Investigations in molecular structure: from scattering to molecular complexes of brominated compounds

QD Chemistry

O'Neill, Andrew ; Wilson, Chick C.

University:University of Glasgow

Department:School of Chemistry

关键词: X-ray diffraction, nucleation, polymorphism, crystallography, hydrogen and halogen bonding interactions, focussed beam reflectance measurements;   

Others  :  http://theses.gla.ac.uk/1709/1/2009oneillphd.pdf

来源: University of Glasgow

【 摘 要 】

The main focuses of this research were to examine the capabilities of solutiontechniques to attempt to monitor the nucleation process in crystallisation, and toinvestigate structural outcomes of crystallisation processes, with reference topolymorphism and intermolecular interactions.To achieve this, work on the investigation of nucleation and early-stage crystallisationwas carried out at the Department of Pharmaceutical Sciences at the University ofStrathclyde and also at the central synchrotron facility of Station 2.1 at the SRSDaresbury. Small angle X-ray scattering (SAXS) was carried out on solutions ofmethyl-4-hydroxybenzoate (pMHB) and 2-bromobenzoic acid. These studies werecarried out after developing solution methods to enable us to determine the point atwhich crystals emerged from solution. This was achieved using Focussed BeamReflectance Measurements. Structural studies were also carried out on pMHB toexamine its polymorphic behaviour and crystal structures were solved at varioustemperatures from 100K to 300K. The crystal structure of methyl-2,5-dibromobenzoate was also solved at 100K after discovering it sublimes at roomtemperature. This structure could only be solved from a twinned crystal and indicatedthe appearance of interesting halogen interactions occurring.Structural studies have also been carried out using the bromanilic acid molecule as afocus to generate a number of co-crystal complexes to examine their halogen bondingcapability and to determine any structural significances in their formation.Co-crystal complexes of bromanilic acid and a variety of molecules were made in 1:1and 1:2 ratios to see if any additional halogen interactions could be observed orinduced, in addition to the expected hydrogen-binding interactions. The co-crystalsincluded a range of picolines and lutidines as well as bromo-substituted pyridines toattempt to induce halogen interactions. This generated a number of new compoundswhose structures were determined using single crystal X-ray diffraction and theinteractions were monitored to observed whether any defined patterns with regards tothe tendency of bromanilic acid co-crystallisations to produce predictable patterns ofintermolecular interactions could be determined.