Spectroscopic Studies Concerning Certain Biologically Important Substances

Morman, James Forrester (1961) Spectroscopic Studies Concerning Certain Biologically Important Substances. PhD thesis, University of Glasgow.

Abstract

The object of the research described in this thesis has been to utilise infrared spectroscopy in the study of the detailed structure and the interactions of some biologically important molecules capable of inter- and intra-molecular hydrogen bonding. Interest has been particularly directed towards the study of a number of salicylates which have been used therapeutically with some degree of success by the late Dr. James Reid and his colleagues of the Medical Research Council, at the Clinical Chemotherapy Research Unit, Western Infirmary, Glasgow. The research falls into five convenient sections. The reasons for undertaking the work in each section, a description of the work and its results are given below. Section 1. The Ethynyl-Hydrogen Bond. Association In solution. A number of interesting acetylenic compounds were available for study. These acetylenes offered an excellent opportunity to obtain first hand experience of intermolecular associations by proton donating groups where steric interferences were at a minimum. The spectra of these compounds were obtained for liquid or solid state, in hexane, carbon disulphide, and ether solutions. The effects of self association and association with ether have been evaluated. Section 2. Infrared Spectra of Aryl Carboxylic Acids and their Esters. As a necessary preliminary to the interpretation of substituted salicylic acid spectra, some substituted benzoic acids and esters were studied. Complex carbonyl absorption in ortho halogeno-benzoic acids and esters was observed and ascribed to conformational isomerism rather than Fermi Resonance. This finding initiated a larger scale investigation into the spectra of substituted benzoic acids, esters, benzaldehydes and acetophenones. Some correlations between relative acidity and infrared spectra have been considered. Section 3. Infrared Spectra of Substituted Salicylic Acids and their Esters. As mentioned above, the biological importance of some substituted salicylic acids merits detailed investigation into their structures and inter-actions. Spectra of a large number of substituted salicylic acids and esters in several solvents have been recorded. Marked frequency shifts by 6-alkyl or bulky 3-alkyl groups have been ascribed to steric enhancement of chelation by compression of the phenolic hydroxyl group. Section 4. Infrared Spectra of Substituted Salicylaidehydes. The two main objectives of this section were to ascertain (a) if competitive intramolecular bonding existed between a phenolic hydroxyl group and carbonyl or nitro groups as alternative proton acceptor sites, in a series of 3-nitrosalicylaldehydes and (b) if the steric enhancement of chelation, found for substituted salicylic acids and esters, also existed in the corresponding substituted salicylaldehydes. A parallel trend to (b) has indeed been found. However the subject matter of this section is mostly concerned with the competitive intramolecular bonding afforded by the 3-nitro substituents. The character of the hydroxyl, carbonyl and nitro absorptions (in a non polar medium) shows that the phenolic group is bonded principally to the nitro group, but that the chelated o-hydroxy-carbonyl species predominates in 2-hydroxy-3-nitro-acetophenone and methyl 3-nitrosalicylate. Section 5. Phenol-Ether Association. It is difficult to interpret the true nature of the effects due to bulky alkyl groups ortho to a grouping involved in intermolecular association. Both steric inhibition to association and deactivation of acidic protons by inductive effects are equally reasonable explanations for the resultant spectral characteristics normally identified with hydrogen bond weakening. Spectroscopically detected entropy effects of considerable magnitude are found in the association of a range of ortho alkyl substituted phenols with a series of dialkyl ethers. This system was chosen for a more detailed quantitative investigation of the problems mentioned above. It has been found that systematic alkyl substitution in the ortho positions of phenols and the a-positions of the ether molecules lowers the equilibrium coefficients for the phenol-ether association. However the strength of the bond, as indicated by the hydroxyl frequency shift, is affected by steric factors due to the phenol, only in solutions of 2,6-di-t-butyl phenol. Of the ethers, di-t-butyl ether shows some bond weakening but only with the ortho dialkyl phenols.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Analytical chemistry, Organic chemistry
• Date of Award: 1961
• Depositing User: Enlighten Team
• Unique ID: glathesis:1961-79433
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 31 Mar 2020 09:09
• Last Modified: 31 Mar 2020 09:09
• URI: https://theses.gla.ac.uk/id/eprint/79433