Grown-like macrocycle zinc complex derived from beta-diketone ligand for the polymerization of rac-lactide

Enolic Schiff base zinc (II) complex 1 was synthesized. XRD revealed 1 was a novel crown-like macrocycle structure consisted of hexanuclear units of (LZnEt)(6) via the coordination chelation between the Zn atom and adjacent amine nitrogen atom. Further reaction of 1 with one equivalent 2-propanol at RT produced Zn-alkoxide 2 by in situ alcoholysis. Complex 2 was used as an initiator to polymerize rac-lactide in a controlled manner to give heterotactic enriched polylactide. Factors that influenced the polymerization such as the polymerization time and the temperature as well as the monomer concentration were discussed in detail in this paper.

Computer simulation of Zn(II) speciation and effect of Gd(III) on Zn(II) speciation in human blood plasma

The speciation and distribution of Zn(II) and the effect of Gd(III) on Zn(II) speciation in human blood plasma were studied by computer simulation. The results show that, in normal blood plasma, the most predominant species of Zn(II) are [Zn(HSA)] (58.2%), [Zn(IgG)](20.1%), [Zn(Tf)] (10.4%), ternary complexes of [Zn(Cit)(Cys)] (6.6%) and of [Zn(Cys)(His)H] (1.6%), and the binary complex of [Zn(CYS)(2)H] (1.2%). When zinc is deficient, the distribution of Zn(II) species is similar to that in normal blood plasma. Then, the distribution changes with increasing zinc(II) total concentration. Overloading Zn(II) is initially mainly bound to human serum albumin (HSA). As the available amount of HSA is exceeded, phosphate metal and carbonate metal species are established. Gd(III) entering human blood plasma predominantly competes for phosphate and carbonate to form precipitate species. However, Zn(II) complexes with phosphate and carbonate are negligible in normal blood plasma, so Gd(III) only have a little effect on zinc(II) species in human blood plasma at a concentration above 1.0x10(-4) M.

Synthesis of iminophosphine and phosphinoiminol cyclometallated Pt (II) and Pt (IV) chloro complexes and studies into their biological and photophysical properties

This thesis focuses on the synthesis and analysis of novel chloride based platinum complexes derived from iminophosphine and phosphinoamide ligands, along with studies on their reactivity towards substitution and oxidation reactions. Also explored here are the potential applications of these complexes for biological and luminescent purposes. Chapter one provides an extensive overview of platinum coordination chemistry with examples of various mixed donor ligands along with the history of platinum anticancer therapy. It also looks at metals in medicine, both for biological functions as well as for therapeutic purposes and gives a background to some other applications for platinum complexes. Chapter two outlines the design and synthetic strategies employed for the development of novel platinum (II) chloride complexes from iminophosphine and phosphinoamide ligands. Also reported is the cyclometallation of these complexes to form stable tridentate mixed donor platinum (II) compounds. In Chapter three the development of a direct method for displacing a chloride from a platinum metal centre with a desired phosphine is reported. Numerous methods for successful oxidation of the platinum (II) complexes will also be explored, leading to novel platinum (IV) complexes being reported here also. The importance of stabilisation of the displaced anion, chloride, by the solvent system will also be discussed in this chapter. Chapter four investigates the reactivity of the platinum (II) complexes towards two different biomolecules to form novel platinum bio-adducts. The potential application of the platinum (II) cyclometallates as chemotherapeutics will also be explored here using in-vitro cancer cell testing. Finally, luminescence studies are also reported here for the ligands and platinum complexes reported in chapter two and three to investigate potential applications in this field also. Chapter five provides a final conclusion and an overall summary of the entire project as well as identifying key areas for future work.

pKa values of aqua ligands of platinum (II) anticancer complexes: [1H, 15N] and 195Pt NMR Studies of cis- and trans- [PtCl2 (NH3) (Cyclohexylamine)]

Syntheses and NMR studies are reported of two 15N-labelled Pt(II) complexes of anticancer interest: cis-PtCl2(15NH3)(c-C6H1115NH2), a metabolite of the orally-active Pt(IV) complex cis,trans,cis-[PtCl2(acetate)2(c-C6H11NH2)(NH3), and trans-[PtCl2(15NH3)(c-C6H1115NH2), a reduction product of the active Pt(IV) complex trans,trans,trans-[PtCl2(OH)2(c-C6H11NH2). For cis-[PtCl2(15NH3)(c-C6H1115NH2), hydrolysis was faster for the chloride ligand trans to cyclohexylamine, and the pKa values determined by [1H, 15N NMR spectroscopy for the two cis monoaqua isomers were the same (6.73). The trans monoaqua complex was a stronger acid with pKa of 5.4 (determined by 195Pt NMR). For the cis diaqua complex, pKa values of 5.68 and 7.68 were determined.

The isolation and purification of tris-2,2'-bipyridine complexes of ruthenium(II) containing unsymmetrical ligands

Monomeric ruthenium(II) complexes [Ru(L)3]2+ containing unsymmetric bipyridine ligands [Where L = 5-methyl-2,2'-bipyridine (L1), 5-ethyl-2,2'-bipyridine (L2), 5-propyl-2,2'-bipyridine (L3), 5-(2-methylpropyl)-2,2'-bipyridine (L4), 5-(2,2-dimethylpropyl)-2,2'-bipyridine (L5) and 5-(carbomethoxy)-2,2'-bipyridine (L6)] have been studied and the meridional and facial isomers isolated by the use of cation-exchange column chromatography (SP Sephadex C-25) eluting with either sodium toluene-4-sulfonate or sodium hexanoate. The relative yield of the facial isomer was found to decrease with increasing steric bulk, preventing the isolation of fac-[Ru(L5)3]2+. The two isomeric forms were characterized by 1H NMR, with the complexes [Ru(L1-3)3]2+ demonstrating an unusually large coupling between the H6 and H4 protons. Crystals suitable for X-ray structural analysis of [Ru(L1)3]2+ were obtained as a mixture of the meridional and facial isomers, indicating that separation of this isomeric mixture could not be achieved by fractional crystallisation. The optical isomers of the complex [Ru(L3)3]2+ were chromatographically separated on SP Sephadex C-25 relying upon the inherent chirality of the support. It is apparent that chiral interactions can inhibit geometric isomer separation using this technique.

A modular approach to luminescent dinuclear ruthenium(II) and rhenium(I) complexes

A series of dinuclear (bipyridine)tricarbonylrhenium(I) and tris(bipyridine)ruthenium(II) complexes have been isolated and characterised, bridged by a flexible diamido ethylene glycol chain. A new stepwise synthetic pathway has been investigated to heterometallic complexes, with the rhenium(I) complexes exhibiting an unusual configuration and inequivalence of the metal centres potentially arising from a surprising hydrogen-bonding interaction between an Re–CO group and an amide proton in low-polarity solvents. This interaction appears to be broken by competing hydrogen-bonding species such as dihydrogen phosphate. This effect was not observed in the corresponding ruthenium(II) complexes, which showed very little interaction with anions. The photophysical characterisation shows that the inclusion of two ester/amide groups to the rhenium centre effectively quenches the fluorescence at room temperature. The ruthenium(II) complexes have considerably stronger fluorescence than the rhenium species, and are less affected by theinclusion of ester and amide groups to the 2,2'-bipyridine chelating group.

Polynuclear metal complexes obtained from the task-specific ionic liquid betainium bistriflimide

The task-specific ionic liquid betainium bis(trifluoromethylsulfonyl)imide, [Hbet][Tf2N], was used to dissolve metal oxides and hydroxides. The crystal structures of the resulting metal betaine bistriflimide complexes exhibit a rich structural variety. A trimeric structure was found for the cobalt(II) compound, [Co-3(bet)(8)(Hbet)(2)(H2O)(2)][Tf2N](9)[Hbet], a tetrameric structure for the manganese(II) and zinc(II) compound, [Mn-4(bet)(10)(H2O)(4)][Tf2N](8) and [Zn-4(bet)(10)(H2O)(2)][Tf2N](8), respectively, a pentameric structure for the nickel(II) compound, [Ni-5(bet)(12)(H2O)(6)][Tf2N](10), an oxo-hydroxo-cluster formation for the lead(II) compound, [(Pb4O)Pb(OH)(bet)(8)(Tf2N)3] [Tf2N](4)center dot MeOH, and a polymeric structure for the silver(I) compound, [Ag-2(bet)(2)(Tf2N)Ag-2(bet)(2)][Tf2N](3). The zwitterionic nature of the betaine ligand and the weakly coordinating ability of the bis(trifluoromethylsulfonyl)imide [Tf2N]- anion facilitates the incorporation of metal ions into oligonuclear and polynuclear metal complexes.

The comparison of fac and mer ruthenium(II) trischelate complexes in anion binding

The synthesis of three new homoleptic trischelate ruthenium( II) complexes bearing new 2,2'-bipyridine ligands, 5,5'-dibenzylamido-2,2'-bipyridine (L1) and 5-benzylamido-2,2'- bipyridine (L2) has been achieved. In the case of [Ru(L2)(3)](2+), the mer and fac isomers have been separated. H-1 NMR spectroscopic anion binding studies indicate that the two C-3-symmetric pockets provided by [ Ru(L1)(3)](2+) is conducive to receive a range of anions, although this is not readily reflected in the photophysical behaviour. The fac-isomer of [Ru(L2)(3)](2+) does appear to have an enhancement in the binding interactions over the mer form with dihydrogenphosphate salts, although the difference is much less marked with the spherical chloride ions. From X-ray crystallographic evidence, the ability to hold water in the "anion" binding cleft can inhibit the strength of the interactions with anions, giving rise to the observed selectivity for directional oxoanions such as dihydrogen phosphate.

Mandelohydroxamic acid as ligand for copper(II) 15-metallacrown-5 lanthanide(III) and copper(II) 15-metallacrown-5 uranyl complexes

The formation of pentanuclear copper(ii) complexes with the mandelohydroxamic ligand was studied in solution by electrospray ionization mass spectrometry (ESI-MS), absorption spectrophotometry, circular dichroism and H-1 NMR spectroscopy. The presence of lanthanide(iii) or uranyl ions is essential for the self-assembly of the 15-metallacrown-5 compounds. The negative mode ESI-MS spectra of solutions containing copper(II), mandelohydroxamic acid and lanthanide(iii) ions (Ln = La, Ce, Nd, Eu, Gd, Dy, Er, Tm, Lu, Y) or uranyl in the ratio 5:5:1 showed only the peaks that could be unambiguously assigned to the following intact molecular ions: {Ln(NO3)(2)[15-MCuIIN(MHA)-5](2-)}(-) and {Ln(NO3)[15-MCCuIIN(MHA)-5](3-)}(-), where MHA represents doubly deprotonated mandelohydroxamic acid. The NMR spectra of the pentanuclear species revealed only one set of peaks indicating a fivefold symmetry of the complex. The pentanuclear complexes synthesized with the enantiomerically pure R- or S-forms of mandelohydroxamic acid ligand, showed circular dichroism spectra which were mirror images of each other. The pentanuclear complex made from the racemic form of the ligand showed no signals in the CD spectrum. The UV/ Vis titration experiments revealed that the order in which the metal salts are added to the solution of the mandelohydroxamic acid ligand is crucial for the formation of metallacrown complexes. The addition of copper(ii) to the solutions containing mandelohydroxamic acid and neodymium(iii) in a 5:1 ratio lead to the formation of a pentanuclear complex in solution. In contrary, titration of lanthanide(iii) salt to the solution containing copper(ii) and mandelohydroxamic acid did not show any evidence for the formation of pentanuclear species. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Asymmetric Carbon-Carbon Bond Forming Reactions Catalysed by Metal(II) Bis(oxazoline) Complexes Immobilized using Supported Ionic Liquids

A series of bis(oxazoline) metal(II) complexes has been supported on silica and carbon supports by non-covalent immobilisation using an ionic liquid. The catalytic performance of these solids was compared for the enantioselective Diels-Alder reaction between N-acryloyloxazolidinone and cyclopentadiene and the Mukaiyama-aldol reaction between methyl pyruvate and 1-methoxy-1-trimethylsilyloxy-propene. In both reactions the enantioselectivity was strongly influenced by the choice of support displaying enantioselectivies (ee values) up to 40% higher than those conducted under homogeneous reaction conditions.

Alkynyl-Bridged Ruthenium(II) 4 '-Diferroceny1-2,2 ':6 ',2 ''-terpyridine Electron Transfer Complexes: Synthesis, Structures, and Electrochemical and Spectroscopic Studiese

The novel ligand 4'-diferrocenylallcyne-2,2':6',2 ''-terpyridine (7; Fc-C C-Fc-tpy; tpy = terpyridyl; Fc = ferrocenyl) and its Ru2+ complexes 8-10 have been synthesized and characterized by single-crystal X-ray diffraction, cyclic voltammetry, and UV-vis and luminescence spectroscopy. Electrochemical data and UV absorption and emission spectra indicate that the insertion of an ethynyl group causes delocalization of electrons in the extended pi* orbitals. Cyclic voltammetric measurements of 7 show two successive reversible one-electron-oxidation processes with half-wave potentials of 0.53 and 0.78 V. The small variations of the E-1/2 values for the Fe2+/Fe3+ redox couples after the coordination of the Ru2+ ion suggest a weak interaction between the Ru2+ and Fe2+ centers. After insertion of an ethynyl group, UV-vis absorption spectra show a red shift of the absorption peak of the (1)[(d(pi)(Fe))(6)]->(1)[(d(pi)(Fe))(5)(pi*(Ru)(tpy))(1)] MMLCT of the Ru2+ complexes. The Ru2+ complex 8 exhibits the strongest luminescence intensity (lambda(em)(max) 712 nm, Phi(em) = 2.63 x 10(-4), tau = 323 ns) relative to analogous ferrocene-based terpyridine Ru(II) complexes in H2O/CH3CN (4/1 v/v) solution.

Ruthenium(II) bis(terpyridine) electron transfer complexes with alkynyl-ferrocenyl bridges: synthesis, structures, and electrochemical and spectroscopic studies

Two novel alkynyl-bridged symmetric bis-tridentate ligands 1,2-bis(1'-[4'-(2,2':6', 2 ''-terpyridinyl)]-ferrocenyl)ethyne (3a; tpy-Fc-C C-Fc-tpy; Fc = ferrocenyl; tpy = terpyridyl) and 1,4-bis(1'-[4'-(2,2':6', 2 ''-terpyridinyl)]ferrocenyl)-1,3-butadiyne (3b; tpy-Fc-C C-C C-Fc-tpy) and their Ru2+ complexes 6a and 6b have been synthesized and characterized by cyclic voltammetry, UV-vis and luminescence spectroscopy, and in the case of 3b by single-crystal X-ray diffraction. Cyclic voltammograms of both compounds, 3a and 3b, display two severely overlapping ferrocene-based oxidative peaks with only one reductive peak. The redox behavior of 6a and 6b is dominated by the Ru2+/Ru3+ redox couple (E-1/2 from 1.33 to 1.34 V), the Fe2+/Fe3+ redox couples (E-1/2 from 0.46 to 0.80 V), and the tpy/tpy(-)/tpy(2-)redox couples (E-1/2 from -1.19 to -1.48 V). The UV-vis spectra of 6a and 6b show absorption bands assigned to the (1)[(d(pi)(Fe))(6)] -> (1)[(d(pi)(Fe))(5)(pi*(Ru)(tpy))(1)] MMLCT transition at similar to 555 nm. Complexes 6a and 6b are luminescent in H2O-CH3CN (4 : 1, v/v) solution at room temperature, and 6b exhibits the strongest luminescence intensity (lambda(em)(max): 710 nm, Phi(em): 2.28 x 10(-4), tau: 358 ns) relative to analogous ferrocene-based bis(terpyridine) Ru(II) complexes reported so far.

N,O-Ligated Pd(II) Complexes for Catalytic Alcohol Oxidation

N,O-ligated Pd(II) complexes show considerable promise for the oxidation of challenging secondary aliphatic alcohols. The crystal structures of the highly active complexes containing the 8-hydroxyquinoline-2-carboxylic acid (HCA) and 8-hydroxyquinoline-2-sulfonic acid (HSA) ligands have been obtained. The (HSA)Pd(OAc)2 system can effectively oxidise a range of secondary alcohols, including unactivated alcohols, within 4–6 h using loadings of 0.5 mol%, while lower loadings (0.2 mol%) can be employed with extended reaction times. The influence of reaction conditions on catalyst degradation was also examined in these studies.

Ruthenium(II)-trithiacyclononane complexes as potential antitumourals

Os únicos complexos metálicos presentemente utilizados em quimioterapia compreendem exclusivamente compostos de platina, com as desvantagens de apresentarem um leque de acção restrito e de provocarem sérios efeitos secundários. Na constante procura por novos fármacos antineoplásicos metálicos, os complexos de ruténio têm sido apresentados como uma alternativa adequada e existem já dois complexos de Ru(III) em ensaios clínicos. Estes são descritos como pró-fármacos, postulando-se que o seu mecanismo de acção envolva redução in vivo para originar complexos de Ru(II) activos. Assim, o actual desenvolvimento de fármacos antitumorais baseados em ruténio passará por criar novos complexos de Ru(II). O trabalho aqui descrito enquadra-se neste objectivo, tendo sido sintetizados complexos de ruténio(II)-tritiaciclononano com ligandos biologicamente activos, e avaliada a sua actividade antitumoral in vitro. Os ligandos utilizados compreendem um hidroxifenilpirazole, aminoácidos e derivados, flavonóides e quinonas. No primeiro capítulo do trabalho são apresentados os actuais desafios no desenvolvimento de complexos metálicos para quimioterapia e é ilustrada a importância dos complexos de Ru(II) aqui descritos no panorama actual de investigação. No capítulo dois, é apresentada uma descrição pormenorizada dos procedimentos experimentais, materiais e equipamentos utilizados na síntese, caracterização e ensaios biológicos. O capítulo três é dividido em duas sub-secções, a primeira analisando os resultados das sínteses e a caracterização estrutural dos complexos, e a segunda apresentando os resultados da sua actividade antiproliferativa. Foram obtidos onze novos complexos de ruténio(II)-tritiaciclononano, com rendimentos razoáveis. São apresentadas propostas das suas estruturas moleculares, sendo que estas mostram uma variedade interessante de modos de coordenação de acordo com os diferentes ligandos, ou seja, N, N,O, O,O e O. A actividade antiproliferativa dos complexos e dos respectivos ligandos foi avaliada em quatro linhas celulares tumorais, representativas de três tipos de cancro: osso (MG-63), próstata (PC-3) e mama (MCF-7 e MDA-MB-231). Quatro dos novos complexos demonstraram uma actividade antiproliferativa promissora, ou seja, aqueles que apresentam um hidroxifenilpirazole, a 3,7-dihidroxiflavona, a plumbagina ou a juglona na sua esfera de coordenação. Entre estes resultados, destacam-se os valores de IC50 para a linha celular MDA-MB-231 por se apresentarem inferiores ao apresentado pelo complexo de Ru(II)-tritiaciclononano mais activo descrito na literatura.

Spectroscopie électronique de complexes du nickel(II), de lor(I), du ruthénium(II) et de certains lanthanides : caractéristiques inhabituelles de leur structure électronique

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal