• (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.
    • (A) Constructing a Three-Dimensional DNA Nanomachine to Achieve Rapid Isothermal Signal Amplification for Nucleic Acid Detection (B) Regulation of DNA Strand Displacement Using an Allosteric DNA Toehold

      Yang, Xiaolong; Department of Chemistry
      (A) We developed a new strategy to achieve rapid isothermal signal amplification through the construction of DNA nanomachine. DNA nanomachine built from a DNA functionalized gold nanoparticle (DNA−AuNP), which moves a DNA walker along a three-dimensional (3-D) DNA−AuNP track and executes the task of releasing signal reporters (SRs) to generate fluorescence. The movement of the DNA walker is powered by a nicking endonuclease that cleaves specific DNA substrates on the track. During the movement, each DNA walker cleaves multiple substrates, resulting in the rapid release of SRs to achieve signal amplification at a constant temperature. The 3-D DNA nanomachine is highly efficient due to the high local effective concentrations of all DNA components that have been co-conjugated on the same AuNP. Moreover, the activity of the 3-D DNA nanomachine can be controlled by introducing a protecting DNA probe that can hybridize to or dehybridize from the DNA walker in a target-specific manner. This property allows us to tailor the DNA nanomachine into a DNA nanosensor that is able to achieve rapid, isothermal, and homogeneous signal amplification for detection of nucleic acids in both buffer and a complicated biomatrix. (B) Toehold-mediated DNA strand displacement has proven extremely powerful in the construction and operation of DNA devices, including reconfigurable structures, DNA circuits, and amplifications. To achieve the construction of such DNA devices, toeholds are required for controllable activation and regulation. Usually, the complicated strand displacement behaviors and functions are achieved by combining conventional toehold-mediated strand displacement, associative toehold-mediated strand displacement, and remote toehold strand displacement toehold activation mechanisms. We still need to enrich the toolbox of strand displacement techniques with alternative approaches for toehold activation to construct devices of higher complexity. Here we introduce an allosteric DNA toehold (A-toehold) design that allows flexible activation or regulation of DNA strand displacement.
    • (A) BODIPY as a versatile fluorophore (B) Synthesis of PNAs via Staudinger reaction

      Yang, Lijing; Department of Chemistry (Brock University, 2013-11-05)
      (A) In recent years, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores have attracted considerable interest due to their unique photochemical properties. However detailed studies on the stability of BODIPY and analogues under acidic and basic conditions have been lacking. Thus the stability of a series of BODIPY analogues in acidic (di- and trichloroacetic acid) and basic (aqueous ammonium hydroxide) conditions was investigated using 11B NMR spectroscopy. Among the analogues tested, 4,4-diphenyl BODIPY was the most stable under the conditions used in the experiments. It was found that reaction of 4,4-dimethoxy BODIPY with dichloroacetic acid gave mixed anhydride 4,4-bis(dichloroacetoxy) BODIPY in good yields. Treatment of the latter mixed anhydride with alcohols such as methanol and ethanol in the presence of a base afforded corresponding borate esters, whereas treatment with 1,2-diols such as ethylene glycol and catechol in the presence of a base gave corresponding cyclic borate esters. Furthermore treatment of 4,4-difluoro-8-methyl-BODIPY with secondary amines in dihalomethane resulted in carbon–carbon bond formation at the meso-methyl position of BODIPY via Mannich-type reactions. The resulting modified BODIPY fluorophores possess high fluorescent quantum yields. Five BODIPY analogues bearing potential ion-binding moieties were synthesized via this Mannich-type reaction. Among these, the BODIPY bearing an aza-18-crown-5 tether was found to be selective towards copper (II) ion, resulting in a large blue shift in absorption and sharp fluorescent quenching, whereas aza-15-crown-4 analogue was selected towards fluoride ion, leading to effective florescent quenching and blue shift. (B) Peptide nucleic acids (PNA), as mimics of natural nucleic acids, have been widely applied in molecular biology and biotechnology. Currently, the preparation of PNA oligomers is commonly achieved by a coupling reaction between carboxyl and amino groups in the presence of an activator. In this thesis attempts were made towards the synthesis of PNA through the Staudinger ligation reactions between C-terminal diphenylphosphinomethanethiol thioesters and N-terminal α-azido PNA building blocks.
    • A29 NMR spin-lattice relaxation study of paramagnetics -doped orthosilictes

      Sliwinski, David R.; Department of Chemistry (Brock University, 1991-10-02)
      A ~si MAS NMR study of spin-lattice relaxation behaviour in paramagnetic-doped crystalline silicates was undertaken, using synthetic magnesium orthosilicate (forsterite) and synthetic zinc orthosilicate (willemite) doped with 0.1% to 20% of Co(II), Ni(II), or CU(II), as experimental systems. All of the samples studied exhibited a longitudinal magnetization return to the Boltzmann distribution of nuclear spin states which followed a stretched-exponential function of time: Y=exp [- (tjTn) n], O<n<l For the most reliable experimental data, there is a bias toward n=O.Sj the few genuine cases of deviation from 1/2power are for dopant concentrations equal to or exceeding 2.5 percent dopant. In some cases we find agreement with theory, and observe a direct proportionality between the spin-lattice relaxation time and paramagnetic dopant ion concentration, with Tni[M2+]i=Tnj[M2+]j for a given dopant and mineral. There are many cases where this correlation is not apparent, however, and this is attributed to the structural, phase, and ion distribution complexities inherent in many of these systems.
    • Analyses, persistence an degradation of the synthetic pyrethroid insecticides permethrin and fenvalerate

      Tan, Cynthia Shwe Yin.; Department of Chemistry (Brock University, 1983-07-09)
      Studies on persistence and degradation of the synthetic pyrethroid insecticides, permethrin and fenvalerate, were carried out under natural environmental conditions of the Niagara Peninsula. Permethrin and fenvalerate were treated on apple foliage atrat~s of 0.21 kg(AI)!ha and 0.14 kg(AI)/ha, respectively. The initial cis- and trans-permethrin spray deposits were found to be 13.5 ppm and 19.2 ppm, respectively and 38.0 ppm was observed for the fenvalerate treated sample. Twenty-three days and 84 days after spray application, permethrin residues were 4.0 ppm and 2.7 ppm for the cis-isomer, whereas they were 7.9 ppm and 4.7 ppm for the trans-isomer, respectively. Residues of fenvalerate 23 days and 84 days after spray application were 13.4 ppm and 8.0 ppm, respectively. The values of observed half-life of cis-permethrin, trans-permethrin and fenvalerate were found to be 42 days, 46 days and 51 days, respectively. Studies were extended to quantitatively determine some of the major degradation compounds of permethrin and fenvalerate, which were expected to be produced as results of ester cleavage of the parent compounds. A permethrin treated sample, 84 days after initial spray application, showed 0.25 and 0.8 ppm of cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (C12CA (18), respectively. These two acids were not found as free acids, but found as conjugated compounds. The other expected degradation compounds, 3-phenoxybenzyl alcohol (PBalc (~)),3-phenoxybenz.aldehyde (PBald (38)) and 2- (4-chlorophenyl) isovaleric acid (CPIA (31)) were not detected by the methods employed in this study. The results indicate that these degradation compounds were not present, or, if they were present, their concentrations were too low to detect by the methods used.
    • Analysis Of The A11a22 X 11a11 And A 33a22 X 1 electronic transitions in selenocarbonyl difluoride

      Boluk, Mehmet Yaman.; Department of Chemistry (Brock University, 1982-10-02)
      The absorption spectrum of F2CSe in the 18800-21900 cm-1 region has been recorded at -770 C and 220 C under the conditions of medium resolution. The responsible electronic promotion is TI* + n excitation which leads to 3A2 and lA2 excited states. Progressions in vI', v2', v3" v4' and v4" have been identified in the spectrum and have been analyzed in terms of vibronic transitions between a planar ground state and a nQnplanar excited state. The - 3 - 1 - 1 - 1 origins of the a A2 + X Al and A A2 + X Al systems were assigned to the bands at 19018 cm-l and 19689 cm-l . This has given a singlet-triplet splittl. n g lA2 - 3A2 P f 671 cm -1 The out-of-plane wagging levels were found to be anharmonic. 1 -1 Barrier heights of 2483 cm- and 2923 cm were obtained for the lA2 and 3A2 upper states from a fitting of the energy levels of a Lorentzian-quadratic function to the observed levels in the out-of-plane wagging modes. 1 3 For the A2 and A2 states nonplanar equilibrium angles of 30.10 and 31.40 have been evaluated respectively. i
    • An analysis of the methyl rotation dynamics in the So (x' A) and T (a A) states of thioacetaldehyde from Pyrolysis jet spectra /

      Bascal, Hafed Ashur.; Department of Chemistry (Brock University, 1991-07-14)
      Jet-cooled, laser-induced phosphorescence excitation spectra (LIP) of thioacetaldehyde CH3CHS, CH3CDS, CD3CHS and CD3CDS have been observed over the region 15800 - 17300 cm"^ in a continuous pyrolysis jet. The vibronic band structure of the singlet-triplet n -* n* transition were attributed to the strong coupling of the methyl torsion and aldehydic hydrogen wagging modes . The vibronic peaks have been assigned in terms of two upper electronic state (T^) vibrations; the methyl torsion mode v^g, and the aldehydic hydrogen wagging mode v^^. The electronic origin O^a^ is unequivocally assigned as follows: CH3CHS (16294.9 cm"'' ), CH3CDS (16360.9 cm"'' ), CD3CHS (16299.7 cm"^ ), and CD3CDS (16367.2 cm"'' ). To obtain structural and dynamical information about the two electronic states, potential surfaces V(e,a) for the 6 (methyl torsion) and a (hydrogen wagging) motions were generated by ab initio quantum mechanical calculations with a 6-3 IG* basis in which the structural parameters were fully relaxed. The kinetic energy coefficients BQ(a,e) , B^(a,G) , and the cross coupling term B^(a,e) , were accurately represented as functions of the two active coordinates, a and 9. The calculations reveal that the molecule adopts an eclipsed conformation for the lower Sq electronic state (a=0°,e=0"') with a barrier height to internal rotation of 541.5 cm"^ which is to be compared to 549.8 cm"^ obtained from the microwave experiment. The conformation of the upper T^ electronic state was found to be staggered (a=24 . 68° ,e=-45. 66° ) . The saddle point in the path traced out by the aldehyde wagging motion was calculated to be 175 cm"^ above the equilibrium configuration. The corresponding maxima in the path taken by methyl torsion was found to be 322 cm'\ The small amplitude normal vibrational modes were also calculated to aid in the assignment of the spectra. Torsional-wagging energy manifolds for the two states were derived from the Hamiltonian H(a,e) which was solved variationally using an extended two dimensional Fourier expansion as a basis set. A torsionalinversion band spectrum was derived from the calculated energy levels and Franck-Condon factors, and was compared with the experimental supersonic-jet spectra. Most of the anomalies which were associated with the interpretation of the observed spectrum could be accounted for by the band profiles derived from ab initio SCF calculations. A model describing the jet spectra was derived by scaling the ab initio potential functions. The global least squares fitting generates a triplet state potential which has a minimum at (a=22.38° ,e=-41.08°) . The flatter potential in the scaled model yielded excellent agreement between the observed and calculated frequency intervals.
    • An analysis of the photoelectron and Rydberg states of formaldehyde /|nby Carol R. Lessard. -- 260 St. Catharines [Ont.] : Dept. of Chemistry, Brock University,

      Lessard, Carol R.; Department of Chemistry (Brock University, 1975-07-09)
      Although it is generally accepted that Rydberg orbitals are very large and diffuse, and that electron promotion to a Rydberg orbital is not too different from ionization of the molecule, analysis of the two types of transitions proves otherwise. The photoelectron spectrum of the 2B2 (n) ion has very little vibrational structure attached to the origin band; on the other hand, several of the Rydberg transitions which involve the promotion of the n(bZ) electron exhibit a great deal of vibrational activity. In particular, the members of the n=3 Rydberg\ series interact with and perturb each other through pseudo-Jahn-Teller vibronic coupling. The vacuum ultraviolet spectrum contains a number of features which are difficult to explain, and two unusually sharp bands can only be identified as representing some form of electron promotion in formaldehyde.
    • An anharmonic contribution to the Helmholtz free energy O(lambda 6)

      Gad El-Rab, Shenouda; Department of Chemistry (Brock University, 1973-10-02)
      The anharmonic contributions of order A6 to the Helmholtz free energy for a crystal in which every atom is on a site of inversion symmetry, have been evaluated The cor~esponding diagrams in the various orders of the perturbation theory have been presented The validity of the expressions given is for high temperatures. Numerical calculations for the diagrams which contribute to the free energy have been worked out for a nearest-n~ighbour central-force model of a facecentered cubic lattice in the high-temperature limit and in the leading term and the Ludwig approximations. The accuracy of the Ludwig approximation in evaluating the Brillouin-zone sums has been investigated. Expansion for all diagrams in the high-temperature limit has been carried out The contribution to the specific heat involves a linear as well as cubic term~ We have applied Lennard-Jones, Morse and Exponential 6 types of potentials. A comparison between the contribution to the free energy of order A6 to that of order A4 has been made.
    • Anharmonic Helmholtz free energy to O(lambdaâ ´) in the non- leading term approximation /|nby Leslie Wilk. -- 260 St. Catharines, Ont. : [s. n.],

      Wilk, Leslie.; Department of Chemistry (Brock University, 1972-07-09)
      Expressions for the anharmonic Helmholtz free energy contributions up to o( f ) ,valid for all temperatures, have been obtained using perturbation theory for a c r ystal in which every atom is on a site of inversion symmetry. Numerical calculations have been carried out in the high temperature limit and in the non-leading term approximation for a monatomic facecentred cubic crystal with nearest neighbour c entralforce interactions. The numbers obtained were seen to vary by a s much as 47% from thos e obtai.ned in the leading term approximati.on,indicating that the latter approximati on is not in general very good. The convergence to oct) of the perturbation series in the high temperature limit appears satisfactory.
    • Application of Density Functional Theory to Study the Mechanism of Alkali Metal Enolate Oxidation by N-sulfonyloxaziridines, Umpolung Amide Synthesis from Halo-Amino-Nitro Alkanes, Alkali-Metal Catalyzed Transfer Hydrogenation of Ketones, and Asymmetric Catalyzed Aza-Henry Reactions

      Foy, Hayden; Department of Chemistry
      Density functional theory (DFT) and other computational methods are useful tools for determining reaction mechanisms and the factors governing stereoselectivity. To illustrate the versatility of DFT methods, the following reactions were studied: (1) Li+, Na+, and K+ enolate addition to chiral N-sulfonyloxaziridines, stereoselectivity was found to be controlled by enolate, sulfonyl, and oxaziridine oxygen-cation chelation and steric contacts. From this study it was found that the mechanism proceeded in a SN¬1 rather than SN¬2 like fashion. (2) umpolung amide synthesis working from 1,1,1,1-halo-amino-nitro-alkanes leading to the finding that the amide oxygen originates from the nitro group but also from explicitly interacting water molecules in competing pathways. (3) alkali (Li+, Na+, and K+) metal-catalyzed transfer hydrogenation of acetophenone, the mechanism of which was found to proceed via a six-membered transition state affording direct hydrogen transfer to acetophenone generating the product phenylethanol. The TMEDA ligand had a profound effect in stabilizing the transition state which in turn, lowered the activation energy in comparison to the use of isopropanol ligands. Lastly, (4) asymmetric catalyzed Aza-Henry reactions. Controlling the stereoselectivity of such reactions catalyzed by HMeOQuin((Anth)Pyr)-BAM was an H-bonding manifold of specific hetero- and homonuclear hydrogen bonding motifs (N-H-O and N-H-N respectively) observed in the favored transition state structure (syn-(2S,3R)-TS(eq)). There was a central theme of sterics and other non-covalent interactions, such as - stacking or CH/ interactions, which also played significant roles in determining the stereoselectivity in the investigated reactions.
    • The application of the structural correlation method to determine the reaction coordinate for a putative ring closure reaction

      Pandya, Naresh.; Department of Chemistry (Brock University, 1985-07-09)
      The cr ystal structure of the compound 2-benzoylethylidene-3-(2,4- dibromophenyl)-2,3-dihydro-5-phenyl-l,3,4-thiadiazole* C23H16Br2NZOS (BRMEO) has been determined by using three dimensiona l x-ray diffraction data. The crys tal form is monoclinic, space group P21/c, a = 17.492(4), o -.t' 0 R 0 b =: 16.979(1), c = 14.962(1) A, "X. =o= 90 ',= 106.46(1) , z = 8, graphite-monochromatized Mo~ rad iation, Jl= 0.710J3~, D = 1.62g/cc and o D = 1.65g/cc. The data were col lected on ~ Nonius CAD-4 c diffractometer. The following atoms were made anisotropic: Br, S, N, 0, C7, and C14-C16 for each i ndependent molecu le ; the rest were left isotropic. For 3112 independent refl ec tions with F > 6G\F), R == 0.057. The compound has two independent molecules within the asymmetric unit. Two different conformers were observed which pack well together. /l The S---O interaction distances of 2.493(6) and 2 . 478(7) A were observed for molecules A and B respectively. These values are consistent with earlier findings for 2-benzoylmethylene-3-(2,4-dibromophenyl)- ~~ 2,3-dihydro-5-phenyl-l,3,4-thiadiazole C22H14Br2N20S (BRPHO) and 2-benzoylpropylidene-3-(2,4-dibromophenyl)-2,3-dihydroiii ,'r 5-phenyl-l,3,4-thiadiazole C24H18Br2N20S (BRPETO ) where S---O distances are l ess than the van der Waals (3.251\) but greater than those expected for () a single bond (1.50A). From the results and the literature it appears obvious that the energy/reaction coordinate pathway has a minimum between the end structures (the mono- and bicyclic compounds). * See reference (21) for nomenclature.
    • Application of thermal ion-molecule reactions in tackling spectroscopic inferences in inductively coupled plasma mass spectrometry

      Wang, Yong; Department of Chemistry (Brock University, 2013-04-19)
      Part I: Ultra-trace determination of vanadium in lake sediments: a performance comparison using O2, N20, and NH3 as reaction gases in ICP-DRC-MS Thermal ion-molecule reactions, targeting removal of specific spectroscopic interference problems, have become a powerful tool for method development in quadrupole based inductively coupled plasma mass spectrometry (ICP-MS) applications. A study was conducted to develop an accurate method for the determination of vanadium in lake sediment samples by ICP-MS, coupled with a dynamic reaction cell (DRC), using two differenvchemical resolution strategies: a) direct removal of interfering C10+ and b) vanadium oxidation to VO+. The performance of three reaction gases that are suitable for handling vanadium interference in the dynamic reaction cell was systematically studied and evaluated: ammonia for C10+ removal and oxygen and nitrous oxide for oxidation. Although it was able to produce comparable results for vanadium to those using oxygen and nitrous oxide, NH3 did not completely eliminate a matrix effect, caused by the presence of chloride, and required large scale dilutions (and a concomitant increase in variance) when the sample and/or the digestion medium contained large amounts of chloride. Among the three candidate reaction gases at their optimized Eonditions, creation of VO+ with oxygen gas delivered the best analyte sensitivity and the lowest detection limit (2.7 ng L-1). Vanadium results obtained from fourteen lake sediment samples and a certified reference material (CRM031-040-1), using two different analytelinterference separation strategies, suggested that the vanadium mono-oxidation offers advantageous performance over the conventional method using NH3 for ultra-trace vanadium determination by ICP-DRC-MS and can be readily employed in relevant environmental chemistry applications that deal with ultra-trace contaminants.Part II: Validation of a modified oxidation approach for the quantification of total arsenic and selenium in complex environmental matrices Spectroscopic interference problems of arsenic and selenium in ICP-MS practices were investigated in detail. Preliminary literature review suggested that oxygen could serve as an effective candidate reaction gas for analysis of the two elements in dynamic reaction cell coupled ICP-MS. An accurate method was developed for the determination of As and Se in complex environmental samples, based on a series of modifications on an oxidation approach for As and Se previously reported. Rhodium was used as internal standard in this study to help minimize non-spectral interferences such as instrumental drift. Using an oxygen gas flow slightly higher than 0.5 mL min-I, arsenic is converted to 75 AS160+ ion in an efficient manner whereas a potentially interfering ion, 91Zr+, is completely removed. Instead of using the most abundant Se isotope, 80Se, selenium was determined by a second most abundant isotope, 78Se, in the form of 78Se160. Upon careful selection of oxygen gas flow rate and optimization ofRPq value, previous isobaric threats caused by Zr and Mo were reduced to background levels whereas another potential atomic isobar, 96Ru+, became completely harmless to the new selenium analyte. The new method underwent a strict validation procedure where the recovery of a suitable certified reference material was examined and the obtained sample data were compared with those produced by a credible external laboratory who analyzed the same set of samples using a standardized HG-ICP-AES method. The validation results were satisfactory. The resultant limits of detection for arsenic and selenium were 5 ng L-1 and 60 ng L-1, respectively.
    • 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.
    • Arsenic and germanium determination by hydride generation in the D.C. plasma optical emission spectrometer

      Ceccarelli, Claudio M.; Department of Chemistry (Brock University, 1986-07-09)
      Modifications to the commercial hydride generator, manufactured by Spectrametrics, resulted in improved operating procedure and enhancement of the arsenic and germanium signals. Experiments with arsenic(III) and arsenic(V) showed that identical reiults could be produced from both oxidation states. However, since arsenic(V) is reduced more slowly than arsenic(III), peak areas and not peak heights must be measured when the arsine is immediately stripped from the system (approximately 5 seconds reaction). When the reduction is allowed to proceed for 20 seconds before the arsine is stripped, peak heights may be used. For a 200 ng/mL solution, the relative standard deviation is 2.8% for As(III) and 3.8% for As(V). The detection limit for arsenic using the modified system is 0.50 ng/mL. Studies performed on As(V) standards show that the interferences from 1000 mg/L of nickel(II), cobalt(II), iron(III), copper(II), cadmium(II), and zinc(II) can be eliminated with the aid of 5 M Hel and 3% L-cystine. Conditions for the reduction of germanium to the corresponding hydride were investigated. The effect of different concentrations of HCl on the reduction of germanium to the covalent hydride in aqueous media by means of NaBH 4 solutions was assessed. Results show that the best response is accomplished at a pH of 1.7. The use of buffer solutions was similarly characterized. In both cases, results showed that the element is best reduced when the final pH of the solution after reaction is almost neutral. In addition, a more sensitive method, which includes the use of (NH4)2S208' has been developed. A 20% increase in the germanium signal is registered when compared to the signal achieved with Hel alone. Moreover, under these conditions, reduction of germanium could be accomplished, even when the solution's pH is neutral. For a 100 ng/mL germanium standard the rsd is 3%. The detection limit for germanium in 0.05 M Hel medium (pH 1.7) is 0.10 ng/mL and 0.09 ng/mL when ammonium persulphate is used in conjunction with Hel. Interferences from 1000 mg/L of iron(III), copper(II), cobalt(II), nickel(II), cadmium(II), lead(II), mercury(II), aluminum(III), tin(IV), arsenic(III), arsenic(V) and zinc(II) were studied and characterized. In this regard, the use of (NH4)ZS20S and Hel at a pH of 1.7 proved to be a successful mixture in the sbppression of the interferences caused by iron, copper, aluminum, tin, lead, and arsenic. The method was applied to the determination of germanium in cherts and iron ores. In addition, experiments with tin(IV) showed that a 15% increase in the tin signal can be accomplished in the presence of 1 mL of (NH4)2S20S 10% (m/V).
    • Arsenic speciation by ion-exchange chromatography with on- line determination by hydride generation: electronic modification of the D.C. plasma by photon counting

      Morozink, Darren S.; Department of Chemistry (Brock University, 1994-07-09)
      A method using L-cysteine for the determination of arsenous acid (As(III)), arsenic acid (As(V)), monomethylarsonic acid (MMAA), and dimethylarsinic acid (DMAA) by hydride generation was demonstrated. The instrument used was a d.c. plasma atomic emission spectrometer (OCP-AES). Complete recovery was reported for As(III), As(V), and DMAA while 86% recovery was reported for MMAA. Detection limits were determined, as arsenic for the species listed previously, to be 1.2, 0.8, 1.1, and 1.0 ngemL-l, respectively. Precision values, at 50 ngemL-1 arsenic concentration, were f.80/0, 2.50/0, 2.6% and 2.6% relative standard deviation, respectively. The L-cysteine reagent was compared directly with the conventional hydride generation technique which uses a potassium iodide-hydrochloric acid medium. Recoveries using L-cysteine when compared with the conventional method provided the following results: similar recoveries were obtained for As(III), slightly better recoveries were obtained for As(V) and MMAA, and significantly better recoveries for DMAA. In addition, tall and sharp peak shapes were observed for all four species when using L-cysteine. The arsenic speciation method involved separation by ion exchange .. high perfonnance liquid chromatography (HPLC) with on-line hydride generation using the L.. cysteine reagent and measurement byOCP-AES. Total analysis time per sample was 12 min while the time between the start of subsequent runs was approximately 20 min. A binary . gradient elution program, which incorporated the following two eluents: 0.01 and 0.5 mM tri.. sodium citrate both containing 5% methanol (v/v) and both at a pH of approximately 9, was used during the separation by HPLC. Recoveries of the four species which were measured as peak area, and were normalized against As(III), were 880/0, 290/0, and 40% for DMAA, MMAA and As(V), respectively. Resolution factors between adjacent analyte peaks of As(III) and DMAA was 1.1; DMAA and MMAA was 1.3; and MMAA and As(V) was 8.6. During the arsenic speciation study, signals from the d.c. plasma optical system were measured using a new photon-signal integrating device. The_new photon integrator developed and built in this laboratory was based on a previously published design which was further modified to reflect current available hardware. This photon integrator was interfaced to a personal computer through an AID convertor. The .photon integrator has adjustable threshold settings and an adjustable post-gain device.
    • Aryl hydroxamic acid analogues as potential therapeutic agents /

      Tays, Kevin.; Department of Chemistry (Brock University, 1997-05-21)
      A new synthetic pathway to analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-l,4-benzoxazin-3-ones) has been developed. The new pathway involves the coupling of substituted nitrophenols wdth /-propyl-abromo- O-methoxymethylglycolate. These materials were reductively cyclised to reveal the hydroxamic acid functionality. Removal of the C-2 0-methoxymethyl protecting group was achieved chemoselectively using boron trichloride. The analogue 7-methoxy-2,4-dihydroxy-l,4-benzoxazin-3-one (DIMBOA) was assayed with papain and a semilog plot of activity of papain in the presence of excess DIMBOA was found to be linear. A single exponential equation was suggested as the model for kinetic analysis. '^ Nuclear magnetic resonance (NMR) spectra of a couple of hydroxamates were acquired as reference standards for future mechanistic studies of these compounds as thiol protease inhibitors. A 10% '^-labeled sample ofDIMBOA was also prepared for future mechanistic studies using NMR techniques.
    • An aryne route to aporphine alkaloids and related topics / |nIjaz Ahmad Chanda. -- 260 St. Catharines, Ont. : [s. n.],

      Chanda, Ijaz Ahmad.; Department of Chemistry (Brock University, 1972-07-09)
      This research was directed towards the investigation and development of an aryne route to the syntheses of aporphi ne and dibenzopyrrocolinium (dibenzoindolizinium) alkaloids and to the stability of the latter under the conditions used for aryne formation. The work c an be divided into three main sections . i) - Synthesis of Glaucine 6-Bromo-3,4-dimethoxyphenylacetic acid, prepared by the action of bromine i n acetic acid on3,4-dimethoxyphenylacetic a cid, was converted into its acid chloride by t he action of thionyl chloride. This on treatment with 3,4- dimethoxyphenylethylamine pr ovided N-(3, 4-dimethoxyphenylethyl)- 2-(2-bromo-4,S-dimethoxyphenyl)-acetamide which on dehydration with phosphoryl chloride (Bischler Napieralski reaction) in dry benzene afforded l -(2-bromo-4,S-dimethoxybenzyl)- 3,4-dihydro-6,7-dimethoxyisoquinoline, isolated as hydrochl oride. A new method o f destroying the excess of phosphoryl chloride was developed which proved to be quite useful. Methylation of the dihydroisoquinoline'with methyl iodide in methanol , and subsequent reduction with sodium borohydride provided (±)-6-bromolaudanosine. Act ion of potassamide or sodamide in anhydrous liquid ammonia on (±)-6-bromolaudanosine yielded the corresponding amino derivative along with other products. Diazotization and ring closure of (±)-6-aminolaudanosine then a f forded (±)-glaucine which was isolated as methiodide. ii) - Intramolecular Capture of Aryne During Glaucine Synthesis, and Subsequent Reactions . This section deals with the by-products formed under the conditions of the aryne stage of t he glaucine synthesis. The crude product, obtained in the reaction of potassamide or sodamide in liquid ammonia on (±)-6-bromolaudanosine, was s eparated by chromatography, Three products were separated and identified. a ) - 5,6-Dimethoxy-2-( 3,4-dimethoxy-6-ethylphenyl)-lmethylindole. Two mechanisms are proposed for the formation of this interesting product. This compound also was prepared by the action of potassamide in l,iquid ammonia on 5,6 ,l2,l2atetrahydro- 2,3,9,lO-tetramethoxy-7-methyldibenz[b,g]indolizinium i odide . b) - 5,6-Dimethoxy-2-(3,4-dimethoxy-6-vinylphenyl)-lmethylindoline. Its formation represented a new method of Hofmann degradation . Further confirmation of structure was done by performing the normal Hofmann reaction on 5, 6,12,12a-tetrahydro -2/3,9,lO-tetramethoxy ~7-methyldibe nz[ b,g]indolizinium iodide. The indoline prepared i n this way was identical in all respects with that prepared above . c) - 1- (2-amino-4,5-dimethoxybenzyl ) -l,2,3,4-tetrahydro-2- methyl-6,7-dimethoxyisoquinoline, was converted t o glaucine as stated in section 1 . iii) - Attempt:,ed Sxnthesis of Liriodenine Piperonal was converted into 3,4-methylenedioxyinitrostyrene which on reduction with lithium aluminium hydride provided 3,4-methylenedioxyphenylethylamine. The method of extraction after the reduction was improved t o some extent. The amine on condensation with m-chlorophenylacetyl chloride, prepared by the action of oxalyl chloride on 3,4-methylenedioxyphenylacetic acid, provided N-[ ~ -(3,4-methylenedioxyphenyl)- e thyl)-3-chlorophenylacetamide. This on dehydration with phosphoryl chloride in dry benzene followed by air oxidation afforded l-(3-chlorobenzoyl)-6,7-methylenedioxyi soquinoline. This compound on r eaction with potassamide in liquid ammonia afforded a crude product from which. one product was separated by chromatography i n a pure condition . This yellow compound analysed as,c17Hl ON2021 and was t he main product i n the reaction ; a t entative structure is proposed. A second compound, not obtained in pure condition, was submitted to Pschorr reaction in the hope of obtaining liriodenine, but without success.
    • 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.
    • Asymmetric cyclopropanation via catalysts incorporating the 1,4-diol ligands and the newly designed dioxaborolane /

      Ye, Feng.; Department of Chemistry (Brock University, 2000-07-14)
      The development of new methodology for the asymmetric synthesis of chiral organic compounds is a major focus in modem organic chemistry. The use of chiral catalysts is replacing chiral auxiliaries as a new tool for synthetic chemists. An efficient chiral catalyst allows for large quantities of optically active product to be obtained on use of relatively small amount of enantiopure material, without the need for the removal and recovery of a chiral auxiliary. Furthermore, the most practical catalytic methods utilize an inexpensive and readily available chiral ligand that can provide high and predictable enantioselectivity across a wide range of substrates. In our project, two type of versatile, upgraded chiral ligands have been designed and synthesized. Their application in Simmons-Smith type cyclopropanation is investigated, and the pleasing results suggest that they are the potential catalytic enantioselective candidates to build C-C bonds.