• A study of the thermal decomposition of allyl t-butyl peroxide and 3-hydroperoxy-1-propene (allyl hydroperoxide) in toluene /|nby Krishnankutty Nair V. G. -- 260 St. Catharines [Ont. : s. n.],

      Nair, Krishnankutty V. G.; Department of Chemistry (Brock University, 1976-07-09)
      Kinetics and product studies of the decompositions of allyl-t-butyl peroxide and 3-hydroperoxy- l-propene (allyl hydroperoxide ) in tolune were investigated. Decompositions of allyl-t-butyl peroxide in toluene at 130-1600 followed first order kinetics with an activation energy of 32.8 K.cals/mol and a log A factor of 13.65. The rates of decomposition were lowered in presence of the radical trap~methyl styrene. By the radical trap method, the induced decomposition at 1300 is shown to be 12.5%. From the yield of 4-phenyl-l,2- epoxy butane the major path of induced decomposition is shown to be via an addition mechanism. On the other hand, di-t-butYl peroxyoxalate induced decomposition of this peroxide at 600 proceeded by an abstraction mechanism. Induced decomposition of peroxides and hydroperoxides containing the allyl system is proposed to occur mainly through an addition mechanism at these higher temperatures. Allyl hydroperoxide in toluene at 165-1850 decomposes following 3/2 order kinetics with an Ea of 30.2 K.cals per mole and log A of 10.6. Enormous production of radicals through chain branching may explain these relatively low values of E and log A. The complexity of the reaction is indicated a by the formation of various products of the decomposition. A study of the radical attack of the hydro peroxide at lower temperatures is suggested as a further work to throw more light on the nature of decomposition of this hydroperoxide.
    • A study of thermal decompositions of an allylic hydroperoxide /|nby Thomas A. McCarrick. -- 260 St. Catharines [Ont.] : Dept. of Chemistry, Brock University,

      McCarrick, Thomas A.; Department of Chemistry (Brock University, 1974-07-09)
      The thermal decomposition of 2,3-di~ethy l - J-hydr operox y- 1 - butene , p r epared f rol") singl e t oxygen, has been studied i n three solvents over the tempe r a ture r ange from 1500e to l o00e and t!1e i 111 t ial ~oncentrfttl nn r Ange from O. 01 M to 0.2 M. Analys i s of the kine tic data ind ica te s i nduced homolysis as the n ost probRble mode of d e composition, g iving rise to a 3/2 f S order dependence upon hy d.roperoxide concent :r8.tl on . Experimental activation e nergies for the decomposition were f ound to be between 29.5 kcsl./raole and 30.0 k cal./mole .• \,iith log A factors between 11 . 3 and 12.3. Product studies were conducted in R variety of solvents a s well as in the pr esence of a variety of free r adical initiators . Investigation of the kinetic ch a in length indicated a chain length of about fifty. A degenerat i ve chain branching mechanism 1s proposed which predicts the multi t ude of products which Rre observed e xperimentally as well as giving activation energies and log A factors si~il a r to those found experimentally .
    • The suppression of the Haller-Bauer scission for synthetic purposes /|nby S. M. Vines. -- 260 St. Catharines, Ont. : [s. n.],

      Vines, S. M.; Department of Chemistry (Brock University, 1971-07-09)
      A number of 2-chlorobenzophenones, containing electron releasing groups (e.g. hydroxy, thiomethoxy and methoxy) in the 4' - position, were prepared by the Friess rearrangement, or the Friedel-Crafts reaction. These ketones, when treated with potassamide in liquid ammonia, underwent partial Haller-Bauer scission, unlike 2-chlorobenzophenone which is known to undergo complete scission. Under similar conditions 4-nitrobenzophenone also underwent partial scission, but the main reaction in this case was nucleophilic amination of the nitro containing ring. This amination reaction was shown not to be a useful general reaction for aromatic nitro compounds. 3-Methylxanthone was then prepared by treatment of 2- and 3- chloro-2'-hydroxy-5'-methylbenzophenone with . little, if any, attendant scission. The corresponding 2fluoro- compound also gave the xanthone, but as the 3-fluoro compound did not, it was concluded that the 2-fluoro compound reacted through a nucleophilic substitution mechanism, rather than the benzyne mechanism invoked for the chloro and bromo compounds. 3-Methylthioxanthone was synthesised by treatment of methyl 4-tolyl sulphide and 2-chlorobenzoyl chloride with aluminum chloride in carbon disu1phide, followed.by heating. This compound was also prepared by treatment of 3-chloro-2'thiomethoxy- 5'-methylbenzophenone with potassamide in liquid ammonia.
    • Synthesis and characterization of BODIPY-α-tocopherol : a new ligand to explore the intracellular transfer of Vitamin E

      West, Ryan.; Department of Chemistry (Brock University, 2009-01-28)
      Since its discovery nearly a century ago, a-tocopherol (vitamin E) research has been mainly focused on its ability to terminate the cycle of lipid peroxidation in membranes. Nitrobenzoxadiazole fluorescent analogues were made previously to study the intracellular transfer of vitamin E in cells. However, these molecules were reportedly susceptible to photobleaching while under illumination for transfer assays and microscopy. Here is reported the synthesis of a series of fluorescent analogues of vitamin E incorporating the more robust dipyrrometheneboron difluoride fluorophore (BDP-a-Tocs; Aex = 507 nm, Aem = 511 nm). C8-BDP-a-Toc 42c, having an eight-carbon chain between the chromanol and fluorophore, wa<; shown to bind specifically to a-tocopherol transfer protein with a dissociation constant of approximately 100 nM. Another fluorescent analogue of vitamin E with a thienyl derivative of BODIPY that is excited and fluoresces at longer wavelengths (Aex = 561 nm, Aem = 570 nm) is in development.
    • The Synthesis and Coordination Chemistry of Two Families of Polydentate Ligands - Exploring Their Potential for the Preparation of Molecule-Based Magnets

      ZARRABI, NILOOFAR; Department of Chemistry (Brock University, 2013-04-19)
      The synthesis and studies of two classes of poly dentate ligands are presented as two projects. In project 1, four new carboxamide ligands have been synthesised via the condensation of 2,2',6,6'-tetrachloroformyl-4,4'-bipyridine or 2,6-dichloroformyl pyridine together with heterocyclic amines containing pyridine or pyrazole substituents. The coordination chemistry of these ligands has been investigated and studies have shown that with a Cu(II) salt, two carboxamide ligands LJ and L2 afford large clusters with stoichiometries [Cu8(L1)4Cl16].CHCl3.5H2O.7CH3OH (I) and [Cu9(L2)6Cl6].CH3OH.5H2O.(C2H5)3N (II) respectively. [molecular diagram availabel in pdf]. X-ray diffraction studies of cluster (I) reveal that it has approximate S4 symmetry and is comprised of four ligands and eight copper (II) centers. Here, coordination takes place via amide 0 atoms, and pyrazole nitrogens. This complex is the first reported example of an octanuclear copper cluster with a saddle-shaped structure. The second cluster comprises nine copper ions that are arranged in a cyclic array. Each ligand coordinates three copper centers and each copper ion shares two ligands to connect six ligands with nine copper ions. The amide nitrogens are completely deprotonated and both amide Nand 0 atoms coordinate the metal centres. The cluster has three-fold symmetry. There are six chloride ions, three of which are bridging two neighbouring Cu(II) centres. Magnetic studies of (I) and (II) reveal that both clusters display weak antiferromagnetic interactions between neighbouring Cu(II) centers at low temperature. In the second project, three complexes with stoichiometries [Fe[N302](SCN)2]2 (III), R,R-[Fe[N3O2](SCN)2 (IV) and R,R-]Fe[N3O2](CN)2] (V) were prepared and characterized, where [N302] is a pentadentate macrocycle. Complex (III) was prepared via the metal templated Schiff-base condensation of 2,2',6,6'-tetraacetyl-4,4'-bipyridine together with 3,6-dioxaoctane-I,8-diamine and comprises of a dimeric macro cycle where the two Fe(II) centres are in a pentagonal-bipyramidal environment with the [N302] ligands occupying the equatorial plane and two axial NCS ligands. Complexes (IV) and (V) were prepared via the condensation of 2,6-diacetylpyridine together with a chiral diamine in the presence of FeCh. The synthetic strategy for the preparation of the chiral diamine (4R,5R)-4,5-diphenyl-3,6-dioxa-I,8-octane-diamine was elucidated. The chirality of both macrocycles (IV) and (V) was probed by circular dichroism spectroscopy. The crystal structure of (IV) at 200 K contains two independent molecules in the unit cell, both of which contain a hepta-coordinated Fe(II) and axial NCS ligands. Variable temperature magnetic susceptibility and structural studies are consistent with a high spin Fe(II) complex and show no evidence of any spin crossover behaviour. In contrast, the bis cyanide derivative (V) crystallizes with two independent molecules in the unit cell, both of which have different coordination geometries consistent with different spin states for the two Fe(II) centres. At 250 K, the molecular structure of (V) shows the presence of both 7- and a 6-coordinate Fe(II) complexes in the crystal lattice. As the temperature is lowered, the molecules undergo a structural change and at 100 K the structural data is consistent with a 6- and 5-coordinate Fe(II) complex in the unit cell. Magnetic studies confirm that this complex undergoes a gradual, thermal, spin crossover transition in the solid state. Photomagnetic measurements indicate this is the first chiral Fe (II) sea complex to exhibit a LIESST.
    • Synthesis and Coordination of the Arylazo Ligands 1-(2-pyridylazo)-2-phenanthrol and 1-(8-quinolynazo)-2-phenanthrol

      Taylor, Robin; Department of Chemistry
      The use of ligands 1-(2-pyridylazo)-2-phenanthrol and 1-(8-quinolinazo)-2-phenanthrol has afforded twelve new complexes that feature many different structural, mag- netic, and electronic properties. Chapter one deals with the aspects of materials chemistry which are pertinent to the material presented in this thesis. This includes inorganic chemistry, mag- netism, luminescence, and redox active ligands. The second chapter includes the experimental details of all the complexes and ligands presented herein. The main body of this work has been split into three parts. The first part presented in chap- ter three includes complexes of 1-(2-pyridylazo)-2-phenanthrol with the following transition metals [V(V), Cu(II), Co(II), Ru(II), Fe(II) and Fe(III)]. Of particular interest in this chapter is the Co(II) complex which exhibits thermal spin-crossover, and the Fe(II) complexes which offer interesting structural properties including a structural phase transition. The second part (chapter four) examines three lanthanide complexes (Gd, Tb, and Dy) with the ligand 1-(2-pyridylazo)-2-phenanthrol. These complexes feature intense absorptions in the visible region which results in these complexes having dye-like properties. Of particular note is the luminescence studies performed on these complexes. The final part (chapter five) of the work presented examines the synthesis and characterization of the ligand 1-(8-quinolinazo)-2-phenanthrol, and it’s coordina- tion chemistry (Fe(II), and Co(III)). The ligand offers quasi-reversible ligand cen- tered reductions at low potentials, which should offer the first step in the synthesis of valence-tautomer or charge-transfer complexes.
    • Synthesis and Evaluation of Trans-bilayer Cross Linking Phospholipids Based on Click (Azide-Alkyne) Chemistry

      Hosseini, Yasaman; Department of Chemistry
      This thesis describes the synthesis of two phosphatidylcholine (PC) derivatives that are capable of coupling with each other from the alkyl chain through click reaction to form bola-PC. Successful coupling of monomeric phosphatidylcholine derivatives would lead to synthesis of corresponding phosphatidylinositol molecules as future work. PC derivatives that were synthesized in this work were phosphatidylcholine containing terminal azide and terminal alkyne on the alkyl chain of sn2 position. Sn-glycero-3-phosphocholine (GPC) was used as glycerol back bone with two available hydroxyl groups for esterification. The first esterification was done using dibutyltin oxide as catalyst and palmitoyl chloride as acylating agent on the primary hydroxyl group, sn1 position. Secondary hydroxyl group in the sn2 position of GPC was esterified by terminal alkyne and terminal azide fatty acids through Steglich esterification. PC analogues with suitable functional groups for click chemistry were, then, incorporated in the 100 nm-vesicles in buffer solution and exposed to copper catalyst/L-histidine complex and sodium ascorbate solution at room temperature. Formation of bola-PC were observed in the hydrophobic core of lipid bilayer and this was the main objective of this study.
    • Synthesis and Investigation of Light Responsive Molecules Containing Cyclopropenium Ions

      Le Sueur, Richard; Department of Chemistry
      The present thesis describes recent advances in the pursuit of novel light-responsive molecules containing cyclopropenium ions. In an effort to understand the underlying factors regarding the photophysical properties of cyclopropenium ions, emphasis was placed on the previously reported “Janus sponge”, where systematic structural modifications to four individual components of the molecule led to measurable and predictable changes in molar extinction coefficients, quantum yields, and Stokes shifts. Using time-dependent density functional theory calculations, the origin of these trends were traced to internal charge transfer. Additionally, modulating hydrogen bonding between intermolecular, bifurcated, and intramolecular interactions by choice of counterion was used to alter the quantum yield of cyclopropenium ion-containing fluorophores. The basis of this switchability was examined using X-ray diffraction analysis, 1H NMR spectroscopy, density functional theory calculations, and fluorescence spectroscopy. Notably, this work led to the development of the first cyclopropenium ion containing “true” proton sponge. As an extension, light responsive molecules are not isolated to fluorescence. This thesis also outlines the development of the first cyclopropenium ion containing an azo group. Key findings include the fact that cyclopropenium ion containing azo compounds are stable and cyclopropenium ions red-shift the absorbance wavelength in comparison to azobenzene by 75 nm. The synthetic, structural, electronic, and photophysical properties of these compounds are discussed.
    • Synthesis and properties of some 4H-1, 3, 4 benzothiadiazines /|nby Darko J. Vukov. -- 260 St. Catharines, Ont. : [s. n.],

      Vukov, Darko J.; Department of Chemistry (Brock University, 1972-07-09)
      The work herein has been divided into five sections. In the first section, a new method of converting N-aroyl- hydrazines to hydrazidic halides is described. The second section deals with the products of reaction of hydrazidic halides with thioacetate ion in acetonitrile at room temperature. A number of new acetylthiohydrazides has been isolated together with corresponding hyclrazidic sulphides. Examination of x-ray data for bis-[~ -(2,6- dibromophenylhydrazono) - benZYl] sulphide revealpd the symmetrical structure as the most probable. In the third section, which consists of the three subsections, the synthesis of the 4H-l,3,4 benzothiadiazine ring system has been extended to 4H-l,3,4 benzothiadiazines with substituents in the 5 and 6-positions. Extension of synthesis also involves 4H-l,3,4 benzothiadiazines with mora than one substituent. Nuclear magnetic resonance spectra of 5 and 6 substituted 4H-l,3,4 benzothiadiazines have been ,. recorded. The section ends with a discussion of the mass spectra of some 4H-l.3,4 benzothiadiazines. In the fourth section, which is divided into two sub- -sections, preparation of 7-nitro substituted 4H-l,3,4 benzothiadiazine from N-thiobenzoyl hydrazine and2,4-dinitro -fluorobenzene is found to be satisfactory. Thiohydrazides react with acetic anhydride, in some cases, to give products identical with acetylthiohydrazides obtained from the hydrazidic halides with thioacetate ion at room temperature. In most of the cases thiohydrazides are found to give anomalous products on reaction with acetic anhydride and mechanisms for their formation are discussed. In the fifth section, which forms three subsections, the 4H-l,3,4 benzothiadiazine ring system with a halogen substituent in the 7-position undergoes electrophilic attack preferentially in 5-posi tion. \fuen the 5-posi tion is occupied by a halogen atom, electrophilic substitution occurs at the 7-position of 4H-l,3,4 benzothiadiazine ring system. Substitution at the 4-nitrogen atom in 4H w l,3,4 benzo- -thiadiazine is extremely slow, probably due to delocalisa- -tion of the nitrogen lone pair in the system. Oxidation of 4H-l,3,4 benzothiadiazines occurs at the sulphur atom under relatively mild conditions. t The Appendix deals with the reaction of N-benzoyl-N - -(2,5-dibromophenyl)hydrazine with p-nitrothiophenol~ The proposed p-nitrothiophenoxy - intermediate may undergo benzothiadiazine formation in a proton exchange system.
    • Synthesis and spectral studies of methyl heterocylic systems

      Doyle, Paul P.; Department of Chemistry (Brock University, 1979-07-09)
      2-Carboxy-2?-methyldiphenyl sulfide was prepared by the Ullmann reaction and cyclodehydrated by sulfuric acid to afford 4-methylthioxanthone. 1-Methylthioxanthone was separated from the reaction mixture obtained upon cyclodehydration of 2-carboxy-3f-methyldiphenyl sulfide. In addition, 1-, 2-, 3- and 4-methylthioxanthone 10,10-dioxides were synthesized by oxidation of the corresponding thioxanthones. o-, m- and p-N-Tolylanthranilic acids were prepared by the Ullmann reaction and used as precursors for the preparation of 1-, 2- and 4- methyl-9-chloroacridine and finally 1-, 2-, 3- and 4-methylacridone. High resolution, 60 MHz PMR spectra were obtained on the four monomethyl isomers of xanthone, thioxanthone, thioxanthone 10,10-dioxide and acridone, and on 1-, 2- and 4-methyl-9-chloroacridine. For some compounds, coupling of all three different aromatic protons to the methyl was observed, two of the couplings typically being smaller than the third. With the large (ortho) coupling being on the order of 0.5 to 1.0 Hz, it was necessary to decouple the aromatic part of the spectrum. The magnitude of the ortho benzylic constant may be related to an incomplete Tr-bond delocalization in the molecules.
    • Synthesis of 3', 5'-cyclic diguanylic acid (c-di-GMP) analogues

      Heidari, Nazanin; Department of Chemistry
      In the past few years, interest in signaling networks involving 3ʹ, 5ʹ -cyclic diguanylic acid (c-di-GMP) has increased dramatically. Evidence started to emerge that connects c-di-GMP to the regulation of a range of biological processes in bacteria, such as bacterial biofilm formation, virulence, extracellular polysaccharide synthesis, however, much remains to be explored in the signaling pathways that involve this secondary messenger. This molecule has also been shown to be a very powerful immunostimulating agent and potent mucosal vaccine adjuvant.
    • Synthesis of 3’, 5’-cyclic diguanylic acid (c-di-GMP) as mucosal vaccine adjuvant and bacterial second messenger

      Milah, Khatma; Department of Chemistry
      The present study describes the synthesis of 3’,5’- cyclic diguanylic acid (c-di-GMP), attempts were made to synthesize guanosine bearing a 2’-O-(hexyn-6-yl)- and 2’-O-(6-azidohexyl)-modification using 2,6-diaminopurine riboside as starting material. The synthesis of 2’-O-(hexyn-6-yl) guanosine started with the alkylation of 2,6-diaminopurine riboside with 6-iodo-1-hexyne, which gave a mixture of 2’- and 3’-O-alkylated 2,6-diaminopurine riboside. Treatment of this product with isobutyryl chloride, followed by ammonium hydroxide gave N2-isobutyryl-2’-O-2’-O-(hexyn-6-yl)-2,6-diaminopurine riboside. Subsequent deamination reaction was carried out with sodium nitrite in a mixed solvent gave the desired N2-isobutyryl-2’-O-2’-O-(hexyn-6-yl) guanosine. N2-Isobutyryl-2’-O-(6-azidohexyl) guanosine was also obtained in the similar manner. Synthesis of a second building block, a suitably protected guanosine H-phosphonate was also attempted using guanosine as starting material. Experimental and spectral data are provided for new compounds.
    • Synthesis of 4-hydroxycinnamic amides of di-, tri-, and tetraamines : potential insect toxins /

      Fixon-Owoo, Solomon N. K.; Department of Chemistry (Brock University, 2000-05-21)
      The monoconjugates of phenolic acids (i.e. coumaric acid) with polyamines such as spermidine and spermine are strikingly similar to some toxins from spiders and predatory wasps. Many plants contain phenolic acid polyamine conjugates and there is some reliable information supporting their roles as plant defense chemicals. Eleven monoacylated compounds of diamines, triamines, tetraamines and oxa-polyamine amines were prepared in three to seven steps: 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 and 32. The synthesis proceeds through stepwise construction of the polyamine backbone (as in 62 and 72), followed by protection and deprotection steps of the amino functions. Desymmetrization of readily available and prepared symmetrical polyamines is a key step in the synthesis. The protecting groups employed were tert-butoxycarbonyl (BOC) and trifluoroacetyl (TFA) group which were removed under different conditions: acid and base respectively. Deprotection and refunctionalization of the polyamine reagent demonstrated the versatility of these systems for N-acylation.
    • Synthesis of a 7-Membered Biaryl Guanidine Catalyst and its Use in the Vinylogous Aldol Reaction

      Hassan, Mohamed; Department of Chemistry (Brock University, 2014-07-23)
      The present thesis outlines the preparation of a 7-membered guanidine. Initial efforts to obtain this guanidine via 2-chloro-1,3-dimethylimidazolinium chloride induced ring forming chemistry failed to provide the target in a reproducible fashion. Changing strategies, we were able to obtain the desired guanidine through CuCl mediated amination of a 7-membered thiourea intermediate to arrive at the target. In addition, the catalytic activity of this compound was evaluated in a vinylogous aldol reaction of dibromofuranone and four aromatic aldehydes to generate chiral γ-butenolides with modest to good enantiomeric excess. It was found that electron-poor aldehydes resulted in higher, 81% ee, whereas electron rich aldehydes led to low, 41% ee, levels of enantiomeric excess.
    • The synthesis of a-Tocohexaenol, a new fluorescent analogue of a-Tocopherol

      Wang, Yongsheng.; Department of Chemistry (Brock University, 2008-11-04)
      Since its discovery in 1922, vitamin E has been widely investigated for its role as a powerful, chain-breaking antioxidant that is required for human health. However, some basic issues still remain unclear, such as the mechanism and dynamics of the intracellular trafficking of a-tocopherol. To better understand tocopherol's biological activity at the cellular level, fluorescence spectroscopy and microscopy have been found to be valuable tools. This thesis reports the synthesis of a new fluorescent analogue of a-tocopherol, atocohexaenol, an intrinsically fluorescent analogue of a-tocopherol. Different methodologies of preparation have been attempted and a strategy using a preformed chromanol head plus ClO and Cs portion of the polyene side chain finally provided us the desired a-tocohexaenol. a-Tocohexaenol shows a strong fluorescence in both ethanol and hexanes with maximum Aab = 368 nm and maximum /...em = 521 nm. This compound is stable for a couple of weeks in ethanol or hexane solution if stored at 0 °C and protected form light. It decomposes slowly at room temperature and light will accelerate its decomposition (within 5 hours). Thus, a-Tocohexaenol may be a useful fluorescent probe to study the biochemistry and cell biology of vitamin E.
    • Synthesis of Chiral Benzimidazolylidenes from 1,10-Phenathrolines and 1,10-Phenathroline-2,9-dione /

      Wang, Yao.; Department of Chemistry (Brock University, 2007-06-29)
      A^-heterocyclic carbenes (NHCs) have become the focus of much interest as ancillary ligands for transition metal catalysts in recent years. Their structural variability and strong cy-donation properties have led to the preparation of demonstrably useful organometallic catalysts. Among the three general structural types of NHCs (imidazolylidenes, imidazolinylidenes, and benzimidazolylidenes), benzimidazolylidenes are the least investigated because of the limitation of current synthetic approaches. The preparation of chiral analogues is even more challenging. Previously, our group has demonstrated an alternative approach to synthesizing benzimidazolylidenes with a tetracyclic framework in three steps from 1,10-phenanthroline. This thesis is focused on approaches to chiral benzimidazolylidenes derived from substituted 1,10-phenanthrolines. A key step in the preparation of these ligands involves a reduction of the pyridyl rings in 1,10-phenanthrolines. Chirality can be introduced to phenanthrolines before, during, or after the reduction as illustrated by three approaches: 1) de novo construction of the phenanthroline from chiral ketones with endo and exo faces to provide a degree of diastereoselectivity during subsequent reduction; 2) introduction of substituents into the 2- and 2,9- position of phenanthroline by nucleophilic aromatic substitution, followed by a reduction-resolution sequence; and 3) use of the protected octahydrophenanthroline as a substrate for chiral induction a to nitrogen.
    • SYNTHESIS OF CYCLIC AZOBENZENE ANALOGUES FOR INCORPORATION INTO OLIGONUCLEOTIDES, PEPTIDES AND POLYMERS

      Joshi, Dhruval Kumar; Department of Chemistry (Brock University, 2014-02-21)
      (A) In recent years, considerable amount of effort has contributed towards enhancing our understanding of the new photoswitch, cyclic azobenzene, particularly from the theoretical point of view. However, the challenging part with this system was poor efficiency of its synthesis from 2,2’- dinitrodibenzyl and lack of effective methods for further modification which would be useful to incorporate this system into biomolecules as a photoswitch. We report the synthesis of cyclic azobenzene and analogues from 2,2’-dinitrodibenzyl, which would allow for further incorporation of this cyclic azobenzene into biomolecules. Reaction of 2,2’-dinitrodibenzyl with zinc metal powder in the presence of triethylammonium formate buffer (pH-9.5) gave a cyclic azoxybenzene, 11,12-dihydrodibenzo[c,g][1,2]diazocine-5-oxide. The latter compound was converted into cyclic azobenzene analogues (bromo-, chloro-, cyano-, and carboxyl) through subsequent transformations. The carboxylic acid analogue was reacted with D-threoninol to give the corresponding amide, which readily undergoes photo-isomerization upon illumination with light. Upon illumination with light at 400 nm, approximately 70% of cis- isomer of amide was isomerized to trans- isomer. It was observed that cis- to trans- isomerization reached the maximum steady state of light transmission after approximately 40 min, whereas the trans- to cis- isomerization approximately acquired in 2 h to regain full recovery of light transmission. Cyclic azobenzene phosphoramidite was synthesized from DMT-protected D-threoninol linked cyclic azobenzene. (B) In recent years, there has been considerable interest invested towards the synthesis of azobenzene analogues for incorporation into proteins. Among the many azobenzene analogues, the synthesis of bi-functional cyclic azobenzene analogues for the incorporation into proteins is relatively new. In this thesis, we report the synthesis of a cyclic azobenzene biscarboxylic acid from 4-(bromomethyl)benzonitrile. (C) Azobenzene has been widely used in the field of polymer science to study the surface morphology and surface properties of polymers. In this thesis, we report the incorporation of cyclic azobenzene into a commercial polymer 2- (hydroxyethyl)methacrylate. Samples collected after 24 h from the reaction solution showed approximately 9% of incorporation of cyclic azobenzene into polymer compared to samples collected after 10 h, which showed approximately 6% incorporation.
    • Synthesis of fluorinated nucleosides for probing DNA conformations via 19F NMR spectroscopy

      Solodinin, Andrei; Department of Chemistry
      Work described in this thesis explored the synthesis of 5-fluoro-2’-deoxycytidine and 8-fluoro-2’-deoxyguanosine, and subsequent incorporation of these modified nucleosides into d(CG) repeat oligonucleotides through the phosphoramidite chemistry-based solid phase synthesis, in order to investigate the B-Z junction through 19F NMR spectroscopy. Toward this goal, 5-fluoro-2’-deoxycytidine was successfully synthesized from 5-fluoro-2’-deoxyuridine. Choices of protecting groups for the exocyclic amine of 5-fluoro-2’-deoxycytidine were examined, and N-acetyl was found to be most suitable in terms of the stability of the protected nucleoside and the readiness of its removal. 8-Fluoro-2’-deoxyguanosine was prepared by fluorination of suitably protected 2’-deoxyguanosine using N-fluorobenzenesulfonimide as the fluorinating agent. Circular dichroism and UV/vis spectroscopic studies showed that the fluoro-modification does not affect the overall conformation of the oligonucleotides, both in the B- and Z-form. 19F NMR spectra of single fluoro-modified d(CG)6 sequence at 3’-end (11-FdC) were recorded in solution containing 0.1 – 4 M NaCl. The results supported a theoretical model for B-/Z-DNA transition, where initiation starts from the ends, progressing to eventual transition.
    • Synthesis of Heteroleptic Redox-active and Spin-crossover Complexes

      Pelaccia, Mark; Department of Chemistry
      The following research regarding heteroleptic redox-active complexes with the potential for spin-crossover is synthetic in nature. The intent behind incorporating the Schiff base ligand N-(8-quinolyl)salicylaldimine with some redox-active species into a mixed ligand complex featuring a d4-d7 metal ion center was to prime the material for spin-crossover based on strong intermolecular interactions that would enhance cooperativity of the system. Single component systems that display spin-crossover behaviour paired with other physical properties like electrical conductivity hold significance in the field of multifunctional materials, of which there are few examples that feature mixed ligand systems. Information describing this type of chemistry and the magnetic interactions that govern these characteristics is introduced in the first chapter of this work. The synthetic strategies toward mixed ligand complexes in the form of [(Qsal)Fe(RAL)]+X- and [(Qsal)Co(RAL)]+X- have been realized from the use of mononuclear [(Qsal)FeCl2(CH3OH)] and [(Qsal)Co(OAc)]+OAc- species, respectively. The redox-active ligand (RAL) component is an arylazo ligand like 10-(8-quinolylazo)-9-phenanthrol (Qapl) or 1-(2-Pyridylazo)-2-phenanthrol (Papl), which possess a low-lying π* MO that makes them susceptible to multi-step reductions that give rise to radical intermediates. Heteroleptic complexes that were synthesized and isolated like [(Qsal)Fe(Qapl)]+BPh4-, [(Cl-Qsal)Fe(Qapl)]+BPh4-- and homoleptic [Fe(Qapl)2]+BPh4- were diffracted and measured several intermolecular π-π contacts of distances typically between 3.5-3.7 Å, often between the phenanthrene rings of adjacent Qapl ligands. Complexes In the form of [(Qsal)Fe(Qapl)]+X (X= BPh4- or SCN-) showed early onset of spin transition in solution usually beyond 298 K. These complexes were overly reduced in the glovebox which resulted in their deterioration, presumably from the cleavage of the RAL azo bond. The framework developed for the heteroleptic Fe3+ coordination chemistry was applied to cobalt, with some amendments, and afforded several heterleoptic Co3+ complexes using Qsal with the arylazo ligands Qapl and Papl. The heteroleptic cobalt complexes presented here were found to be LS Co3+ which is diamagnetic. However, there is potential under inert atmosphere to produce Co2+ and possibly a phenoxyl radical species with redox-active valence tautomers.
    • The Synthesis of Imidazole Fatty Acid Conjugates as Inhibitors of Apoptosis

      Venkata Krishna Rao, Garapati; Department of Chemistry (Brock University, 2013-03-14)
      Ionizing radiation is known to initiate apoptosis in mammalian cells by causing the transformation of cytochrome c into a peroxidase, which results in the specific peroxidation of the mitochondrial phospholipid cardiolipin. Here we report the design and synthesis of 8 imidazole fatty acid derivatives that bind to the cyt c:CL complex and inhibit the peroxidase activity required for the initiation of apoptosis. We postulate that imidazole acts as a sixth ligand to the haem iron and stops the interaction with H2O2. Two mitochondrially directed analogues (3-hydroxypropyl)triphenylphosphonium esters) of 12-imidazole-stearic acid and 12-imidazole-oleic acid not only were demonstrated to be peroxidase inhibitors in vitro, but were also extraordinarily effective in protecting mice from lethal doses (9 Gy) of ionization radiation. We studied the structure activity relationship to a group of triphenyl phosphonium derivatives containing imidazole at different positions on the fatty acid chain, and observed that the C8-imidazole stearate analogue had marginally better activity than the others. But overall, the structure activity result were remarkable “flat” with all compounds prepared having rather similar inhibitory strength. We also synthesized carnitine mono and di-esters of 12-imidazole fatty acids but full biological data is not yet available for these compounds.