Now showing items 21-40 of 222

    • Ligand Design for Metal-Organic Frameworks and Single Molecule Magnets

      Regier, Jeffery; Department of Chemistry
      This thesis describes two projects in which ligand design has been employed for the synthesis of coordination compounds exhibiting interesting structural and magnetic properties. In Project 1 a flexible, polydentate 4,4'-bipyridine ligand (LI) was prepared and fully characterized. Its coordination chemistry with Cu2(OAc)4 afforded a new complex with stoichiometry [Cu4(LI)1.5(OAc)2(py)2(OH2)]n (III). Single crystal X-ray diffraction experiments revealed that (III) crystallized as a porous, 3-D MOF with a structurally unique trinodal 4,4,5-c net topology. Variable temperature powder X-ray diffraction and TGA experiments revealed that (III) became amorphous upon desolvation, but that the crystallinity of the complex was fully restored after resolvation, rendering it a new addition to the family of breathable MOFs. Project 2 presents a joint synthetic, experimental and theoretical approach towards the discovery of Ln-based SMMs. The synthesis and characterization of a new dual-compartmental macrocycle (LII), with an N3O2 cavity suitable for the preparation of seven-coordinate lanthanide complexes was achieved. Reaction of (LII) with LnCl3∙6H2O, (where Ln3+ = Dy, Tb and Er), in the presence of NaOH afforded three novel complexes with stoichiometry [Ln2Na2(LII)2(Cl)4(MeOH)]·xH2O (IVa-c). X-ray diffraction studies revealed that the complexes were isostructural, comprising two coordinated macrocycles linked via a bridging 2 chloride to afford a dimer. Both macrocycles of each dimer contained a Ln3+ ion with pseudo D5h geometry that is coordinated equatorially by the five donor atoms in the N3O2 pocket together with two axial chloride ligands, as well as a 6-coordinate Na+ ion, residing in the O3O22− pocket. All three complexes have been magnetically characterized. A frequency dependence to the out of phase component of the ac susceptibility data was observed for the Dy3+complex (IVa), consistent with SMM behaviour. The ac data was successfully modelled to a single component Debye equation and a fit of the temperature dependence of c to the Arrhenius equation afforded an effective energy barrier (Ueff) of 12.6 cm−1 and a pre-exponential factor, τ0 of 2.91 x 10−7 s for this complex. Unfortunately, no slow relaxation of the magnetization was observed for the Tb3+ and Er3+ derivatives (IVb) and (IVc). Comprehensive ab initio studies carried out on (IVa-c) shed important light on the relaxation dynamics in all three complexes, revealing that deviation from idealised D5h geometry results in less well isolated ground states and active quantum tunnelling mechanisms, further supporting the experimental observations of predominantly field induced SMM behaviour for (IVa), but no SMM properties for complexes (IVb and c).
    • The Synthesis of α-Tocopentaenol (αT5), a Fluorescent Analogue of α-Tocopherol

      Hildering, Andrew; Department of Chemistry
      This thesis is focused on the investigation of synthesizing a fluorescent analogue of vitamin E, α-tocopentaenol (αT5). α-Tocopentaenol contains five conjugated double bonds across the phytyl tail, resulting in its fluorescence characteristics. Different methodologies of preparation were attempted to synthesize an all trans-configuration in the five-conjugated double bonds. Unfortunately, across the C3’ bond on the tail, geometric isomers were obtained. However, TBSO-αT5 was produced in what appeared to be ≈ 2:1 E:Z mixture across the C3’ bond (having the four other olefins with trans-configurations). α-Tocopentaenol showed a strong absorbance in ethanol with a maximum λab= 338 nm. This compound is stable as an oil, stored at -78˚C and protected from light for over a month with minimal degradation. Because αT5 resembles the naturally occurring form of the vitamin E, this analogue will enhance our ability to study the biological activity of vitamin E and will create an easy method of monitoring its presence in solution and cells.
    • 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.
    • Epimeric Pyrroloimidazolone Auxiliaries in the Diastereoselective Synthesis of Chiral N-Ferrocenyl/N-Phenyl Ligands and Arene-Chromium Tricarbonyl Complexes

      Wilson-Konderka; Department of Chemistry
      This thesis describes the synthesis and use of an N-based L-proline derived chiral auxiliary/directing group for selective synthesis of planar chiral and central chiral products. A series of planar chiral ferrocenes were prepared, and converted to chloroimidazoliums and complexed to palladium via oxidative addition. In addition to this, a centrally chiral Ir(I) catalyst was prepared for the purpose of evaluating the importance of planar chirality for the induction of enantioselectivity in the Ir(I) catalyzed hydrogenations of 2-substituted quinolines. A lower enantioselectivity was observed, allowing the conclusion that planar chirality does contribute to the enantioselectivity. The pyrroloimidazolone directing group used to induce high diastereoselectivity in ferrocene lithiations (>95:5 dr) has been applied (with minor modifications) towards the diastereoselective lithiation of η6-arene chromium tricarbonyl complexes. The anti-epimer of the pyrroloimidazolone auxiliary undergoes pro-R lithiation in >95:5 dr. The syn-epimer of this auxiliary undergoes pro-S lithiation in >95:5 dr. The origin of selectivity is believed to be caused by a conformational bias exerted by the O-group. The selectivity of lithiations, and stereochemistry of all the products has been confirmed by a combination of X-ray analysis, transmetalation and deuteration experiments and by the preparation and comparison of solely planar chiral enantiomers.
    • Development of a Class of Cyclopropenimine Based Compounds for Application in Catalysis

      Stoyanov, Petyo; Department of Chemistry
      The present thesis outlines our latest findings in the pursuit of novel bis(diisopropylamino)cyclopropenimine (DAC) compounds. Particular focus was placed on the synthesis and investigation of DAC-substituted proton sponges, as well as their application in organo-catalysis. Herein, we report the synthesis of a non-symmetric DAC-functionalized proton sponge coined “Janus” sponge. Theoretical and experimental investigation of this sponge provided a monoprotonated salt, without a N-HN intramolecular hydrogen bond and a relatively low freebase strain. Instead, DFT calculations and X-ray crystallography revealed the presence of a hydrogen bond to the Cl- counter ion, leading to the unprecedented ¬in-out geometry of the molecule. Furthermore, the salt of the Janus sponge was found to be highly fluorescent both in the solid state and solution. Its experimentally measured pKa of 23.8 was found to be in good agreement with the calculated value of 23.9. The use of Janus, as well as the previously synthesized DACN (a naphthalene DAC derivative) sponge in phase transfer catalysis was also explored. The DACN proton sponge was found to be a highly efficient bifunctional phase-transfer catalyst, facilitating the movement of charged intermediates from the interface to the organic layer via favourable partitioning of hydrophilic/hydrophobic surface areas.
    • Polynuclear 3d/4f-Metal Complexes as Molecular Magnetic Refrigerants and Single-Molecule Magnets

      Richardson, Paul; Department of Chemistry
      The use of two different chelating/bridging ligands, naphthalene-2,3-diol (ndH2) and acenaphthenequinone dioxime (acndH2), in heterometallic 3d/4f-metal cluster chemistry has yielded two new families of polynuclear CuII/LnIII clusters. These complexes were found to exhibit interesting magnetic properties, specifically single-molecule magnetism and the magnetocaloric effect. In this thesis, Chapter 1 lays the foundation for the research presented within. This section covers the fundamentals of polynuclear metal complexes, molecular magnetism, and the magnetocaloric effect, as well as the approaches used for the synthesis of new polynuclear metal complexes and the choice of ligands. Chapters 2 and 3 report the results of the current thesis. In Chapter 2, the synthesis and characterization of a family of {Cu4Ln} complexes (LnIII = GdIII (1), TbIII (2), DyIII (3)), employing the ligand ndH2 is presented. The complexes join a handful of previously reported {Cu4Ln} clusters, however, the family reported in this thesis are the first ‘propeller’-like clusters that exhibit single-molecule magnetism and magnetic refrigeration properties. In Chapter 3, a family of {Cu6Ln2}n chains (LnIII = GdIII (4), TbIII (5), DyIII (6)) obtained through the employment of ligand acndH2 is presented. This family of 1D-chains is a novel motif that has not been previously reported in the literature, with only a few discrete {Cu6Ln2} 0D-clusters having been previously reported. The complexes were magnetically characterized, with 4 and 5 exhibiting ferromagnetic exchange interactions while 6 revealed a more complex magnetic behaviour with both ferromagnetic and antiferromagnetic interactions dominating at different temperature regimes. Furthermore, 5 was found to behave as a single-molecule magnet and 4 was shown to act as a molecular magnetic refrigerant.
    • Ligand Design for Dual Property Single Molecule Magnets

      Pham, Trinh N.K.; Department of Chemistry
      This thesis describes two different approaches for the preparation of polynuclear clusters with interesting structural, magnetic and optical properties. Firstly, exploiting p-tert-butylcalix[4]arene (TBC4) macrocycles together with selected Ln(III) ions for the assembly of emissive single molecule magnets, and secondly the preparation and coordination of a chiral mpmH ligand with selected 3d transition metal ions, working towards the discovery of chiral polynuclear clusters. In Project 1, the coordination chemistry of the TBC4 macrocycle together with Dy(III) and Tb(III) afforded two Ln6[TBC4]2 complexes that have been structurally, magnetically and optically characterized. X-ray diffraction studies reveal that both complexes contain an octahedral core of Ln6 ions capped by two fully deprotonated TBC4 macrocycles. Although the unit cells of the two complexes are very similar, the coordination geometries of their Ln(III) ions are subtly different. Variable temperature ac magnetic susceptibility studies reveal that both complexes display single molecule magnet (SMM) behaviour in zero dc field and the energy barriers and associated pre-exponential factors for each relaxation process have been determined. Low temperature solid state photoluminescence studies reveal that both complexes are emissive; however, the f-f transitions within the Dy6 complex were masked by broad emissions from the TBC4 ligand. In contrast, the Tb(III) complex displayed green emission with the spectrum comprising four sharp bands corresponding to 5D4 → 7FJ transitions (where J = 3, 4, 5 and 6), highlighting that energy transfer from the TBC4 macrocycle to the Tb(III) ion is more effective than to Dy. Examples of zero field Tb(III) SMMs are scarce in the chemical literature and the Tb6[TBC4]2 complex represents the first example of a Tb(III) dual property SMM assembled from a p-tert-butylcalix[4]arene macrocycle with two magnetically derived energy barriers, Ueff of 79 and 63 K. In Project 2, the coordination of both enantiomers of the chiral ligand, α-methyl-2-pyridinemethanol (mpmH) to Ni(II) and Co(II) afforded three polynuclear clusters that have been structurally and magnetically characterized. The first complex, a Ni4 cluster of stoichiometry [Ni4(O2CCMe3)4(mpm)4]·H2O crystallizes in a distorted cubane topology that is well known in Ni(II) cluster chemistry. The final two Co(II) complexes crystallize as a linear mixed valence trimer with stoichiometry [Co3(mpm)6]·(ClO4)2, and a Co4 mixed valence complex [Co(II)¬2Co(III)2(NO3)2(μ-mpm)4(ONO2)2], whose structural topology resembles that of a defective double cubane. All three complexes crystallize in chiral space groups and circular dichroism experiments further confirm that the chirality of the ligand has been transferred to the respective coordination complex. Magnetic susceptibility studies reveal that for all three complexes, there are competing ferro- and antiferromagnetic exchange interactions. The [Co(II)¬2Co(III)2(NO3)2(μ-mpm)4(ONO2)2] complex represents the first example of a chiral mixed valence Co4 cluster with a defective double cubane topology.
    • High-Spin and Emissive Molecular Materials: Synthesis and Characterization of New Polynuclear Ni(II) Complexes from the Use of Aromatic Schiff Bases as Bridging Ligands

      Perlepe, Panagiota; Department of Chemistry
      The employment of the bridging/chelating Schiff bases, N-salicylidene-4-methyl-o-aminophenol (samphH2) and N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH2), in nickel cluster chemistry has afforded eight polynuclear Ni(II) complexes with new structural motifs, interesting magnetic and optical properties, and unexpected organic ligand transformations. In the present thesis, Chapter 1 deals with all the fundamental aspects of polynuclear metal complexes, molecular magnetism and optics, while research results are reported in Chapters 2 and 3. In the first project (Chapter 2), I investigated the coordination chemistry of the organic chelating/bridging ligand, N-salicylidene-4-methyl-o-aminophenol (samphH2). The general NiII/tBuCO2-/samphH2 reaction system afforded two new tetranuclear NiII clusters, namely [Ni4(samph)4(EtOH)4] (1) and [Ni4(samph)4(DMF)2] (2), with different structural motifs. Complex 1 possessed a cubane core while in complex 2 the four NiII ions were located at the four vertices of a defective dicubane. The nature of the organic solvent was found to be of pivotal importance, leading to compounds with the same nuclearity, but different structural topologies and magnetic properties. The second project, the results of which are summarized in Chapter 3, included the systematic study of a new optically-active Schiff base ligand, N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH2), in NiII cluster chemistry. Various reactions between NiX2 (X- = inorganic anions) and nacbH2 were performed under basic conditions to yield six new polynuclear NiII complexes, namely (NHEt3)[Ni12(nacb)12(H2O)4](ClO4) (3), (NHEt3)2[Ni5(nacb)4(L)(LH)2(MeOH)] (4), [Ni5(OH)2(nacb)4(DMF)4] (5), [Ni5(OMe)Cl(nacb)4(MeOH)3(MeCN)] (6), (NHEt3)2[Ni6(OH)2(nacb)6(H2O)4] (7), and [Ni6(nacb)6(H2O)3(MeOH)6] (8). The nature of the solvent, the inorganic anion, X-, and the organic base were all found to be of critical importance, leading to products with different structural topologies and nuclearities (i.e., {Ni5}, {Ni6} and {Ni12}). Magnetic studies on all synthesized complexes revealed an overall ferromagnetic behavior for complexes 4 and 8, with the remaining complexes being dominated by antiferromagnetic exchange interactions. In order to assess the optical efficiency of the organic ligand when bound to the metal centers, photoluminescence studies were performed on all synthesized compounds. Complexes 4 and 5 show strong emission in the visible region of the electromagnetic spectrum. Finally, the ligand nacbH2 allowed for some unexpected organic transformations to occur; for instance, the pentanuclear compound 5 comprises both nacb2- groups and a new organic chelate, namely the anion of 5-chloro-2-[(3-hydroxy-4-oxo-1,4-dihydronaphthalen-1-yl)amino]benzoic acid. In the last section of this thesis, an attempt to compare the NiII cluster chemistry of the N-naphthalidene-2-amino-5-chlorobenzoic acid ligand with that of the structurally similar but less bulky, N-salicylidene-2-amino-5-chlorobenzoic acid (sacbH2), was made.
    • A Bicyclic L-Proline Derived Chiral Auxiliary for Asymmetric Synthesis

      Emberson, Kassandra; Department of Chemistry
      This thesis describes the use of an L−proline-derived chiral auxiliary for diastereoselective lithiation and ligand synthesis. Such compounds have been utilized in the Metallinos research group previously for the synthesis of N−substituted planar chiral ferrocenes. The first project describes the use of this chiral auxiliary as a directing group for N−benzyl substitution, providing products in up to 10:1 diastereomeric ratio (dr). These derivatives may serve as chiral ylidene precursors to serve as ligands in transition metal catalysis. In addition, an N−substituted planar chiral ferrocene ylidene ligand derived from the same chiral auxiliary was used to prepare rhodium complexes that were explored as potential catalysts for asymmetric hydroformylation.
    • DFT Studies of the Organocatalytic Aldol Reaction and a Frustrated Lewis Pair

      Movahedi, Shahab; Department of Chemistry
      The computational study, and in particular the density functional theory (DFT) study of the organocatalytic α-chlorination-aldol reaction and the chiral backbone Frustrated Lewis Pair (FLP) system served as a valuable tool for experimental purposes. This thesis describes methods to consider different transition states of the proline- catalyzed α-chlorination aldol reaction to determine the reasonable transition state in the reaction between the enamine and α-chloro aldehydes. Moreover, the novel intramolecular Frustrated Lewis pair based on a chiral backbone for the asymmetric hydrogenation of imines and enamines was designed and the ability of hydrogen splitting by this new FLP system was examined by computational modeling and calculating the hydrogen activation energy barrier.
    • Approach to the Synthesis of Aza-Analogues of Narciclasine through an Intramolecular Heck Reaction

      W'Giorgis, Zemane; Department of Chemistry
      This thesis describes work towards the total synthesis of a 7-aza analogue of the Amaryllidaceae alkaloid narciclasine, a potent anticancer compound which suffers from a poor solubility profile. A key strategy in the formation of the C-ring is the biotransformation of bromobenzene by E.coli JM109. The densely substituted heterocyclic A-ring is obtained by sequential directed ortho-metalation and the fragment union accomplished with an amide coupling and subsequent intramolecular Heck reaction.
    • (A) Photoregulation of DNA Functions by Cyclic Azobenzene-tethered Oligonucleotides (B) Site-specific Fluorescent Labeling of DNA using Inverse Electron Demand Diels-Alder Reaction between trans-Cyclooctene Derivatives and BODIPY-Tetrazine Adducts

      Eljabu, Fatma Mohamed; Department of Chemistry
      (A) Most azobenzene-based photoswitches require UV light for photoisomerization, which limit their applications in biological systems due to possible photodamage. Cyclic azobenzene derivatives, on the other hand, can undergo cis-trans isomerization when exposed to visible light. A shortened synthetic scheme was developed for the preparation of a building block containing cyclic azobenzene and D-threoninol (cAB-Thr). trans-Cyclic azobenzene was found to thermally isomerize back to the cis-form in a temperature-dependent manner. cAB-Thr was transformed into the corresponding phosphoramidite and subsequently incorporated into oligonucleotides by solid phase synthesis. Melting temperature measurement suggested that incorporation of cis-cAB into oligonucleotides destabilizes DNA duplexes, these findings corroborate with circular dichroism measurement. Finally, Fluorescent Energy Resonance Transfer experiments indicated that trans-cAB can be accommodated in DNA duplexes. (B) Inverse Electron Demand Diels-Alder reactions (IEDDA) between trans-olefins and tetrazines provide a powerful alternative to existing ligation chemistries due to its fast reaction rate, bioorthogonality and mutual orthogonality with other click reactions. In this project, an attempt was pursued to synthesize trans-cyclooctene building blocks for oligonucleotide labeling by reacting with BODIPY-tetrazine. Rel-(1R-4E-pR)-cyclooct-4-enol and rel-(1R,8S,9S,4E)-Bicyclo[6.1.0]non-4-ene-9-ylmethanol were synthesized and then transformed into the corresponding propargyl ether. Subsequent Sonogashira reactions between these propargylated compounds with DMT-protected 5-iododeoxyuridine failed to give the desired products. Finally a methodology was pursued for the synthesis of BODIPY-tetrazine conjugates that will be used in future IEDDA reactions with trans-cyclooctene modified oligonucleotides.
    • Assessing the Reproducibility of Clustering of Molecular Dynamics Conformations on Self-Organizing Maps

      Eisner, Michelle; Department of Chemistry
      The goal of most clustering algorithms is to find the optimal number of clusters (i.e. fewest number of clusters). However, analysis of molecular conformations of biological macromolecules obtained from computer simulations may benefit from a larger array of clusters. The Self-Organizing Map (SOM) clustering method has the advantage of generating large numbers of clusters, but often gives ambiguous results. In this work, SOMs have been shown to be reproducible when the same conformational dataset is independently clustered multiple times (~100), with the help of the Cramérs V-index (C_v). The ability of C_v to determine which SOMs are reproduced is generalizable across different SOM source codes. The conformational ensembles produced from MD (molecular dynamics) and REMD (replica exchange molecular dynamics) simulations of the penta peptide Met-enkephalin (MET) and the 34 amino acid protein human Parathyroid Hormone (hPTH) were used to evaluate SOM reproducibility. The training length for the SOM has a huge impact on the reproducibility. Analysis of MET conformational data definitively determined that toroidal SOMs cluster data better than bordered maps due to the fact that toroidal maps do not have an edge effect. For the source code from MATLAB, it was determined that the learning rate function should be LINEAR with an initial learning rate factor of 0.05 and the SOM should be trained by a sequential algorithm. The trained SOMs can be used as a supervised classification for another dataset. The toroidal 10×10 hexagonal SOMs produced from the MATLAB program for hPTH conformational data produced three sets of reproducible clusters (27%, 15%, and 13% of 100 independent runs) which find similar partitionings to those of smaller 6×6 SOMs. The χ^2 values produced as part of the C_v calculation were used to locate clusters with identical conformational memberships on independently trained SOMs, even those with different dimensions. The χ^2 values could relate the different SOM partitionings to each other.
    • Polynuclear Ni(II) Complexes with Schiff Bases as Bridging Ligands: A Molecular Approach to Nanoscience

      Athanasopoulou, Angeliki; Department of Chemistry
      The initial employment of N-salicylidene-2-amino-5-chlorobenzoic acid (sacbH2) as bridging/chelating ligand in metal cluster chemistry has provided access to five new polynuclear NiII complexes with large nuclearities, unprecedented metal core topologies, and interesting magnetic properties. The obtained results are presented in two projects. The first project includes the investigation of the general Ni2+/RCO2-/sacbH2 reaction system (where R- = CH3-, But-, ButCH2-) in which the nature of the carboxylic acid was found to be of crucial importance, affecting enormously the nuclearity of the resulting complexes. The second project deals with the study of the general Ni2+/X-/sacbH2 reaction system (where X- = inorganic anions) under basic conditions, yielding new cluster compounds with molecular chain-like structures and ferromagnetic exchange interactions between the metal centers.
    • 3-O-Demethylation of thebaine and the synthesis of a flacourtia aglycone from benzoic acid.

      Murphy, Brennan; Department of Chemistry
      Two synthetic projects were embarked upon, both fraught with protecting group nuance and reaction selectivity. Transformations of the opiate skeleton remain a valuable tool for the development of new medicines. Thebaine, a biosynthetic intermediate in the expression of morphine, was converted in three steps to oripavine through two parallel modes. Through the use of protecting group manipulations, two irreversible scaffold rearrangements were avoided during aryl methyl ether bond cleavage. This chemistry constitutes a new path in manipulations of the morphinan scaffold through protective groups. A new compound family, the flacourtosides, contains an unusual cyclohexenone fragment. The newly described compounds show in preliminary tests antiviral activity against dengue and chikungunya. This aglycone was approached on three pathways, all beginning with the chemoenzymatic dihydroxylation of benzoic acid. A first attempt from a known vinyl epoxide failed to epimerize and cooperate under deprotective conditions. A second and third attempt made use of a diastereoselective dihydroxylation reaction, which was critical in reaching the correct stereochemistry and oxidation state. The methyl ester of the aglycone was prepared, constituting the first synthesis of the non-trivial natural product framework.
    • Predicting the Pose of β-Casomorphin-5 and 7 in the Opioid Receptors

      Oberc, Christopher; Department of Chemistry
      The opioid receptors consist of three main subtypes; μ, δ, and κ. Previous binding studies have shown that fragments of the milk protein, β-casein, known as β-casomorphins are agonists of these receptors which are selective for the μ receptor subtype. Using the crystal structures of these three receptors, computational molecular docking studies were done using the software GOLD to determine the conformation of β-casomorphin-5 and 7 when they bind to these three opioid receptors. GOLD was able to discriminate among the three receptors when docking the rigid ligands co-crystalized with the receptors. However, GOLD could not discriminate among the three receptors for either of the highly flexible β-casomorphins. A per amino acid scoring method was developed to overcome this problem. This method was used to predict the conformation of both β-casomorphin-5 and 7 in the μ receptor and determine that the two amino acid residues, Lys303 and Trp318 of the μ receptor are responsible for discriminating among the three receptor subtypes for binding of the β-casomorphin-5 and 7.
    • 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.
    • Explorations of Intramolecular [5+2] Cycloadditions of Ring-Constrained Vinylcyclopropanes

      Bissett, Tyler; Department of Chemistry (Brock University, 2014-09-19)
      The first example of a [5+2] cycloaddition reaction wherein the olefin of the vinylcyclopropyl moiety is constrained in a carbocycle was explored, and possible reasons on the lack of reactivity of the substrate were studied. A simple model substrate was synthesized and subjected to cycloaddition conditions to determine if the reason for the lack of reactivity was related to the complexity of the substrate, or if the lack of “conjugative character” of the cyclopropyl ring with respect to the olefin is responsible. A more complex bicyclic substrate possessing an angular methyl group at the ring junction was also synthesized and explored, with evidence supporting the current theory of deconjugation of the cyclopropyl moiety.
    • Racemic and Enantioselective Total Syntheses of Mosquito Oviposition Pheromone from a Naturally Available Unsaturated Fatty Acid

      Hurem, David; Department of Chemistry (Brock University, 2014-09-11)
      The unnatural threo-6-acetoxy-5-hexadecanolide and the natural mosquito oviposition pheromone erythro-6-acetoxy-5-hexadecanolide were synthesized in a diastereodivergent fashion in 44% and 33% overall yield respectively from 5-bromovaleric acid and undecanal. The key step utilized a chemoenzymatic epoxidation-lactonization of a naturally available fatty acid to form the 6-hydroxy-5-hexadecanolide core.17 The epoxidation strategy was later adapted to allow for an asymmetric synthesis. Shi epoxidation afforded highly enantioenriched (5R, 6R)-6-hydroxyhexadecanolide (er = 10) in 70 % overall yield. Other derivatives of the chiral ketone catalyst were also screened. Finally, attempts were made to obtain the correct stereochemistry at C(6) of the target with a dynamic kinetic transformation using lipase and a transfer hydrogenation catalyst. Epimerization of the lactol with the transfer hydrogenation catalyst was successful, but lipase mediated reactions halted at <10 % conversion.
    • Diastereoselective Lithiation-Substitution of N-Silyl-Protected-(S)-Tetrahydro-1H-pyrrolo[1,2-c]imidazole-3(2H)-ones and Applications of Their Derivatives

      Sadraei, Seyed Iraj; Department of Chemistry (Brock University, 2014-09-10)
      This thesis describes a method involving the preparation of an L-proline-derived imidazolone protected with an N-triethylsilyl group that undergoes diastereoselective lithiation followed by electrophile quench to give C5-substituted products with syn stereochemistry. The N-silylated derivatives may be more easily N-deprotected as compared to previous N-t-Bu analogues to give secondary ureas. These may serve as precursors to N-phenyl chiral bicyclic guanidines or as NHC precursors for synthesis of corresponding complexes.