Structural studies of organic crystals of pharmaceutical relevance. Correlation of crystal structure analysis with recognised non-bonded structural motifs in the organic solid state
Thesis-Abstract,table of contents.pdf (338.2Kb)Download
Thesis introduction-chapter one.pdf (483.8Kb)Download
Thesis-experimental-chapter 2.pdf (197.5Kb)Download
Chalcones-chapter 3.pdf (1.147Mb)Download
cryptolepines -chapter 4.pdf (1.108Mb)Download
Biguanides-chapter 5.pdf (1.088Mb)Download
xanthines-chapter 6.pdf (1.503Mb)Download
CONCLUSION -chapter 7.pdf (47.30Kb)Download
Thesis-Appendix-A,B and C.pdf (239.4Kb)Download
INFRA_RED-Appendix D.pdf (981.8Kb)Download
PXRD-Appendix E.pdf (1.071Mb)Download
Raman-Appendix F.pdf (776.0Kb)Download
Mass Spec-Appendix G.pdf (302.6Kb)Download
NMR-Appendix H.pdf (2.749Mb)Download
SupervisorScowen, Ian J.
Edwards, Howell G.M.
KeywordSingle crystal structure
; Structural motifs
; Pharmaceutical solids
; Physico-chemical stability
; Crystallization studies
Rights© 2009 Essandoh, E. This work is licensed under a Creative Commons Attribution-Non-Commercial-Share-Alike License (http://creativecommons.org/licenses/by-nc-nd/2.0/uk).
InstitutionUniversity of Bradford
DepartmentSchool of Pharmacy
MetadataShow full item record
AbstractPharmaceutical solids tend to exist in different physical forms termed as polymorphs. Issues about pharmaceutical systems are mainly concerned with the active ingredient's physico-chemical stability and bioavailability. The main aim of this study is to investigate the non-bonded interactions in pharmaceutical solids that govern the physical pharmaceutics performance of such materials and through the use of structural techniques and correlation of these results with crystal structural database to establish the presence of physical motifs in selected systems. Structural motifs were identified by the use of single crystal and crystal packing analysis on diverse range of pharma-relevant materials including chalcones, cryptolepines, biguanides and xanthines. These selected systems were validated using functional group and molecular analysis and correlating them to the Cambridge Structural Database. Crystallization studies are done on these selected systems as well as exploiting those using synthetic analogues. A total of 51 crystal structures were investigated including 16 new structure determinations. Addition synthesis of new xanthines to investigate novel intermolecular patterns was also undertaken. The understanding and exploitation of intermolecular interactions involving hydrogen bonds and coordination complexation during packing can be used in the design and synthesis of solid state molecular structures with desired physical and chemical properties.
Showing items related by title, author, creator and subject.
Design, Synthesis and Evaluation of Novel Biarylpyrimidines ¿ a New Class of Ligand for Unusual Nucleic Acid Structures.Wheelhouse, Richard T.; Jenkins, Terence C.; Jennings, Sharon A.; Pletsas, Dimitrios (2006)Biarylpyrimidines are characterized as selective ligands for higher-order nucleic acid structures. A concise and efficient synthesis has been devised incorporating Suzuki biaryl cross-coupling of dihalopyrimidines. Two ligand series are described based on the parent thioether 4,6-bis[4-[[2-(dimethylamino)ethyl]mercapto]-phenyl]pyrimidine (la) and amide 4,6-bis(4[(2-(dimethylamino)ethyl)carboxamido]phenyl)pyrimidine (2a) compounds. In UV thermal denaturation studies with the poly(dA)·[poly(dT)]2 triplex structure, thioethers showed stabilization of the triplex form (¿Tm ¿ 20 °C). In contrast, amides showed duplex stabilization (¿Tm ¿ 15 °C) and either negligible stabilization or specific destabilization (¿Tm = -5 °C) of the triplex structure. Full spectra of nucleic acid binding preferences were determined by competition dialysis. The strongest interacting thioether bound preferentially to the poly(dA)·[poly(dT)]2 triplex, Kapp = 1.6 x 105 M-1 (40 x Kapp for CT DNA duplex). In contrast, the strongest binding amide selected the (T2G20T2)4 quadruplex structure, Kapp = 0.31 x 105 M-1 (6.5 x Kapp for CT DNA duplex).
Rationalization of Racemate Resolution: Predicting Spontaneous Resolution through Crystal Structure Prediction.Kendrick, John; Gourlay, Matthew D.; Leusen, Frank J.J. (2009-07-14)Crystal structure prediction simulations are reported on 5-hydroxymethyl-2-oxazolidinone and 4-hydroxymethyl-2-oxazolidinone to establish the feasibility of predicting the spontaneous resolution of racemates of small organic molecules. It is assumed that spontaneous resolution occurs when the enantiomorph is more stable than the racemic solid. The starting point is a gas phase conformational search to locate all low-energy conformations. These conformations are used to predict the possible crystal structures of 5- and 4-hydroxymethyl-2-oxazolidinone. In both cases, the racemic crystal structure is predicted to have the lowest energy. The energy differences between the lowest-energy racemic solids and the lowest-energy enantiomorphs are 0.2 kcal mol-1 for 5-hydroxymethyl-2-oxazolidinone and 0.9 kcal mol-1 for 4-hydroxymethyl-2-oxazolidinone. In the case of 4-hydroxymethyl-2-oxazolidinone, where the racemic crystal is known to be more stable and the experimental crystal structures of both the racemate and the enantiomorph are available, the simulation results match the observed data. For 5-hydroxymethyl-2-oxazolidinone, where only enantiopure crystals are observed experimentally, the known experimental structure is found 1.6 kcal mol-1 above the lowest-energy predicted structure. This work shows that it is possible to predict whether the racemate of a small chiral molecule can be resolved spontaneously, although further advances in the accuracy of lattice energy calculations are required.
Parametric design and optimisation of thin-walled structures for food packagingUgail, Hassan (Springer, 2003)In this paper the parametric design and functional optimisation of thin-walled structures made from plastics for food packaging is considered. These objects are produced in such vast numbers each year that one important task in the design of these objects is to minimise the amount of plastic used, subject to functional constraints, to reduce the costs of production and to conserve raw materials. By means of performing an automated optimisation on the possible shapes of the food containers, where the geometry is parametrised succinctly, a strategy to create the optimal design of the containers subject to a given set of functional constraints is demonstrated.