Kinetic study of copolymerization and terpolymerization of N-Carboxyanhydrides of ornithine, glycine and aspartic acid

Siyasanga, Mbizana (2014-12)

Thesis (MSc)--Stellenbosch University, 2014.

Thesis

ENGLISH ABSTRACT: Kinetic studies on polymerization of N-Carboxyanhydrides (NCAs) of ornithine, glycine and aspartic acid are described in this report. The studies involved the synthesis of protected amino acid derivatives which are subsequently phosgenated to afford the respective NCAs. Kinetic studies of homo and copolymerization of the NCAs were conducted via in situ 1H NMR spectroscopy through monitoring the decrease of relevant proton intensities. NCA homopolymerization studies revealed the effect of side chains on NCA monomers, with NCAs bearing larger side chain groups being less reactive as observed on derivatives of aspartic acid and ornithine in comparison to glycine. In subsequent kinetic copolymerization studies, it was observed that glycine (Gly) NCA incorporated more readily in the growing copolymer chain when copolymerized with β-benzyl-L-aspartate (Bz-Asp) NCA. In contrast, when Bz-Asp was copolymerized with protected ornithine NCAs, it was observed that Bz-Asp incorporated into the growing chain at a high rate compared to the Orn-based NCAs. Upon copolymerization of Gly NCA with Nδ-9-fluorenylmethyloxycarbonyl-L-ornithine (f-Orn) NCA, it was observed that the protons used to monitor the kinetics of Gly NCA were overlapping with those of f-Orn NCA protecting group. To overcome this problem, the carbobenzyloxy (Z) group was introduced as a protecting group on the ornithine side chain to afford Z-Orn NCA. The effect of the side chain protecting group on reactivity of ornithine NCAs (f-Orn and Z-Orn NCAs) was minimal as seen in the copolymerization with Bz-Asp. On the basis of binary copolymerizations, kinetic parameters were determined with the Contour software program, which uses the nonlinear least squares methodology in conjunction with the terminal unit copolymerization model and were found to be rg = 2.51 and ra = 0.46 for Gly/Bz-Asp system, ra = 3.92 and rof = 0.40 for Bn-Asp/f-Orn system and ra = 3.27 and roz = 0.48 for Bz-Asp/Z-Orn system. The reported reactivity ratios were calculated by plotting copolymer composition versus feed composition and the experimental data fitted with constant relative error. A preliminary terpolymerization reaction at approximately equimolar fractions of Gly, Bz-Asp and Z-Orn NCAs was conducted. From the terpolymerization mixture, the behaviour of NCAs as a function of conversion agreed with the monomer reactivities observed in the binary copolymerizations. It was observed that the ternary mixture initially led to a high overall fraction of Gly in comparison to Bz-Asp and Z-Orn in the terpolymer, but with increase in conversion the incorporation of the latter two monomers gradually increased in the terpolymer. The NCAs can be arranged in terms of their reactivities as follows, Gly ≥ Bz-Asp ≥ f-Orn ≈ Z-Orn.

AFRIKAANSE OPSOMMING: Kinetiese studies van die polimerisasie van N-Karboksi-anhidriede (NCA) van ornitien, glisien en aspartiensuur was in hierdie studie ondersoek. Die sintese van beskermde aminosuur afgeleides was uitgevoer voor dit gefosgeniseerd was na die onderskeie NCA’s. Kinetiese studies van homo- en kopolimerisasies van die NCA’s is gedoen via in situ 1H-KMR spektroskopie, deur die afname van die relevante proton intensiteite te monitor. NCA homopolimerisasie studies het die effek van sykettings op NCA monomere getoon; NCA’s met groter sykettinggroepe is minder reaktief vir afgeleides van aspartiensuur en ornitien in vergelyking met glisien. In daaropvolgende kinetiese kopolimerisasie studies, is daar waargeneem dat glisien (Gly) NCA makliker opgeneem word in die groeiende kopolimeer ketting as dit gekopolimeriseer word met β-bensiel-L-aspartaat (Bz-Asp) NCA. In teenstelling hiermee was bevind dat as Bz-Asp gekopolimeriseer word met beskermde ornitien NCA, was dit waargeneem dat Bz-Asp teen ‘n hoër tempo opgeneem word in die groeiende ketting in vergelyking met die Orn-gebaseerde NCA. By kopolimerisasie van Gly NCA met Nδ-9-fluorenielmetieloksikarboniel-L-ornitien (f-ORN) NCA, is daar waargeneem dat die protone wat gebruik is om die kinetika van Gly NCA te monitor, oorvleuel met dié van f-Orn NCA beskermingsgroep. Om hierdie probleem te oorkom, is die karbobensieloksie (Z) groep gebruik om as 'n beskerming groep op die ornitien syketting Z-Orn NCA te dien. Die effek van die sykettingbeskermingsgroep op reaktiwiteit van ornitien NCA (f-Orn en Z-Orn NCA) was minimaal soos waargeneem in die kopolimerisasie met Bz-Asp. Op die basis van binêre kopolimerisasies is kinetiese parameters bepaal met die Contour sagteware program, wat gebruik maak van die lineêre kleinste kwadrate metode in samewerking met die terminale eenheid kopolimerisasie model en is bevind rg = 2.51 en ra = 0.46 vir Gly / Bz-Asp stelsel, ra = 3.92 en rof = 0.40 vir Bn-Asp / f-Orn stelsel en ra = 3.27 en Roz = 0.48 vir Bz-Asp / Z-Orn stelsel. Die reaktiwiteit verhoudings is bereken deur die eksperimentele data (met 'n konstante relatiewe fout) deur die kopolimeer samestelling teenoor die invoer samestelling te plot. 'n Voorlopige terpolimerisasie reaksie op ongeveer ekwimolêre fraksies van Gly, Bz-Asp en Z-Orn NCA is uitgevoer. In die terpolimerisasie mengsel, het die gedrag van NCA’s as 'n funksie van die omskakeling ooreengekom met die monomeer reaktiwiteite vanaf die binêre kopolimerisasies. Dit is waargeneem dat die drieledige mengsel aanvanklik gelei het tot 'n hoë algehele inhoud van Gly in vergelyking met Bz-Asp en Z-Orn in die terpolimeer, maar met toename in die omskakeling het die inkorporering van die twee laasgenoemde monomere geleidelik toegeneem in die terpolymer. Die NCA kan in terme van hul reaktiwiteit rangskik word soos volg, Gly ≥ Bz-Asp ≥ f-Orn ≈ Z-Orn.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/95791
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