Mass spectrometry has frequently been employed in the analysis of biologically relevant molecules; however, mass spectrometry alone may not always be sufficient for the differentiation and characterization of isomeric and isobaric ions. In this work, infrared multiple photon dissociation (IRMPD) spectroscopy and ion mobility spectrometry (IMS) were evaluated as complementary techniques for the characterization and separation of isomeric and isobaric ions of biological relevance. In the first project, analysis of experimental IRMPD spectroscopy data shows that this technique is useful in the differentiation of hydroxyproline isomers. Absorption bands allow for the differentiation of three isomeric species: 1640 cm-1 (trans-4-hydroxyproline), 1718 cm-1 (cis-4-hydroxyproline), and 1734 cm-1 (cis-3-hydroxyproline). In the second project, theoretical CCS and IR spectroscopy predictions of isobaric modified amino acids and isomeric drugs have been carried out as predictions of IMS and IRMPD spectroscopy suitability. Preliminary IMS measurements suggest that the CCS predictions are at least qualitatively useful.

Dissertation (PhD)--University of Stellenbosch, 2004. / 175 Leaves printed single pages, preliminary pages i-xiii and 147 numberd pages. Includes bibliography. List of figures, List of tables. / ENGLISH ABSTRACT: This study forms part of a larger investigation which has as a primary objective the development of a comprehensive theoretical description of all the processes which contribute to the continuum in the interaction of 12C and 16O with nuclei. Previous investigations of 12C and 16O induced reactions on targets with mass close to A = 100 have shown that the experimental excitation functions and recoil range distributions of heavy residues can be reproduced satisfactorily by means of a theoretical model which takes relatively few dominant reaction mechanisms into account. These include the complete fusion of the projectile with the target, the incomplete fusion of break-up α-type fragments (i.e. single α particles, 8Be fragments and for the 16O induced reactions also 12C fragments) with the target and single-nucleon transfer at incident energies above about 15 MeV/nucleon. The mean-field interaction is mainly responsible for these interactions. The thermalization of the intermediate excited nuclei produced in this first stage of the reaction is described by an intranuclear interaction cascade, during which pre-equilibrium emission of particles and clusters may occur, followed by evaporation after statistical equilibrium has been attained. The model also included the probability that break-up α particles may escape with a large fraction of their initial energy after only a few interactions with individual target nucleons following their initial incomplete fusion. The theory also predicted an enhanced isobaric yield for residues with mass similar or near to that of the target. The subsequent analysis of the emission spectra of intermediate mass fragments in these reactions, however, indicated that two additional aspects need to be considered as well in order to reproduce the experimental data. The first is that the projectile may lose a substantial amount of energy in an initial-state interaction before breaking up, which can be described as a friction dissipative process. The second is that several other incomplete fusion channels of “non-α-cluster”- type fragments should also be included in a more complete description of these reactions as their contributions are not negligible. The present study has two main objectives. Firstly, to investigate the isobaric yield in the neartarget mass region by measuring production cross sections for 103Pd, 103mRh and 103Ru. Previous studies only provided data for 103Ag, which constitute only a few percent of the A = 103 isobaric yield. The new data constitute more than 80% of the A = 103 isobaric yield, which provide experimental confirmation of the enhanced isobaric yield in the near-target mass region. The second objective is to perform extensive new calculations of the excitation functions and recoil ranges in order to investigate the predictive power of the extended model in a priori calculations for the entire available data set. / AFRIKAANSE OPSOMMING: Hierdie studie maak deel uit van ‘n meer omvattende ondersoek wat as ‘n primêre doelwit die beskrywing van al die bydraende prosesse tot die kontinuum in die interaksie van 12C en 16O met kerne behels. In vorige ondersoeke van 12C en 16O geïnduseerde reaksies op skywe met massa naby A = 100 kon die eksperimentele opwekkrommes van swaar reskerne en reikwydte distribusies van terugslagkerne bevredigend gereproduseer word met behulp van ‘n teoretiese model wat slegs enkele dominante reaksiemeganismes in berekening bring. Hierdie sluit in die volledige versmelting van die projektiel met die skyfkern, die onvolledige versmelting van opbreek α-tipe fragmente (d.w.s. α- deeltjies, 8Be fragmente, en in die geval van 16O geïnduseerde reaksies ook 12C fragmente) met die skyfkern, en enkel-nukleon oordrag by invalsenergië wat hoër is as ongeveer 15 MeV/nukleon. Die gemiddelde-veld interaksie is hoofsaaklik verantwoordelik vir bogenoemde reaksie meganismes. Die oorgang na termiese ewewig van die opgewekte tussenkerne wat in hierdie eerste stadium van die reaksie gevorm word, word beskryf deur ‘n intrakern interaksie kaskade wat gekenmerk word deur die voorewewigs emissie van deeltjies en klonte van deeltjies, gevolg deur verdamping nadat statistiese ewewig bereik is. Dié model sluit ook die waarskynlikheid in dat opbreek α-deeltjies kan ontsnap met ‘n betekenisvolle fraksie van hul aanvanklike energie na slegs enkele interaksies met individuele skyfnukleone nadat hulle aanvanklik onvolledig versmelt het. In latere studies van die emissiespektra van intermediêre massa fragmente in hierdie reaksies het dit egter geblyk dat twee addisionele aspekte ook in berekening geneem moet word om die eksperimentele data te reproduseer. Eerstens kan die projektiel ‘n substansiële hoeveelheid energie verloor in ‘n aanvangstoestand interaksie voordat dit opbreek, wat beskryf kan word as ‘n wrywingdissipatiewe proses. Tweedens kan verskeie ander onvolledige versmeltingskanale van fragmente met ‘n nié-α-karakter ook betekenisvol bydra en kan hulle dus nie verwaarloos word in ‘n meer volledige beskrywing van hierdie reaksies nie. Die huidige studie het twee hoofdoelwitte. Eerstens word die isobariese opbrengs in die nabyskyfgebied ondersoek deur die produksie kansvlakke van 103Pd, 103mRh en 103Ru te meet. In vorige studies is slegs data verkry vir 103Ag, wat net ‘n klein persentasie van die A = 103 isobariese opbrengs verteenwoordig. Die nuwe data verteenwoordig meer as 80% van die A = 103 isobariese opbrengs, wat eksperimetele bevestiging verleen dat ‘n verhoging in die isobariese opbrengs in die nabyskyfgebied bestaan. Die tweede doelwit is om ‘n volledige stel nuwe a priori berekeninge te doen vir al die opwekkrommes van reskerne en reikwydte distribusies van terugslagkerne wat tans beskikbaar is om sodoende die voorspellings van die nuwe uitgebreide teoretiese model te toets.

Construction of heavily loaded shallow foundations adjacent to deep foundation is generally avoided in common geotechnical engineering practice to minimize additional loads on deep foundations. However, with the growing trend of urbanization leading to a demand of new construction, it is not always possible to avoid such situation where a heavily loaded shallow foundation will be right next to the infrastructure resting on deep foundations. When this situation cannot be avoided, influence of soil pressures and deformations in soil, created by shallow foundation on adjacent deep foundation, must be evaluated. The study of interaction between deep foundations has been carried out by several researchers in terms of pile-soil-pile interaction. Similarly, there are many published studies on interaction between closely spaced shallow foundations in terms of bearing capacity and settlement. However, not much published literature is available for practicing engineers to analyze and design deep and shallow foundations when they are constructed adjacent to each other. Construction of heavily loaded mat adjacent to drilled shafts would cause complex interaction between the foundations. However, lateral stress and drag forces on the shafts resulting from the heavy load on the mat foundation are the two major factors that would affect the design and performance of shafts. Since there is not much literature and guidance available to analyze and design such kind of situation, a preliminary investigation was first carried out where magnitude of the drag forces and lateral forces on drilled shafts were estimated using simple geotechnical engineering principles. The limitations of preliminary analysis led to the need of more sophisticated analysis using finite element techniques. As a part of this research, a detailed parametric study using finite element techniques has been performed to better understand stress and deformation distributions, and develop simplified methods to analyze this type of problems. A stress bulb for lateral stresses under a uniformly loaded square foundation, similar to the pressure bulb for vertical stresses which is widely used in the geotechnical engineering practice, has been proposed, which provides a significant tool for practicing engineers to understand lateral stress distribution below a uniformly loaded square area and estimate lateral stresses on nearby deep foundations. Similarly, a deformation bulb under a uniformly loaded square foundation is proposed. A new term “Isodefers” has been proposed to refer the lines of equal deformation. Isodefers are also a significant tool for practicing engineers to understand vertical deformation distribution below a uniformly loaded square area and estimate drag forces on nearby deep foundations. A case study emerging from similar real life scenario has also been analyzed and results are discussed with suitable recommendations.

Ces travaux de thèse sont consacrés au développement de nouvelles méthodologies pour l’analyse structurale et quantitative de composés isomères ou isobares en mélange par spectrométrie de masse en tandem (MS/MS) ainsi que par la technique des ions survivants (SY). À l’aide de cette technique, nous avons développé une méthode de « purification collisionnelle en phase gaz » consistant à purifier un composé par fragmentation sélective du contaminant isomère ou isobare afin de permettre l’analyse structurale et quantitative du composé d’intérêt. Nous avons montré que cette approche peut être utilisée avec succès à la fois lors de l’étape d’excitation collisionnelle (CID) d’une expérience MS/MS, mais également lors du processus d’ionisation (in-source CID). Utilisant cette approche MS/MS sur une fenêtre de 15 m/z, nous avons ainsi pu quantifier, par la méthode de l’étalon interne, un peptide trypsique malgré la présence d’un contaminant isobare. L’optimisation des performances de quantification pour la technique SY a ensuite été étudiée sur des peptides isomères topologiques en mélange et comparée à l’analyse par microscopie infrarouge. Parmi les alcalins, alcalino-terreux et métaux de transition testés, nous avons obtenu les meilleurs résultats avec les adduits au césium. Des résultats comparables à la technique infrarouge ont confirmé la pertinence de notre approche avec de surcroît de meilleures performances analytiques, en particulier en terme de rapidité d’exécution, de sensibilité, d’erreur de prédiction et de limite de quantification. / This PhD work focused to the development of new methodologies for the structural and quantitative analysis of isomers or isobars compounds in mixture using tandem mass spectrometry (MS/MS) and the Survival Yield technique (SY).Using this technique, we have developed a method of « gas phase collisional purification » of purifying a compound by selective fragmentation of the isomeric or isobaric contaminant to allow the structural and quantitative analysis of the compound of interest. We have shown that this approach can be used successfully both during the collisional excitation step (CID) of a MS/MS experiment, but also during the ionization process (in-source CID). Using this MS/MS approach on an isolation window of 15 m/z, we were able to quantify, by the internal standard method, a tryptic peptide despite the presence of an isobaric contaminant.Optimization of quantification performances for the SY technique was then studied on topological isomeric peptides in mixture and compared with infrared microscopy analysis. Among the alkali, alkaline earth and transition metals tested, we obtained the best results with cesium adducts.Results comparable to the infrared technique confirmed the relevance of our approach with, moreover, better analytical performances, in particular in terms of speed of execution, sensitivity, prediction error and limit of quantification.