A series of experiments was completed in which the morphology, anatomy and biochemistry of two Melilotus species, Melilotus alba and Melilotus officinalis, were studied. The purposes of the study were to illustrate whether the variability of specimens was due to polymorphism or speciation and to isolate the factors that have separated these specimens as competitors.The effects of impaction and scarification on the germination of M. alba and M. officinalis seeds were studied, as were the effects of light and temperature stimuli on germination and growth The rate of plant maturation and the chronology of flowering for the two species were investigated. Maturation differences were minor, but the chronologies of flowering deviated markedly.The techniques of one- and two-directional thin layer chromatography were used to separate the free amino acids in Melilotus seed extract preparations. The technique of polyacrylamide gel electrophoresis was used to separate the proteins in these preparations. In every experiment, the two Melilotus "species" were genus specific with no species variables in terms of the amino acid and protein complements.

EPR spectra of Fe³⁺ in a natural crystal of brookite have been investigated at X- and Q-band frequencies at room temperature and 573°K. Part of the paramagnetic resonance spectrum observed has been interpreted on the assumption that Fe³⁺occupies eight equivalent Ti⁴⁺ sites in brookite, with four inequivalent orientations.. The spectra show an "intermediate" zero-field splitting at X-band and a "normal" zero field splitting at Q-band frequencies. The spin Hamiltonian parameters which fit the spectra are the following: g = 2.002 ± 0.005 . D = (1170 ± 30) x 10⁻⁴cm⁻¹ E = (330 ± 20) x 10⁻⁴cm⁻¹ [pa + (l/l2)qF]₀₁₀ = (13±10) x 10⁻⁴cm⁻¹ [pa + (l/l2)qF]₁₀₀ = (-13±15) x l0⁻⁴cm⁻¹ [pa + (l/l2)qF]₀₀₁ = (-66±4) x l0⁻⁴cm⁻¹ / Science, Faculty of / Physics and Astronomy, Department of / Graduate

Long-chain molecules are widely used in many commercial products, including waxes, oils, fats and soaps. This study focuses on the primary n-alkylammonium chlorides that have applications as surfactants, detergents and as models for bio-membranes. The specific topic of this investigation is the polymorphism of three series of n-alkylammonium halides. Polymorphism is the ability of a substance to exist in more than one crystal form. Due to the conformational flexibility of the long alkyl chain and the forces (hydrogen bonding and van der Waals interactions) dictating the packing in these compounds, more than one type of molecular packing is possible, resulting in the crystallization of various polymorphs for each compound. Various investigations of the polymorphism of n-alkylammonium halides have been published in the scientific literature. This includes mainly studies on the polymorphism and structures of n-alkylammonium chlorides. Only a few reports on investigations of the polymorphism of n-alkylammonium bromides were found in the literature, but no investigation of the polymorphism of n-alkylammonium iodides could be located. This study is limited to the medium chain length primary n-alkylammonium halides, CnH2n+1N+H3X- where n = 11 to 18 (except 17) and X = Cl, Br and I. It is expected that in this chain length range, both packing forces (hydrogen bonding and van der Waals interactions) will play a role in dictating the molecular packing. It was attempted to crystallize the maximum number of polymorphs of each compound by extensive variation of the crystallization conditions. The parameters varied include crystallization temperature, solvent and crystallization method. Information regarding the polymorphism of a compound crystallized under specific conditions were collected by the complementary techniques of X-ray diffraction and thermal analysis. X-ray diffraction is the ideal technique to study polymorphism because the result of such an investigation is the three-dimensional packing in the crystal structure. Due to the wide scope of the investigation, only the polymorphic forms stable at room temperature were investigated. The single crystal X-ray technique allows the determination of the crystal structure of a polymorph, but due to the tendency of the compounds to crystallize in thin plates, very few single crystals of good diffraction quality were obtained. Nine crystal structures were, however, determined. Most polymorphic forms were available as polycrystalline powders. The new techniques for crystal structure determination from powder data were employed to determine two crystal structures from powder diffraction data, although at lower precision, and further refined them by the Rietveld technique. Conventional X-ray powder diffraction is well suited to the identification of polycrystalline materials. The technique does not give direct information regarding the structural nature of the polymorph, but gives a unique fingerprint for each polymorphic form. All polymorphs that were obtained by the various crystallization techniques were characterised by X-ray powder diffraction, and the unique long Summary iispacing of each polymorphic form was determined from the position of the low angle diffraction peaks in the diffraction pattern. Linear correlations between the chain lengths and long spacings were used to search for the presence of isostructural series amongst the phases. More than one isostructural series could be identified for each homologous series of compounds. Thermal analysis techniques were employed to determine the phase transition temperatures and enthalpies of phase transitions occurring at temperatures above room temperature. In this investigation the thermal behaviour of polymorphs were investigated by differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA) and hot stage microscopy (HSM). A stepwise melting behaviour that includes various solid-solid phase transitions was observed for all compounds studied. The sequence of phase transitions that occur with an increase in temperature were found to be unique to a specific polymorphic form. Thermogravimetric analysis provided information regarding the incorporation of solvent in the crystal lattice by monitoring the change of sample weight with increase in temperature. Hot stage microscopy allowed the visual observation of changes occurring in the morphology and texture of the sample with temperature. This investigation contributed a large amount of information to the pool of knowledge on the crystalline phases of the n-alkylammonium halides. Up to now, not much structural data on the crystal forms of these compounds were available in the literature. In this study, complex patterns of crystal packing and phase transitions were revealed. Six isostructural series of n-alkylammonium chlorides were identified, three of which have not been reported previously, and the crystal structure of one of the novel forms was determined. Four isostructural polymorphic forms of n-alkylammonium bromides were identified. Only two forms have been reported previously in the literature. Six crystal structures of compounds with a novel crystal form were determined. For the homologous series of n-alkylammonium iodides, four novel isostructural series were identified, and one structure was determined. Relationships between chain lengths and structural parameters like long spacings, unit cell parameters and phase transition temperatures were determined and expressed as mathematical functions. An analysis of all the known structures (structures reported in the literature and structures determined in this investigation) indicated that different molecular conformations and hydrogen bonds are responsible for differences in the packing, as expressed in the formation of polymorphs. A choice of anion for a specific compound (chloride, bromide or iodide) influenced not only the cell volume, as would be expected, but also dictated the preferential formation of pseudo-polymorphs and complex hydrogen bonding networks in the crystals themselves. Phase transition temperatures were found to be not simply a function of chain length, but to be significantly influenced by the anion and polymorphic form present. / Prof. G.J. Kruger

A new approach to the investigation of the optical properties of polytypic minerals that combines spindle stage techniques, X-ray diffraction methods, electron microprobe analysis, and dielectric tensor calculations has been developed and applied to zinc sulfides and chloritoids. For the first time, X—ray diffraction studies of natural anisotropic zinc sulfides have documented the simultaneous occurrence of twinning and stacking disorder along more than one of the four symmetry equivalent <111> directions of sphalerite. Precession photographs of optically anisotropic zinc sulfides are characterized by twin—equivalent diffraction maxima and diffuse diffraction streaking along lattice rows with (h-k) ≠ 3n (equivalent hexagonal indices) in one or two <111> directions. A system of linear equations has been used to calculate the approximate volume fractions of each twin domain and the sphalerite host domain. Dielectric tensor calculations have been performed to illustrate that mixtures of cubic and hexagonal zinc sulfide may be optically biaxial if the intergrowth occurs along more than one of the symmetry equivalent <111> directions of sphalerite (cubic). The dependence of the optical properties upon the chemical variation and polytypic intergrowth in the Hg-Fe chloritoids has been investigated. The effects of the variation in chemical composition of specific polytypic compositions were analyzed first. The refractive indices of 10 approximately pure 2M₂ Hg-Fe chloritoids show strong correlations (R² ≥ 0.094) to the proportion of Hg cations in the H(1B) site, Hg/(Hg + Fe + Hn) - HGN. Correlations between the optical orientation angles and HGN were weaker (R² ≤ 0.87). The optical orientation is very sensitive to small variations in the polytypic composition, especially orientation angles that have fixed values in 2M₂ chloritoid. The parameter showing the most sensitivity is ∠ X ⋀ b, which is 0° in an ideal 2M₂ chloritoid, but increases to about 6° for a chloritoid containing 10% by volume 1Tc polytype. The sum of ∠ Y ⋀ c* and ∠ Z ⋀ c* for an ideal 2M₂ chloritoid has a value of 90°, whereas a chloritoid with 10% 1Tc has a sum of 92°. Although not as sensitive as ∠ X ⋀ b, this parameter can be determined with only a spindle stage or universal stage. The observed dependence of the optical properties on polytypic intergrowth and chemical variation has been modeled using dielectric tensor calculations based on the properties of a 1Tc layer and assuming that the 2M₂ polytype is derived by twinning the 1Tc polytype about [010] with an (001) composition plane. / Ph. D.

Spectroscopy is increasingly used to investigate and monitor the solid state forms of pharmaceutical materials and products. Spectroscopy�s speed, nondestructive sampling, compatibility with fibre optics and safety also make it attractive for in-line monitoring. In this thesis, the spectroscopic techniques Fourier transform Raman spectroscopy, terahertz pulsed spectroscopy and second harmonic generation were used to characterise and quantify polymorphism and crystallinity of pharmaceutical compounds. Where possible, the multivariate analysis technique partial least squares was used for quantitative analysis. Fourier transform Raman spectroscopy detects polarisability changes mainly associated with molecular vibrations. Terahertz pulsed spectroscopy is a new spectroscopic technique that operates between the infrared and microwave regions of the electromagnetic spectrum and detects dipole moment changes mainly associated with crystalline phonon vibrations in the solid state. Second harmonic generation is a nonlinear optical phenomenon that depends on the dipole moment in crystals and crystal symmetry. Several materials capable of existing in different solid state forms were used. FT-Raman spectroscopy was able to differentiate carbamazepine forms I and III, enalapril maleate forms I and II and γ-crystalline and amorphous indomethacin. Combined with partial least squares the technique could quantify binary mixtures of CBZ forms I and III with a limit of detection as low as 1%, and mixtures of enalapril maleate with a limit of detection of as low as 2%. Terahertz pulsed spectroscopy obtained very different spectra for carbamazepine forms I and III, enalapril maleate forms I and II, γ-crystalline and amorphous indomethacin, crystalline and supercooled thermotropic liquid crystalline fenoprofen calcium, three forms of lactose, and five forms of sulphathiazole. At present the modes in the spectra cannot be attributed to specific phonon modes. Quantitation of binary mixtures of different forms of a compound using partial least squares analysis usually resulted in a limit of detection of about 1%. Second harmonic generation was used to quantify binary mixtures of different forms of enalapril maleate and lactose, as well as binary mixtures of enalapril maleate form II and polyvinylpyrrolidone. A quantitative relationship was present for each of the mixtures, however the limits of detection were usually above 10%. The high value is probably due to the machine being a prototype and univariate analysis associated with a single output variable. Future improvements to the apparatus and measurement parameters are likely to reduce the limits of detection. Ranitidine hydrochloride polymorphs could also be differentiated using second harmonic generation, however γ-crystalline and amorphous indomethacin and forms I and III of carbamazepine could not. The methods used in this thesis were successfully used for qualitative and quantitative analysis of polymorphism and crystallinity of pharmaceutical compounds. TPS and SHG are useful additions to the range of experimental techniques that can be used to investigate and monitor properties of pharmaceutical solids.

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Polymorphic crystal forms in food fats contribute to physical characteristics of the fats and consequently to their performance in fat based foods. In the present study the phase transitions associated with polymorphism behavior of common food fats were investigated. The polymorphism of butters, margarines, cocoa butter and cocoa butter products were determined and the effects of certain ingredients and conditions of temperature were studied. The following polymorphic forms were detected: sub-alpha, alpha, beta' , beta'3, beta' 2, beta, beta2, and beta1; however, not all forms were observed in all fats. Margarines contained beta' and beta forms depending on their fat constituents, while butter, cocoa butter, and fat blends consisted of alpha, beta' and beta; only the beta' form of butter showed a sharp melting point. Rapeseed oil exhibited alpha, beta1 and beta 2 forms, depending on the degree of hydrogenation. / DSC measurements of fat blends were correlated with viscosity index measurements from Universal Material Testing Machine (UMTM) using a single cycle, back extrusion technique. A correlation of R2 = 0.70 (p = 0.95) was obtained. Viscosity index decreased as temperature increased, suggesting a possible relationship between viscosity index and solid fat fraction. This suggests that viscosity index could be a potential indicator of food fat textural properties which are evaluated by DSC. (Abstract shortened by UMI.)

Several pseudopolymorphic forms of sodium naproxen were crystallized from methanol-water and ethanol-water solutions, including hydrated and alcohol-solvated forms. Results showed that the transitions of the pseudopolymorphic forms occur at temperatures that depend upon the solvent concentration. Results also revealed that water activity is a controlling factor for the transitions because regardless of which alcohol solvent mixture was used. The heats of solution for each pseudopolymorph were estimated by fitting the solubility data with the van't Hoff equation. The stability of hydrated forms over solvated forms at higher temperatures was proven for enantiotropic systems from a thermodynamic cycle. A 1:1 methanol-solvated form of sodium naproxen was discovered and fully characterized using a variety of analytical techniques. For further analysis, a single crystal was performed and revealed a two to three ratio solvate of sodium naproxen to methanol. The 1.5 solvate was shown to not be representative of the entire sample, but still provided insight into the bonding of the methanol solvent in sodium naproxen. Additionally, the ability of sodium naproxen to solvate with other alcohol solvents was explored, specifically looking at comparisons between pure ethanol, 1-propanol, 2-propanol, 1-butanol, and isobutanol solvents. It was shown that as the size of the alcohol increases and/or branching increases the ability to solvate decreases in relation to the molar amount of the alcohol present in the crystal structure. Additionally larger, branched alcohols required more energy to desolvate.

Spectroscopy is increasingly used to investigate and monitor the solid state forms of pharmaceutical materials and products. Spectroscopy�s speed, nondestructive sampling, compatibility with fibre optics and safety also make it attractive for in-line monitoring. In this thesis, the spectroscopic techniques Fourier transform Raman spectroscopy, terahertz pulsed spectroscopy and second harmonic generation were used to characterise and quantify polymorphism and crystallinity of pharmaceutical compounds. Where possible, the multivariate analysis technique partial least squares was used for quantitative analysis. Fourier transform Raman spectroscopy detects polarisability changes mainly associated with molecular vibrations. Terahertz pulsed spectroscopy is a new spectroscopic technique that operates between the infrared and microwave regions of the electromagnetic spectrum and detects dipole moment changes mainly associated with crystalline phonon vibrations in the solid state. Second harmonic generation is a nonlinear optical phenomenon that depends on the dipole moment in crystals and crystal symmetry. Several materials capable of existing in different solid state forms were used. FT-Raman spectroscopy was able to differentiate carbamazepine forms I and III, enalapril maleate forms I and II and γ-crystalline and amorphous indomethacin. Combined with partial least squares the technique could quantify binary mixtures of CBZ forms I and III with a limit of detection as low as 1%, and mixtures of enalapril maleate with a limit of detection of as low as 2%. Terahertz pulsed spectroscopy obtained very different spectra for carbamazepine forms I and III, enalapril maleate forms I and II, γ-crystalline and amorphous indomethacin, crystalline and supercooled thermotropic liquid crystalline fenoprofen calcium, three forms of lactose, and five forms of sulphathiazole. At present the modes in the spectra cannot be attributed to specific phonon modes. Quantitation of binary mixtures of different forms of a compound using partial least squares analysis usually resulted in a limit of detection of about 1%. Second harmonic generation was used to quantify binary mixtures of different forms of enalapril maleate and lactose, as well as binary mixtures of enalapril maleate form II and polyvinylpyrrolidone. A quantitative relationship was present for each of the mixtures, however the limits of detection were usually above 10%. The high value is probably due to the machine being a prototype and univariate analysis associated with a single output variable. Future improvements to the apparatus and measurement parameters are likely to reduce the limits of detection. Ranitidine hydrochloride polymorphs could also be differentiated using second harmonic generation, however γ-crystalline and amorphous indomethacin and forms I and III of carbamazepine could not. The methods used in this thesis were successfully used for qualitative and quantitative analysis of polymorphism and crystallinity of pharmaceutical compounds. TPS and SHG are useful additions to the range of experimental techniques that can be used to investigate and monitor properties of pharmaceutical solids.

Thesis (Ph.D.)--Chemical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Dr Rousseau, Ronald W; Committee Co-Chair: Dr Grover Gallivan, Martha; Committee Member: Dr Realff, Matthew; Committee Member: Dr Garmestani, Hamid; Committee Member: Dr Nenes, Athanasios.