Poly-proline-based chiral stationary phases are relatively new stationary phases and have shown to be competitive to other commercially available chiral stationary phases for high performance liquid chromatography (HPLC). The conformational studies, solvation properties and enantio-selective mechanism of this chiral stationary phase are the main focus of this thesis. Semi-flexible models are developed based on an extensive series of ab initio calculations for proline selectors from di- to hexa-proline and a series of six chiral analytes. Then molecular dynamics simulations are performed to study the solvation, conformational preferences at the interface, and the selectivity. The solvation and conformational preferences of poly-proline selectors at the interface are examined in a normal phase n-hexane/-2propanol and a reverse phase water/methanol solvent. We noticed a significant difference between conformational preferences of poly-proline chains in these solvents indicating the effect of solvent polarity and hydrogen bonding on the relative stabilities of poly-proline conformers. Solvent partitioning occurs at the interface and this creates a polarity gradient between the stationary phase and the bulk that encourages analyte docking at the interface. Hydrogen bonding to the poly-proline selectors is shown to be a function of solvent composition and poly-proline conformation at the interface. The selectivity of the poly-proline chains was studied by molecular dynamics simulations of chiral analytes docking into the interface. The selectivity factors for a set of enantiomers were predicted successfully. Enantio-resolution has been shown to mostly happen with hydrogen bonding to poly-proline carbonyl oxygens located close to the interface. Steric interactions and conformational flexibility of the analytes are also contributing factors for enantio-resolution. / Thesis (Ph.D, Chemistry) -- Queen's University, 2013-01-28 14:31:53.316

Orientador: Isabel Cristina Sales Fontes Jardim / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-06T15:47:25Z (GMT). No. of bitstreams: 1 Lourenco_Josimara_M.pdf: 719895 bytes, checksum: c0f8473e3a648286f7a03cc8d8056bc9 (MD5) Previous issue date: 2005 / Resumo: Em cromatografia líquida de alta eficiência (CLAE), a coluna é freqüentemente considerada como o "coração do sistema cromatográfico", pois é nela que ocorre a separação. Dessa forma, a busca por fases estacionárias capazes de realizar separações com alta eficiência e desempenho tem sido uma constante em muitos laboratórios de pesquisa. Polissiloxanos fenil substituídos têm sido extensivamente utilizados em cromatografia gasosa, mas a sua aplicação em CLAE tem despertado pouca atenção. Neste trabalho foram preparadas fases estacionárias para CLAE, com grupos fenil, a partir da sorção e subseqüente imobilização por tratamento térmico do copolímero de dimetil(52-48%)-metil-fenil(48-52%) siloxano sobre a sílica (Kromasil, 5 mm). Medidas da quantidade de carbono, volume de poro, área superficial específica, espectroscopia no infravermelho e RMN de C e Si foram realizadas para caracterizar físico-quimicamente as fases estacionárias. Também foram feitas avaliações cromatográficas utilizando misturas teste de compostos orgânicos de diferentes polaridades. As fases estacionárias preparadas a partir do copolímero de dimetil(52-48%)-metil-fenil(48-52%) siloxano sobre a sílica e imobilizadas termicamente a 150 °C, por 4,5 horas apresentaram alta eficiência (77000 N m), picos simétricos (As = 0,9) e bom desempenho cromatográfico. Os parâmetros cromatográficos indicaram que o tratamento térmico melhorou o desempenho das fases estacionárias e proporcionou um aumento da estabilidade frente a fases móveis neutras e alcalinas / Abstract: In high-performance liquid chromatography (HPLC), the column is frequently considered as the "heart of the chromatographic system", because is in the column that the separation occurs. In this way, the search for stationary phases able to achieve separations with high efficiency and performance has been a constant in many research laboratories. Phenyl substituted polysiloxanes have been used extensively in gas chromatography, but their application in HPLC has received little attention. In this work were prepared stationary phases for HPLC, with phenyl groups, using sorption and subsequent thermal immobilization of the copolymer of dimethyl(52-48%)-methyl-phenyl(48-52%) siloxane on silica (Kromasil, 5 mm). Measurement of amount of carbon, pore volume, specific surface area, infrared spectrum and NMR of C and Si were used to physical-chemically characterize the stationary phases. Chromatographic evaluations using test mixtures of organic compounds of different polarity were also carried out. The stationary phases prepared from the copolymer of dimethyl(52-48%)-methyl-phenyl(48-52%) siloxane on silica gel and thermally immobilized for 4.5 h at 150 °C show high efficience (77000 N m), symmetrical peaks (As = 0.9) and good chromatography performance. The chromatographic parameters show that the thermal treatment improved the performance of stationary phases and provided an increase of stability in neutral and basic mobile phases / Mestrado / Quimica Analitica / Mestre em Química

Direct chiral separations of the non-steroidal drugs of 2-methylarylpropionic acids (profens) on the chiral stationary phases (CSPs) of amylose tris(3,5-dimethylphenyl-carbamate), Chiralpak AD, and cellulose tris(3,5-dimethylphenylcarbamate), Chiralcel OD, were investigated. Chiralpak AD and Chiralcel OD are CSPs coated on silica gel and have the same type of constituents. However, they have different higher order structures arising from their different arrangements of the glucose units, i.e., the former has an a-(1,4)-D-glucose linkage and the latter has a b-(1,4)-D-glucose linkage. The orders of optimum enantioselectivity of racemic acids were reversed on the two CSPs which demonstrated that the enantioseparating abilities of these CSPs are complementary. This phenomenon also confirmed that the chiral recognition abilities of both CSPs were dependent on their higher order structures. Mechanisms for retention and chiral recognition for the separation of racemic 2-methylarylpropionic acids on Chiralpak AD and Chiralcel OD were explored. In depth studies of the dependence of retention and enantioselectivity on temperature and mobile phase compositions were made. The thermodynamic parameters, the differences in free energy, enthalpy, and entropy of association between enantiomers and the CSP were evaluated. The results indicated that the retention of racemic acids on both CSPs is mainly dependent on the hydrogen bonding interaction between the acid proton of the carboxyl moiety of the analyte and the carbonyl oxygen of the carbamate moiety of the CSP. The chiral recognition mechanism for Chiralpak AD involves: (1) the formation of transient diastereomeric analyte-CSP complexes through hydrogen bonding interactions between the carboxyl and the carbamate moieties of the acid and CSP, respectively; (2) stabilization of these complexes by insertion of the aromatic portion of the analytes into the chiral cavities of the CSP, as well as pi-pi, dipole-dipole, and additional hydrogen bonding interactions between analyte and CSP; and (3) chiral discrimination between enantiomer analytes arising from the additional hydrogen bond between analyte and CSP. For Chiralcel OD, the chiral recognition mechanisms involve: (1) the formation of transient diastereomeric analyte-CSP complexes through hydrogen bonding interactions between the carboxyl and the carbamate moieties of the acid and CSP, respectively; (2) stabilization of these complexes by insertion of the aromatic portion of the analytes into the chiral cavities of the CSP, as well as pi-pi and dipole-dipole interactions between analyte and CSP; and (3) chiral discrimination due to: (a) the difference in the steric fit of enantiomers into the chiral cavity of the CSP (entropy controlled); and (b) dipole-dipole or p-p interactions between enantiomer analytes and CSP (enthalpy controlled). Chromatographic and quantitative thermodynamic data showed that there are at least two different chiral recognition mechanisms for Chiralcel OD. One mechanism was characterized by negative values for the enthalpy and entropy differences of the association between enantiomers and CSP that classifies the enantioseparation to be enthalpy controlled. This behavior was exhibited by racemic 2-methylarylpropionic acids with fused rings that were favorably separated at low temperatures. The other mechanism was associated with positive values for the enthalpy and entropy differences of the association between enantiomers and CSP, and the enantioseparation is said to be entropy controlled. The analytes with "free" phenyl moieties favored high temperatures for their enantioseparations. Both studies on the effects of temperature and mobile phase composition also indicated that the higher order structures of CSPs influence their chiral recognition abilities. / Ph. D.

The aim of this study is a preparation of polyaniline stationary phases doped with silver for application in HPLC. Various polyaniline coated stationary phases differing in the addition of AgNO3 were polymerized. Some of them were subjected to Ag sedimentation, in others AgNO3 was added after polymerization. Stationary phases were investigated by scanning electron microscopy, atomic absorption spectroscopy, Raman spectroscopy, and Fourier transformation infrared spectroscopy. Columns filled with prepared stationary phases were compared with silver-free polyaniline column by separating a mixture consisting of caffeine, theobromine and theophylline in three chromatographic modes (NP-pure ACN, HILIC-98/2 (v/v) ACN/water and RP-20/80 (v/v) ACN/water) at a flow rate of 5 µL/min with UV detection at 265 nm and also by separating a mixture of 2'-aminoacetophenone, 3'-aminoacetophenone and 4'-aminoacetophenone in the same chromatographic modes, at a flow rate of 5 µL/min except from RP mode where a flow rate of 10 µL/min was used to accelerate separation. Polyaniline-coated columns doped with silver showed different selectivity in the RP mode of the mixture of caffeine, theobromine and theophylline when compared to polyaniline-coated columns without the addition of silver. Further, the columns were tested for...

Advances in micro-electro-mechanical-systems (MEMS) along with nanotechnology based methods have enabled the miniaturization of analytical chemistry instrumentation. The broader aim is to provide a portable, low-cost, and low-power platform for the real-time detection and identification of organic compounds in a wide variety of applications. A benchtop gas chromatography (GC) system is considered a gold standard for chemical analysis by analytical chemists. Similarly, miniaturization of key GC components (preconcentrator, separation column, detector, and pumps) using micro- and nanotechnology based techniques is an on-going research field. This dissertation specifically deals with the design, fabrication, coating, and chromatographic testing of microfabricated separation columns for GC. This work can be broadly categorized into three research areas: design and development of new column designs, introduction of new stationary phases and the development of novel fabrication methodologies for integrating functionalized thin-film into microchannels for chromatographic separations. As a part of this research, two high performance new micro column designs namely width-modulated and high-density semi-packed columns are introduced for the first time. Similarly, two new types of functionalized stationary phases are also demonstrated i.e. a highly stable and homogenous silica nanoparticles coating deposited using a layer-by-layer self-assembly scheme and a highly conformal functionalized thin aluminum oxide film deposited using atomic layer deposition. Moreover, novel thin-film patterning methods using different microfabrication technologies are also demonstrated for high-aspect ratio multicapillary and semi-packed columns. / Ph. D.

In this study, four different chromatographic column chemistries (octadecylsilane/ C18, pentafluorophenyl/ PFP, octadecylated polystyrene-divinylbenzene/ PRP and underivatized silica/ HILIC) were compared under optimal conditions to evaluate the relative strengths and weaknesses of the phases for use in the determination of pain management drugs by LC-MS. Furthermore, different column scaffoldings, traditional silica, porous shell, and porous polymer, were also compared. The drugs included in this study included buprenorphine, fentanyl, methadone, naloxone, oxycodone, and tramadol. Factors such as peak area, peak resolution, theoretical plates, and reproducibility were compared among the columns and analytes using a 2-way analysis of variance (ANOVA). Because of the lipophilic nature of these drugs, the C18 columns tended to offer the best performance; however, PFP and PRP columns were viable alternatives. Finally, HILIC separation was also suitable for most of the compounds under study; often providing higher peak areas (sensitivity) likely associated with higher organic (% B) conditions, thus favoring mass spectrometric detection. To our knowledge, this is the first study to explore viability of other non-C18 stationary phases such as PRP and HILIC for this drug class.

Micellar electrokinetic chromatography (MEKC) and capillary electrochromatography (CEC) are two of the major capillary electrophoresis (CE) modes that have been interfaced to mass spectrometry (MS) for sensitive and selective analysis of chiral compounds. This research combines these two modes and expands their applications in chiral CE analysis. Chapter 1 is a review of amino acid based molecular micelles used in MEKC-MS for enantioselective analysis over the past five years. In this chapter, a typical MEKC-MS experiment setup as well as detailed standard operating procedure in synthesis of molecular micelles and running a typical MEKC-MS experiment using the molecular micelles is discussed. Chapter 2 described a multivariate MEKC-MS optimization for the simultaneous analysis of two negatively charged model chiral compounds in negative ion mode with molecular micelles. In this chapter, a central composite design (CCD) is used to first construct a series of experiments to optimize all the important MEKC-MS parameters. Next, response surface methodology (RSM) was used to analyze the interactions between the factors, picking up the best separation and detection conditions, predicting the result of the chiral separation/MS detection, and finally running the actual experiment and comparing the chromatographic results with the predicted parameters. Chapter 3 demonstrates a similar multivariate MEKC-MS optimization for analysis of a positively charged model chiral compound in a positive ion mode. The same CCD and RSM methods were used to optimize the separations and MS sensitivity. Chapter 4 describes a chiral analysis of four neutral benzoin derivatives (hydrobenzoin, benzoin, benzoin methyl ether, and benzoin ethyl ether) using MEKC coupled to atmospheric pressure photo-ionization mass spectrometry (APPI-MS). The same multivariate experimental design strategy was used to optimize the MEKC as well as APPI-MS parameters. Simultaneous chiral separation of all four benzoin derivatives was achieved with high detection sensitivity compared to UV-detection. Chapter 5 introduces a novel one-pot synthesis scheme for an acryloyl-terminated, carbamate-linked surfactant-bound monolith with leucine head group and different chain lengths. The method promises to open up the discovery of new amino acid based polymeric monoliths for chiral separations and enhanced chemoselectivity for simultaneous chiral separations and enhanced detection in CEC and CEC-MS. In Chapter 6, five amide-linked surfactant-bound monoliths with different chain lengths and head groups (leucine, valine, and phenylalanine) were synthesized and characterized. Enantioseparation of several test compounds was achieved by CEC using the monolithic columns. One of the chiral surfactant, sodium 11-acrylamidoundecanoyl-L-leucinate (SAAUL), was polymerized in aqueous solution under 60Co radiation to form molecular micelle poly-SAAUL. MEKC experiments were carried out with the poly-SAAUL molecular micelle to separate ten cationic chiral compounds. The result was compared with the CEC separation using the AAUL monolithic column. This study is the first comparison of chiral CEC and MEKC with the same surfactant monomer, which has the capability of forming both chiral stationary phase for CEC and chiral pseudophase for MEKC.

The mechanism by which chiral selectivity takes place is complicated by the surface morphology, the possible involvement of the solvent, and the characteristics of the chiral molecules at the surface. My goal is to model and understand the factors which lead to significant discrimination in the case of three closely related chiral stationary phases: N-(1-phenylethyl)-N’-[3-(triethoxysilyl)propyl]-urea (PEPU), [(3,5-dinitrobenzoyl)-amino]-N-[3-(triethoxysilyl)propyl]-2-phenylacetamide (DNB-phenyglycine), and [(3,5-dinitrobenzoyl)amino]-N-[3-(triethoxysilyl)propyl]-4-methylpentanamide (DNB-leucine). Ab initio calculations are used to develop molecular models of these chiral selectors. These models are employed in molecular dynamics (MD) simulations, which provide the theoretical framework for modelling chiral interfaces in different solvent mixtures. The MD simulations of PEPU interfaces show that, in alcohol/water mixtures, the alcohols form domains at the interface with the hydrophobic portions of the molecule tending to orient towards the surface. This disrupts the water hydrogen bonding networks at the interface and leads to the exclusion of water from the surface region relative to the bulk. The MD simulations of DNB-phenylglycine and DNB-leucine selectors in hexane/2-propanol mixtures demonstrate that the interfaces are distinct both in terms of the selector orientations at the surface and in the number of hydrogen bonds formed with 2-propanol. This occurs despite the structural similarity between these two selectors. The interfaces are also prepared experimentally by attaching the chiral selectors onto oxidized Si(111) samples and AFM tips. In particular, for DNB-phenylglycine and DNB-leucine samples, two synthetic routes have been explored. Using AFM, the morphologies of the resulting chiral interfaces are obtained. X-ray photoelectron spectroscopy and refraction-absorption infrared spectroscopy provide information regarding the relative distribution of the compounds on the surface. Using chemical force microscopy (CFM) measurements, chiral self-selectivity is examined in various solvent mixtures. For PEPU interfaces, the extent of hydrogen bonding at the surface is the dominant contributor to the measured forces. In the case of DNB-phenylglycine and DNB-leucine, CFM measurements of the chiral self-selectivity in 2-propanol demonstrate that chiral discrimination is present in both systems, but larger forces are observed for DNB-phenylglycine, consistent with the molecular dynamics study that shows much weaker solvent interactions with this species. / Thesis (Ph.D, Chemistry) -- Queen's University, 2008-08-14 11:26:37.436

Orientador: Carol Hollingworth Collins / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-05T16:30:01Z (GMT). No. of bitstreams: 1 Magalhaes_DanielRodrigues_D.pdf: 3095259 bytes, checksum: 34caab6a50b8a2f3071fca69103ab15f (MD5) Previous issue date: 2005 / Doutorado / Quimica Analitica / Doutor em Ciências

Orientador: Carol H. Collins / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-08T05:15:55Z (GMT). No. of bitstreams: 1 Auler_LuciaMariaLaboissieredeAlencar_D.pdf: 1289805 bytes, checksum: c5c314fa95e1f395031bfe5e731325d3 (MD5) Previous issue date: 2006 / Resumo: Uma nova fase estacionária foi desenvolvida utilizando a sílica como suporte, para aplicação em Cromatografia por Troca Iônica na separação de ânions. A preparação desse suporte cromatográfico envolveu a modificação da sílica com cloropropiltrimetoxissilano seguido pela reação com a piridina para produzir 0,5 mmol g de grupos propilpiridínio carregados positivamente sobre a superfície da sílica. Esses grupos atuam como sítios de troca aniônica durante a separação cromatográfica. A nova fase foi caracterizada por análise elementar, espectroscopia na região do infravermelho, ressonância magnética de C e Si no estado sólido e por cromatografia. A capacidade de troca da sílica modificada foi determinada pela concentração de íons cloreto trocáveis, por meio da análise por ativação neutrônica . O estudo da estabilidade química do suporte cromatográfico, nas mesmas condições da separação, demonstra que a fase, mesmo sem nenhuma proteção, é estável até 12000 volumes de coluna. A avaliação dos parâmetros cromatográficos das separações realizadas em um sistema com detecção por condutividade, sem supressão mostra que a sílica com o grupo propilpiridínio quimicamente ligado é uma fase estacionária bastante promissora para a separação de ânions em amostras contendo baixos teores dessas espécies / Abstract: A new stationary phase based on silica was developed for application in Ion Exchange Chromatography for anion separation. The preparation of the new phase involved silanization of chromatographic silica particles with chloropropyl-trimethoxysilane to yield chloropropyl silica. The modified silica was then reacted with pyridine to produce positively charged propylpyridinium groups on the surface, which are the anion exchange sites. The new phase was characterized by elemental analysis and infrared and solid state C and Si NMR spectroscopies. The exchange capacity of the modified silica was investigated by determining its exchangeable chloride content using neutron activation analysis. The stability of this phase, tested under the same conditions as for the separation, shows that this phase, although without protection, is stable to 12000 column volumes. Chromatographic parameters evaluated using unsuppressed conductivity detection indicate that the chloropropylpyridiniun silica is promising for separation and quantification of anions in samples with low concentrations of these species / Doutorado / Quimica Analitica / Doutor em Ciências