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Item Synthesis of [alpha]-farnesene autoxidation products and cross-conjugated polyenes : presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University(Massey University, 2000) Fielder, Simon3-Sulfolenes (2,5-dihydrothiophene-1,1-dioxides) are well known as diene equivalents which are readily unmasked by the cheleotropic elimination of sulfur dioxide under thermal conditions. This chemistry has been used in the synthesis of conjugated triene autoxidation products of α-farnesene and previously unknown cross-conjugated polyene hydrocarbons. α-Farnesene (3,7,11-trimethyldodeca-1,3E,6E,10-tetraene) is a sesquiterpene found in the surface coating of apples. The in vivo autoxidation of α-farnesene is believed to cause superficial scald, a serious post harvest disorder of the fruit. The principal α-farnesene autoxidation product, "Anet's Trienol" (1.8a), was prepared in five steps from geraniol. The isomeric 3Z-trienol (1.8b) was also observed as a minor component (ca. 5%). Key steps involved the use of TMEDA to effect the regioselective alkylation of 3-methyl-3-sulfolene and the cheleotropic elimination of sulfur dioxide from the resultant 2,3-disubstituted-3-sulfolene. The acid catalysed hydroperoxidation of "Anet's Trienol" was achieved with anhydrous hydrogen peroxide in THF and gave the conjugated trienyl hydroperoxide (1.7a) as a single regioisomer in good yield (47%) together with traces of the stereoisomeric 3Z-trienyl hydroperoxide (1.7b) (ca. 4%). The trienyl hydroperoxides (1.7a) and (1.7b) (96:4) were cyclised efficiently under an oxygen atmosphere in the presence of "samarium peroxide" to afforded a diastereoisomeric mixture (ca. 1:1.2) of endoperoxy hydroperoxides (1.11a) and (1.11b) (85:15). Selective reduction of the hydroperoxides (1.11a) and (1.11b) gave the corresponding endoperoxy alcohols (1.12a) and (1.12b) (85:15) again as a mixture of diastereoisomers (ca. 1:1.2). Alternative syntheses of these α-farnesene autoxidation products were investigated. Three regioisomeric allylic alcohols (2.1), (2.2) and (2.3a) were prepared from geranial and, when exposed to water or anhydrous hydrogen peroxide in the presence of an acid catalyst, underwent highly regioselective oxygen transposition reactions to give "Anet's Trienol" (1.8) and the corresponding trienyl hydroperoxide (1.7) respectively as mixtures of stereoisomers. The secondary allylic alcohol (2.1) gave only the 3E-isomeric trienes (1.7a) and (1.8a), while the tertiary alcohol (2.2) and primary alcohol (2.3a) gave mixtures of the isomeric 3E and 3Z-trienes (1.7a)/ (1.7b) and (1.8a)/ (1.8b) dependant upon on the regiochemistry of the allylic alcohol starting material. E/Z isomeric ratios of transposition products indicated that intermediate carbocations did not interconvert under the reaction conditions. An analogous radical mechanism has been presented to explain the formation of minor 3Z-trienyl species formed under conditions consistent with the generation of farnesene peroxy radicals. The Stille cross-coupling of simple iodinated and stannylated sulfolene derivatives was investigated as a route to bis-sulfolenes. 3-Iodo-3-sulfolene (3.37), prepared in 4 steps from 3-sulfolene, was coupled with 3-tributylstannyl-3-sulfolene (3.33) to give the bis-3-sulfolene (3.26) in excellent yield (95%). This constitutes the first synthesis of a bis-sulfolene. Molecules of this type represent masked cross-conjugated polyenes ([n]-dendralenes). In an effort to access the higher, unknown [n]-dendralenes, the Stille cross-coupling of 3-iodo-3-sulfolene (3.37) with a variety of mono- and bis-stannanes was investigated and bis-sulfolene precursors to [4]-, [5]-, [6]- and [8]-dendralene were prepared. The utility of 3-iodo-3-sulfolene (3.37) as a coupling partner in the Stille reaction was briefly investigated and a range of other, novel cross-conjugated polyene precursors were prepared. The carbonylative Stille cross-coupling of 3-iodo-3-sulfolene (3.37) was also achieved. 3,4-Diiodo-3-sulfolene (4.15) was prepared in four steps from 2-butyne-1,4-diol and coupling with 3-tributylstannyl-3-sulfolene (3.33) yielded the first example of a tris-3-sulfolene (4.13) in 43% yield. Capillary pyrolysis (CP) was developed as a practical alternative to flash vacuum pyrolysis and proved a valuable technique for the cheleotropic elimination of sulfur dioxide from the cross-conjugated polyene precursors prepared by the Stille coupling of iodo-3-sulfolenes. Using CP, [3]-, [4]-, [5]-, [6]- and [8]-dendralene were prepared (52-89%) and their spectral characterisation was achieved. This constitutes the first general strategy for the synthesis of this poorly represented class of fundamental hydrocarbons. The synthesis of other novel cross-conjugated polyenes was achieved using CP and further demonstrated the value of this technique. The diene-transmissive Diels-Alder reaction of the [n]-dendralenes with 4-phenyl-1,2,4- triazoline-3,5-dione (PTAD) was investigated briefly and evidence for the occurrence of the theoretical maximum number of diene-transmissive Diels-Alder reactions, viz. [n-1] was obtained.Item [Pi]-loaded rhenium complexes : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University, Palmerston North, New Zealand(Massey University, 2000) Steedman, AndrewA range of rhenium(VII) tris(imido) complexes, XRe(NR)3 (X=Me3SiO, R=Ar'; X=Cl, R=Ar', mes, Ar), have been synthesized either from [ReO4]-, RNH2 (R=Ar', mes, Ar), Et3N and Me3SiCl or Re(NR)2Cl3(py), RNH2 (R=Ar', Ar) and Et3N. An X-ray crystal structure of Me3SiORe(NAr')3 and ClRe(NAr)3 showed a slightly bent Re-N-C angle (158.8(5)° and 168.8(7)° respectively) and short Re-N distances (1.749(6)Å and 1.758(7)Å). Mixed tris(imido) complexes, ClRe(NR)2(NR') (R=Ar, R'=Ar, p-tol; R=Ar, R'=Ar, p-FC6H4, p-NO2C6H4, p-tol, AMP, o-ClC6H4, m-ClC6H4, o-tBuC6H4) have been synthesized from Re(NR)2Cl3(py) (R=Ar', Ar), R'NH2 (R'= Ar, p-tol, Ar', p-FC6H4, p-NO2C6H4, AMP, o-ClC6H4, m-ClC6H4, o-tBuC6H4) and Et3N. An X-ray crystal structure of ClRe(NAr)2(NAr') showed near linear Re-N-C angles (165(2)-172.5(19)°) and short Re-N distances (1.70(2)-1.766(19)Å). The crystal structure of ClRe(NAr)2(N-o-tBu) showed 2 near linear Re-N-Ar angles (172.4(2)° and 171.2(2)°) and one bent Re-N-o-tBu angle (160.8(2)°). Intermolecular imido ligand exchange was shown to occur slowly at room temperature between NAr' and Nmes. However, exchange between NAr' and NAr required heating to 60°C for exchange to occur. A chiral tetrahedral complex, ClRe(NAr')(NAr)(N-o-tBu), was synthesized from Re(NAr')(NAr)Cl3(py), o-tBuC6H4NH2 and Et3N. Alkyl/aryl derivatives of the mixed tris(imido) complexes, R"Re(NR)2(NR') (R=Ar', Ar, R'-Ar', Ar, R"=Me, p-tol, CH2Ph), have been synthesized from ClRe(NR)2(NR') (R=Ar, R'=Ar'; R=Ar', R'=Ar) and the Grignard, R"MgX (R"=Me, p-tol, X=Br; R"=CH2Ph, X=Cl). An X-ray crystal structure of MeRe(NAr)2(NAr') showed near linear Re-N-C angles (168.5(3)-171.2(3)°) and short Re-N lengths (1.753(4)-1.763(4)Å). The Re-N-Ar' angle was found to be ~ 10° larger than those found for tris(Ar'-imido) Re(VII) tetrahedral complexes. An oxo-bridging species, [Re(NAr)2(p-tol)(µ-O)]2, was isolated presumably from the hydrolysis of p-tolRe(NAr)3. The crystal structure of [Re(NAr)2(p-tol)(µ-O)]2 showed the rhenium atoms to be in a distorted square pyramidal geometry, as indicated by the Re-O bond distances (1.948(2) and 1.985(3)Å). Bis(imido) complexes, Re(NR)(NR')Cl3(py) (R=Ar', R'=Ar', Ar; R=R'=Ar), were synthesized from ClRe(NR)2(NR') (R=Ar', R'=Ar', Ar; R=Ar, R'=Ar', Ar) and pyHCl. An X-ray crystal structure of Re(NAr')2Cl3(py) showed near linear Re-N-C angles (171.8(12) and 174.4(3)°) and short Re-N distances (1.734(18) and 1.760(14)Å). The Cl ligands in the cis positions to the imido ligands are bent away from the imido ligands at an angle of 166.10(19)°. Amido complexes, p-tolNHRe(NR)(NR')(NR"), have been synthesized from ClRe(NR)(NR')(NR") (R=R'=Ar, R"=Ar, o-tBu; R=Ar, R'=Ar', R"=o-tBu) and LiNHp-tol. An X-ray crystal structure of p-tolNHRe(NAr)3 showed a bent Re-NH-C angle (129.6(3)°) typical of amido nitrogens. A range of Re(V) tris(imido) complexes, [Re(NR)2(NR')]- (R=R'=Ar'; R=Ar, R'=Ar', Ar, o-tBu), have been synthesized from XRe(NR)2(NR') (X=Me3SiO, Cl) and elemental sodium. These anions were found to be very sensitive both in solution and as solids. An X-ray crystal structure of [Re(NAr')3]- showed the complex to possess a 2-fold axis of symmetry through one of the imido ligands. The counter ion was found to be Na+ with 6 coordinated molecules of thf. The anions were found to react with ClSnMe3 and ClAuPPh3 to form Re-Sn (Me3SnRe(NAr)2(NR), R=Ar', Ar, o-tBu) and Re-Au (Ph3PAuRe(NR)2(NR'), R=R'=Ar'; R=Ar, R'=Ar', Ar) complexes respectively. The crystal structure of Me3SnRe(NAr)3 and Me3SnRe(NAr)2(NAr') showed near linear Re-N-C angles (170.2(5)-172.9(2)°) and short Re-N distances (1.752(6)-1.779(3)Å). Rhenium(VI) dimeric complexes were synthesized from the anion, [Re(NR)2(NR')]- (R=R'=Ar'; R=Ar, R'=Ar', Ar, o-tBu) and ferrocenium, [Cp2Fe]+. Both Re2(NAr')6 and Re2(NAr)4(NAr')2 contain bridging imido ligands, while Re2(NAr)6 and Re2(NAr)4(N-o-tBu)2 contain only terminal imido ligands, as indicated by proton NMR. An X-ray crystal structure of [Re(NAr')2(µ-NAr')]2 showed slightly bent terminal imido angles (156.2(3) to 168.8(3)°), short Re-N(terminal) distances (1.750(4) to 1.763(3)Å) and typical Re-N(bridging) distances of 1.951-1.959(4)Å. The average Re-Re distance of 2.735(4)Å indicates a weak metal-metal interaction. The crystal structure of Re2(NAr)6 showed the complex adopts an ethane-like geometry with the imido ligands arranged in a staggered orientation. The Re-Re bond lies on a crystallographic S6 axis. A Re(VII) cation, [Re(NAr)3]+, is implicated on the basis of formation of a ferrocene complex, (C5H5)Fe(C5H4)Re(NAr)3.Item Porphyrins for surface modification : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University, Palmerston North, New Zealand(Massey University, 2001) Campbell, Wayne MasonThe controlled synthesis of a variety of benzoic acid porphyrins ranging from monomers to arrays for the modification of TiO2 and GaAs semiconductors, and sulfur functionalised porphyrin monomers for attachment to GaAs and Au surfaces was achieved. A semi-quantitative study of the photosensitisation of TiO2 by the porphyrin acids was carried out. The syntheses of β-styryl linked porphyrin benzoic acids and some meso-substituted benzoic acid porphyrins was successfully carried out employing Wittig chemistry and classical porphyrin-forming condensation reactions with appropriate formyl methyl esters. Hydrolysis of the resulting porphyrin esters provided a facile and reliable acid synthesis, particularly where multi-step reactions were necessary. It was also demonstrated that acid functionality on porphyrins could be generated from aldehydes via esters, even though direct oxidation of the aldehydes to acids could not be achieved. The syntheses of "dipole" and "collinear" diporphyrins were achieved, providing two different porphyrin light harvesting arrays for evaluation on semiconductor surfaces. As a result of the synthesis of a new linear diporphyrin Building Block C, an alternative pathway to the controlled syntheses of mixed-metal and mixed-porphyrin arrays was achieved. This provided an alternative strategy for the controlled placement of three different metals into three different porphyrins of a linear triporphyrin, pentaporphyrin and a larger star-shaped nonaporphyrin. The exploitation of the stepwise controlled synthesis of the triporphyrin systems was expanded to include mixed-porphyrin systems synthesised with a unique tetraester porphyrin phosphonium salt. This phosphonium salt afforded mixed-diporphyrin and mixed-triporphyrin arrays, which were hydrolysed to give "sticky" mixed-diporphyrin and triporphyrin acid arrays. An alternative milder and higher yielding stepwise Wittig method was developed for the synthesis of a star shaped TXP pentaporphyrin. This new method involving milder base conditions gives advantages over the traditional acid catalysed approach developed in these laboratories. It is now possible to build these arrays in a stepwise manner with acid labile metals present in the porphyrin moieties. Access to the controlled synthesis of "sticky" mixed-pentaporphyrin arrays was then achieved using this new methodology. With the synthesis of a variety of unique benzoic acid functionalised porphyrin monomers and multiporphyrin array systems, evaluation of their performance in the dye-sensitised TiO2 Grätzel cell was carried out. The development of a reliable solar cell testing apparatus and procedures required to assess the solar cell performance of these chromophores is presented. None of the conditions employed have been optimised, but insights into the significance of the porphyrin photoelectrochemical cell variables has been obtained. It was determined that the porphyrin acids are better photosensitisers than their salts, and that Zn(II) metalloporphyrins performed best as dyes. The results also suggest that Cu(II) metalloporphyrins are worth pursuing in future where long term stability of the chromophores is required in solar cells. It was also found that adsorption solvent choice, electrolyte composition and dye concentrations are all critical to cell performance, and should all be optimised in future studies. The tetraaryl β-substituted monoporphyrin acids were found to have a significant advantage over the multiporphyrin arrays and other monoporphyrins synthesised and examined in this work. A variety of new disulfide porphyrins and some new 2- and 3-thienylporphyrins were successfully synthesised. A new class of terthiophene-appended porphyrins was also synthesised. Using a combination of Wittig chemistry and classical condensation reactions, β-substituted, and bis- and tetra-meso-porphyrin variants were synthesised and characterised. Both the bis- and tetraterthienylpoprhyrins were isolated as mixtures of atropisomers.Item Synthesis and characterisation of biomaterials for use as markers of health and disease : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University(Massey University, 2001) Desai, Rakesh NatverlalThe bicyclic[4.3.0]nonane ring system is commonly found in many complex bioactive natural products, such as spongians and several novel steroids. Previous examples of ester tethered cycloaddition reactions were limited to activated dienes and dienophiles. The synthesis of a range of precursors, in which an unactivated diene and dienophile were linked via an ester tether is described. Model studies into the synthesis of monocyclic and bicyclic lactones as possible pre requisites for the formation of the C/D rings of the spongian skeleton utilising intramolecular Diels-Alder reaction (IMDA) or alternative cyclisation methods such as free radical catalysed and Heck reaction were carried out with these substrates. However it was discovered that when the carbonyl group of the ester tether was in conjugation with the diene it caused a formidable challenge as none of the applied methods were found to be suitable for the cyclisation reactions. Chapters two to five were focused on attempts to synthesise glucuronides of phytoestrogen metabolites (isoflavones and isoflavans) glucuronide due to their potential interest as anti cancer agents. Also the steroidal hormone estrone glucuronide (for fertility testing) and testosterone glucuronide (for use in clinical laboratories and for drug testing) for the purpose of developing multipurpose home monitor by adapting the platform technology previously developed and used in a point-of-care monitoring device known as the Ovarian Monitor. The synthesis of phytoestrogen glucuronide is a relatively new concept and the literature revealed no successful chemical method to date. The desired phytoestrogen isoflavones required for stereoselective glucuronidation were successfully prepared from precursor deoxybenzoins using a new convenient and facile route. Reduction of the isoflavones to isoflavans was also carried out using standard literature procedures. Various activated and deactivated phenols (including a sterically hindered phenol) were successfully glucuronidated using various synthetic routes as model studies. The information garnered from the model studies was utilised for the glycosylation of isoflavones and isoflavan but numerous attempts to obtained the glucuronides by using direct methods failed. Even more reactive glycosyl donors such as the sulfoxide sugar and acetimidate sugar also failed to effect glycosylation of these phytoestrogen metabolites. The relative insolubility and instability of the chromene ring under acid-base reaction conditions were compounding problems for the isoflavones. A new alternative route involving synthesis of the O-glucuronides by the prior synthesis of the glycosides, hydrolysis to the glucosides and then TEMPO mediated selective oxidation of the primary alcohol was successful for simple phenol, sterically hindered phenol and the steroids estrone and testosterone. However, this alternative route also failed to effect glucuronidation of the isoflavones. Attention was thus focused on the synthesis of isoflavone glucuronides using UDP-glucuronyl transferase. Towards this end (±) methoxy equol glucuronide has been synthesised enzymatically, and purified using chromatographic methods. The attempted enzymatic synthesis of formononetin gave instead the cleavage product 2-hydroxy, 4'-methoxy deoxybenzoin glucuronide. The glucuronides were fully characterised by 1H-1H 2D-COSY, 1H-13C 2D-HETCOR and DEPT spectra and the results unambiguously showed the β-linkage of the glucuronide ring with the aglycon moieties. The presence of the glucuronide ring at the C-4 position in 2-hydroxy, 4'-methoxy deoxybenzoin glucuronide was also confirmed by a long range coupling experiment(HMBC). The stereochemical integrity of the estrone glucuronide (E1G) obtained using perester coupling, acetimidate coupling and TEMPO catalysed oxidation methods were clinically tested by comparison with a standard curve obtained with a sample produced by the Koenigs-Knorr method. Testosterone glucuronide was studied for use as a biomarker to validate the concept of a multi-purpose home monitor for a variety of analyte glucuronides of clinical interest. Testosterone glucuronide antibodies with high affinity were generated by immunisation of sheep and testosterone glucuronide-HEW lysozymes conjugates were prepared. The standard curve for TG clearly showed it can be used for measurement of urinary TG at physiological concentrations. This methodology can be extended for analyte glucuronides of interest and can be used for development of biomarkers for health and disease. Thus a multi-purpose home monitor is now a reality and exciting commercial and practical applications are expected in the future.Item The synthesis and properties of polyether substituted oligothiophenes : a thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University, Palmerston North, New Zealand(Massey University, 2003) Grant, Daina KimA number of novel dialkoxystyryl-substituted terthiophenes were synthesised as precursors to form conducting polymers. These compounds contained either crown ethers or polyether chains designed to complex metal cations, and polymerisable terthiophene moieties. Two isomeric cross-linked bis(terthiophene) crown ethers were also synthesised as monomers for conducting polymer synthesis, but could not be investigated further due to their insolubility. The solubility issue was circumvented by the formation of hemicrown compounds, containing two styryl-terthiophene units linked by a polyether chain. Thiophene analogues of the crown ether, open-chain ether, bis(terthiophene) crown ether and hemicrown compounds were also successfully synthesised and characterised. The response of the terthiophene crown compounds, open-chain compounds and hemicrowns to a large range of metal cations was investigated by UV and fluorescence spectroscopy. The results obtained from this work were consistent with complexation based on size-fit and charge density of ions, and with hard-soft-acid-base theory. Chemical polymerisation of the terthiophene crown monomers and open-chain ether terthiophene compounds was carried out using FeCl3. This led to the isolation of dimeric sexithiophene compounds in high yield. Characterisation of the pure sexithiophene derivatives showed that they were the product of regioselective dimerisation, caused by the asymmetric reactivity of the terthiophene-based monomers. This is believed to be due to uneven electron spin-density distribution, and theoretical calculations on the radical cation support this view. Producing dialkoxystyryl-substituted sexithiophenes by this synthetic route gave excellent yields of isomerically-pure product. Chemical oxidation of terthiophene compounds using Cu(ClO4)2 was observed with UV/VIS/NIR spectroscopy. This allowed the observation and identification of absorption bands due to oxidised species. Reduction of these species led to sexithiophene dimers, as seen for chemical polymerisation using FeCl3. Electrochemical polymerisations of the terthiophene, thiophene and sexithiophene compounds were carried out by cyclic voltammetry. Those that formed adherent films were analysed by UV/VIS/NIR spectroscopy in both the neutral and oxidised form. The electrochemical and spectroscopic evidence again pointed to the formation of dimers as the primary product of oxidation from terthiophene-based monomers. The surface morphology of the films was investigated by scanning electron microscopy, and showed a variety of morphologies.Item Supramolecular helical arrangement of porphyrins along DNA : a thesis submitted in the partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry, Massey University, Palmerston North, New Zealand(Massey University, 2010) Stephenson, Adam Wayne IanPorphyrins are useful chromophores and have been used in numerous biological applications including light harvesting, oxygen transport and energy transfer. DNA is a perfect template for the controlled assembly of organic chromophores. By combining DNA and porphyrins in a controlled manner we have developed a novel range of porphyrin-DNA supramolecular constructs for future applications in nanobiotechnology. A number of β-pyrrolic functionalised porphyrin precursors were synthesised to be used as building blocks in the construction of both covalently and non-covalently modified DNAs. Using these porphyrins we have created several lipophilic porphyrin-DNA complexes through non-covalent attachment methods. Using a CuI catalysed azide alkyne cycloaddition (CuAAC) reaction of azido functionalised porphyrins we have developed a versatile approach for the covalent, site specific internal porphyrin insertion into oligonucleotides in a post-synthetic manner. We have investigated a number of duplex structures where porphyrins were located in the major or minor grooves of the duplex. Additionally, porphyrins were studied as intercalating moieties when they were inserted as a bulge in the middle of the duplexes or parallel triplexes. Additionally, when porphyrins were placed in both strands of the duplex they formed a zipper type structure in the minor groove. This resulted in a significant increase in the duplex thermal stability due to the formation of porphyrin H-aggregates. UV-Vis and CD spectroscopy as well as molecular modelling were used to help understand the interactions between porphyrins in the duplex. These findings lay the foundation for the future design of artificial DNA-chromophore supramolecular architectures and for their applications in material science and nanotechnology.Item Mercury clusters from van der Waals to the metallic solid : a thesis presented in partial fulfillment of the requirements of the degree of Doctor of Philosophy in Theoretical Chemistry at Massey University, Albany, New Zealand(Massey University, 2003) Gaston, NicolaThe nature of mercury clusters is studied in an attempt to reconcile the behaviour of the solid with that of the smallest molecules. Related systems such as Zn, Cd, and Ba are investigated for comparison. A range of ab initio methods are employed, and their accuracy assessed. Density functional theory (DFT) based methods are shown to be unreliable. Different functionals vary widely in their description of a particular system, such as the dimer, while individual functionals vary in accuracy when applied across a range of system sizes. This is related to the neglect of van der Waals forces by DFT for the smaller systems, but raises interesting questions about the solid. Wavefunction-based methods are seen to be much more reliable than DFT, although a high-level description of correlation is required. Hartree-Fock (HF) calculations are shown to be consistent in their description of systems of all sizes, and therefore although inadequate on its own the addition of a correlation potential derived from the many-body perturbational (MP2) calculation for the dimer corrects HF to produce exactly the correct bond lengths (when compared to the best known data) for all sizes up to the bulk lattice. The use of higher order many-body potentials is investigated and compared to the situation observed for the noble gases, since for small sizes these are the closest analogues of the neutral mercury clusters. The question of how to simulate transitions in large clusters is addressed. Transitions of interest in clusters are the liquid to solid phase transition, the metal to non-metal transition, or a structural transition from one isomeric motif to another. Therefore the ability to calculate the properties of these clusters accurately is as important as the question of structure. Four-component DFT calculations for the mercury dimer polarisability agree well with the anisotropy derived from Raman spectroscopy. Various isomers proposed in the literature are compared for the smaller mercury clusters. The structures of cationic clusters are also optimised, and their electronic excitation spectra are investigated through CIS(D) and TD-DFT calculations and compared to experimental results. The structures of anionic zinc clusters are obtained and the density of states compared with experiment. The structures and spectra of these clusters are related to those seen for the magnesium analogues, and the effect of the d-electrons in perturbing the jellium model description of these clusters is considered.Item An investigation into the regulation of the topoisomerase IIα promoter in breast cancer cells exposed to doxorubicin : a thesis presented to Massey University in partial fulfillment of the requirement for the degree of Doctor of Philosophy in Biochemistry(Massey University, 2003) Allen, Kirsty AnnChemotherapeutic drugs, such as doxorubicin, are some of the most effective agents for the treatment of breast cancer. Acquired resistance to these drugs often develops, however, and may preclude effective treatment. Such resistance is multifactorial in origin, but may include down-regulation of topoisomerase IIα (topo IIα) - an essential enzyme involved in normal DNA metabolism and a target for some of the anticancer drugs. A reduction in the levels of this enzyme is thought to reduce DNA damage induced by the drug-topo IIα complex and so increases the chances of survival. The mechanisms involved in this down-regulation and the development of resistance to doxorubicin are the focus of this study. Stable breast cancer cell lines, containing deletion constructs of the topo IIα promoter linked to the hGH reporter gene, were exposed to doxorubicin and both the reporter and endogenous gene expression were analysed in the surviving cells. It was shown that the reporter and endogenous topo IIα gene expression in the cell line containing the full length topo IIα promoter construct was no longer correlated in the surviving cells negating the use of this experimental system. Instead the endogenous expression of topo IIα and putative regulatory factors were investigated. Data suggest that specific cell lines show a down-regulation in the levels of the topo IIα protein. These changes were not due to changes in cellular proliferation rates, cell cycle profile or promoter sequence. Selected cell lines were analysed for changes in the relative amounts of specific transcription factors with putative roles in topo IIα gene regulation and for the expression of proteins proposed to have a role in the development of drug resistance. In specific cell lines, a reduction in topo IIα protein levels correlated with alterations in the relative amounts of NF-YA and/or Sp1. It was shown that the drug efflux pumps MDR1 and MRP1, as well as the heat shock factor Hsp70 were not involved in the survival of cells that were exposed to the drug. In vivo footprinting was attempted to detect changes in the in vivo binding of proteins to the topo IIα promoter after short term drug exposure.Item Synthesis of cyclodextrin composites incorporating targeting and drug carrying capabilities : a thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry, Massey University, Turitea Campus, Palmerston North, New Zealand(Massey University, 2010) White, Rachel JaneA selective, versatile, and robust methodology for the bi-functionalisation of - cyclodextrin has been developed which allows for the attachment of peptides and/or sulfonamides in varying C- and N-terminal combinations on resin using NFluorenylmethoxycarbonyl (Fmoc) Solid Phase Peptide Synthesis (SPPS). Mono-6Afluorenylmethyloxycarbonylamino- mono-6X-succinyl-b-cyclodextrin, an amino acid based bi-functionalised derivative of b-cyclodextrin, has been functionalised with the bioactive peptide, bradykinin, and/or sulfonamides using Fmoc SPPS on Rink resin. The all-in-one molecule contains a carrier (cyclodextrin), targeting agent (bradykinin) and/or drug (sulfonamide). Varying combinations of these bradykinin-focused molecules have been synthesised in an attempt to determine the structure-function relationship against cancer cell lines using cell-based screening in vitro. This study commenced with the synthesis of two linkers on to cyclodextrin. This enabled selective binding directly on to the resin, or a peptide attached to the resin. Peptide growth and/or cleavage from the resin followed allowing for the synthesis of peptide-cyclodextrin species in various combinations. Fmoc SPPS techniques have been employed to allow for the addition and synthetic extension of peptides on to cyclodextrin. Peptide purification was achieved by reverse phase high pressure liquid chromatography, and nuclear magnetic resonance spectroscopy and mass spectrometry were used to determine the success of the coupling reactions and identification of cyclodextrin regio isomers. Sulfonamide additions to the cyclodextrin and/or peptide compounds were obtained after numerous studies investigating the optimal reaction conditions. 4-Fluorenylmethyloxycarbonylaminobenzenesulfonyl chloride was found to give the highest yields for the synthesis of C-terminal peptide sulfonamides with 4- carboxybenzenesulfonamide giving the highest optimal yields for N-terminal peptide sulfonamides. Peptide coupling efficiency of cyclodextrin and sulfonamides were investigated and optimised by comparing different SPPS resins and solvents. The incorporation of spacers between the peptide/cyclodextrin and/or resin have also been investigated in an attempt to improve overall reaction yields. Preliminary bioassay testing against tumour cell lines HT-29 Human Duodenum, Hs700T Human pancreatic adenocarcinoma, and MA-104 Human pancreatic adenocarcinoma were performed. The MTT assay and the flow cytometry assay were used to show the effect of varying combinations of these cyclodextrin-peptidesulfonamide molecules against the three cell lines and compared to a known anticancer drug, 5-Fluorouracil. Despite employment of simple entities in the construction of these compounds, an increase in cell proliferation (ca 10-20%) was seen for some cyclodextrin-bradykinin complexes. In addition, an exposed C-terminus on the bradykinin-sulfonamide moiety and an exposed N-terminus on the cyclodextrinbradykinin sulfonamide moiety both gave positive results. Mixed results were obtained with the addition of a linker between the cyclodextrin and the bradykinin molecules (less then 5% increase or decrease) compared to their non-linker counterparts.Item Static electric dipole polarizabilities of atoms and molecules : a thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University, Albany, New Zealand(Massey University, 2004) Lim, Ivan S.The static dipole polarizabilities and ionization potentials of the first and second main group elements, including the charged ions, are obtained from all-electron relativistic coupled-cluster theory using a scalar relativistic Douglas-Kroll Hamiltonian. Spin-orbit coupling effects are investigated using a fully relativistic four-component Dirac-Coulomb-Hartree-Fock scheme followed by a second-order many-body perturbation treatment to account for electron correlation. Periodic trends in the dipole polarizabilities and the ionization potentials are discussed. In each case, a detailed discussion on electron correlation and relativistic effects are given. A relationship for relativistic and electron correlation effects between the dipole polarizability and the ionization potential is established. Particular attention is paid to the evaluation of a near basis set limit quality of the dipole polarizabilities. This is accomplished by the evaluation of all-electron basis sets used, followed by an extensive study on the convergence behavior of the dipole polarizabilities with respect to a finite basis set expansion. The present all-electron dipole polarizabilities are believed to be very precise, especially for charged ions where the availability of experimental values are limited. Scalar relativistic small-core pseudopotentials are fitted and their performance is tested in terms of static dipole polarizabilities and ionization potentials. It is demonstrated that the small core definition of the pseudopotential (nine-valence electron for the main group 1 and ten-valence electron for the main group 2 elements) enables us to safely omit core-valence correlation without scarifying accuracy. Following atomic dipole polarizabilities, applications are made to molecules starting with alkali dimers and their singly charged ions. The scalar relativistic pseudopotentials of this study are used to calculate equilibrium bond lengths, dissociation energies, vibrational frequencies and the dipole polarizabilities of these dimers. The change in the molecular dipole polarizabilities from the corresponding atomic dipole polarizabilities are discussed in terms of molecular bonding models. Simple ammonia complexes of the alkali-metals and their singly charged ions are studied. The equilibrium geometries, dissociation energies, harmonic vibrational frequencies as well as the dipole polarizabilities of these complexes are given.