced lighting technology includes the use of Solid State Lighting (SSL) based on organic light-emitting diodes (OLEDs). The advantages involve higher quality lighting in terms of energy efficiency, quality (robustness, longer lifetime, colour tunability), and therefore cost reduction and energy saving. Lighting represents around 19% of electricity consumption worldwide and the replacement of old lighting technologies such as incandescent bulbs with SSL systems will allow to save up to 70% of energy. With all of this in mind, it is evident that the development of light technology based on SSL is of paramount importance. Nowadays most of the luminescent complexes applied in SSL are based on lanthanides and d-block metals of the second and third transition series. Platinum(II) and iridium(III) are commonly used as emitters for OLEDs due to their long-lived triplet states. However, recent studies have demonstrated that it is possible to obtain highly luminescent complexes based on first-row transition elements, such as chromium(III), iron(III), manganese(II), copper(I) and zinc(II). These elements have the advantage to be less expensive and toxic, as well as more abundant. The main focus of the following PhD thesis is the synthesis and characterization of luminescent manganese(II), copper(I) and zinc(II) complexes. As concerns the first one, the metal-centred emission related to the 4T1(4G) → 6A1(6S) transition is strongly dependent upon the coordination sphere: tetrahedral complexes are normally green emitters, while octahedral species emit in the red range. The presence of rigid structures and light harvesting fragments in the ligand skeleton allows to enhance the luminescent features as well as the UV-light absorption. Several [O=P]-donor ligands were considered for the preparation of both tetrahedral and octahedral derivatives, sometimes affording dual emissions in the corresponding manganese(II) complexes due to concurrent metal- and ligand-centred transitions. As regards copper(I) complexes, derivatives containing polydentate N-donors based on indazole and benzotriazole were synthesized and their emission properties were attributed to metal-to-ligand charge transfer mechanisms involving triplet emitting states. Small changes in the ligand skeleton determined appreciable variations in the photophysical properties, as testified by the complexes obtained using 2,1,3-benzothiadiazole as N-donor. The [O=P]-donors previously used for manganese(II) revealed to be suitable ligands also for the preparation of luminescent zinc(II) halide complexes thanks to the enhancement of ligands fluorescence due to coordination. In selected cases intersystem crossing was observed, causing intense green phosphorescence or dual emission.
According to Horizon 2020, Europe's photonics industry is strong (e.g. in laser-based manufacturing, medical photonics, sensing, lighting) and has the possibility to exploit new emerging market opportunities. Advanced lighting technology includes the use of Solid State Lighting (SSL) based on organic light-emitting diodes (OLEDs). The advantages involve higher quality lighting in terms of energy efficiency, quality (robustness, longer lifetime, colour tunability), and therefore cost reduction and energy saving. Lighting represents around 19% of electricity consumption worldwide and the replacement of old lighting technologies such as incandescent bulbs with SSL systems will allow to save up to 70% of energy. With all of this in mind, it is evident that the development of light technology based on SSL is of paramount importance. Nowadays most of the luminescent complexes applied in SSL are based on lanthanides and d-block metals of the second and third transition series. Platinum(II) and iridium(III) are commonly used as emitters for OLEDs due to their long-lived triplet states. However, recent studies have demonstrated that it is possible to obtain highly luminescent complexes based on first-row transition elements, such as chromium(III), iron(III), manganese(II), copper(I) and zinc(II). These elements have the advantage to be less expensive and toxic, as well as more abundant. The main focus of the following PhD thesis is the synthesis and characterization of luminescent manganese(II), copper(I) and zinc(II) complexes. As concerns the first one, the metal-centred emission related to the 4T1(4G) → 6A1(6S) transition is strongly dependent upon the coordination sphere: tetrahedral complexes are normally green emitters, while octahedral species emit in the red range. The presence of rigid structures and light harvesting fragments in the ligand skeleton allows to enhance the luminescent features as well as the UV-light absorption. Several [O=P]-donor ligands were considered for the preparation of both tetrahedral and octahedral derivatives, sometimes affording dual emissions in the corresponding manganese(II) complexes due to concurrent metal- and ligand-centred transitions. As regards copper(I) complexes, derivatives containing polydentate N-donors based on indazole and benzotriazole were synthesized and their emission properties were attributed to metal-to-ligand charge transfer mechanisms involving triplet emitting states. Small changes in the ligand skeleton determined appreciable variations in the photophysical properties, as testified by the complexes obtained using 2,1,3-benzothiadiazole as N-donor. The [O=P]-donors previously used for manganese(II) revealed to be suitable ligands also for the preparation of luminescent zinc(II) halide complexes thanks to the enhancement of ligands fluorescence due to coordination. In selected cases intersystem crossing was observed, causing intense green phosphorescence or dual emission.

Thesis (M.S.)--East Tennessee State University, 2004.
Title from electronic submission form. ETSU ETD database URN: etd-1113104-182005 Includes bibliographical references. Also available via Internet at the UMI web site.

碩士
淡江大學
化學學系
88
Title of Thesis: Studies of Catecholase-like Model Copper( II ) Complexes Key word: Copper(II) complex,Magnetic properties, Catecholase-like Name of Institute:Graduate Institute of Chemistry Tamkang University Graduate date: June, 2000 Degree conferred: Master Name of student: Sheng-Chuan Cheng Advisor:Dr. Ho-Hsiang Wei 鄭 勝 權 Abstract: This thesis essentially has been separated into two parts : Ⅰ. The synthesis of dinuclear copper(II) complexes and the correlation between their structures and magneticbehavior；Ⅱ.The reactive activities of catecholase-like.Part Ⅰ.: The simplified formula for dinuclear copper(II) complexes are represented as follows: 1.{Cu2[-C5H4NCH2O]2(NCS)2} 2.{Cu2[-C5H3CH3NCH2O]2(CH3COO)2}．2H2O 3.{Cu2[-C5H4NCH2CH2O]2(NCO)2} 4.{Cu2[-(CH3)2NC(CH3)2CH2O]2(NCS)2} 5.{Cu2[-(CH3)2NCH2CH(CH3)O]2(NCS)2} 6.{Cu2[-(CH3)2NC(CH3)2CH2O]2(Cl)2} The theoretical fitting has been simulated to obtain the values of exchange integral 2J by using Bleaney-Blowers equation. The magnetic behaviors of these dinuclear copper(II) complexes all show antiferromagnetic interaction. Part Ⅱ.:Reactive activities of catecholase-like studies Dinuclear copper(II) complexes were found to be readily reduced to copper(Ⅰ) complexes by 3,5-di-tert-butylcatechol(dtbc). The reaction of copper(II) complexes in MeOH has been studied. The dtbc has been oxidized to quinone, and characetrized by absorption band at 400nm of UV-visible spectra. The reactive activity of these oxo-bridged catecholase-like reactions is correlated to the Cu-Cu distances in the complexes. Temperature dependence of magnetic susceptibility and Mőssbauer measurements for these complexes revealed that the style of spin transition s=5/2 ↔ s=1/2 of Iron(Ⅲ ) atom in complexes is dependent on the chemical enviromment. All these form complexe 1-4 exhihit catalase- like activity toward H2O2 disproportionation.

博士
國立清華大學
化學系
92
The tetraaza-macrocyclic ligands were synthesized by two methods. (1) The protecting group method reported by Richman and Atkins was used for the synthesis of isocyclam. (2) The general organic method with Michael addition reaction was employed to prepare 3-10-C-meso-Me8[14]dieneN4.2HClO4. The structures and components of these ligands were analyzed and identified by NMR, IR, UV-vis, mass, and X-ray studies. The complexes of Ni(II) and Cu(II) were synthesized by using Ni(ClO4)2.6H2O, Ni(OAc)2.4H2O, or Cu(ClO4)2.6H2O in hot methanol solution and recrystallized from water or acetonitrile. According to the results of NMR and X-ray studies, the structures of isomers, LB and LC, from reduction of 3-10-C-meso- Me8[14]dieneN4·2HClO4 and their complexes of Ni(II) and Cu(II) are indeed different from literature reports. We could not get the isomer LA following the experimental methods described in the published paper and in our work. The melting point of LB is greater than that of LC and the melting point of LA is anticipated to be higher than that of LB. The solubility of LB in organic solvent is less than that of LC, while that of LA is expected to be lower compared to LB. The 1H NMR spectrum of LB shows four methyl resonances for eight methyl groups suggesting that LB is a symmetric molecule whereas the isomer LC shows eight methyl resonances indicating that LC is an asymmetric molecule. The 13C NMR spectrum of LB displayed only nine peaks due to pairwise equivalence of carbon atoms. In contrast, isomer LC displayed eighteen peaks of corresponding to eighteen nonequivalent carbon atoms indicating the absence of symmetry in the molecule. We have studied the X-ray diffractional analysis of isomeric LB, LC and their transition metal complexes. (1) Crystal structure of 3,10-C-meso-5,12-C-meso-Me8[14]aneN4 (LB). The molecule is located at an inversion. This determination indicates that the ring lies in a chair form with tetramine equatorial positions. The configurations of the four chiral carbon centers are 3S, 5S, 10R and 12R. The methyl groups in 3S and 10R are disposed on opposite sides of the macrocyclic plane, and have an axial orientation. In addition, the methyl groups in 5S and 12R are also disposed on opposite sides of the macrocyclic plane, and have an equatorial orientation. (2) Crystal structure of 3,10-C-meso-5,12-C-rac-Me8[14]aneN4 (LC) The compound has a butterfly structure. The configurations of the four chiral carbon centers are 3S, 5S, 10R and 12S. The methyl groups in 3S and 10R are disposed on opposite sides of the macrocyclic plane, and have an axial orientation. On the other side, the methyl groups in 5S and 12S are disposed on the same sides of the macrocyclic plane, and have an equatorial orientation. (3) Crystal structure of [CuLB(H2O)2](ClO4)2 The molecule is located at an inversion. The compound is a six-coordinated octahedral complex with four N atoms of the macrocyclic ligand in the equatorial positions and two axial water O atoms in the trans axial positions; it belongs to the “4 + 2” type with four stronger Ni-N and two weaker Ni-O. The ligand is in its most stable, planar configuration with both the six-membered rings in chair forms and both the five-membered rings in gauche forms. The configurations of the four chiral nitrogen centers are 1R, 4S, 8S and 11R. The methyl groups in 3S and 10R are disposed on opposite sides of the macrocyclic plane, and have an axial orientation. The methyl groups in 5S and 12S are also disposed on opposite sides of the macrocyclic plane, and have an equatorial orientation. (4) Crystal structure of [CuLC(ClO4)2] The compound is a six-coordinated octahedral complex with four N atoms of the macrocyclic ligand in the equatorial positions and two axial perchlorate O atoms in the trans axial positions; it belongs to the “5 + 1” type with four stronger Ni-N bounds, one stronger Cu(1)-O(3) and one weaker Cu(1)-O(6). The ligand consists of both the six-membered rings in chair forms and both the five-membered rings in gauche forms. The configurations of the four chiral nitrogen centers are 1S, 4R, 8R and 11S. The methyl groups in 3S and 10R are disposed on opposite sides of the macrocyclic plane, and have an axial orientation. On the other hand, the methyl groups in 5S and 12S are disposed on the same sides of the macrocyclic plane, which the methyl group in 5S has an equatorial orientation and the methyl group in 12S has an axial orientation. (5) Crystal structure of [NiLB](ClO4)2 The compound is a four-coordinated square planar complex with both the six-membered rings in chair forms and both the five-membered rings in gauche forms. The configurations of the four chiral nitrogen centers are 1R, 4S, 8S and 11R. The methyl groups in 3S and 10R are disposed on opposite sides of the macrocyclic plane, and have an axial orientation. The methyl groups in 5S and 12S are also disposed on opposite sides of the macrocyclic plane, and have an equatorial orientation. (6) Crystal structure of [NiLC](ClO4)2 The compound is a four-coordinated distorted planar complex with two six-membered rings-one in a chair form and the other in a twist-boat form, and two five-membered rings-one of which is in a gauche form and the other in an eclipsed form. The configurations of the four chiral nitrogen centers are 1S, 4R, 8S and 11S. The methyl groups in 3S and 10R are disposed on opposite sides of the macrocyclic plane, in which the methyl group in 3S has an equatorial orientation and the methyl group in 5S has an axial orientation. On the other side, the methyl groups in 5S and 12S are disposed on the same sides of the macrocyclic plane, in which the methyl group in 5S has an axial orientation and the methyl group in 12S has an equatorial orientation. Ni(II) complexes with the tetraaza-macrocyclic ligands exist in aqueous solution as an equilibrium mixture of cis, trans, and planar species. The distribution ratios of the three species are related to temperature, ionic strength, pH value, and steric effect, etc. The blue-to-yellow reactions were carried out with a UV-vis spectrophotometer. The results of spectrophotometric studies indicate that the proportion of planar species increases by either an increase in temperature or by an increase of ionic strength. In addition, the proportion of planar species also increases by an increase of the number of methyl groups on the macrocyclic ligand. Furthermore, the axial methyl groups contribute to raise the standard equilibrium constant, ΔHo and ΔSo. This may be due to the steric effect and the distorted structure. In conclusion, [13]aneN4 provide the best fit cavity size for a square-planar Ni(II) complex. The order of the values of V (d-d) for square-planar Ni(I1) complexes is [13]aneN4 > [12]aneN4 > [14]aneN4 > [15]aneN4. In order to examine the effects of coordinated hydroxide ion and free hydroxide ion in configurational conversion of a tetramine macrocyclic ligand complex, the kinetics of the cis-to-planar interconversion of cis-[Ni(isocyclam)(H2O)2]2+ (isocyclam, 1,4,7,11- tetraazacyclotetradecane) has been studied spectrophotometrically in basic aqueous solution. The interconversion requires the inversion of one sec-NH center of the folded cis-complex to have the planar species. The proposed mechanism is a free-base catalyzed pathway because the metal-bound hydroxide ion cannot form a hydrogen-bonded chelate ring with the adjacent sec-NH。Furthermore, the kinetic data satisfactorily fits as the rate law, R = kOH[OH-][cis-[Ni(isocyclam)(H2O)2]2+], where kOH = 3.84 ´ 103 dm3 mol-1 s-1 at 25.0 ± 0.1 oC with I = 0.10 mol dm-3 (NaClO4). The large ΔH¹, 61.7 ± 3.2 kJ mol-1, and the large positive ΔS¹, 30.2 ± 10.8 J K-1 mol-1, strongly support a free-base-catalyzed mechanism for the reaction. On the other hand, the coordinated-base-catalyzed pathway results in a small ΔH¹ and a large negative ΔS¹ for cis-folded Ni(II) complexes of [13]aneN4, cyclam, C-meso-5,12-Me2cyclam, and C-rac-5,12-Me2cyclam. In higher base media, the kinetic studies were carried out by using a stopped-flow spectrophotometer and the resulting kinetic data provide different rate constants which are functions of ionic strength. This phenomenon gives good evidence for a free-base-catalyzed mechanism.

博士
淡江大學
化學學系
87
We synthesize a new hexaazamacrocyclic ligand(H2HAPP) and their cobalt(II)、nickel(II)、copper(II) complexes, and the N-substituted methyl derivative(DMHAPP) was also obtained by reactng with methyl iodide. The X-ray stacking structures of i-H2HAPP and H4HAPP(CF3COO)2 show that both ligands exist a type of face-to-face aggregates between macrocyclic molecules and a strong  interaction exists in aggregates according to the distance of plane-to-plane in the aggregates(3.28~3.29 ). The study of aggregate behavior in solution proved the formation of face-to-face dimer in both i-H2HAPP and [CoII(H2HAPP)(TFA)2]. Two stable tautomers of H2HAPP,i-H2HAPP and o-H2HAPP respectively, was found to exist in crystal structures of the complexes and ligand. We also observed their tautomerism occurred in the solution by using UV/VIS spectrum of model compound DMHAPP. The electrochemistry in H2HAPP、nickel and copper complexes shows one electron reduction on ligand, but the cobalt complex shows metal-centered redox reaction. The chemical oxidation of H2HAPP and [NiII(HAPP)] by (Thian+.)ClO4 and (Phenox+.)SbCl6 oxidants shows the formation of  cation radical species, but the nickel  cation radical complex at room temperature is transformed into [NiIII(HAPP)(Cl)2] complex at liquild nitrogen temperature by intramolecular electron transfer mechanism. [CoII(H2HAPP)(TFA)2] complex will react with O2 and formate irreversible oxygen-carrier complex in the presence of axial bases. Two oxygenation adducts, mononuclear superoxide and dinuclear -peroxide complex, are observed in oxygenation reaction. We proposed that a CoIII-hydroperoxyl intermediate is produced by protonation of superoxide ion of mononuclear superoxide complex or is stablized by hydrogen-bonding interaction of methanol molecule, but the deprotonation reaction of the species will lead to the formation of the dinuclear -peroxide complex. All the factors affecting the oxygenation adducts will be related to the CoIII-hydroperoxyl intermediate. The catalytic oxidation of di-tert-butyl pheno by using [CoII(H2HAPP)(TFA)2] complex indicates that the major product is DPQ dimer and the sub-product is DTBQ monomer. We proposed that the activity of the dinuclear -peroxide complex determines the distribution of catalytic products. The homogeneous electrochemical catalytic reduction of oxygen by using [CoII(H2HAPP)(TFA)2] complex is proved to formate two-electron reduction product, H2O2. The electrocatalytic mechanism indicates that hydrogen peroxide is produced by one-step two electrons reduction in pH<4.3, and by two-step one electron reduction in pH>4.3. The study of H2HAPP monomer luminescence displayed the E-type delayed fluorescence and triplet phosphorescece properties and H2HAPP will formate the excimer in very low concentration(10-7 M).

博士
國立東華大學
化學系
98
This dissertation discusses the synthesis, structural characterizations, related properties and further applications of N-heterocyclic carbene (NHC) complexes of palladium (II), copper (I), ruthenium (II) and platinum (II). In Chapter 1, the basic principles of N-heterocyclic carbene ligand and the related background of their metal complexes are conceptually described. The properties of metal complexes bearing chelate- or pincer-type NHC ligand are introduced. The main ideas of each chapter in this dissertation are illustrated. In Chapter 2, the homoleptic bis-chelate tetracarbene palladium(II) complex , [(BuCCmeth)2Pd][BF4]2, have been synthesized through Ag2O method and characterized spectroscopically. Single crystal structure of resulting complex has been studied. The dicarbene ligand is proposed to enhance the basic property on the Pd center, and increase the stability of the active Pd species by chelating effect. [(BuCCmeth)2Pd][BF4]2 shows excellent air and thermal stability at high temperature and also exhibits good catalytic activity with full recyclability in DMF towards Heck reaction. The dicarbene ligand is further modified by attaching pyridinum moiety on the side arms of the NHC rings. The Pd(II) complexes of the pyridinum-tagged NHC ligand, [(PyBuCCmeth)2Pd][PF6]6 and [(PyBuCCmeth)PdCl]2[PF6]6, are also applied and compared with other type of Pd(II)-NHCs in Heck reaction under identical reaction condition. Heck reaction in pure aqua phase using bis-chelate Pd(II)-NHCs is performed as well. In Chapter 3, the methylenebis(N-alkylimidazolium) chloride, [alkylCCMe-H]Cl2 (alkyl = methyl or n-butyl group), are converted to dialkyl-biimidazoles by cuprous oxide with concurrent C-N bond cleavage and C-C bond formation. This unusual C-N bond cleavage is proposed to involve a Cu(I)-NHC complex. The reaction is unique as it involves C-N bond cleavage and C-C bond formation. In Chapter 4, reaction of [RCPC-H]Cl2, where the RCPC is 2,6-bis(methylimidazol-2-ylidene)-pyrazine (R = me) or 2,6-bis(butylimidazol-2-ylidene)-pyrazine (R = Bu), with RuCl3 under high temperature generated the [(RCPC)2Ru]Cl2 complexes. The anion-exchanged products, [(RCPC)2Ru][PF6]2 were obtained by the reaction of NH4PF6 with [(RCPC)2Ru]Cl2 in aqueous solution. The structural analyses of [(BuCPC)2Ru]Cl2, [(meCPC)2Ru][PF6]2 and [(BuCPC)2Ru][PF6]2 showed that all three complexes are in six-coordinated geometry with two tridentated ligands and one metal center, , and are analogous to Ru(II)(terpy)2 system. Their absorption and emission spectra showed dramatic variation upon addition of the acid, indicating a possible application on acid detection. Introducing a methyl group on the nitrogen atom of the pyrazine of [(BuCPC)2Ru][PF6]2 led to a similar UV-vis spectrum pattern to that of the protonated [(BuCPC)2Ru][PF6]2. In Chapter 5, a novel class of Pt(II) complexes with pyridine-based pincer-type NHC ligand, denoted as RCNC, where R = Bu or Mestyl ring, was synthesized. The R groups on the pincer ligand were found to be responsible for the formation of dimmer, as evidenced by the single crystal X-ray analysis of the reported complexes. All Pt(II)-NHCs in this work are emissive in solution at room temperature, which are attributed to the incorporation of NHC moieties with strong σ-donating nature. The dimeric Pt(II)-NHCs shows aquachromic photoluminescence in the solid state upon hydration and dehydration.

博士
國立臺灣師範大學
化學系
84
Four series of mixed ligand tridentate picolinamido copper(II) complexeshave been prepared. They are :(1) Cu(pmpa)( L)(X)(H2O)n type, where pmpa stands for N-(2-picolinyl)- picolinamido, and L for imidazole(ImH), N-methylimidazole(NMIm), 4-methylimidazole(4MImH), pyridine(py), 2-methylpyridine(2Mpy), 3-methylpyridine(3Mpy), and 4-methylpyridine(4Mpy), and X for ClO4-, or BF4-,and n = 0, 1 or 2.(2) Cu(pepa)(L)(X)(H2O)n type, where pepa stands for (N-(2-(2''-pyridine)-aminoethyl) picolinamido, and L for Imidazole(ImH), N-methylimidazole(NMIm), 2-methylimidazole(2MImH), 4-methylimidazole(4MImH),pyridine(py), 3-methylpyridine(3Mpy), and 4-methylpyridine(4Mpy) and X forClO4-, or BF4-, n=0, 1 or 2. (3) Cu(depa)(L)(X)(H2O)n type, where depa stands for N-(2-(N,N-dimethylaminoethyl)picolinamido and L for 2-methylimidazole(2MImH), 4-methylpyridine(4Mpy), and X for ClO4-, and n= 1. (4) Cu(L)(X)(H2O)n type, where L stands for pepa, pmpa, depa, and X for Cl-ClO4-, or BF4-, and n= 0, 1, 2, 3, or 4. The mixed ligand copper(II) complexes have been characterized byelemental analyses, and electronic, vibrational, and EPR spectroscopicmeasurements. X-ray crystal structures of the following complexes have beendetermined from three-dimensional X-ray diffraction data.(1) [Cu(pmpa)(4MImH)(H2 O)](H2O)(ClO4), tirclinic, a = 7.536(1) A, b =10.269(1) A, c = 14.113(3) A,α = 75.09(1), β = 76.48(1), γ = 88.45(1) °, Z= 2, space group P1-, R = 0.056, Rw = 0.062.(2)[Cu(pmpa)(4Mpy)(H2 O)](H2O)(ClO4) tirclinic, a = 7.704(1) A, b = 10.457(4)A , c = 13.917(2) A, α = 79.98(2), β = 75.81(1), γ = 87.33(2) °, Z = 2, spacegroup P1-, R = 0.051, Rw = 0.55.(3) [Cu(pepa)(4MImH)(H2 O)](H2O)(ClO4), monoclinic, a = 7.337(2) A, b =12.294(1) A , c = 22.293(2) A, β = 98.37(2)°, Z = 4, space group P21/c, R =0.070, Rw = 0.083.(4) [Cu(pepa)(3Mpy)(H2O)](ClO4), monoclinic, a = 7.493(3) A, b = 12.591(2)A , c = 22.403(5) A, β = 98.38(2)°, Z = 4, space group P21/n, R = 0.046, Rw= 0.049.(5) [Cu(pepa)(4Mpy)(H2O)](ClO4), monoclinic, a = 7.322(1) A, b = 24.426(2)A , c = 12.077(1) A, β = 96.38(2)°, Z = 4, space group P21/c, R = 0.043, Rw =0.065.(6) [Cu(depa)(2MImH)(H2O)]( ClO4), monoclinic, a = 19.779(3) A, b =10.580(2) A , c = 18.919(4) A, β = 94.28(1)°, Z = 8, space group C2/c, R =0.045, Rw = 0.049.(7) [Cu(pepa)(Cl)], monoclinic, a = 9.176(2) A, b = 11.993(2) A , c = 11.017(4)A, β = 93.41(2)°, Z = 4, space group P21/n, R = 0.047, Rw = 0.069.(8) [Cu(pepa)(H2O)2](ClO4), monoclinic, a = 7.175(2) A, b = 22.337(9) A , c =11.190(4) A, β = 91.80(2)°, Z = 4, space group P21/n, R = 0.095, Rw = 0.104.(9) [Cu(pepa)(H2O)2](BF4), monoclinic, a = 7.163(1) A, b = 21.944(4) A , c =11.135(1) A, β = 91.99(1)°, Z = 4, space group P21/n, R = 0.083, Rw =0.098. Comparing the Gaussian component bands of electronic spectra, thesequences of the d orbitals were assigned as dx2-y2 >> dz2 >dyz > dxy > dxz forelongated square pyramidal complexes, and dx2-y2 >> dyz > dxy > dxz >dz2 forsquare plannar complexes. It is obvious that the energy of the dyz orbital of the mixed ligandcopper(II) complexes was raised significantly, suggesting that the central amidoN atom of the N-(2-picolinyl)picolinamido and the (N-(2-(2''-pyridine)-aminoethyl)picolinamido are π-donor.

碩士
國立臺灣師範大學
化學系
84
Copper(II) complexes of two types, Cu(A)(LL)(ClO4) and Cu( pa)(L)(ClO4), where A = glycine(gly) and L-alanine(L-ala); pa = N-picolyl-(L)-alanine; LL = 1,10-phenanthroline(phen), 2,2'-bipyridine(bipy), neocuproine(neoc) and ethylenediamine( en); L = N-methylimidazole(NMIm), 4-methylimidazole(4MImH), 4-methylpyridine(4Mpy) and pyridine(py), have been synthesized andcharacterized by elemental analyses, IR, UV-VIS, CD and EPR spectroscopicmeasurements.

碩士
高雄醫學大學
醫藥暨應用化學研究所
101
Copper-containing nitrite reductases active site contains a type II copper catalytic center possessing a (His)3 coordination sphere. A new type asymmetry N,N-substituted ??-diketiminato ligand sets bearing different kinds of arms ( L1H、L2H、L3H、L4H ) are design for the type II coordination environment. The synthesis of lithium complexes ( L1Li、L2Li、L3Li、L4Li ) show the tridentate chelating nature. Asymmetry N,N-substituted ??-diketiminato copper(II) complexes ( L1CuCl、L2CuCl、L3CuCl、L4CuCl ) could be obtained by reaction of the corresponding lithium complex with CuCl2. Treatment of the L1CuCl、L2CuCl、L3CuCl and L4CuCl with NaNO2 leads to formation of the copper(II)-nitrito complexes containing asymmetry N,N-substituted ??-diketiminato ligand ( L1CuNO2、L2CuNO2、L3CuNO2 and L4CuNO2 ). All copper (II) complexes were characterized by routine spectroscopy and X-ray crystallography to confirm their formula and structure.

碩士
輔仁大學
化學系
88
Palladium(II) and copper(II) complexes ([(Cn)2-imyH][MCl4] , n = 8, 10,12, 14, 16, 18 ) were synthesized, and their liquid crystalline properties investigated. Two compounds, [(C12)2-imyH]2[CuCl4] and [(C12)2-imyH]2 [PdCl4] were structurally determined by single crystal X-ray diffraction. Tetra-chloropallate adopts a square-planar geometry while tetrachlorocuprate has a distorted tetrahedral structure. Liquid crystalline behavior of these compounds was studied by differential scanning calorimetry and polarized optical microscopy. The typical fan texture, the spontaneous homeotropic, and the X-ray diffraction results, suggest a smectic mesophase. Both the melting and isotropic transition temperatures increase with the alkyl chain lengths, and the palladium(II) complexes always have higher phase transition temperatures than those of the copper(II) ones. When n=8, there is no mesophase in copper(II) complex. All these compounds decomposed above clearing temperatures, therefore only the heating cycle is reported. Thermal decompositions are severe with shorter chains. Compounds with PdBr42- anion have better thermal stability than the corresponding PdCl42- complexes. Decomposition reactions were traced by 1H-NMR, FAB, TGA. The powder EPR spectrum at 77K suggests that the paramagnetic copper(II) complexes are rhombic-compressed with three different g-values. Lyotropic properties of these compounds are also investigated. Mixing with water or imidazolium salts, the melting and the clearing temperatures decrease. Mixing with imidazolium salts provides wider temperature ranges of mesophase than those with water. SmA phase is also observed for these lyotropic systems.

碩士
國立清華大學
生醫工程與環境科學系
104
Cu(I) quantum yields were measured at 313 nm for copper(II)-amino acid complexes with eight amino acids in aqueous solutions. Photochemical formation of copper(I) has been systematically studied for copper(II) complexes in different conditions (changing pH and ligand concentration). Bathocuproine method was used to determine copper(I) concentration. For the 1:1 Cu(II) complexes (CuL), the Cu(I) quantum yields at 313 nm (ΦCu(I),CuL) are in the sequence (25 0C, ionic strength = 0.10 M): 2-AIBA > β-ala > ala, 2-ABA, nor > val > 4-ABA > gly, ranging from 0.279 to 0.06 (mol einstein-1). Experimental data show that the photoreactivity of Cu(II)/amino-acid complexes can be predicted by Cu(II) speciation in a wide range of the solution conditions, varying in pH and the total concentration of ligand. The stability of the carbon-center radical plays an important role on the Cu(I) quantum yield. The six-membered chelate ring of Cu(II)/amino-acid complexes has larger Cu(I) quantum yields than five-membered chelate ring, probably owing to the increasing of the intra-molecular electron-transfer rate.

The present thesis deals with different aspects of the chemistry and photo-biology of various ferrocene-conjugated metal complexes, their interaction with double helical DNA, DNA photocleavage and photo-enhanced cytotoxicity in visible light. Phenyl analogues of the active complexes have been synthesized and used for comparison in biological assays. Chapter I provides an introduction to the potential of metal complexes as photochemotherapeutic agents with special reference to organometallic compounds. A brief overview of Photodynamic Therapy (PDT) as a new modality of cancer treatment has been given. Various modes of non-covalent interactions of small molecules with duplex DNA are mentioned. Recent reports on the metal-based photocytotoxic and DNA cleaving agents including photoactivatable organometallic compounds are discussed. The objective of the present investigation is also presented in this chapter. Chapter II presents the synthesis, characterization, structure, DNA binding, DNA photocleavage, photocytotoxicity, mechanism of cell death and cellular localization of ferrocene-conjugated L-methionine reduced Schiff base Cu(II) complexes of phenanthroline bases. To explore the role of the ferrocenyl moiety the phenyl analogues of the ferrocenyl complexes are synthesized and used as controls for comparison purpose. Chapter III deals with the photo-induced DNA cleavage and photo-enhanced cytotoxicity of ferrocene-appended L-tryptophan Cu(II) complexes of heterocyclic bases. The synthesis, characterization, structural comparisons, DNA binding, DNA photocleavage, photocytotoxic activity and cell death mechanism in visible light are discussed in detail. Chapter IV describes the synthesis, characterization and structure of ferrocenylmethyl-L-tyrosine Cu(II) complexes of phenanthroline bases. The complexes are evaluated for DNA binding, DNA photocleavage and photocytotoxic activity in visible light. The cellular localization of the complexes and the mechanism of cell death induced by the complexes are also discussed. Chapter V presents the photocytotoxic effect of ferrocene-conjugated L-amino acid reduced Schiff base Cu(II) complexes of anthracenyl/pyrenyl imidazophenanthroline. The ability of the complexes to bind to double helical DNA and cleave it under photo-illumination conditions is described. Evaluation of the complexes as photochemotherapeutic agents and comparison with currently clinically available drug Photofrin are presented. The mechanism of cancer cell death and cellular localization of the complexes are studied by fluorescence microscopy. Chapter VI describes the synthesis, characterization and photochemotherapeutic efficacy of Cu(II) complexes having ferrocene-appended L-amino acid reduced Schiff base ligands and the naturally occurring polyphenol curcumin. Stabilization of curcumin by complexation to metal for improved photodynamic effect in cancer cells is described with comparison to the parent dye and clinically used drug Photofrin. The mechanism of cell death induced by the copper complexes and their localization in cancer cells are also presented. Finally, the summary of the dissertation and conclusions drawn from the present investigations are presented. The references in the text have been indicated as superscript numbers and compiled at the end of each chapter. The complexes presented in this thesis are represented by bold-faced numbers. Crystallographic data of the structurally characterized complexes are given in CIF format in the enclosed CD (Appendix-I). Due acknowledgements have been made wherever the work described is based on the findings of other investigators. Any unintentional omission that might have happened due to oversight or mistake is regretted.