• Dynamic DNA Nanotechnology for Probing Single Nucleotide Variants and DNA Modifications

      Wang, Guan; Department of Chemistry
      In the last decades, various DNA hybridization probes have been developed that attempt to conquer the challenge of single-nucleotide-variants (SNVs) detection. Even though a powerful toolbox including the toehold-exchange reaction, the dynamic ‘sink’ design, and the polymerase chain reaction (PCR) has been built, it still faces practical problems. For example, the natural DNA is usually in double-stranded form whereas most hybridization probes aim for single-stranded targets; the concentration of extracted DNA samples is totally unknown thus may lay outside the optimal design of probes/primers. To achieve ultra-high sensitivity and specificity, expensive and sophisticated machines such as digital droplet PCR and next-generation-sequencing may be inapplicable in rural areas. Therefore, the quantitative PCR method is still the gold standard for clinical tests. Thus motivated, my PhD career was mainly focused on the fundamental understanding of the challenges in SNVs discrimination and developing robust, versatile, and user-friendly probes/strategies. In this thesis, Chapter 1 provides a general introduction of dynamic DNA nanotechnology and its representative applications in discriminating SNVs. Chapter 2 to 4 describe three completed projects that aim to understand the thermodynamic and kinetic properties of strand displacement reactions and to circumvent the challenges of discriminating SNVs through finely tuned probes/assays.
    • Electron Transfer Involving the Phylloquinone (A1) Cofactor of Photosystem I Examined with Time Resolved Absorbance and Electron Paramagnetic Resonance Spectroscopy

      Mula, Samuel Jr.; Department of Chemistry (Brock University, 2015-01-23)
      The dependence of the electron transfer (ET) rate on the Photosystem I (PSI) cofactor phylloquinone (A1) is studied by time-resolved absorbance and electron paramagnetic resonance (EPR) spectroscopy. Two active branches (A and B) of electron transfer converge to the FX cofactor from the A1A and A1B quinone. The work described in Chapter 5 investigates the single hydrogen bond from the amino acid residue PsaA-L722 backbone nitrogen to A1A for its effect on the electron transfer rate to FX. Room temperature transient EPR measurements show an increase in the rate for the A1A- to FX for the PsaA-L722T mutant and an increased hyperfine coupling to the 2-methyl group of A1A when compared to wild type. The Arrhenius plot of the A1A- to FX ET in the PsaA-L722T mutant suggests that the increased rate is probably the result of a slight change in the electronic coupling between A1A- and FX. The reasons for the non-Arrhenius behavior are discussed. The work discussed in Chapter 6 investigates the directionality of ET at low temperature by blocking ET to the iron-sulfur clusters FX, FA and FB in the menB deletion mutant strain of Synechocyctis sp. PCC 6803, which is unable to synthesize phylloquinone, by incorporating the high midpoint potential (49 mV vs SHE) 2,3-dichloro-1,4-naphthoquinone (Cl2NQ) into the A1A and A1B binding sites. Various EPR spectroscopic techniques were implemented to differentiate between the spectral features created from A and B- branch electron transfer. The implications of this result for the directionality of electron transfer in PS I are discussed. The work discussed in Chapter 7 was done to study the dependence of the heterogeneous ET at low temperature on A1 midpoint potential. The menB PSI mutant contains plastiquinone-9 in the A1 binding site. The solution midpoint potential of the quinone measures 100 mV more positive then wild-type phylloquinone. The irreversible ET to the terminal acceptors FA and FB at low temperature is not controlled by the forward step from A1 to FX as expected due to the thermodynamic differences of the A1 cofactor in the two active branches A and B. Alternatives for the ET heterogeneity are discussed.
    • Half-sandwich Complexes of Ruthenium Supported by N-Heterocyclic Carbene Ligands: Synthesis and Application to Catalysis

      Mai, Van Hung; Department of Chemistry
      This thesis presents the preparation and catalytic reactivity of novel half-sandwich ruthenium complexes supported by N-Heterocyclic Carbene (NHC) ligands. The cationic half-sandwich ruthenium complexes [Cp(IPr)Ru(CH3CN)2]+ show interesting reactivities toward the transfer hydrogenation of different unsaturated substrates, such as ketones, olefins, N-heterocycles, and nitriles. Kinetic studies disclose that a neutral trishydride ruthenium complex is actually involved in the catalytic cycle, playing the role as a resting state. Further investigations on the sub-class of trishydride ruthenium complexes bearing NHC ligands (Cp'(NHC)RuH3) reveal that these complexes have an unusual and great catalytic performance toward the hydrodefluorination (HDF) of fluorinated aromatic and aliphatic compounds. The combined kinetic studies, cross-over experiments and rate law analysis suggest an unusual mechanistic pathway for the Cp*(IPr)RuH3 catalyzed HDF. This study is one of the rare examples where isopropanol is employed as a reducing agent for the metal-mediated HDF reaction. A class of silyl dihydride ruthenium complexes, derived from Cp(IPr)RuH3 are prepared. These silyl hydrido derivatives are great compounds for the study of the inter ligand hypervalent interaction (IHI), an interesting phenomenon for many non-classical silane complexes. This study also suggests that the replacement of phosphines by their isolobally analogous NHC ligands result in stronger IHI interactions in the corresponding compounds. Another type of non-classical interaction was systematically scrutinized in a ii series of new cationic and neutral silane sigma complexes of ruthenium bearing different silyl moieties. These new NHC-supported ruthenium complexes allow for direct comparation with the known phosphine analogues, which reveals interplay of steric and electronic factors on the extent of Si-H complexation to metal and the extent of additional interligand interactions between Ru-Cl and chlorosilane ligand. Finally, new trishydride ruthenium complexes bearing NHC ligands (Cp'(NHC)RuH3) catalyze the H/D exchange reaction of various N-heterocycle substrates; their catalytic performance can be considered as one of the mildest, and most efficient approaches.
    • Half-sandwich Complexes of Ruthenium; Synthesis and Application to Catalysis

      Lee, Sun Hwa; Department of Chemistry (Brock University, 2014-09-15)
      This thesis describes syntheses and catalytic reactivity of several half-sandwich complexes of ruthenium. The neutral ruthenium trihydride complex, Cp(PPri3)RuH3(1), can efficiently catalyse the H/D exchange reaction between various organic substrates and deuterium sources, such as benzene-d6. Moreover, the H/D exchange reactions of polar substrates were also observed in D2O, which is the most attractive deuterium source due to its low cost and low toxicity. Importantly, the H/D exchange under catalytic conditions was achieved not only in aromatic compounds but also in substituted liphatic compounds. Interestingly, in the case of alkanes and alkyl chains, highly selective deuterium incorporation in the terminal methyl positions was observed. It was discovered that the methylene units are engaged in exchange only if the molecule contains a donating functional group, such as O-and N-donors, C=C double bonds, arenes and CH3. The cationic half-sandwich ruthenium complex [Cp(PPri3)Ru(CH3CN)2]+(2) catalyses the chemoselective mono-addition of HSiMe2Ph to pyridine derivatives to selectively give the 1,4-regiospecific, N-silylated products. An ionic hydrosilylation mechanismis suggested based on the experiments. To support this mechanistic proposal, kinetic studies under catalytic conditions were performed. Also, the 1,4-regioselective mono-hydrosilylation of nitrogen containing compounds such as phenanthroline, quinoline and acridine can be achieved with the related Cp*complex [Cp*(phen)Ru(CH3CN)]+(3) (phen = 1,10-phenanthroline) and HSiMe2Ph under mild conditions. The cationic ruthenium complex 2 can also be used as an efficient catalyst for transfer hydrogenation of various organic substrates including carbonyls, imines, nitriles and esters. Secondary alcohols, amines, N-isopropylidene amines and ether compounds can be obtained in moderate to high yields. In addition, other ruthenium complexes, 1,3 and [Cp*(PPri3)Ru(CH3CN)2]+(4), can catalyse transfer hydrogenation of carbonyls although the reactions were sluggish compared to the ones of 2. The possible intermediate, Cp(PPri3)Ru(CH3CN)(H), was characterized by NMR at low temperature and the kinetic studies for the transfer hydrogenation of acetophenone were performed. Recently, chemoselective reduction of acid chlorides to aldehydes catalysed by the complex 2 was reported. To extend the catalytic reactivity of 2, reduction of iminoyl chlorides, which can be readily obtained from secondary amides, to the corresponding imines and aldehydes was investigated. Various substituted iminoyl chlorides were converted into the imines and aldehydes under mild conditions and several products were isolated with moderate yields.
    • Half-sandwich silane complexes of ruthenium and iron : synthesis, structure and application to catalysis

      Gutsulyak, Dmitry V.; Department of Chemistry (Brock University, 2012-04-04)
      The present thesis describes syntheses, structural studies, and catalytic reactivity of new non-classical silane complexes of ruthenium and iron. The ruthenium complexes CpRu(PPri3)CI(T]2-HSiR3) (1) (SiR3 = SiCh (a), SiClzMe (b), SiCIMe2 (c), SiH2Ph (d), SiMe2Ph (e» were prepared by reactions of the new unsaturated complex CpRu(PPri3)CI with silanes. According to NMR studies and X-ray analyses, the complexes la-c exhibit unusual simultaneous Si··· H and Si··· CI-Ru interactions. The complex CpRu(PPri3)CI was also used for the preparation of the first examples of late transition metal agostic silylamido complexes CpRu(PPri3)(N(T]2-HSiMe2)R) (2) (R= Ar or But), which were characterized by NMR spectroscopy. The iron complexes CpFe(PMePri2)H2(SiR3) (3) (SiR3 = SiCh (a), SiClzMe (b), SiCIMe2 (c), SiH2Ph (d), SiMe2Ph (e» were synthesized by the reaction of the new borohydride iron complex CpFe(PMePri2)(B~) with silanes in the presence NEt3. The complexes 3 exhibit unprecedented two simultaneous and equivalent Si··· H interactions, which was confirmed by X-ray analyses and DFT calculations. A series of cationic ruthenium complexes [CpRu(PR3)(CH3CN)(112-HSiR'3)]BAF (PR3 = PPri 3 (4), PPh3 (5); SiR'3 = SiCh (a), SiClzMe (b), SiClMe2 (c), SiH2Ph (d), SiMe2Ph (e» was obtained by substitution of one of the labile acetonitrile ligands in [CpRu(PR3)(CH3CNh]BAF with sHanes. Analogous complexes [TpRu(PR3)(CH3CN)(T]2 -HSiR' 3)]BAF (5) were obtained by the reaction of TpRu(PR3)(CH3CN)CI with LiBAF in the presence of silanes. The complexes 4-5 were characterized by NMR spectroscopy, and the observed coupling constants J(Si-H) allowed us to estimate the extent of Si-H bond activation in these compounds. The catalytic activity in hydrosilylation reactions of all of the above complexes was examined. The most promising results were achieved with the cationic ruthenium precatalyst [CpRu(PPri3)(CH3CN)2t (6). Complex 6 shows good to excellent catalytic activity in the hydrosilylation of carbonyls, dehydrogenative coupling of silanes with alcohols, amines, acids, and reduction of acid chlorides. We also discovered very selective reduction of nitriles and pyridines into the corresponding N-silyl imines and l,4-dihydropyridines, respectively, at room temperature with the possibility of catalyst recycling. These chemoselective catalytic methods have no analogues in the literature. The reactions were proposed to proceed via an ionic mechanism with intermediate formation of the silane a-complexes 4.
    • High-Nuclearity Lanthanide(III) Complexes as Single-Molecule Magnets and Luminescent Materials

      Mazarakioti, Eleni; Department of Chemistry
      The employment of the bridging/chelating Schiff base ligands, N-salicylidene-o-aminophenol (saphH2), N-salicylidene-o-aminocyclohexanol (sachH2) and N-salicylidene-2-amino-5-chlorobenzoic acid (sacbH2), in lanthanide (LnIII) cluster chemistry has afforded four families of polynuclear and dinuclear complexes with new structural motifs, and interesting magnetic and optical properties. Chapter 1 deals with most of the fundamental aspects within the areas of polynuclear metal complexes, molecular magnetism and optics as these are applied to 4f-metal based systems, while the research results are reported in Chapters 2, 3 and 4. In the first project (Chapter 2), the coordination chemistry of the organic chelating/bridging ligand, N-salicylidene-o-aminophenol (saphH2) in lanthanide cluster chemistry was investigated. The general LnIII/X-/saphH2/base reaction system has led to a family of (NHEt3)[Ln7(OH)2(saph)10(Me2CO)2] (Ln = Gd (1); Tb (2); Dy (3)) clusters with a new core topology that comprises two {Ln4} butterflies sharing a common metal vertex. The {DyIII7} analogue exhibits slow magnetization relaxation, whereas all heptanuclear compounds show ligand-centered blue-green emissions. The second project of this thesis, which is discussed in Chapter 3, comprises the first use of the Schiff base ligand N-salicylidene-2-aminocyclohexanol (sachH2; mixture of cis- and trans-analogue) in metal cluster chemistry which has afforded a new family of [Ln7(OH)6(CO3)3(sach)3(sachH)3(MeOH)6] (Ln = Gd (4); Tb (5); Dy (6)) clusters with ideal D3h point group symmetry and metal-centered trigonal prismatic topology. Solid-state and solution studies revealed single-molecule magnetism (SMM) and photoluminescence behaviors. Moreover, in order to investigate the steric and stereoisomerism effects of the ligand on the chemical and structural identity of the {Ln7} clusters, the pure trans-analogue of the sachH2 ligand was utilized. As a result, a new family of octanuclear [Ln8(OH)4(CO3)2(trans-sach)8(EtOH)4] (Ln = Gd (7); Tb (8); Dy (9); Eu (10)) clusters were obtained, while the solid-state studies revealed SMM behavior and lanthanide-centered emissions. In the last chapter of this thesis (Chapter 4), the Schiff base ligand N-salicylidene-2-amino-5-chlorobenzoic acid (sacbH2) was introduced for a first time in lanthanide cluster chemistry. This has afforded a family of dinuclear [Ln2(NO3)4(sacbH)2(H2O)2(MeCN)2] compounds (Ln = Gd (11); Tb (12); Dy (13)) with the Dy-analogue exhibiting SMM behaviour with a high-energy barrier for the magnetization reversal and interesting magnetization dynamics. All research-based Chapters (Chapters 2-4) are divided into subsections in order to facilitate the understanding of the research concepts by the familiar and non-familiar readers and contextualize the messages, goals and conclusions of each individual project. I felt it prudent to always begin with a short preface of the work that summarizes the most important aspects of the specific project, followed by the complete experimental part and discussion of the results, and finishing up with conclusions and some future perspectives.
    • High-Nuclearity Metal Complexes and Single-Molecule Magnets from the Employment of Oximato- and Alkoxido-based Ligands

      Giannopoulos, Dimosthenis; Department of Chemistry
      The employment of 2-pyrrolyloximes, pyridine-2,6-diketones and 3-hydroxy-2-naphthohydroxamic acid in homometallic 3d- and heterometallic 3d/4f-metal cluster chemistry has yielded new families of Fe, Mn and Mn/Dy clusters. These complexes were shown to possess interesting structural motifs and single-molecule magnetism (SMM) behaviour. The introductory chapter discusses the fundamentals of molecular magnetism, polynuclear metal complexes, as well as the approaches used for the synthesis of new polynuclear metal complexes and the selection criteria for the chelating/bridging ligands. Chapters 2, 3 and 4 report the results of the current thesis. In Chapter 2, the synthesis and characterization of a family of complexes resulting from the employment of 2-pyrrolyloximes in high-nuclearity transition metal cluster chemistry is reported. Complexes {Fe10} (1) and {Fe12} (2) are two of the highest nuclearity iron clusters containing an oximate ligand, while complex 3 is a barrel-like {Mn25Na} complex that exhibits SMM behaviour. Although there are previously reported examples of discrete {Mn25} barrel-like SMMs, complex 3 is the highest nuclearity Mn cluster organized into a 1D polymer through chelation with diamagnetic metal centers. Chapter 3 includes the synthesis and characterization of new Mn complexes featuring ligands that result from the metal-assisted reactivity of pyridyl- and pyrazine-based diketones. Complexes {Mn6} (4) and {Mn10} (5) are the highest nuclearity Mn clusters containing any form of the ligand 2,6-di-(2-pyridylcarbonyl)pyridine [(py)CO(py)CO(py)]. Despite the large number of {Mn6} and {Mn10} complexes reported in the literature, both complexes 4 and 5 possess unique topologies in their respective oxidation state levels. Complex {Mn3Na2} (6) possesses a iii unique metal stoichiometry and is the only compound containing any form of the ligand pyridine-2,6-diylbis(pyrazine-2-ylmethanone) [(pz)CO(py)CO(pz)]. More interestingly, complex 6 contains the first {MnIII3(μ3-O2−)}7+ triangular core where the Mn centers are solely bridged by an oxido group, essentially being a unique ‘edge-naked’ equilateral triangle. In Chapter 4, the synthesis and characterization of complexes bearing the ligand 3-hydroxy-2-naphthohydroxamic acid are presented. The {Mn10} complexes 7 and 8 are the highest nuclearity 3d-metal and the first homometallic Mn clusters containing the hydroxime form of the ligand. Both compounds possess unique metal topologies, which are affected by the nature of the carboxylate ligand present in the reaction mixture, and they behave as SMMs. The use of 3-hydroxy-2-naphthohydroxamic acid in Mn/Dy cluster chemistry has afforded the {Mn4Dy} complexes 9 and 10, as well as a family of {Mn8Dy2} complexes (11 and 12). These compounds are the first Mn/Dy complexes containing this particular hydroxime ligand and they also possess unique metal stoichiometries and topologies. The reported heterometallic products resulted from our efforts to deliberately replace the divalent Mn atoms located in 7 and 8 with DyIII as a means of enhancing the magnetic properties of the former. Complexes 11 and 12 were found to be single-molecule magnets.
    • Hydrosilylation and hydroboration catalyzed by imido-hydride complexes of molybdenum (IV)

      Shirobokov, Oleg G.; Department of Chemistry (Brock University, 2012-04-04)
      This thesis describes the synthesis, structural studies, stoichiometric and catalytic reactivity of novel Mo(IV) imido hydride complexes (Cp)(ArN)Mo(H)(PMe3) (1) and (Tp )(ArN)Mo(H)(PMe3) (2). Both 1 and 2 catalyze hydrosilylation of a variety of carbonyls. Detailed kinetic and DFT studies found that 1 reacts by an unexpected associative mechanism, which does not involve Si-H addition either to the imido group or the metal. Despite 1 being a d2 complex, its reaction with PhSiH3 proceeds via a a-bond metathesis mechanism giving the silyl derivative (Cp )(ArN)Mo(SiH2Ph)(PMe3). In the presence of BPh3 reaction of 1 with PhSiH3 results in formation of (Cp)(ArN)Mo(SiH2Ph)(H)2 and (Cp)(ArN)Mo(SiH2Ph)2(H), the first examples ofMo(VI) silyl hydrides. AI: 1 : 1 reaction between 2, PhSiD3 and carbonyl substrate established that hydrosilylation is not accompanied by deuterium incorporation into the hydride position of the catalyst, thus ruling out the conventional mechanism based on carbonyl insertion carbonyl. As 2 is nomeactive to both the silane and ketone, the only mechanistic alternative we are left with is that the metal center activates the carbonyl as a Lewis acid. The analogous nonhydride mechanism was observed for the catalysis by (ArN)Mo(H)(CI)(PMe3), (Ph3P)2(I)(O)Re(H)(OSiMe2Ph) and (PPh3CuH)6. Complex 2 also catalyzes hydroboration of carbonyls and nitriles. We report the first case of metal-catalyzed hydroboration of nitriles as well as hydroboration of carbonyls at very mild conditions. Conversion of carbonyl functions can be performed with high selectivities in the presence of nitrile groups. This thesis also reports the first case of the HlH exchange between H2 and Si-H of silanes mediated by Lewis acids such as Mo(IV) , Re(V) , Cu(I) , Zn(II) complexes, B(C6Fs)3 and BPh3.
    • Investigating the Cluster Chemistry of α-Methyl-2-pyridine methanol (mpmH) with Select 3d Ions

      Abbasi, Parisa; Department of Chemistry
      This thesis describes an investigation of the coordination chemistry of the potentially chiral bridging, chelating ligand, α-methyl-2-pyridinemethanol (mpmH) with select 3d ions for the discovery of polynuclear clusters with single molecule magnet (SMM) properties. Chapter 1 introduces the theory of molecular magnetism, SMMs and the concepts of chiral SMMs, magnetochiral dichroism and multiferroics. In Chapter 2, two NiII clusters, {Ni8} and {Ni18} prepared from rac-mpmH are reported. The {Ni8} cluster crystallizes in a trapezoidal prismatic topology and contains tetrazolate ligands that are formed via a metal-assisted click reaction. The molecular structure of the second {Ni18} cluster is highly disordered comprising of eight edge-sharing cubane subunits. Dc magnetic susceptibility measurements reveal dominant ferromagnetic interactions down to ~18 K, stabilizing spin states with large values, whereas at T < 18 K the antiferromagnetic contribution results in the population of smaller, but appreciable non-zero spin states. Ac magnetic susceptibility measurements confirm the presence of two relaxation processes at two temperature regimes that is extremely rare for a 3d-metal based SMM. The first at low temperature (5 K) is attributed to conventional SMM behavior with τ0 = 3.26 × 10-10 s and Ueff = 11 K. The origin of high temperature (15 K) relaxation process with a large Ueff = 381 K and τ0 = 2.7 × 10-15 s is less clear, but tentatively assigned to spin-glass properties. In Chapter 3, the synthesis and structure of a large mixed-valence [MnII2MnIII28MnIV] polynuclear cluster with a closed cage-like conformation is presented. Ac magnetic susceptibility measurements show the compound is an SMM with Ueff of 58 K, that is large for a 3d cluster, and a τ0 = 3 × 10−8 s. Chapter 4 describes the coordination chemistry of racemic and chiral-mpmH with CuII and FeIII, where the synthesis and magnetostructural properties of a chiral {Cu4} tetramer, a non-chiral 1-D chain, as well as a chiral {Fe6} and a non-chiral{Fe8} cluster are reported. Dc magnetic susceptibility measurements on all four complexes reveal the presence of dominant antiferromagnetic exchange interactions affording S = 0 spin ground states at low temperature that precludes the observation of any SMM behavior.
    • Ligand design for molecule-based magnetic and/or conducting materials

      ACHA, ROLAND; Department of Chemistry (Brock University, 2013-06-04)
      Work in the area of molecule-based magnetic and/or conducting materials is presented in two projects. The first project describes the use of 4,4’-bipyridine as a scaffold for the preparation of a new family of tetracarboxamide ligands. Four new ligands I-III have been prepared and characterized and the coordination chemistry of these ligands is presented. This project was then extended to exploit 4,4’-bipyridine as a covalent linker between two N3O2 macrocyles. In this respect, three dimeric macrocycles have been prepared IV-VI. Substitution of the labile axial ligands of the Co(II) complex IV by [Fe(CN)6]4- afforded the self-assembly of the 1-D polymeric chain {[Co(N3O2)H2O]2Fe(CN)6}n•3H2O that has been structurally and magnetically characterized. Magnetic studies on the Fe(II) complexes V and VI indicate that they undergo incomplete spin crossover transitions in the solid state. Strategies for the preparation of chiral spin crossover N3O2 macrocycles are discussed and the synthesis of the novel chiral Fe(II) macrocyclic complex VII is reported. Magnetic susceptibility and Mössbauer studies reveal that this complex undergoes a gradual spin crossover in the solid state with no thermal hysteresis. Variable temperature X-ray diffraction studies on single crystals of VII reveal interesting structural changes in the coordination geometry of the macrocycle accompanying its SCO transition. The second project reports the synthesis and characterization of a new family of tetrathiafulvalene derivatives VIII – XII, where a heterocyclic chelating ligand is appended to a TTF donor via an imine linker. The coordination chemistries of these ligands with M(hfac)2.H2O (M( = Co, Ni, Mn, Cu) have been explored and the structural and magnetic properties of these complexes are described.
    • Magnetically Interesting Coordination Complexes Based on Macrocyclic Ligands

      Ras Ali, Zineb; Department of Chemistry
      The synthesis and study of select 3d and/or 4f coordination complexes prepared from crown ether and Schiff-base dual compartmental macrocycles are described herein, working towards the discovery and study of new families of macrocyclic-based single molecule magnets (SMMs). Chapter 1 introduces the general theory of magnetism, molecular magnetism and SMMs and provides the reader with a brief overview of the relevant coordination chemistry of the two families of macrocycles. In Chapter 2, two 15-crown-5 complexes [Ln(NO3)3(OH2)2(MeOH)], (where Ln(III) = Tb (I) and Dy (II)) have been prepared and characterized. X-ray diffraction studies reveal the two complexes crystallize as 1-D chains. Variable temperature ac magnetic susceptibility studies reveal that (II) is an SMM with two effective energy barriers, Ueff = 26 K (18 cm−1); τ0 = 4.10 × 10−7 s and Ueff = 41 K (29 cm−1); τ0 = 1.35 × 10−8 s, whereas ab initio studies suggest that the observation of slow relaxation of magnetization in the Tb complex (I) is hindered by the presence of rapid quantum tunneling mechanisms (QTM). Solid state photoluminescence measurements reveal the two complexes have well-resolved f–f transitions, where a Gaussian fit of the fine structure of the highest-energy emission band for the Dy(III) complex allows the Stark splitting of the ground state to be determined. In Chapter 3, select Ln(III) complexes with benzo and dibenzo 15-crown-5 macrocycles were synthesized and characterized. Reaction of Dy(III) together with benzo 15-crown-5 afforded a unique [Dy(OH2)8]3+ complex (III), where the hydrated Dy(III) cation is fully encapsulated within a supramolecular cage formed by three benzo 15-crown-5 macrocycles. Interestingly, the close to perfect square antiprismatic geometry of the 4f ion enhances its axial anisotropy, which suppresses quantum tunnelling mechanisms (QTM) in the ground and first excited states, resulting in the observation of SMM behavior in zero dc field. For this system the magnetic data were further supported by solid-state photoluminescence and ab initio studies, The introduction of a second benzene ring into the organic framework of the macrocycle increases its rigidity, where on coordination to Dy(III), affords the partially encapsulated complex (IV), which displays slow relaxation of magnetisation, consistent with SMM properties. In Chapter 4, the coordination chemistry of a dual compartmental Schiff-base macrocycle H2L3 containing O3O2 and N3O2 cavities was explored together with select 3d and 4f ions. In the first part of this chapter, the coordination chemistry of H2L3 with 3d metal ions is presented, where in the presence of NaOH, the Na(I) ions reside in the O3O2 cavity and the 3d ions occupy the second N3O2 cavity. Three coordination complexes containing Cu(II), Zn(II), and Mn(II) ions were prepared and characterized. The Cu(II), and Zn(II) complexes are monomeric with molecular formulae [CuNa(L3b)ClCH3OH]‧6H2O (V) and [ZnNa(L3b)(CH3COO)(CH3OH)]‧H2O (VI) respectively, while the Mn(II) complex crystallizes as a trimer with stoichiometry [Mn3Na2(L3)2(CH3COO)4]·5.75CH3OH·0.5H2O (VII). For complexes (V) and (VI), nucleophilic addition of the NH of the N3O2 cavity to the carbon atom of the adjacent imine results in a contraction of the N3O2 cavity and the formation of a five-membered imidazoline ring to afford the modified ligand L3b.The magnetic properties of (V) and (VII) are also reported. In the second part of this chapter, coordination of the macrocycle to select 4f ions in the absence of any base afforded the mononuclear complexes [Dy(H2L3)(H2O)2(CH3OH)2]Cl3·CH3OH, (VIII), and [Ln(H2L3)(H2O)3(CH3OH)] Cl3, where Ln(III) = Tb (IX), Er (X), and Gd (XI), in which the Ln(III) ion is coordinated in the O3O2 cavity. Magneto-structural studies on these complexes reveal that the Dy complex has a slightly different structure than the other three complexes, however all four 4f ions crystallize with square antiprismatic geometries, where only the Dy(III) complex (VIII) displays SMM properties.
    • Mirroring Enzymes: The Role of H-Bonding In HQuin-BAM Catalyzed Asymmetric Aza-Henry Reactions: A DFT Study into the Reactivity, Mechanism, and Origins of Selectivity

      Taimoory, Seyedeh Maryamdokht; Department of Chemistry
      The exact mechanistic understanding of various organocatalytic systems in asymmetric reactions such as Henry and aza-Henry transformations is important for developing and designing new synthetic organocatalysts. The focus of this dissertation will be on the use of density functional theory (DFT) for studying the asymmetric aza-Henry reaction. The first part of the thesis is a detailed mechanistic investigation of a poorly understood chiral bis(amidine) (BAM) Brønsted acid catalyzed aza-Henry reaction between nitromethane and N-Boc phenylaldimine. The catalyst, in addition to acting as a Brønsted base, serves to simultaneously activate both the electrophile and the nucleophile through dual H-bonding during C-C bond formation and is thus essential for both reaction rate and selectivity. Analysis of the H-bonding interactions revealed that there was a strong preference for the formation of a homonuclear positive charge-assisted H-bond, which in turn governed the relative orientation of substrate binding. Attracted by this well-defined mechanistic investigation, the other important aspect of my PhD research addressed a detailed theoretical analysis accounting for the observed selectivity in diastereoselective versions of this reaction. A detailed inspection of the stereodetermining C-C bond forming transition states for monoalkylated nitronate addition to a range of electronically different aldimines, revealed that the origins of stereoselectivity were controlled by a delicate balance of different factors such as steric, orbital interactions, and the extent of distortion in the catalyst and substrates. The structural analysis of different substituted transition states established an interesting dependency on matching the shape and size of the catalyst (host molecule) and substrates (guest molecules) upon binding, both being key factors governing selectivity, in essence, offering an analogy to positive cooperative binding effect of catalytic enzymes and substrates in Nature. In addition, both intra-molecular (intra-host) and inter-molecular (host-guest, guest-guest) stabilizing interactions play a key role to the high π-facial selectivity. The application of dispersion-corrected functionals (i.e., ωB97X-D and B3LYP-D3) was essential for accurately modeling these stabilizing interactions, indicating the importance of dispersion effects in enantioselectivity. As a brief prelude to more extensive future studies, the influence of a triflate counterion on both reactivity and selectivity in this reaction was also addressed.
    • Molybdenum (IV) imido silylamido and hydride complexes : stoichiometric and catalytic reactivity, mechanistic aspects of hydrosilation reactions

      Khalimon, Andrey Y.; Department of Chemistry (Brock University, 2011-05-17)
      This thesis describes the synthesis, structural studies, and stoichiometric and catalytic reactivity of novel Mo(IV) imido silylamide (R'N)Mo(R2)(173_RIN-SiR32-H)(PMe3)n (1: Rl = tBu, Ar', Ar; R2 = Cl; R32 = Me2, MePh, MeCl, Ph2, HPh; n = 2; 2: R' = Ar, R2 = SiH2Ph, n = 1) and hydride complexes (ArN)Mo(H)(R)(PMe3)3 (R = Cl (3), SiH2Ph (4». Compounds of type 1 were generated from (R'N)Mo(PMe3)n(L) (5: R' = tBu, Ar', Ar; L = PMe3, r/- C2H4) and chlorohydrosilanes by the imido/silane coupling approach, recently discovered in our group. The mechanism of the reaction of 5 with HSiCh to give (ArN)MoClz(PMe3)3 (8) was studied by VT NMR, which revealed the intermediacy of (ArN)MCh(172 -ArN=SiHCl)(PMe3)z (9). The imido/silyl coupling methodology was transferred to the reactions of 5 with chlorine-free hydrosilanes. This approach allowed for the isolation of a novel ,B-agostic compound (ArN)Mo(SiHzPh)(173 -NAr-SiHPhH)(PMe3) (10). The latter was found to be active in a variety of hydrosilation processes, including the rare monoaddition of PhSiH3 to benzonitrile. Stoichiometric reactions of 11 with unsaturated compounds appear to proceed via the silanimine intermediate (ArN)M(17z-ArN=SiHPh)(PMe3) (12) and, in the case of olefins and nitriles, give products of Si-C coupling, such as (ArN)Mo(R)(173 -NAr-SiHPh-CH=CHR')(PMe3) (13: R = Et, R' = H; 14: R = H, R' = Ph) and (ArN)Mo(172-NAr-SiHPh-CHR=N)(PMe3) (15). Compound 13 was also subjected to catalysis showing much improved activity in the hydrosilation of carbonyls and alkenes. Hydride complexes 3 and 4 were prepared starting from (ArN)MoCh(PMe3)3 (8). Both hydride species catalyze a diversity of hydrosilation processes that proceed via initial substrate activation but not silane addition. The proposed mechanism is supported by stoichiometric reactions of 3 and 4, kinetic NMR studies, and DFf calculations for the hydrosilation of benzaldehyde and acetone mediated by 4.
    • New Pyrazole-Based Ligands and Their Complexes for Application in Transfer Hydrogenation and Hydrosilylation

      Alshakova, Iryna; Department of Chemistry
      A series of bidentate and tridentate ligands bearing pyrazolyl moiety in combination with phosphine, oxazoline, amine, and sulfide were synthesized. These ligands were applied for the synthesis of ruthenium complexes, that would be efficient in catalyzing transfer hydrogenation reaction in alcohol. From a number of obtained complexes, a mixture of two isomeric ruthenium complexes was found to be the most efficient in reduction of acetophenone and N-benzylideneaniline, as model substrates, with 2-propanol. These ruthenium complexes were successfully applied in transfer hydrogenation of nitriles, heterocyclic compounds, olefins, and alkynes. Activated esters were reduced under similar catalytic conditions when ethanol was used as a hydrogen source. These isomeric ruthenium complexes were also applied in the synthesis of secondary amines via hydrogen borrowing methodology. A number of primary amines and anilines were combined with primary alcohols under the conditions, optimized for transfer hydrogenation of nitriles, resulting in corresponding secondary amines. Furthermore, ammonium formate was used as a nitrogen source for alcohol amination. Thus, secondary and tertiary amines were obtained from primary alcohols. Another project was focused on transfer hydrogenation of carbonyl compounds with lithium isopropoxide. Addition of various ligands and small molecules was found to improve the reaction efficiency for aromatic substrates. Further studies revealed that lithium cation forms stable adduct with aromatic alcohols, while different additives help to break this interaction, thus resulting in significant improvement of the conversion to alcohols. Another strategy that was applied to improve the reaction yields was the addition of a cheap source of lithium cations, such as LiCl. Finally, a new zinc complex was synthesized and applied in the catalytic hydrosilylation of carbonyl compounds. The optimization of reaction conditions reviled that the presence of substoichiometric amounts of methanol in the system significantly accelerates the process. The reaction can proceed at very low catalyst load (down to 0.1mol%) under relatively mild reaction conditions. The substrate scope analysis showed the tolerance to carbon-carbon double bond. Thus, this procedure is efficient for the synthesis of allylic alcohols from α,β-unsaturated aldehydes and ketones.
    • New Synthetic Approaches and Structural Models of the Oxygen-Evolving Complex in Photosystem II from the Use of Oximato-Based Ligands

      Alaimo, Alysha; Department of Chemistry
      The employment of the chelating/bridging ligands salicylhydroxime (shiH3), quinoline-2-aldoxime (qaoH) and 2,6-diacetylpyridine dioxime (dapdoH2) in heterometallic Mn‒Ca chemistry has afforded various compounds with diverse topologies, metal stoichiometries and Mn oxidation state descriptions. Chapter 1 provides a general introduction to the oxygen-evolving complex (OEC) of Photosystem II (PSII) including discussions of fundamental aspects such as composition, structural proposals, mechanism of O‒O bond formation and synthetic approaches. My research results are reported in Chapter 2, 3 and 4. In the first project (Chapter 2), one-pot reactions between Mn(ClO4)2∙6H2O, Ca(ClO4)2∙4H2O and the potentially tetradentate chelating/bridging ligand salicylhydroxime (shiH3), resulting from the in situ metal ion-assisted amide-iminol tautomerism of salicylhydroxamic acid (shaH2), in the presence of various fluorescence carboxylate groups (2-naphthoic acid = L1-H; 9-anthracenecarboxylic acid = L2-H; 1-pyrenecarboxylic acid = L3-H) and base NEt3 has led to a family of structurally similar {MnIII4Ca} clusters (1‒4¬) with distorted square pyramidal topologies. The combined results demonstrate the ability of shiH3 and fluorescence carboxylates to yield new heterometallic Mn‒Ca clusters with (i) the same Mn‒Ca ratio as the OEC of PSII, (ii) structural stability in solution, (iii) a pronounced redox and optical activity and (iv) predominant antiferromagnetic exchange interactions with S = 0 spin ground states. These complexes may be relevant to lower oxidation level species of the catalytic cycle of the OEC. The second project of this thesis, discussed in Chapter 3, involved one-pot reactions between the [Mn3O(O2CPh)6(py)x]+/0 triangular precursors and either CaBr2∙xH2O or CaCl2∙6H2O in the presence of shaH2. This afforded the heterometallic complexes [MnIII4Ca2(O2CPh)4(shi)4(H2O)3(Me2CO)] (5) and (pyH)[MnII2MnIII4Ca2Cl2(O2CPh)7(shi)4(py)4] (6), respectively, in good yields. Further reactions but using a more flexible synthetic scheme comprising the Mn(NO3)2∙4H2O/Ca(NO3)2∙4H2O and Mn(O2CPh)2∙2H2O/Ca(ClO4)2∙4H2O “metal blends” and shaH2 in the presence of external base NEt3, led to the new complexes (NHEt3)[MnIII4MnIV4Ca2(OEt)2(shi)10(EtOH)2] (7) and (NHEt3)4[MnIII8Ca2(CO3)4(shi)8] (8), respectively. Solid-state dc magnetic susceptibility studies of 5‒8 revealed the presence of predominant antiferromagnetic exchange interactions between the Mn centers, leading to S = 0 spin ground state values. From a bioinorganic chemistry perspective, these compounds may demonstrate some relevance to both the high-valent scheme (7) and lower oxidation level species (5, 6 and 8) of the catalytic cycle of the OEC. In the last chapter of this thesis (Chapter 4), the ligands quinoline-2-aldoxime (qaoH) and 2,6-diacetylpyridine dioxime (dapdoH2) were introduced for a first time in heterometallic Mn‒Ca chemistry. This afforded a mixed-valence {MnII/III22Ca2} (9) cluster containing several {Mn4CaOx} subunits and a butterfly-like {MnIV2Ca2} (10) complex, respectively. These compounds demonstrate structural and magnetic relevance to both the low- and high-valent states of the OEC. All research-based Chapters (Chapter 2‒4) are divided into subsections in order to facilitate the understanding of the research concepts by the familiar and non-familiar readers and contextualize the messages, goals and conclusions of each individual project. I felt it was appropriate to begin each Chapter with a short preface of the work that summarizes the most important aspects of the specific project, followed by the complete experimental work and discussion of the results, and end with conclusions and some future perspectives.
    • Novel Magnetic Materials Based on Macrocyclic Ligands: Towards High Relaxivity Contrast Agents and Mononuclear Single-Molecule Magnets

      Stares, Emma; Department of Chemistry
      The preparation and characterization of coordination complexes of Schiff-base and crown ether macrocycles is presented, for application as contrast agents for magnetic resonance imaging, Project 1; and single-molecule magnets (SMMs), Projects 2 and 3. In Project 1, a family of eight Mn(II) and Gd(III) complexes of N3X2 (X = NH, O) and N3O3 Schiff-base macrocycles were synthesized, characterized, and evaluated as potential contrast agents for MRI. In vitro and in vivo (rodent) studies indicate that the studied complexes display efficient contrast behaviour, negligible toxicity, and rapid excretion. In Project 2, DyIII complexes of Schiff-base macrocycles were prepared with a view to developing a new family of mononuclear Ln-SMMs with pseudo-D5h geometries. Each complex displayed slow relaxation of magnetization, with magnetically-derived energy barriers in the range Ueff = 4 – 24 K. In Project 3, coordination complexes of selected later lanthanides with various crown ether ligands were synthesized. Two families of complexes were structurally and magnetically analyzed: ‘axial’ or sandwich-type complexes based on 12-crown-4 and 15-crown-5; and ‘equatorial’ complexes based on 18-crown-6. Magnetic data are supported by ab initio calculations and luminescence measurements. Significantly, the first mononuclear Ln-SMM prepared from a crown ether ligand is described.
    • Probes of tocopherol biochemistry: fluorophores, imaging agents, and fake antioxidants

      Ghelfi, Mikel; Department of Chemistry
      The body has many defence systems against reactive radical species, but none are as crucial in the protection of lipid membranes as vitamin E. As a result of a selection process mediated by the α-tocopherol transfer protein (α-TTP), α-tocopherol is the only form of vitamin E retained in the body. This chaperon protein has been well studied because of its role in vitamin E transport. Furthermore, malfunctions of α-TTP cause vitamin E deficiency leading to ataxia and other neurodegenerative disease. Protection of neuronal tissue is critical and is reflected in the high retention of α-tocopherol in the central nervous system. Neuronal tissues receive α tocopherol from astrocytes, cells that are linked to hepatic tissue and able to express α-TTP, however the exact path of delivery between these cells is still unclear. A technique called fluorescent microscopy allows the tracking of fluorescent molecules in cells to find their location and interactions with other parts of the cell. The focus of this study is the synthesis of a fluorescent tocopherol analogue with a long absorption wavelength, high photostability, and that binds selectively to  α-TTP with high affinity. Most health benefits associated with vitamin E consumption are based on its capability to inhibit lipid peroxidation in cell membranes by scavenging reactive oxygen species (ROS). Oxidative damage in membranes puts cells in a “stressful” state, activating signalling events that trigger apoptosis. Vitamin E down-regulates apoptotic functions like inflammation, macrophage activation and cell arrest in a stressed state, returning the cell back to normal functioning. At the same time, vitamin E has a preventive effect for atherosclerosis, Alzheimer’s and cancer. With the deeper understanding of cell signalling processes associated with vitamin E the question arose whether protein interactions or the ROS scavenging is responsible for cell survival. To test this hypothesis, a non-antioxidant but α-TTP binding tocopherol analogue was synthesized and administered into oxidatively stressed, α-TTP deficient cells. If the cells were unable to restore homeostasis and stop apoptosis with the new molecule, this would suggest that the antioxidant function of α-tocopherol is the reason for survival. Cancer is regarded as one of the most detrimental diseases with a high mortality rate. One key aspect in medical research is the increased drug specificity towards targeting cancer. Chemotherapy applies cytotoxic compounds, which weaken the immune system because both malignant and healthy cells are destroyed. The specificity of the anti-cancer drugs are enhanced when encapsulated into liposomes that bear target-directing molecules such as antibodies which recognize cancer cell specific antigens on the cell membrane. The question remains if the encapsulated drug reaches the cancer or not. Magnetic resonance imaging (MRI) and computed tomography (CT) are used to find malignant tissue in the body. CT imaging uses highly charged X-ray particles to scan the patient, possibly having damaging cytotoxic effects. Obtaining MRI results require the use of contrast agents to enhance the quality of images. These agents are based on transition metals, which potentially have chronic toxicity when retained in the body. Alternatively short-lived radiotracers that emit a γ-photon upon positron decay are used through a process called positron emission tomography (PET). Rapid decay times make the use of PET a less toxic alternative, however the decay products might be toxic to the cell. For this reason a vitamin E based PET agent was created, which produces naturally safe decay products based on known metabolites of vitamin E, useful to track liposomal delivery of chemotherapeutic agents. This work describes the non-radioactive synthetic procedures towards a variety of vitamin E PET analogues. The cytotoxicity of the most promising vitamin E PET tracer was evaluated along with its synthetic byproducts.
    • Reactivity of a Low Valent Gallium Compound

      Kassymbek, Aishabibi; Department of Chemistry
      The work described in this thesis is conducted to expand the reactivity of the β-diketiminate gallium(I) compound, NacNacGa (NacNac=[ArNC(Me)HC(Me)NAr]−, Ar=2,6-iPr2C6H3). The reactivity of NacNacGa towards various unsaturated compounds is studied. In particular, reaction between NacNacGa and phenyl isothiocyanate resulted in the oxidative addition of the C=S bond under ambient conditions, leading to the isolation cyclization product NacNacGa(κ2-S2CNPh) and sulfide isocyanide-bridged dimer (NacNacGa)2(μ-S)(μ-CNPh). Additionally, a [1+4] cycloaddition with a conjugated aldehyde (methacrolein) and a [1+2+3] cycloaddition with isocyanate and carbodiimide are presented. The oxidative cleavage of P=S bond of triphenylphosphine sulfide at increased temperatures gave the previously reported sulfide bridged gallium dimer. In situ oxidation of NacNacGa in the presence of substrates featuring donor sites led to the C-H activation reactions. As such, C-activation of pyridine N-oxide, pyridine, cyclohexanone, DMSO, and Et3P=O by a transient NacNacGa=O resulting in the corresponding gallium hydroxides is demonstrated. DFT calculations suggested initial formation of adducts between substrates and NacNacGa=O followed by a C-H bond abstraction from the substrate. Similarly, a transient gallium imide NacNacGa=NSiMe3, generated from the reaction of NacNacGa with trimethylsilyl azide, is shown to cleave C-H bonds of pyridine, cyclohexanone, ethyl acetate, DMSO, and Et3P=O with the formation of gallium amides. In an attempt to isolate a gallium alkylidene, NacNacGa was treated with trimethylsilyl(diazomethane). Instead, a monomeric gallium nitrilimine and a metalated diazomethane were obtained. The gallium nitrilimine undergoes 1,3-addition reaction with phenylsilane and catecholborane forming gallium hydrazonides. Its reaction with diborane resulted in the formal nitrene insertion into the B-B bond to produce a gallium diborylamide. DFT calculations revealed intermediate gallium alkylidene formation from the reaction of NacNacGa with diazomethane that upon reaction with the second equivalent of diazomethane leads to a gallium nitrilimine.
    • Reactivity of Aluminum Carbenoid with Unsaturated Substrates

      Dmitrienko, Anton; Department of Chemistry
      Reactivity patterns of the β-diketiminate aluminum(I) complex NacNacAl towards a variety of unsaturated molecules were determined. Reaction of NacNacAl with one equivalent of benzophenone affords η2(C,O) adduct III-2 that undergoes cyclization reactions with benzophenone (III-3), aldimine (III-4), quinoline (III-5), pyridine (III-6), phenyl nitrile (III-7), trimethylsilyl azide (III-8), and a saturated cyclic thiourea (III-9). The latter reacted via unusual C−N cleavage. Analogous η2-coordination products were prepared with p-tolyl benzoate (IV-6), N,N-dimethylbenzamide (IV-9) and (1‐phenylethylidene)aniline (IV-13). Addition of pyridine to such species results in [2+2] cycloaddition products analogous to III-6, except for the case of p‐tolyl benzoate when a migration of the alkoxy group from the ester moiety accompanied by hydrogen transfer from pyridine preserves the aromaticity within the latter. Chemoselective couplings between aliphatic ketones and pyridine were exemplified by reactions with non-enolizable (1R)-(‒) fenchone and enolizable yet sterically encumbered isophorone. The reaction with the CH‐acidic ketone (1R) (+) camphor afforded a hydrido alkoxide (IV-11) as the result of enolization. Whereas the reaction of NacNacAl with (1R)‐(−)‐fenchone in the absence of pyridine led to CH activation in the isopropyl group of the NacNac ligand. NacNacAl demonstrated diverse reactivity in reactions with N‐heterocycles. 4 Dimethylaminopyridine induces rearrangement of NacNacAl by deprotonation of backbone methyl group of the ligand. C−H activation of the methyl group of 4‐picoline produced a species with a reactive terminal methylene. Reaction of NacNacAl with 3,5 lutidine led to the cleavage of the sp2 C−H bond (4‐position). Another reactivity mode was observed for quinoline, which undergoes 2,2′‐coupling. Finally, a reaction of NacNacAl with phthalazine produced a product of the N−N bond cleavage. NacNacAl reacted with a series of polycyclic aromatic hydrocarbons via [4+1] cycloaddition. While a reaction with anthracene was irreversible, with the formation of products of activation of the lateral and central rings, reactions with phenanthrene, triphenylene, and fluoranthene were reversible. Heating reaction mixtures at 90 °C yielded dialuminum hydride VI-6. Mechanistic studies showed that the reaction proceeds via dissociation of polycycles with the release of NacNacAl that undergoes further intermolecular transformations. All novel complexes were characterized by spectroscopic methods and X-ray diffraction analysis for most of them.