Salt formation provides a means of altering the physicochemical and resultant biological characteristics of a drug entity without modifying its molecular structure. Many published reviews have indicated the importance of the selection of the most appropriate salt form. This work is an investigation into the salt formation of two heterocyclic drugs. This is done by the physicochemical and the crystallographic studies of 19 high resolution single crystal diffraction studies. The particular targets of the work are the selection of the most appropriate salt forms, investigations into the tautomerism and polymorphism (or pseudopolymorphism) and an understanding of the interactions most likely between these heterocyclic drugs and their specific receptor sites. Section 1 describes the effect of protonation on the absorption of drugs, the rationale for using various salt forms and the resultant effect this has on a number of physicochemical properties of the parent compound. Section 2 is a description of the experimental techniques used in the physicochemical investigations and in crystal structure determination. In Sections 3 and 7, the preparation and characterisation of the salts and modifications of the two heterocyclic drugs, GU and IM is described. In Sections 4 and 8, the physicochemical investigations into the hygroscopicity and solid-state stabilities of the salts of GU and IM is described. Van't Hoff solubility studies are used to determine the enthalpies of solution and where appropriate the relative thermodynamic stabilities of the various phases produced. The structures of 19 of the salts or modifications of GU and IM, together with their packing and hydrogen bonding interactions is described in Sections 5 and 9. Sections 6 and 10 describe the ionisation properties of these molecules. Both the guanidine and imidazole moieties of GU and IM, respectively, are tautomeric, the particular form(s) found in these investigations and the effect of protonation is discussed. The conformations of these structures are discussed and the effect of protonation, especially on the puckering of the piperazine ring, is described.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

This thesis is concerned with the structural analysis of dyestuffs in their natural solid state by the application of solid-state nuclear magnetic resonance. These dysetuffs are all derived from the phenylazobenzene group, but tautomerism can produce structural changes, which have so far been uncharacterised in the solid-state for many of the dyestuffs currently under investigation. The information obtainable from (^13)C and (^15)N chemical shifts, both isotropic and anisotropic will be applied in this structure determination. Under magic-angle spinning the anisotropic nature of solid-state interactions is partially averaged or removed. The rotational resonance technique will be presented, which reintroduces the homonuclear dipolar interaction allowing dipolar coupling constants to be measured. Second-order effects arising from the (^14)N quadrupole interaction broaden spin-1/2 lines (RDC) in such a manner that bond lengths can be determined. This RDC analysis will be applied to a series of hydrazone structures to determine the (^15)N-(^14)N bond length within the hydrazone linkage. Finally, the two-dimensional magic-angle turning experiment will be discussed and applied to both the (13)C and (^15)N nuclei for a range of dyestuffs to show that accurate shielding tensor information can be obtained from large molecules.

Thesis (Ph. D.)--University of Hong Kong, 1988.

No description available.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references.

No description available.

No description available.

Thesis (Ph. D.)--Dept. of Pharmacology, University of Sydney, 1999. / Title from title screen. Interactive three dimensional molecular data and multiple colour images. Text presented in Hypertext Markup Language (.htm); images in standard formats (.jpg, .gif); molecules presented mostly as Cambridge Protein Data Bank format (.pdb); some molecules presented in alternative X. Mol cartesian co-ordinates format (.xyz); search facility in PERL script. Includes bibliographical references. A printed form was produced with limited features as a Faculty requirement; may also be issued in CD-ROM.

Thesis (Ph. D.)--University of Wisconsin, 1964. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Bibliography: leaves 77-70.