Structural studies of organic crystals of pharmaceutical relevance. Correlation of crystal structure analysis with recognised non-bonded structural motifs in the organic solid state

View/ Open
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
references.pdf (159.0Kb)
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
structures.pdf (28.45Kb)
Download
Publication date
2010-10-07T11:36:24ZAuthor
Essandoh, ErnestSupervisor
Scowen, Ian J.Edwards, Howell G.M.
Keyword
Single crystal structure; Structural motifs
; Pharmaceutical solids
; Polymorph
; Physico-chemical stability
; Chalcones
; Cryptolepines
; Biguanides
; Xanthines
; Crystallization studies
Rights

The University of Bradford theses are licenced under a Creative Commons Licence.
Institution
University of BradfordDepartment
School of PharmacyAwarded
2009
Metadata
Show full item recordAbstract
Pharmaceutical 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.Type
ThesisQualification name
PhDCollections
Related items
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).
-
Inclined reinforcement around web opening in concrete beamsYang, Keun-Hyeok; Ashour, Ashraf F. (2007)Twelve reinforced-concrete continuous deep beams having web openings within interior shear spans were tested to failure. The main variables investigated were the opening size and the amount of inclined reinforcement around openings. An effective inclined reinforcement factor combining the influence of the amount of inclined web reinforcement and opening size is proposed and used to analyse the structural behaviour of continuous deep beams tested. It was observed that the end support reaction, diagonal crack width and load capacity of beams tested were significantly dependent on the proposed effective inclined reinforcement factor. As this factor increased, the end support reaction and increasing rate of diagonal crack width were closer to those of companion solid deep beams. In addition, a higher load capacity was exhibited by beams having an effective inclined reinforcement factor above 0.077 than the companion solid deep beam. A numerical procedure based on the upper-bound analysis of the plasticity theory was proposed to estimate the load capacity of beams tested. Comparisons between the measured and predicted load capacities showed good agreement.
-
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.