Metal-nucleic acid interaction studies have been gaining attention due to their biological and chemical importance. Nucleic acids are negatively charged bio-polymers and neutralization of their negative charge is essential for the stability and function. In the cells, organic positive ions (positively charged amino acids and polyamines) and some of the metal ions (e.g. Na+, K+, Mg2+...etc) neutralize the charge of nucleic acids. Whereas, interactions of some metal ions (e.g. Cd2+, Hg2+…etc) with nucleic acids destabilize the structure. The stability and conformation of nucleic acids alter due to metal interactions. Further, metal interactions with nucleic acids can bring changes in conformation of ribose, H-bonding and π-π stacking interactions. To understand the metal interactions with nucleic acids, various spectroscopic techniques are being used. However, X-ray crystallographic technique is advantageous over all other spectroscopic techniques since it gives thorough detail of coordination mode and structure. However, crystallization of large molecules like nucleic acids with metals is associated with great difficulty. In order to simplify the problem, nucleic acid constituents and derivatives have been used as model systems for metal-nucleic acid interactions. Nucleic acid constituents and derivatives are multidentate ligands. Moreover, binding mode of metal with nucleic acid constituents and derivatives depends on various factors include pH, temperature, type of metal…etc. Further, understanding of metal nucleic acid interactions can aid to develop new anticancer drugs targeting nucleic acids. For example, cisplatin is a platinum based anticancer drug, which coordinates to N(7) of guanine in DNA brings cell death. There have been several reports in literature on the complexes of metal nucleic acid constituents. However, much more research is warranted for thorough understanding of metal-nucleic acid interactions. On the other hand, nucleic acid constituents and derivatives are used extensively in anticancer drug development. Some of nucleic acid constituent derivatives, 5-Fluro uracil and 6-Mercaptopurine, are currently in use for the treatment of colorectal cancer and leukemia, respectively. Moreover, cisplatin is a platinum based anticancer drug used in the treatment of various types of cancers. However, use of these drugs for long time poses severe side effects and drug resistance. Most of the side effects are due to non bio-compatibility of drugs. To overcome problems associated with present anticancer drugs, bio-compatible metal based anticancer drug development could be an attractive and alternative strategy. To address this, in this study, we report synthesis of a number of new metal complexes of nucleic acid constituents and their derivatives and characterization by various spectroscopic techniques. Also, the interactions of Ni, Cu and Zn ions with various nucleic acid constituents and their derivatives have been elucidated by single crystal X-ray crystallography. Interestingly, Ni, Cu and Zn ions showed various coordination modes to nucleic acid constituents and their derivatives. Further, anticancer studies were carried out for all these complexes in various cancer cell lines. Several complexes showed better cytotoxicity than the well-known drug cisplatin. My thesis work is divided into five parts based on the nature of molecules. I. Synthesis, X-ray crystallographic and anticancer studies on metal (Zn/Ni) complexes of guanine (G) based nucleic acid constituents In order to understand (Zn/Ni) interactions with guanine based nucleic acid constituents and their anticancer activity, several (Zn/Ni) complexes of 5′-GMP, 5′-IMP and hypoxanthine complexes were prepared. The synthesized complexes are (1) [Zn (5′-GMP)]n.11H2O, (2) [Ni (5′-GMP)2 Na2 (μ-OH2)3 (H2O)8].2H2O, (3) [Ni (5′-IMP)2Na2 (H2O)12]n.5H2O and (4) [Ni (hx)2 (H2O)4] Cl2 [Here 5′-GMP = 5′-Guanosine Mono Phosphate, 5′-IMP = 5′-Inosine Mono Phosphate and hx = Hypoxanthine). These complexes were characterized by various spectroscopic and X-ray crystallography techniques. Complex 1: The X-ray structure revealed that zinc is coordinated to 5′-GMP through N(7) position of purine and phosphate moieties, the uncoordinated water molecules are making interesting complicated network of hydrogen bonds in the unit cell. The geometry of zinc coordination centre is distorted tetrahedral. Fascinatingly, zinc exhibited two different coordination environments. In one case, all phosphate oxygens participated in coordination with zinc. In second case, N(7) position of purine and phosphate oxygens participated in coordination with zinc. Moreover, zinc formed a coordination polymer with 5′-GMP. The conformation of ribose changed upon zinc interaction with 5′-GMP from C(3′)-endo to C(2′)-endo, these results suggest that zinc interaction with nucleic acids may change their conformation. Complex 1 is stabilized in solid state by H-bonding and π-π stacking interactions. Complex 2: In complex 2, 5′-GMP is coordinated to nickel through N(7) position of purine but phosphate moiety did not take place in coordination. Two molecules of 5′-GMP and four water molecules coordinated to nickel and formed distorted octahedral geometry. The charge of complex 2 is balanced by sodium coordination to sugar hydroxyl groups and nickel coordinated water molecules. The geometry of sodium coordination centre is distorted octahedral. The conformation of 5′-GMP is altered due to nickel interaction. Moreover, complex 2 is stabilized in solid state by H-bonding and π-π stacking interactions. Complex 3: Nucleotide 5′-IMP also showed similar coordination modes like 5′-GMP towards nickel, where N(7) position of purine participated in coordination with nickel and phosphate moieties did not coordinate to nickel. Two molecules of 5′-IMP and four water molecules participated in coordination with nickel and formed distorted octahedral geometry. Interestingly, the charge of complex 3 is balanced by sodium coordination to sugar hydroxyl moieties. The geometry of sodium coordination centre is distorted octahedral. Moreover, nickel is forming coordination polymer with 5′-IMP. Further, nickel interactions with 5′-IMP brought changes in the conformation of ribose moiety. These results suggest that nickel interactions with nucleic acids may bring changes in their conformation. Interestingly, right hand helical structure formation is observed for complex 3 in crystal structure. Further, the chirality of complex 3 was confirmed by circular dichroism studies. Complex 3 is stabilized by both H-bonding and π-π stacking interactions in solid state. Complex 4: Surprisingly, nickel is coordinated to hypoxanthine through N(9) position of purine in acidic conditions and not through N(7) or N(3). The coordination mode of nickel with hypoxanthine is different from complexes 2 and 3. Two hypoxanthine moieties are coordinated to nickel in axial manner. The geometry of nickel coordination centre is distorted octahedral. Further, complex 4 is stabilized by H-bonding and π-π stacking interactions in solid state. Cytotoxicity studies of complexes 1-4 on various cancer cell lines revealed that complex 1 is better cytotoxic than complexes 2-4. Moreover, complex 1 exhibited comparable cytotoxicity with cisplatin on various cells lines and induced apoptotic cell death. II. Synthesis, structure elucidation and anticancer activity of copper-adeninyl complexes In order to understand copper-adenine interactions and anticancer activity, several copper complexes of adenine derivatives were prepared. Here, most of adenine derivatives used in complex preparation is known as cycline dependent kinase inhibitors. Prepared copper complexes are 1) [Cu (N6-benzyl adenineH)2Cl3 ].Cl.2H2O, 2) [Cu (2-amino-N6-benzyladenineH)2Cl3].(2-amino-N6-benzyl adenineH)2.3Cl.5H2O, 3) [Cu (α-(Purin-6-ylamino)-p-toluenesulfonamide H)2Cl4], 4) [Cu (kinetinH)2 Cl3].Cl.2H2O, 5) [Cu (N-1H-purine-6-yl-alanineH) (H2O) Cl3].H2O, 6) [(Cu (N-1H-purine-6-yl-alanineH)2Cl3).(Cu(N-1H-purine-6-yl-alanineH)Cl)2(μ-Cl)2].Cl.4H2O. All these complexes were characterized by X-ray crystallography and various spectroscopic techniques. Complex 1: Synthesis and X-ray structures of complex 1 were reported in literature. However, anticancer activity of complex 1 is not known. Therefore, it was prepared based on the reported lines to assess the anticancer activity. The anticancer activity of complex 1 was studied on various cell lines. Interestingly, complex 1 exhibited better cytotoxicity than cisplatin in MCF-7 and MDA-MB-231 cell lines. Complex 2: Ligand 2-amino-N6-benzyl adenine is coordinated to copper through N(9) of purine. In addition, two uncoordinated 2-amino-N6-benzyl adenine, three chloride and five water molecules are making it as a co-complex with uncoordinated ligands. The copper coordination centre adopted distorted trigonal bipyramidal geometry [3+2] with τ = 0.671 (α-β/60, where α, β are two greatest valence angles of coordination centre). Further, complex 2 is stabilized in solid state by both H-bonding and π-π stacking interactions. H-bonding is observed between N-H···Cl. Uncoordinated water molecules formed six-member rings with H-bonding network. The π-π stacking interactions are observed between phenyl and purine moieties. Complex 2 exhibited better cytotoxicity than 2-amino-N6-benzyl adenine and copper salt. Complex 3: Ligand α-(2-Amino purin-6-ylamino)-p-toluene sulfonamide is coordinated to copper through N(9) position and protonation is observed at N(3) position. Two molecules of α-(2-Amino purin-6-ylamino)-p-toluene sulfonamide and four chloride ions are forming a distorted octahedral geometry with copper. Complex 3 is stabilized by N-H···Cl and N-H···O H-bonding. Further, complex 3 exhibited better cytotoxicity than cisplatin in U251 cells. Complex 4: Kinetin is coordinated to copper through N(9) position of purine. Protonation is observed on N(3) position and balanced the charge of complex 4. Two molecules of kinetin and three chloride moieties are coordinated to copper and forming distorted trigonal bipyramidal geometry [3+2] with τ = 0.431. Moreover, complex 4 is stabilized by both H-bonding interactions and π-π stacking interactions. The H-bonding of complex 4 is observed between N-H···Cl and C-H···Cl. The π-π stacking interactions are observed between furanyl aromatic ring and imidazole ring of purine. Complex 4 exhibited better cytotoxicity than kinetin and copper salt. Complex 5: The N-1H-purine-6-yl-alanine is coordinated to copper through N(9) position of purine. Complex 5 crystallizes in the monoclinic space group P21 with Z=4. One molecule of N-1H-purine-6-yl-alanine, two chloride ions and one water molecule coordinated to copper. The geometry of copper coordination centre is distorted trigonal bipyramidal [3+2] with Cu(1) τ1 = 0.613 and Cu(2) τ2= 0.671. Protonation is observed on N(3) position. Complex 5 is stabilized by both H-bonding and π-π stacking interactions. The H-bonding of complex 5 is observed between N-H···Cl and C-H···Cl. The π-π stacking interactions are observed between imidazole moieties. Moreover, complex 5 exhibited better cytotoxicity than N-1H-purine-6-yl-alanine and copper salt. Complex 6: Complex 6 is a co-complex, where two different complexes are co-crystallized. The crystal structure of complex 6 indicate that geometry of Cu(1) and Cu(2) coordination centre are distorted trigonal bipyramidal [3+2] with τ1 = 0.3261 and τ2 = 0.8, respectively. Two molecules of N-1H-purine-6-yl-alanineH are coordinated to Cu(2) through N(9) position of purine. The N-1H-purine-6-yl-alanineH ligands are arranged in geometry in trans manner with respect to axis passing through the N(9) atom and copper. Whereas, in second co-complex two N-1H-purine-6-yl-alanineH are coordinated to Cu(1) through N(9) and N(3) position of purine. Both Cl(1) and Cl(3) coordinated to copper are forming a bridge between copper. In addition, one uncoordinated chloride and two water molecules are present in the unit cell. Complex 6 is stabilized in crystalline state by both H-bonding and π-π stacking interactions. Complex 6 exhibited better cytotoxicity than complex 5, N-1H-purine-6-yl-alanine and copper salt on various cell lines. III. Synthesis, structure and anticancer activity of zinc complexes of adenine derivatives In order to understand zinc interaction with adenine and their anticancer activity, several zinc complexes of adenine derivatives were prepared. The prepared complexes are (1) [Zn (N6-benzyladenineH).Cl3].2H2O, (2) [Zn2 (μ -N6-benzyladenine)2( μ-H2O)2(H2O)4].(OTf)4.H2O, (3) (N6-benzyl adenineH2) [ZnCl4].2H2O, (4) [Zn (2-Amino-N6-Benzylpurine)Cl3).2-Amino-N6-BenzylpurineH).EtOH, (5) (2-Amino-N6-(3-picoyl)purineH2)[ZnCl4].H2O, (6)(2-Amino-N6-(3-picoyl)purineH2)[ZnCl4].HCl, (7) (2-Chloro-N6-(3-picoyl) purineH2) [ZnCl4].H2O, (8) ((α-Purine-6-ylamino)-p-toluene sulfonamide H)2[ZnCl4].2HCl.2H2O. Complex 1: The N6-benzyl adenine is coordinated to zinc through nitrogen atom N(7) of purine. One molecule of N6-benzyl adenine and three chloride ions are coordinated to zinc and forming distorted tetrahedral geometry. Interestingly, the nitrogen atom N(1) of purine is protonated. Complex 1 exhibited strong H-bonding interactions between N-H···O, N-H···Cl and N-H···N. The complex 1 showed better cytotoxicity than N6-benzyl adenine and ZnCl2. Complex 2: The N6-benzyl adenine formed a dimeric complex with zinc at neutral pH. Complex 2 crystallizes in the triclinic space group P-1with Z=1. Two Zn metal centres are bridged by two molecules of N6-benzyl adenine through nitrogen atoms N(3) and N(9) of purine forming a di-nuclear complex, further two zinc centres is bridged by two water molecules and other two water molecules on the other side completing the octahedral coordination for the Zn. Complex 2 is stabilized in crystalline state by H-bonding interactions. The H-bonding of complex 2 is observed between O-H···O and N-H···O. Complex 2 exhibited better cytotoxicity than N6-benzyl adenine and ZnCl2 on various cell lines. Complex 3: The N6-benzyladenine is not coordinated to the Zn metal at acidic pH and forms an ion-pair complex. Ion-pair complex 3 crystallizes in the monoclinic space group Cc with Z=4. The protonation is observed at N(1) and N(9) atoms of N6-benzyl adenine. The positive charges on N6-benzyl adenine is neutralized by the presence of two chloride ions in [ZnCl4]2-. Alternative arrangement of cation and anion arrangement is observed in complex 3. Water channel formation is observed between cation and anion arrangement. Moreover, complex 3 is stabilized by H-bonding and π-π stacking interactions. H-bonding is observed in complex 3 between N-H···Cl, O-H···Cl and N-H···O. The π-π stacking interactions in complex 3 are observed between benzyl six-membered aromatic ring and purine six-membered rings. Complex 3 exhibited better cytotoxicity than N6-benzyl adenine and ZnCl2 in various cell lines. Complex 4: Ligand 2-amino-N6-benzyl adenine resulted in a different structure from N6-benzyl adenine with zinc. One molecule of 2-amino-N6-benzyl purine is coordinated to zinc through nitrogen atom N(7) of purine. Surprisingly, one uncoordinated positively charged 2-amino-N6-benzyl purineH is present in the asymmetric unit, which is balancing the charge of zinc complex 4. Protonation is observed on N(3A) atom. Interestingly, tautomeric proton is located on coordinated purine of N(9) atom and uncoordinated purine of N(7A) atom. Geometry of ‘Zn coordination centre’ is distorted tetrahedral. Complex 4 is stabilized by H-bonding and π-π stacking interactions. The H-bonding interaction in complex 4 is observed between N-H···O and N-H···Cl. The π-π stacking interactions are observed between five-member aromatic rings and six-membered aromatic rings. Complex 4 exhibited better cytotoxicity than 2-amino-N6-benzyl purine and ZnCl2 in various cell lines. Complex 5: 2-Amino-N6-(3-picoyl) purine forms an ion-paired complex with zinc at acidic pH. The protonation in 2-Amino-N6-(3-picoyl) purine is observed at N(3) of the purine and picolyl N(14). The positive charge of 2-Amino-N6-(3-picoyl) purine is neutralized by the presence of two chloride ions in [ZnCl4]2-. Moreover, complex 5 exhibited both H-bonding interactions and π-π stacking interactions. The H-bonding interactions are observed between N-H···Cl, N-H···N, O-H···Cl, N-H···O and C-H···N. One uncoordinated water molecule is present in unit cell, which is involved in H-bonding with both ions. The π-π stacking interactions are observed between purine five-membered rings and purine six-membered ring. Complex 5 exhibited better cytotoxicity than cisplatin in HeLa and MDA-MD-231 cells. Complex 6: 2-Amino-N6-(3-picoyl) purine formed similar structure of complex 5 in strong acidic conditions. Complex 6 exhibited both H-bonding and π-π stacking interactions. The H-bonding in complex 6 is observed between N-H···Cl and N-H···N. In complex 6, the π-π stacking interactions are observed between pyridyl six-membered rings and purine six-membered rings. Purine-Purine stacking interactions are observed between purine six-membered ring and five-membered rings. Complex 6 exhibited better cytotoxicity than cisplatin in HeLa, MCF-7, MDA-MB-231 and HeLa-Dox cells. Interestingly, complex 6 arrested (G2/M phase) cell cycle in HeLa and MCF-7 at higher concentration and induced apoptosis. Complex 7: 2-chloro-N6-(3-picoyl) purine formed ion-pair complex with zinc. The protonation in 2-chloro-N6-(3-picoyl) purine is observed on N(9) of purine and N(14) of picolyl atoms. The positive charge of 2-chloro-N6-(3-picoyl) purine is neutralized by the presence of two chloride ions in [ZnCl4]2-. Complex 7 is stabilized by both H-bonding and π-π stacking interactions. The H-bonding is observed between N-H···Cl, O-H···Cl and N-H···O in complex 7. The π-π stacking interactions are observed between pyridyl six-membered ring and six-membered ring of purine. Complex 7 exhibited better cytotoxicity than cisplatin in HeLa, MCF-7, U251 and HeLa-Dox cells. Complex 8: (α-Purine-6-ylamino)-p-toluene sulphonamide formed ion-pair complex with zinc. Ion-pair complex 8, crystallizes in the triclinic space group P-1 with Z=4. The protonation on (α-Purine-6-ylamino)-p-toluene sulfonamide is observed at N(9) and N(1) atoms of purine. The positive charge of the ligand is neutralized by two chloride ions present in [ZnCl4]2 -. The H-bonding is observed between N-H···Cl, O-H···N, N-H···O and O-H···Cl. The π-π stacking interactions are observed between benzyl rings of benzene sulfonamide moieties. Complex 8 exhibited better cytotoxicity than cisplatin in HeLa, MCF-7 and HeLa-Dox cells. Moreover, these complexes induced apoptotic cell death as revealed by Annexin V/PI assay, FACS and microscopy analysis. IV. Synthesis, structure and cytotoxicity studies of zinc complexes of uracil-1-acetic acid and N6-adeninebutyric acid To understand the zinc interactions with nucleic acid constituent derivatives and their anticancer activity, zinc complexes of uracil-1-acetic acid and N6-adeninebutyric acids were prepared. (1) [Zn (uracil-1-acetato)2 (H2O)4] and complex (2) [Zn (N6-adeninebutyric acid)2 (H2O)2]) were characterized by X-ray crystallography and various spectroscopic techniques. The X-ray structures showed acetate moiety coordination to zinc rather than purine and pyrinidine moities. The geometry of zinc coordination centre is distorted octahedral. Complexes 1 and 2 are stabilized by non-covalent interactions. Anticancer studies of these complexes showed better cytotoxicity than cisplatin in MDA-MB-231cells. V. Copper (II) complexes of 6-mercaptopurine, hypoxanthine and uracil-1-acetic acid: Synthesis, structures, antioxidant and potent anticancer activity To delineate copper interactions with purine and pyrimidine derivatives and anticancer activity, several copper complexes of 6-mercaptopurine, hypoxanthine and uracil-1-acetic acid were prepared. The prepared complexes are (1) [Cu (6-MP) (bpy) Cl2], (2) [Cu (hx) (phen) Cl2].H2O and (3) [Cu (bpy)2 (uracil-1-acetato)].6H2O)] (bpy = 2, 2′-bipyridine, phen = 1, 10-phenanthroline, 6-MP = 6-Mercapto Purine and hx = hypoxanthine). All these complexes were chracterized by various spectroscopic and X-ray diffraction techniques. Complexes 1 and 2 crystallize in the monoclinic space groups Cc and C2/c, respectively with eight molecules in the unit cell. All the complexes 1-3 adopt distorted trigonal bipyramidal geometry. Surprisingly, most potent coordination sites of sulfur in 6-MP and acetato in uracil-1-acetato did not participate in coordination with copper. In complexes 1 and 2, the N(7) position of purine and the N(3) position of pyrimidine in complex 3 are coordinated with copper. All these complexes 1-3 are stabilized by non-covalent interactions in solidstate. Anticancer studies showed better cytotoxicity for copper complexes than cisplatin, 6-meracptopurine and temozolomide in various cell lines. Interestingly, copper complexes of 6-MP and hypoxanthine showed antioxidant activity and reduced ROS level in cells. In contrast, copper complex of uracil-1-acetic acid produced ROS in cells. In contrast, copper hypoxanthine showed better cytotoxicity than cisplatin in HeLa-Dox cells. All these complexes induced apoptotic cell death. In summary, we studied the interaction of metal-nucleic acid constituents and derivatives by X-ray crystallography. We found new coordination modes for Ni, Cu and Zn towards various nucleic acid constituents and derivatives. Some of these complexes showed better cytotoxicity than well known anticncer drugs cisplatin, 6-meracptopurine and temozolomide. Complex [Cu (hx) (phen) Cl2].H2O showed better cytotoxicity than cisplatin in doxorubicin resistant (HeLa-Dox) cells. These complexes induced apoptotic cell death in various cancer cells. All in all, the results of present studies/findings could form a potential lead for the development of newer anticancer therapeutics.

[pt] Câncer é o nome dado a um conjunto de mais de 100 doenças e entre as possibilidades de tratamento está a quimioterapia. Após a descoberta das propriedades antitumorais do complexo de coordenação comumente chamado cisplatina, um dos compostos mais utilizados em neoplasias malignas, o estudo dos complexos metálicos teve um grande impulso e alguns compostos promissores de cobre(II) já foram desenvolvidos. Por outro lado, bases de Schiff derivadas de aminas e aldeídos aromáticos têm apresentado uma ampla aplicação em muitas áreas de pesquisa, sendo que algumas são farmacologicamente utilizadas na terapia anti-hipertensiva, hipnótica e antineoplásica. Neste contexto, no presente trabalho, foi sintetizado e caracterizado um ligante imínico binucleante sulfonado derivado da taurina, já conhecido na literatura: (LIT) e, a partir deste, seus complexos inéditos de Zn(II), Cu(II) e Ni(II), que foram caracterizados pelas seguintes técnicas: espectroscopia vibracional e eletrônica, análise elementar de CHNS, análise termogravimétrica, espectroscopia de ressonância paramagnética eletrônica (EPR) e modelagem molecular computacional. Os novos compostos obtidos neste trabalho são, a saber: composto (1), composto (2) e composto (3), em que LIT representa uma forma parcialmente hidrolisada de LIT. Os complexos 1 e 2 são os primeiros compostos binucleares do ligante LIT descritos. Neles, os centros metálicos são tetracoordenados e apresentam uma ponte exógena acetato coordenada nas formas bidentada, para o composto 1, e monodentada, para 2. Esta diferença na coordenação da ponte se dá, provavelmente, devido aos distintos arranjos geométricos em torno dos metais: enquanto o zinco apresenta um arranjo tetraédrico, o cobre mostra um do tipo quadrático. O complexo 3 é binuclear, composto por um dímero altamente simétrico envolvendo, como dito acima, uma forma parcialmente hidrolisada de LIT. Os centros metálicos são hexacoordenados, ligados por pontes endógenas fenólicas. Tanto 2 quanto 3 são silenciosos ao EPR. Foi realizado também um ensaio de toxicidade aguda em Artemia salina para as espécies hidrossolúveis LIT e complexo 1. Este ensaio mostra boa correlação com a atividade citotóxica para alguns tumores sólidos humanos. / [en] Cancer is a name given to a set of more than 100 diseases and among the possibilities of treatment is chemotherapy. After the discovery of the antitumor properties of the coordination complex commonly called cisplatin, it is one of the compounds most used in malignancies. The study of metal complexes had a big boost and some promising copper(II) compounds have been developed. Furthermore, the Schiff bases derived from aromatic aldehydes and amines present a wide range of applications in many areas of research, some of which are pharmacologically used in antihypertensive, hypnotic, and antineoplastic therapy. In this context, in the present study, we synthesized and characterized a binucleating imine ligand, derivative of taurine, already known in the literature: (LIT). New dinuclear Zn(II), Cu(II) and Ni(II) complexes of this ligand were synthesized, and were characterized by the following techniques: vibrational and electronic spectroscopies, CHNS elemental analysis, thermogravimetric analysis, electron paramagnetic resonance (EPR) and computational molecular modeling. The new compounds obtained in this work are: composite (1), composite (2) composite (3), where LIT represents a LIT partially hydrolyzed form. Complexes 1 and 2 are the first dinuclear compounds of the LIT ligand described. In these, metal centers are tetracoordinated, with the presence of an exogenous acetate bridge, which shows a bidentate coordination mode for compound 1 and a monodentate coordination pattern for 2. This difference occurs probably due to different geometrical arrangements around the metal centers: while zinc has a tetrahedral coordination geometry, copper shows one of the square planar type. On the other hand, compound 3 a dinuclear complex, which is composed of a highly symmetric dimer involving, as mentioned above, a partially hydrolyzed form of LIT. The hexacoordinated metal centers are connected by two endogenous phenolic bridges. Both 2 and 3 are EPR silent. An acute toxicity test on Artemia salina shrimp was also carried out for the hydro-soluble species LIT and 1. This assay shows good correlation with cytotoxic activity for some human solid tumors.

Diese Dissertation unter dem Titel Experimentelle Bestimmung der elektronischen Eigenschaften anwendungsrelevanter Grenzflächen organischer Halbleiter mittels Photoelektronenspektroskopie wurde am Leibniz Institut für Festkürper- und Werkstoffforschung (IFW) Dresden am Institut für Festkörperforschung (IFF) unter der Betreuung von Prof. Dr. B. Büchner angefertigt. Zur wissenschaftlichen Untersuchung kamen hierbei zwei Typen anwendungsrelevanter Grenzflächen. Zum einem wurde der Einfluss einer Elektrodenpräparation unter Normalbedingungen mittels ex-situ Reinigungsverfahren im Vergleich zu insitu präparierten Kontakten auf das elektronische Verhalten des organischen Halbleiters Sexithiophen an Grenzflächen zu metallischen Substraten studiert. Als Substratmaterialien kamen hierbei die Metalle Silber, Palladium, Gold und Platin zum Einsatz. In einer zweiten Studie wurden die Grenzflächen der organischen Halbleiter Sexithiophen und Kupfer(II)- Phthalocyanin in Kontakt zu dünnen Filmen des Übergangsmetalloxides La0.7Sr0.3MnO3 untersucht. Auch hier wurde eine vergleichende Untersuchung für ex-situ und in-situ gereinigte La0.7Sr0.3MnO3-Kontakte durchgeführt. Die hierzu verwendeten Filme wurden im IFW Dresden am Institut für Metallische Werkstoffe (IMW) hergestellt. Auch im Rahmen dieser Untersuchungen stand der Einfluss von Sauerstoff auf das elektronische und chemische Verhalten an den Grenzflächen im Vordergrund.

[pt] Um grande número de complexos de cobre(II) tendo como ligantes compostos biológicos têm sido utilizados como modelos para o entendimento das diversas reações que ocorrem in vivo. Diversas desordens neurodegenerativas são caracterizadas pela presença anormal de proteínas no sistema nervoso central que possuem uma alta afinidade pelo íon cobre(II). Essa coordenação do metal à proteínas favorece o processo de deposição e associado ocorre a produção em excesso de espécies reativas de oxigênio (ROS - reactive oxygen species). A metionina é um antioxidante presente no meio biológico que pode se ligar ao cobre e prevenir os danos oxidativos. No presente trabalho, estudamos em solução aquosa, os complexos binários Cu(II):L1 e Cu(II):L2 e o complexo ternário Cu(II):L1:L2 (L1 = GlyGly e L2 = Met) a 25 °C e μ = 0,1 mol L-1. As constantes de formação dos complexos foram calculadas utilizando o programa BEST7. Os modos de coordenação dos ligantes nos complexos de Cu(II) foram investigados por cálculos DFT utilizando o programa TURBOMOLE 6.1. Foi utilizado o funcional PBE empregando a aproximação da resolução da identidade (RI-J) e com o conjunto de bases def2-SVP. Os efeitos do solvente foram incluídos através do modelo de solvatação COSMO. Os resultados DFT mostraram comportamento bidentado da glicilglicina na espécie Cu(H-1GlyGly), sem a participação do oxigênio do grupo carboxílico na esfera de coordenação do metal. O modelo de cluster-contínuo foi utilizado para obter, para os complexos mais estáveis, as energias livres em fase gasosa e em solução aquosa através dos métodos DFT: B3LYP/def2/TZVP e PBE0/def2-TZVP. Para os complexos mais estáveis foi incluída a segunda camada de solvatação (36 moléculas de água) para verificar a interferência de moléculas explícitas do solvente nos cálculos. Os resultados mostraram comportamento monodentado do ligante glicilglicina no complexo [Cu(GlyGly)(H2O)36]+, sem a participação do oxigênio peptídico na esfera de coordenação do centro metálico. Observou-se que os clusters assumem diferentes geometrias: octaédrica ([Cu(Met)(H2O)36]+), pirâmide de base quadrada ([Cu(GlyGly)(H2O)36]+, [Cu(H-1GlyGly)(H2O)36], [Cu(Met)(OH)(H2O)36], [Cu(Met)(OH)2(H2O)36]-, [Cu(HGlyGly)(Met)(H2O)36], [Cu(GlyGly)(Met)(H2O)36]- e [Cu(GlyGly)(Met)(OH)(H2O)35]2-) e quadrado distorcido ([Cu(GlyGly)(OH)(H2O)35]-). Todos os clusters apresentaram uma configuração eletrônica do estado fundamental t6 2g d22 d1 x2-y2 o que concorda com a distorção Jahn-Teller. Nas doenças neurodegenerativas o pH fisiológico é levemente acidificado. Na espécie ternária [Cu(GlyGly)(Met)(H2O)36]-, que é formada em pH 7, o enxofre não faz parte da esfera de coordenação do cobre, indicando que ele pode exercer uma ação antioxidante em sistemas biológicos sob condições de estresse oxidativo. / [en] A great number of copper(II) complexes that have as ligands biological compounds have been used as models for the understanding of several reactions that occur in vivo. Several neurodegenerative disorders are characterized by the abnormal presence of proteins in the central nervous system that have a high affinity for the copper(II) ion. This coordination of metal to proteins favor the deposition process and associated the production in excess of reactive oxygen species (ROS) occurs. The methionine is an antioxidant present in the biological medium that could bind to copper and prevent the oxidative damages. In the present work we studied in aqueous solution the binary complexes Cu(II):L1 and Cu(II):L2 and the ternary complex Cu(II):L1:L2 (L1 = GlyGly and L2 = Met) at 25C and μ = 0.1 mol L-1. The binding constants of the complexes were determined using the BEST7 program. The coordination modes of the ligands in the Cu(II) complexes were investigated by DFT calculation using the TURBOMOLE 6.1 program. The PBE functional was used employing the resolution of identity approximation (RI-J) and with the def2-SVP basis set. The solvent effects were included through the COSMO solvation model. The DFT results showed bidentate behavior of the glycylglycine in the Cu(H-1GlyGly) species without the participation of the oxygen from the carboxylic group in the metal coordination sphere. The cluster-continuum model was used to obtain for the more stable complexes the free energies in gas phase and in the aqueous solution through DFT methods: B3LYP/def2/TZVP and PBE0/def2-TZVP. The second solvation shell (36 water molecules) was included in the more stable complexes to verify the interference of solvent explicit molecules in the calculation. The results showed monodentate behavior of the glycylglycine ligand in the complex [Cu(GlyGly)(H2O)36]+, without the participation of the peptidic oxygen in coordination sphere of metallic centre. It was observed that the clusters assume different geometries: octahedral ([Cu(Met)(H2O)36]+), square pyramid ([Cu(GlyGly)(H2O)36]+, [Cu(H-1GlyGly)(H2O)36], [Cu(Met)(OH)(H2O)36], [Cu(Met)(OH)2(H2O)36]-, [Cu(HGlyGly)(Met)(H2O)36], [Cu(GlyGly)(Met)(H2O)36]- and [Cu(GlyGly)(Met)(OH)(H2O)35]2-) and distorted square ([Cu(GlyGly)(OH)(H2O)35]-). All the clusters presented an electronic configuration of ground state t6 2g d22 d1 x2-y2 that agree with the Jahn-Teller distortion. In the neurodegenerative diseases the physiologic pH is slightly acidified. In the ternary species [Cu(GlyGly)(Met)(H2O)36]-, that is formed in pH 7, the sulfur is not part of the coordination sphere of copper, indicating that it could exert an antioxidant action in biological systems under oxidative stress conditions.

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.

The mining of sulphidic ore to extract metals such as zinc and copper produces huge quantities of waste material. The weathering and oxidation of the waste produces what is commonly known as Acid Mine Drainage (AMD), a dilute sulphuric acid rich in Fe(II) and heavy metals. This thesis serves to summarise five papers reporting how the precipitation of Fe(III) phases can attenuate the contamination of heavy metals by adsorption processes. Schwertmannite (Fe8O8(OH)6SO4) is a common Fe(III) mineral precipitating in AMD environments at pH 3-4. The stability and surface chemistry of this mineral was investigated. It was shown that the stability depended strongly on pH and temperature, an increase in either promoted transformation to goethite (α-FeOOH). Two pH dependent surface species of SO42- were detected with infrared (ATR-FTIR) spectroscopy. The adsorption of Cu(II), Pb(II) and Zn(II) to schwertmannite occurred at lower pH than to goethite, whereas Cd(II) adsorption occurred in a similar pH range on both schwertmannite and goethite. Extended x-ray absorption fine structure (EXAFS) spectroscopy suggests two surface species for Cu(II) and Cd(II) at the schwertmannite surface. Cu(II) adsorbs monodentately and Cd(II) bridging bidentately to adsorbed SO42-. Both metal ions also adsorb in a bridging bidentate mode to the surface hydroxyl groups. At pH 7.5 up to 2.7 μmol Cd(II) m-2 could be adsorbed to schwertmannite, indicating a large adsorption capacity for this mineral. The acid-base properties of two NOM samples were characterised and could be well described as diprotic acids below pH 6. The adsorption of NOM to schwertmannite and goethite was very similar and adsorption occured in a very wide pH range. High concentrations of NOM increased the adsorption of Cu(II) to goethite at low pH whereas a slight decrease was noted at low concentrations of NOM. No effect was detected in the schwertmannite system. The formation of Fe(III) phases from precipitation of AMD was shown to be very pH dependent. At pH 5.5 a mixture of minerals, including schwertmannite, formed whereas at pH 7 only lepidocrocite (γ-FeOOH) formed. The concentration of Zn(II) in AMD could by adsorption/coprecipitation be reduced to environmentally acceptable levels.

Thirteen new dinuclear complexes of ligand 2,6-bis[(N-methylpiperazine-1- yl)methyl]-4-formyl phenol (L1) were prepared. Copper(II) and palladium(II) salts were used for the syntheses. Following compounds were prepared: [Cu2L1(CH3COO)2]ClO4, [Cu2L1(CF3COO)2(ClO4)][Cu2L1(CF3COO)2]ClO4, [Pd2L1(CH3COO)3], [Pd2L1(CF3COO)3], [Pd2L1(Cl)4]. These ones should act as anion receptors. The acetates were exchanged for phenylphosphinates in the case of the complex cation [Cu2L1(CH3COO)2]+ and the structure of [Cu2L1(phPO2H)2]ClO4 was obtained. Geometry of coordination shell of Cu2+ - ions in prepared complexes is tetragonal pyramid. The UV-VIS spectroscopy was used for study of interactions in system of the ligand - metal - anion. Interactions between the ligand and metals in oxidation state 2 were observed as well as interactions between the complex [Cu2L1(CH3COO)2]ClO4 and sodium salts.

The last two decades have seen extensive growth in interest in metal-ion assemblies, especially for building new polynuclear exchange-coupled magnetic systems. However, the concept of designing polynuclear extended structures has still not matured to the level of retro-synthetic approach developed for the organic and pharmacological molecules. Although some progress has been made with secondary building units (SBUs) in metal-organic-frameworks (MOFs), the control seems to be just an illusion when it comes to bridging ligands such as the azide ion. When it is asserted that the azido ligand is versatile in its bridging capabilities, what is actually meant is that it would be difficult to predict or control its bridging properties, or in other words, the azido based polynuclear complexes are difficult to pre-design. However, this kind of serendipity is not always bad news for the chemists. For example, the azido ligand has been shown to mediate magnetic exchanges between paramagnetic metals in a predictable fashion (usually depending upon the bonding geometries). Therefore, it is a well-respected ligand in polynuclear assemblies of paramagnetic ions. Serendipitous assemblies offer new magnetic structures that we may not otherwise even think about synthesizing. Similarly, there are other ligands, such as alkoxido, oximato, carboxylato etc. which also behave like azide. These ligands are very important in the study of magnetic exchanges to develop an understanding of the underlying mechanisms in molecular magnetism. Serendipitous assemblies have also led to systems like single molecule magnets (SMMs), which have enriched the field with potential applications in computing and have also been used for the confirmation of the quantum magnetic properties like tunneling phenomenon, spin decoherence etc. Investigations incorporated in this thesis work led to several novel strategies for using serendipity as an advantage and build unprecedented structural topologies with interesting new molecular-magnetic properties. All the reported complexes were thoroughly analyzed through elemental analysis, spectroscopy, X-ray structure determination (both single crystal & powder diffractions) and variable temperature magnetic susceptibility measurements. In a few suitable cases, model structures obtained from the X-ray structures were also employed to study the magnetic exchange mechanisms through density functional theory (DFT) calculations and simulations. CHAPTER 1 of the thesis presents a general review on the ever-growing field of metal-ion assembly. In particular, the importance of the ‘serendipitous approach’ to build new and interesting metal-ion clusters and polyclusters is highlighted. This chapter also describes the basic concepts of exchange-based molecular magnetism as applied to the metal-ion assemblies. CHAPTER 2 describes the concept of using lower molar proportions of blocking bidentate chelating ligands in the neutral copper(II)-azido systems, which increases the number of coordination sites for the versatile azido bridges to assemble the metal-ions in higher dimensions, based on smaller cluster units. Syntheses, structures and magnetic properties of ten novel complexes are described in this chapter: [Cu3(tmen)2(N3)6]n (1), [Cu4(Me-hmpz)2(N3)8]n (2), [Cu4(men)2(N3)8]n (3), [Cu6(deen)2(N3)12]n (4), [Cu6(aem)2(N3)12]n (5), [Cu6(dmeen)2(H2O)2(N3)12]n (6), [Cu6(N,N'-dmen)2(N3)12]n (7), [Cu6(hmpz)2(N3)12]n (8), Cu5(N,N-dmen)2(N3)10]n (9), and [Cu5(N,N'-dmen)5(N3)10]n (10) [tmen = N,N,N',N'-tetramethylethylenediamine, Me-hmpz = 1-methylhomopiperazine, men = N-methylethylenediamine, deen = N,N'-diethylethylenediamine, aem = 4-(2-aminoethyl)morpholine, dmeen = N,N-dimethyl-N'-ethylethylenediamine, N,N'-dmen = N,N'-dimethylethylenediamine, hmpz = homopiperazine, N,N-dmen = N,N-dimethylethylenediamine]. Most of these complexes have simple oligonuclear basic building units (Scheme 1), such as trinuclear (1), tetranuclear (2, 3) and hexanuclear (4-8), but the overall arrangements of these cluster units in higher dimensions vary widely and serendipitously. For example, the hexanuclear complexes 4-7, although having almost identical basic structures, assemble in three- (4, 5) or two- (6, 7) dimensions with different connectivity among the basic structures. However, complex 9 is made from two different building units (Cu2 and Cu3). Complex 10, although having metal to blocking molar ratio 1:1, presents an unprecedented 1D structure for such complexes. Analysis of the magnetic susceptibility data for complexes 1-9 using theoretical exchange models for fitting is also described. Density functional theory (DFT, B3LYP) was employed to further analyze the experimental magnetic data for complexes 1, 2, 3 and 9 to better understand the magnetic exchange mechanisms in such systems. CHAPTER 3 continues with the same concepts developed in the previous chapter using multidentate neutral and anionic co-ligands. Using lower molar proportions of these multidentate ligands, seven novel complexes have been synthesized (keeping the initial metal to ligand ratio as 2:1): [Cu4(L1)2(N3)8]n (11), [Cu4(L2)2(N3)8]n (12), [Cu4(L3)2(N3)8]n (13), [Cu4(L4)2(N3)8]n (14), [Cu9(L5)4(N3)18]n (15), [Cu4(L6)2(H2O)2(N3)6] (16) and [Cu4(L7)2(N3)6]n (17) [where L1-5 are the condensation products of 2-pyridinecarboxaldehyde and 2-{2-(methylamino)ethyl}pyridine (L1), N,N-diethylethylenediamine (L2), N,N-dimethylethylenediamine (L3), N-methylethylenediamine (L4), N,N,2,2-tetramethylpropanediamine (L5); HL6 and HL7 are the condensation products of 2-hydroxy-3-methoxybenzaldehyde with N,N-diethylethylenediamine (HL6), and N-ethylethylenediamine (HL7)]. The ligand L1 is particularly interesting, as it is a hemiaminal ether (usually considered to be unstable intermediates in the reactions of aldehydes and secondary amines in alcoholic solvents), and was found to be trapped in 11. Although 11-13 have identical tetranuclear basic structures (with the rare simultaneous end-on and end-to-end bridges between two neighbouring metal-ions, Scheme 2) and extend in one-dimension. However, 13 is differently organized from the other two complexes. For 14, the bridging structure among the peripheral copper(II) ions changes to double end-on (Scheme 2), and the resulting structure extends in two dimensions. However, with L5, metal to ligand ratio is 9:4 (under similar conditions and initial molar proportions of the components) in 15, which can be seen as two different fragments: [Cu4(L5)4(N3)6]2+ and [Cu5(N3)12]2- linked alternately to give an overall 1D structure. HL6 and HL7 have one ionisable phenolic group that replaces one azido anion and generates two pockets for the metal atoms. These monoanionic ligands give tetranuclear complexes (16 and 17) with basic structures resembling (Scheme 2) to 11-14. While 17 is 1D in nature, two coordinated water molecules prevent the structure of 16 to grow and results in a discrete cluster. The variable temperature magnetic properties of these complexes were thoroughly analyzed through experimental and theoretical (DFT) studies. CHAPTER 4 reports the use of a pyridyl substituted propanediolate ligand in the assembly of two novel 1D heterometallic complexes: [Mn3Na(L)4(CH3CO2)(MeOH)2](ClO4)2∙3H2O (18) and [Mn3Na(L)4(CH3CH2CO2)(MeOH)2](ClO4)2∙2MeOH∙H2O (19) [LH2 = 2-methyl-2-(2-pyridyl)propane-1,3-diol, Scheme 3]; both featuring octahedral MnIV ions linked alternately to one trigonal prismatic MnII ion and even more interestingly to one trigonal prismatic NaI ion (Scheme 3). The complexes are essentially identical in structure and magnetic behavior, showing a weak ferromagnetic interaction among the neighboring manganese ions. DFT studies on a model complex supports the S = 11/2 ground spin state, deduced from dc and ac susceptibility measurements. CHAPTER 5 illustrates the use of a few dicarboxylates as potential bridging ligands to assemble tri- and hexanuclear MnIII-clusters. With the salicylaldoximate (salox) as the [MnIII3O(salox)3]+, triangle-generating moiety and keeping the reaction conditions (solvent, base, reaction time and crystallization process) identical, four new extended complexes that differ both in their basic and higher dimensional organizations are reported. When 1,3-phenylenediacetate (phda) is used (in EtOH), in the resulting complex [MnIII6O2(salox)6(EtOH)4(phda)]n∙(saloxH2)n∙(2H2O)n (20), a single type of MnIII6 clusters are linked by the dicarboxylate (interestingly the complex crystallizes with uncoordinated saloxH2 molecules). However, when two differently substituted isophthalate linkers (5-iodoisophthalate and 5-azidoisophthalate) are used, two almost identical complexes [MnIII6O2(salox)6(MeOH)5(5-I-isoph)]n∙(3MeOH)n (21) and [MnIII6O2(salox)6(MeOH)4(H2O)(5-N3-isoph)]n∙(4MeOH)n (22) are isolated, with two different types of Mn6 clusters (Scheme 4) linked alternately in one dimension. More interestingly, use of another substituted isophthalate (5-nitroisophthalate) produced a heteronuclear complex [MnIII3NaO(salox)3(MeOH)4(5-NO2-isoph)]n∙(MeOH)n(H2O)n (23) with only MnIII3 triangles as the basic cluster assembled in two dimensions. Temperature and field dependent dc and ac susceptibility measurements show that the complexes 20-22 behave as non-interacting single molecule magnets with ground spin state S = 4. Complex 23 is dominantly antiferromagnetic with a ground spin state S = 2. The magnetic behaviours of these complexes are also supported by theoretical calculations (DFT) on models generated from the crystal structures.

Diferentes complexos de cobre(II), contendo ligantes do tipo base de Schiff e um grupamento imidazólico, com interesse bioinorgânico, catalítico e como novos materiais, foram preparados na forma de sais perclorato, nitrato ou cloreto e caracterizados através de diferentes técnicas espectroscópicas (UV/Vis, IR, EPR, Raman) e espectrometria de massa Tandem (ESI-MS/MS), além de análise elementar, condutividade molar e medidas de propriedades magnéticas. Alguns destes compostos, obtidos como cristais adequados, tiveram suas estruturas determinadas por cristalografia de raios-X. As espécies di- e polinucleares contendo pontes cloreto, mostraram desdobramentos das hiperfinas nos espectros de EPR, relacionados à presença do equilíbrio com a respectiva espécie mononuclear, devido à labilidade dos íons cloretos, dependendo do contra-íon e do tipo de solvente utilizado. Adicionalmente, em solução alcalina, estes compostos estão em equilíbrio com as correspondentes espécies polinucleares, onde os centros de cobre estão ligados através de um ligante imidazolato. Em meio alcalino, estes compostos polinucleares contendo ponte imidazolato foram também isolados e caracterizados por diferentes técnicas espectroscópicas e magnéticas. Através da variação estrutural e também do ligante-ponte foi possível modular o fenômeno da interação magnética entre os íons de cobre em estruturas correlatas di- e polinucleares. Os respectivos parâmetros magnéticos foram obtidos com ajuste das curvas experimentais de XM vs T, correlacionando-se muito bem com a geometria, ângulos e distâncias de ligação entre os íons, quando comparado com outros complexos similares descritos na literatura. Posteriormente, estudaram-se os fatores relacionados com a reatividade de todas essas espécies como catalisadores na oxidação de substratos de interesse (fenóis e aminas), através da variação do tamanho da cavidade nas estruturas cíclicas ou de variações no ligante coordenado ao redor do íon metálico. Vários deles se mostraram bons miméticos de tirosinases e catecol oxidases. Um novo complexo-modelo da citocromo c oxidase (CcO), utilizando a protoporfirina IX condensada ao quelato N,N,-bis[2-(1,2-metilbenzimidazolil)etil]amino e ao resíduo de glicil-L-histidina, foi sintetizado e caracterizado através de diferentes técnicas espectroscópicas, especialmente EPR. A adição de H2O2 ao sistema completamente oxidado, FeIII/CuII, a -55°C, ou o borbulhamento de oxigênio molecular a uma solução do complexo na sua forma reduzida, FeII/CuI, saturada de CO, resultou na formação de adutos com O2, de baixo spin, estáveis a baixas temperaturas. / Different Schiff base copper(II) complexes containing an imidazole ligand were prepared as perchlorate, nitrate and chloride salts, and characterized by different techniques (UV/Vis, IR, EPR, Raman) and tandem mass spectrometry (ESI-MS/MS), besides elemental analysis, conductivity measurements and magnetic properties. Some of these complexes, suitable crystals were isolated, allowing its structure to be determined by X-ray crystallography. Equilibria involving mono- and dinuclear species containing chloro-bridges were monitored in solution by EPR spectra, indicating a significant dependence on the solvent, and the counter-ion. In alkaline solution, deprotonation of the imidazole moiety promotes a self-assembled process, by coordination of the irnidazolate nitrogen atom to a copper(II) center of an adjacent unit, leading to the macrociclic or zig-zag-chain structures. These complexes were isolated and characterized by different spectroscopy techniques and magnetic susceptibility. The use of different bridging ligands and well-designed polydentate ligands afforded correlated structural features and exchange coupling constant in a series of di- e polinuclear copper(II) complexes. The magnetic parameters of these compounds were determined by temperaturedependent magnetic studies XM vs T, showing that the sign and the magnitude of the exchange coupling constant depends of the geometry, angle at the bridge, as well as on the bond length between paramagnetic ions, when compared with other complexes already described in the literature. The catalytic activity of the obtained complexes toward the usual biological oxidant, molecular oxygen, were then compared. Most of the di- and polynuclear compounds showed to be efficient catalysts of the aerobic oxidation of amines and o henolic substrates. Differinvg in some structural features, their tyrosinase-like catalytic activity was verified to be influenced by several factors, including steric hindrance of the ligands, cavity dimensions and accessibility of the oxidant to the catalytic center. A new biomimetic model system of the cytochrome c oxidase (CcO) derived from protohemin-IX and it contains a glycyl-L-histidine methyl ester arm axially binds the iron; the bis(benzimidazole) group acts as copper-coordinating site. has been prepared and characterized by different spectroscopic techniques, including EPR spectroscopy. The H2O2 addiction to the fully oxidised state of the system at -55ºC, or bubbling molecular oxygen into a CO-saturated solution of the reduced FeII/CuI state of the complex, resulted in a low spin oxygenated intermediate.

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-16T13:10:45Z No. of bitstreams: 1 Romulo Augusto Lins de Campos.pdf: 5930168 bytes, checksum: 7553330ff526456aa81970434c7c3475 (MD5) / Made available in DSpace on 2017-02-16T13:10:45Z (GMT). No. of bitstreams: 1 Romulo Augusto Lins de Campos.pdf: 5930168 bytes, checksum: 7553330ff526456aa81970434c7c3475 (MD5) Previous issue date: 2011-03-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Potentiometric sensors are known for their high sensitivity and selectivity. Such sensors have versatility, low cost and robustness, which ensures their applicability in a wide variety of complex chemical samples. The ion-selective electrodes for polymeric membrane are the best known potentiometric sensors, has by these traits. However, modified carbon paste electrodes have gained prominence due a great advance in their studies. This paper proposes an electrode chemically modified carbon paste for potentiometric determination of copper (II), using a new ionophore lariat-crown ether synthesized from precursor aminopropyl triethoxysilane is a silylating agent known in the literature. Studies were conducted to evaluate the influence of pH on the potential, the best buffer as supporting electrolyte, and the experimental design of mixtures to obtain the best composition of EQMPC. The proposed electrode showed a sensitivity of 38.5 mV/decade of activity with a detection limit of 2.04 x 10-5 mol L-1, and as a supporting electrolyte buffer biftalate/HCl pH = 3.0 proving to be promising for application in the determination of Cu(II). The electrode showed no significant analytical sensitivity to Co(II), Ni(II) and Zn(II) being these their main interferences. / Sensores potenciométricos são conhecidos por sua alta sensibilidade e seletividade. Tais sensores apresentam versatilidade, baixo custo e robustez, o que garante a esses sensores aplicabilidade em uma grande variedade de amostras químicas complexas. Os eletrodos íon-seletivos de membrana polimérica são os sensores potenciométricos mais conhecidos, por possuirem essas características. Contudo, os eletrodos modificados de pasta de carbono têm ganhado forte destaque devido ao avanço em seus estudos. Neste trabalho é proposto um eletrodo quimicamente modificado de pasta de carbono para determinação potenciométrica de cobre (II), utilizando um novo ionóforo lariat-éter coroa sintetizado a partir de precursor aminopropil trietoxisilano que é um agente sililante conhecido na literatura. Foram realizados estudos para avaliar a influência do pH sobre o potencial, o melhor tampão como eletrólito de suporte, além do planejamento experimental de misturas para se obter a melhor composição do EQMPC. O eletrodo proposto apresentou uma sensibilidade de 38,5mV/década de atividade com limite de detecção de 2,04 x 10-5 mol L-1, tendo como eletrólito de suporte um solução-tampão biftalato/HCl pH = 3,0 demonstrando ser promissor para aplicação na determinação de íons Cu(II). O eletrodo não apresentou sensibilidade analítica significativa aos íons Co(II), Ni(II) e Zn(II) sendo esses seus principais interferentes.