The aims of this work were first to synthesize and fully characterize compounds that may function as bleomycin analogues and, second, to test their anticancer activity in vitro. Three novel tetradentate O,N,N,O Schiff base ligands, H₃L¹, H₂L³ and H₂L³ were synthesized by condensation of three different 1,3-diaminoalkane bridging units with two equivalents of (2,4-dihydroxy–phenyl)-(phenyl)methanone. These ligands contain two neutral imine nitrogen donors and two anionic phenolate oxygen donors for the coordination of metal ions. The choice of ligand was guided by the fact that Cu(II) bleomycin analogues with ligands employing O,N,N,O donor atom sets are able to cleave double-stranded DNA via oxygen radical formation. Using these ligands, six novel metal complexes of copper(II), nickel(II) and zinc(II) were synthesized and fully characterised. Two novel ligand crystal structures and six novel metal complex crystal structures are reported in this work. The X-ray structures of the two structurally characterized nickel(II) complexes [Ni(L²)] and [Ni(L³)] adopted the same nominally square planar coordination geometry, with the metal ion bound by the pairs of imine nitrogen and ortho-phenolic oxygen atoms of the ligand’s tetradentate donor atom set. The Ni–N and Ni–O distances averaged 1.892(3) Å and 1.845(2) Å, respectively. However, when reacted with Cu(II) and Zn(II), the ligands favored the formation of multinuclear complexes as a result of metal ion bridging by ionized oxygen donor atoms (either the phenolic oxygen atoms or an alkoxide oxygen atom of the 2-hydroxy substituted alkane bridge in the case of H₃L¹) of the polyfunctional ligands. For the di- and trinuclear copper(II) complexes, the mean Cu–N and Cu–O distances averaged 1.953(3) Å and 2.082(3) Å, respectively. For the dinuclear zinc(II) complex, the mean Zn–N and Zn–O distances averaged 2.074(3) Å and 2.042(3) Å, respectively. Electron spin resonance (ESR) measurements on the paramagnetic trinuclear copper(II) complexes confirmed that the trinuclear solid state structures remain intact in fluid solution (DMF) and that two of the three copper(II) ions are antiferromagnetically coupled, leaving the third as an S = ½ center with a hyperfine coupling constant to the I = 3/2 Cu nucleus of 14.80 G. Super-hyperfine coupling (15.13 G) to two N atoms was also evident, consistent with one of the terminal copper(II) centers (O,N,N,O donor atom set) being the site of the unpaired spin density in the molecule. Density functional theory (DFT) simulations were used to determine the electronic structures of the diamagnetic mononuclear nickel(II) complexes. The simulations reproduced the structures of [Ni(L²)] and [Ni(L³)] accurately with similarity coefficients for the two complexes of 0.982 and 0.990, respectively. The simulated electronic spectra (TD-DFT) of the nickel(II) complexes showed reasonably good agreement with the experimental spectra and were useful for the assignment of the low-lying MLCT state (near 400 nm) for the complexes as well as the higher-lying π-π* transitions between 300–350 nm. All of the metal complexes and one ligand were sent to MINTEK¹ (Project AuTEK) for anticancer screening. The copper(II) complexes (bleomycin analogues capable of generating hydroxyl radicals in vivo) showed significant cytotoxicity against the human cancer cell lines A549, DU145, HT-29, and U21. The trinuclear complexes were the most cytotoxic with mean IC₅₀ values of 6(2) and 7(1) μM for [Cu₃(L²)₂Cl₂(DMF)₂] and [Cu₃(L³)₂(H₂O)₂]Cl₂, respectively. The nickel(II) complexes [Ni(L²)] and [Ni(L³)] were comparatively inactive with mean IC₅₀ values of >50 and 35(16) μM, respectively, consistent with the fact that they do not readily generate reactive oxygen species in a cellular environment. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2013.

A series of oxovanadium(IV) complexes of Schiff bases derived from substituted salicylaldehyde and aminoalcohols has been prepared and characterized. The Schiff bases coordinate through 0, N, and 0 as tridentate bivalent ligands. The primary purpose of the investigation is to describe the structure and bonding in these complexes. The subnormal magnetic properties of the complexes provide much information about both the structure and the bonding in the complexes.

No description available.

The principal goal of this work was to synthesise and fully characterise a range of platinum group metal chelates of bis(pyridine-imine) ligands. These four-nitrogen donor Schiff base ligands are underdeveloped relative to their salen (ONNO donor) counterparts. The purified metal complexes were to be tested for their cytotoxicity against cancer cell lines and their mode of interaction (expected to be intercalation) studied. The syntheses, spectroscopic and structural properties of some novel and some already known bis(pyridine-imine) ligands are described. Furthermore, UV-Vis, IR and NMR spectroscopy, as well as electrospray ionisation mass spectrometry, have been used to characterize the ligands and comparisons were made with relevant literature. Fifteen Schiff base ligands were successfully condensed from a 2-formyl or 2-ketopyridine starting material and a diamine bridging group, while the attempted syntheses of a further three are described. Literature methods or variations thereof were employed in the syntheses of these derivatives, which generally resulted in good yields. X-ray quality crystals were obtained and X-ray structures were determined for four novel ligands and five unexpected cyclised hexahydropyrimidine- and imidazole-containing bidentate ligands, of which three were novel structures. The series of bicationic palladium and platinum complexes synthesised here were analysed by NMR, IR and UV-Vis techniques, as well as X-ray crystallography when possible. The complexes were prepared by reacting the free ligands with platinum group metal salts in refluxing acetonitrile. The complexes exhibit infrared bands for the imine C=N stretch between 1604–1670 cm-1; around 15–40 cm-1 lower than the free ligands. The 1H NMR spectra in the CH=N chemical shift region also display shifts (0.1 to 0.8 ppm for the palladium complexes or 0.4 to 0.9 ppm for the platinum complexes) which are consistent with metallation. X-ray crystal structures were obtained for eight novel metal complexes, which all crystallised in the monoclinic crystal system. The solid state analysis shows changes in the free ligands upon introduction of the metal ions, caused by the coordination process. Metallation of the free ligands led to twisting of the ligands due to size effects and the spatial restrictions of the coordination geometry of the central metal ions. The structures were generally solved by direct methods and refined to R1 = 0.0729 or less. Singlecrystal X-ray diffraction analysis confirmed that the mononuclear complexes exhibit a distorted square planar coordination sphere composed of the four donor nitrogen atoms (two imine and two pyridyl nitrogen atoms) from the Schiff base ligands. The complexes were generally very stable and differed by the type of metal ion (platinum(II) or palladium(II)) and the diamine bridging group (2-carbon or 3-carbon linking chain with various substituted groups). A range of unconventional F···H−C contacts is revealed to play an important role in the overall bonding and crystal packing of many complexes. To better understand our measured data and to separate the intrinsic properties of our molecules from intermolecular interactions, theoretical calculations at the DFT (B3LYP) level were carried out. These calculations predict the structural and spectroscopic properties for the free ligands and their metallated counterparts. DFT simulations were performed for the fifteen synthesised ligands (B3LYP functional, 6-31G** basis set), as well as three projected ligands that could not be synthesised, and for all proposed thirtysix metal complexes (B3LYP functional, SDD basis set). DFT simulations were used to obtain theoretical IR frequency data which was compared to the literature and used to prove the location of a local minimum energy structure in the geometry optimisation rather than a transition state. Our results collectively showed the B3LYP level of theory to be useful in the prediction of IR frequencies for these Schiff base ligands as well as the platinum(II) and palladium(II) complexes. Geometry optimisations performed using density functional theory for the free ligands and metal complexes were compared, where possible, with X-ray data. For the free ligands the main structural differences were observed for the position of the pyridyl-imine "arms" of the ligands with relatively good agreement between the two structures for the bridging groups. On the other hand, the metal complexes showed greater discrepancies for the bridging groups rather than for the pyridine rings. These differences were also affected by the length of the carbon bridge; the longer the carbon bridge, the less variation was observed. The trends in the variation of bond distances and angles with the metal ion identity and ligand structure delineated by DFT simulations were matched by similar trends in the X-ray data. Differences between the gas phase calculated geometries and those determined by Xray diffraction were attributed to packing effects in the solid state and intermolecular interactions not being accounted for during DFT computations. The impressive similarity observed between the structures obtained from X-ray crystallography and computed by DFT shows the applicability of these computations at the B3LYP level of theory. They were able to accurately predict structural and spectroscopic properties for the ligands and complexes presented in this work. The in vitro cytotoxicities of some of the metal complexes were evaluated against two mouse cancer cell lines. The compounds tested had lower than expected cytotoxicity towards the cell lines studied with IC50 values > 100 μM. The interaction of the complexes with calf thymus DNA has been explored by using absorption studies. From the observed changes in absorption possible modes of binding to DNA have been proposed for the metal complexes. Significant changes were observed in the absorption spectra upon interaction of the complexes with DNA, from which large binding constants were determined. The changes were, however, not as intense as expected nor were the spectral variations typical of intercalating drugs. There were also no bathochromic shifts nor any isobestic points observed for most of the metal complexes, except one. For the cationic PGM chelates studied, the lack of shift in the wavelength of the visible range MLCT band maximum and small changes in the band intensity were more indicative of weak electrostatic interactions. Our spectral data were thus interpreted as being consistent with non-intercalative binding; either simple electrostatic adduct formation or major/minor groove binding. The binding constant values (Kb) of the metal complexes estimated from the titration with calf thymus DNA monitored by absorption spectroscopy were all in the range of 105 M-1. This is within the range of those reported for other platinum(II) and palladium(II) metal complexes that have shown intercalation and/or groove binding. With the lack of inhibition of growth of the selected cancer cell lines it is possible that the compounds do not reach nuclear DNA in living cells or that such compounds are possibly substrates for efflux transporters. All the metal complexes in this work were determined to not be pure DNA intercalators as had been expected; however, in some cases partial intercalation cannot be ruled out from the spectral data. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.

Thesis (Ph. D.)--University of Hong Kong, 1999. / Includes bibliographical references.

Thesis (Ph. D.)--Auburn University. / Abstract. Vita. Includes bibliographical references (p. 116-125).

Several Schiff base ligands, N, N‟-(aryl)benzyaldiimine ligands (R-BEN); N, N‟-(aryl)benzyaldiamine dihydrochloride ligands (R-BENH•2HCl); N, N‟-(aryl)benzyaldiamine ligands (R-BENH); N, N‟-bis(cinnamaldiimine) ligands (R-CA2EN) were synthesized for the investigation of the electronic effect of the substituents at para-position of the Schiff base ligands and their copper complexes. The synthesis of Schiff bases was carried out by reacting a series of para-substituted benzyaldehyde, and para-substituted cinnamaldehyde with ethylenediamine. The imine group of Schiff bases, N, N‟-(aryl)benzyaldiimine ligands and N, N‟-bis(cinnamaldiimine)ligands were reduced to corresponding amines with sodium borohydride in methanol These ligands, N, N‟-(aryl)benzyaldiamine ligands (H-BENH), N, N‟-bis(cinnamaldiimine)ligands (CA2EN) were reacted with copper(II) dihalide and copper(I) monohalide ions respectively to form complexes. The ligands and their complexes were analysed using elemental analyses, FT-IR spectroscopy (mid-IR), UV/vis in aprotic and protic solvents,while mass spectrometry, 1H-NMR and 13C-NMR were used to further analyse the ligands. By using substituent parameters, both the single and dual substituent parameters with the spectroscopic data obtained from the spectroscopic techiques mentioned above, it was hoped to monitor and determine whether the electronic effects (resonance or inductive effcets) was predominantly within the Schiff base ligands and copper complexes. The NMR studies with dual substituent parameters suggest that the effects of the substituents are transimitted through the ligands, via resonance effects and that the phenyl group is nonplanar with the azomethine in N, N‟-(aryl)benzyaldiimine ligands. The presence of an extra double bond in Schiff base {(N, N‟-bis(cinnamaldiimine) ligand)} altered the electron density. The UV/vis studies showed that the symmetry of the N, N‟-bis(4-R-benzyl)-1, 2-diaminoethanedihalidecopper(II) complexes were predominantly tetrahedral for both chloro and bromo complexes. The correlation studies from mid-infrared were beneficial in monitoring the effect experienced by N, N‟-(aryl)benzaldiimine ligands, the studies suggest that the inductive effect is more pronounced at the C=N.

No description available.

No description available.

Polystyrene bis(salicylaldehyde)-propylene-1,3-diiminato Cobalt (II) (salen) and Polystyrene bis(acetylacetone)-propylene-1,3-diiminato Cobalt (II) (BAE) were prepared stepwise from polystyrl chloride. The reaction series included substitution of the chloride with a malononitrile carbanion, reduction to a diamine, condensation to form a Schiff base, and complexation with Co(II) acetate to form the active polymeric material. Optimum conditions with regard to time, temperature, reaction ratios, and solvent were determined for each reaction. The ability of the polymer bound cobalt complex to oxidize 3-methyl indole was measure. The BAE catalyst yielded a large amount of the corresponding o-formylaminoacetophenone. However, the exact yield is not known because product could not be separated from the indole. The salen catalyst showed starting material with a small indication of product.