An analysis of the methyl rotation dynamics in the So (x' A) and T (a A) states of thioacetaldehyde from Pyrolysis jet spectra /

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.

Studies in the mass spectra of perfluoroaromatic derivatives of phosphorus and some selected transition metals

The mass spectra and fragmentation of a variety of fluoroaromatic compounds of Group V and some selected transition elements are discussed in some detail, aided by data from metastable defocussed experiments. Results of ,studies on the coupling reaction using unstable organotitanium chloride intermediate species are reported. The preparation of some 5-substituted octafluorodibenzophospho1es is also discussed. Rearrangements under electron bombardment resulting in the loss of heteroatom-fluoride fragments are discussed in the light of presently accepted mechanisms for these processes as are rearrangements observed in compounds involving thionophosphoryl bonds ( p=s ).

Synthetic approaches to syn-diol containing biologically active compounds /

The deoxy derivative of pancratistatin 1.10 was prepared in good yield through the use of a [4+2] Diels-Alder cycloaddition and Bischler-Napieralski cyclization approach. The Bischler-Napieralski cyclization was shown to yield two additional side products 2.9, 2.10, however, under slightly modified hydrolysis conditions, the tetracyclic product 2.11 was obtained exclusively in greater than 84% yield. Initial screening of the di-hydroxylatgd derivative, and the other complementary pair analogue 1.10' previously prepared in our laboratories gave interesting results. Both of these compounds were shown to exhibit cytostatic activity; the mono-alcohol was marginally active while the di-hydroxylated analogue proved to be more potent although one to two magnitudes less potent than pancratistatin itself Human tumour cell line assay results indicated that the di-hydroxylated derivative exhibited selective cytotoxic inhibition in the following cell lines: non-small cell lung cancer line NCI-H226 (ED50 - 0.65 ^g/mL), leukemia cell lines CCRF-CEM (ED30 = 0.55 Hg/mL) and HL-60(TB) (ED50 = 0.89^ig/mL). Our results demonstrated that the pharmacophore is not a mono-alcohol, and that the minimum pharmacophore contains the hydroxyl group at the C4 position in addition to either, or both, of the hydroxyl groups present at C2 and C3.' The minimum pharmacophore has been narrowed to only three possibilities which are current synthetic targets in several research groups. The controlled Grignard addition to the tartaric acid derived bis-Weinreb amide 1.25 afforded a direct entry to a host of 1,4-diflferentiated tartaric acid derived intermediates (2.12-2.18). This potentially usefiil methodology was demonstrated through the efficient synthesis of the naturally occurring lactone 2.23, which bears the inherent syn-dio\ subunit. Based on this result, a similar approach to the synthesis of syn-dio\ bearing natural products looks very promising? A direct 2,3-diol desymmetrization method using TIPS-triflate was shown to be effective on the selective differentiation of Z,-methyl tartrate (and diisopropyl tartrate). The mono-silyl-protected intermediates 2.31 also proved to be useful when they were selectively differentiated at the 1,4-carboxyl position (2.35, 2.36) through the use of a borohydride reducing agent. Furthermore, the mono-silyl-protected derivative underwent periodate cleavage affording two synthetically useful a,P-unsaturated esters 2.43, 2.44, with one of esters being obtained via a silyl-migration method.''

Aryl hydroxamic acid analogues as potential therapeutic agents /

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.

Phonon spectra and thermodynamic properties of rare gas solids based on empirical and semi-empirical (ab initio) two-body potentials : a comparative study /

We study the phonon dispersion, cohesive and thermal properties of raxe gas solids Ne, Ar, Kr, and Xe, using a variety of potentials obtained from different approaches; such as, fitting to crystal properties, purely ab initio calculations for molecules and dimers or ab initio calculations for solid crystalline phase, a combination of ab initio calculations and fitting to either gas phase data or sohd state properties. We explore whether potentials derived with a certain approaxih have any obvious benefit over the others in reproducing the solid state properties. In particular, we study phonon dispersion, isothermal ajid adiabatic bulk moduli, thermal expansion, and elastic (shear) constants as a function of temperatiue. Anharmonic effects on thermal expansion, specific heat, and bulk moduli have been studied using A^ perturbation theory in the high temperature limit using the neaxest-neighbor central force (nncf) model as developed by Shukla and MacDonald [4]. In our study, we find that potentials based on fitting to the crystal properties have some advantage, particularly for Kr and Xe, in terms of reproducing the thermodynamic properties over an extended range of temperatiures, but agreement with the phonon frequencies with the measured values is not guaranteed. For the lighter element Ne, the LJ potential which is based on fitting to the gas phase data produces best results for the thermodynamic properties; however, the Eggenberger potential for Ne, where the potential is based on combining ab initio quantum chemical calculations and molecular dynamics simulations, produces results that have better agreement with the measured dispersion, and elastic (shear) values. For At, the Morse-type potential, which is based on M0ller-Plesset perturbation theory to fourth order (MP4) ab initio calculations, yields the best results for the thermodynamic properties, elastic (shear) constants, and the phonon dispersion curves.

Fluorescence spectra and ab initio theoretical studies of HCOOH /

A fluorescence excitation spectrum of formic acid monomer (HCOOH) , has been recorded in the 278-246 nm region and has been attributed to an n >7r* electron promotion in the anti conformer. The S^< S^ electronic origins of the HCOOH/HCOOD/DCOOH/DCOOD isotopomers were assigned to weak bands observed at 37431.5/37461.5/37445.5/37479.3 cm'''. From a band contour analysis of the 0°^ band of HCOOH, the rotational constants for the excited state were estimated: A'=1.8619, B'=0.4073, and C'=0.3730 cm'\ Four vibrational modes, 1/3(0=0), j/^(0-C=0) , J/g(C-H^^^) and i/,(0-H^yJ were observed in the spectrum. The activity of the antisymmetric aldehyde wagging and hydroxyl torsional modes in forming progressions is central to the analysis, leading to the conclusion that the two hydrogens are distorted from the molecular plane, 0-C=0, in the upper S. state. Ab initio calculations were performed at the 6-3 IG* SCF level using the Gaussian 86 system of programs to aid in the vibrational assignments. The computations show that the potential surface which describes the low frequency OH torsion (twisting motion) and the CH wagging (molecular inversion) motions is complex in the S^ excited electronic state. The OH and CH bonds were calculated to be twisted with respect to the 0-C=0 molecular frame by 63.66 and 4 5.76 degrees, respectively. The calculations predicted the existence of the second (syn) rotamer which is 338 cm'^ above the equilibrium configuration with OH and CH angles displaced from the plane by 47.91 and 41.32 degrees.

Coriolis effects in symmetric top spectra /

The "x-y Coriolis Coupling Theory" as presented by Dilauro and Mills (1966) is reformulated and extended to the determination of Raman intensities. Theoretical Raman and Infrared spectra are computed in order to understand the effects due to this coupling in both types of spectra. Both the Infrared and Raman spectra obtained indicate very real effects due to Coriolis coupling. In some of the cases chosen the computed spectra are grossly different from the normal spectra where coupling is absent. Such large effects can greatly impede the interpretation of experimental results. Theoretical spectra therefore aids in the interpretation of experimental results, as is clearly demonstrated in the results of this work.

Synthesis of chiral homoallylic alcohols and phthalans through the asymmetric allylation of carbonyl compounds /

The implementation of chiral centres within biologically active compounds has been a perplexing yet motivational force in chemistry. This work presents the attempted formation of a concurrent or sequential tandem catalyzed methodology of enantioselective nucleophilic addition and electrophilic cyclization. The 2'- arylalkynyl- aldehyde, ketone, and imine substrates used within were adeptly chosen with a dually activated structure; 1) for nucleophilic addition to the electrophilic substituents; and 2) for carbophilic activation of the alkyne substituent to undergo cyclization. To accomplish the nucleophilic addition, two distinct allylation methodologies were pursued: (/?)-BINOL catalyzed-allylboration and (5)- BINAP-AgF catalyzed-allylsilylation. BINAP catalyzed enantioselective allylation of 2'-arylalkynyl-aldehydes, to form chiral homoallylic alcohols, was successful. Homoallylic alcohols were isolated with high enantio-purity (>80%), which then underwent sequential cyclization to form chiral allylic phthalans, in moderate yields. An application of this methodology towards the construction of biologically active compounds was included with the partial synthesis of the natural product and H. pylori inhibitor, (+)-Spirolaxine methyl ether.

Phonon spectra and thermal properties of some fcc metals using embedded-atom potentials /

By employing the embedded-atom potentials of Mei et ai.[l], we have calculated the dynamical matrices and phonon dispersion curves for six fee metals (Cu,Ag,Au,Ni,Pd and Pt). We have also investigated, within the quasiharmonic approximation, some other thermal properties of these metals which depend on the phonon density of states, such as the temperature dependence of lattice constant, coefficient of linear thermal expansion, isothermal and adiabatic bulk moduli, heat capacities at constant volume and constant pressure, Griineisen parameter and Debye temperature. The computed results are compared with the experimental findings wherever possible. The comparison shows a generally good agreement between the theoretical values and experimental data for all properties except the discrepancies of phonon frequencies and Debye temperature for Pd, Pt and Au. Further, we modify the parameters of this model for Pd and Pt and obtain the phonon dispersion curves which is in good agreement with experimental data.

Synthesis of isotope-labelled methoxypyrazine compounds as internal standards and quantitative determination of aroma methoxypyrazines in water and wines by solid-phase extraction with isotope dilution-GC-MS /

An efficient way of synthesizing the deuterium labelled analogues of three methoxypyrazine compounds: 2-d3-methoxy-3-isopropylpyrazine, 2-d3-methoxy-3- isobutylpyrazine, and 2-d3-methoxy-3-secbutylpyrazine, has been developed. To confirm that the deuterium labels had been incorporated into the expected positions in the molecules synthesized, the relevant characterization by NMR, HRMS and GC/MS analysis was conducted. Another part of this work involved quantitative determination of methoxypyrazines in water and wines. Solid-phase extraction (SPE) proved to be a suitable means for the sample separation and concentration prior to GC/MS analysis.Such factors as the presence of ethanol, salt, and acid have been investigated which can influence the recovery by SPE for the pyrazines from the water matrix. Significantly, in this work comparatively simple fractional distillation was attempted to replace the conventional steam distillation for pre-concentrating a sample with a relatively large volume prior to SPE. Finally, a real wine sample spiked with the relevant isotope-labelled methoxypyrazines was quantitatively analyzed, revealing that the wine with 10 beetles per litre contained 138 ppt of 2-methoxy-3-isopropylpyrazine. Interestingly, we have also found that 2-methoxy-3-secbutylpyrazine exhibits an extremely low detection limit in GC/MS analysis compared with the detection limit of the other two methoxypyrazines: 2- methoxy-3-isopropylpyrazine and 2-methoxy-3-isobutylpyrazine.

Effects of large anphiphilic ligands upon the spectra and kinetics of cytochrome C oxidase

Cytoch ro me c oxidase (ferrocytochrome c : 02 oxidoreductase ; EC 1.9. 3.1) is the terminal enzyme in the mitochondrial electron transport chain, catalyzing the transfer of electrons from ferrocytochrome c to molecular oxygen. The effects of two large amphiphilic molecules .. valinomycin and dibucaine upon the spectra of the isolated enzyme and upon the activity of both isolated enzyme and enzyme in membrane systems are investigated by using spectrophotometric and oxygen electrode techniques. The results show that both valinomycin and dibucaine change the Soret region of the spectrum and cause a partial inhibition in a concentration range higher than that in which they act as ionophores. It is concluded that both valinomycin and dibucain~ binding induce a conformational change of the protein structure which modifies the spectrum of the a3 CUB centre and diminishes the rate of electron transfer between cytochrome a and the binuclear centre.

Exchange reactions of organic halides and organo-silicon compounds with boron tribromide and boron triiodide

Reactions of the boron halides with organic halides and organo-silicon compounds have been investigated. The results show exchange of halogens between the BX3 (X = Br# 1) and the organic halidef exchange of the halogen of the C-X bond being proved. The rates of halogen exchange vary. Reaction of the heavier halides with organo-silicon compounds indicated that the silicon-carbon bonds ruptured in the absence of electronegative atom attached to the silicon. The presence of an electronegative atom (halogen or oxygen) attached to the silicon causes the bond between the silicon and the electronegative atom to be preferentially broken. Products of exchange reactions of the boron halides and the organic halides or the organo-silicon compounds were studied by use of 1H NMR and GC/MS. From these results some possible mechanisms for the exchange reactions are postulated, but further work is indicated to prove the real courses of the reactions

Fast atom bombardment mass spectrometry of the coordination complexes of the ligand 5, 5, 7, 12, 12, 14- hexamenthyl-1, 4, 8, 11-tetraazacycloteradecane

A number of metal complexes containing the ligand 5,5,7,12,12,14-hexamethyl-l,4,8,11-tetra-azatetradecane were synthesized and analyzed using electron impact (EI) and fast atom bombardment (FAB). The FAB mass spectra were obtained in positive and negative ion mode. FAB in the positive ion mode proved to be the most successful technique for the identification of these compounds. In the majority of cases the spectra obtained using positive ion FAB were structurally informative, although not all showed molecular (M+) or quasimolecular ([M+H]+) ions. The fragmentations observed were characteristic of the ligands, and were interpreted based on the chemistry of these compounds.

Fast atom bombardment mass spectrometry studies of ruthenium (II) polypyridy coordination complexes and of group V Triptycenes and related complexes

In order to investigate the use of Fast Atom Bombardment Mass Spectrometry (FAB-MS) as a tool for structural characterization, two groups of complexes are analyzed. The first group is a set of ruthenium(II) coordination complexes containing bidentate polypyridyl ligands. The positive and negative ion FAB-MS spectra are found to be sufficient to allow for an almost complete characterization of the central metal atom, the ligands and the counter anions contained in the intact complex. An unusual observation of mUltiply charged ions in the positive ion FAB-MS spectra (i.e. [RUL 3 ]2+) is explained to be as a result of the oxidative quenching of the excited state of the doubly charged ion by the matrix, 3-nitrobenzyl alcohol. An analysis of a mixture shows that the technique is a good one for identifying components therein. A group of triptycene and related complexes containing Group V elements is also analyzed by FAB-MS and the results. in terms of relative abundances of fragment ions, are found to be consistent with known metal-carbon bond strengths.

Metal complexes involving pyridoxine and pyridoxamine

Solid complexes of pyridoxine with Mn(II) , Cd(II) and Zn(II) have been isolated, as well as compounds containing Cu(II), Ni(II), Co(III), Cd(II) and Zn(II), and pyridoxamine in various protonated forms. Infrared spectra provide evidence for protonation at the pyridine nitrogen site in the complexes, but not in the neutral vitamins and the complexes of anionic pyridoxamine. Thus the complexed vitamins are in zwitterionic forms, with chelation probably occurring through the phenolate oxygen and either the amino or the hydroxy group at the 4' position.