Novel derivatives of sporopollenin for potential applications in solid phase organic synthesis and drug delivery

Kettley, Sarah Jane

Abstract

The outer coat (exine) of plant pollen grains and spores is composed of the material sporopollenin. Sporopollenin is exceptionally resistant to chemical and physical attack and is perhaps one of the most chemically resistant, naturally occurring organic materials known. Its stability to chemical and physical stress is illustrated by its survival in ancient sedimentary rock of around 3.7 billion years old.

Sporopollenin from Lycopodium clavatum has been functionalised in the past for use in the preparation of peptides and for use in ion and ligand exchange. It was found that sporopollenin. had a number of advantages over the synthetic resins commonly used in solid phase synthesis which included a constant chemical structure, constant pore size, chemical and physical stability and commercial availability.

Investigations into the isolation of sporopollenin using various procedures outlined in the literature were reviewed in order to find the most efficient protocol for sporopollenin preparation. Detailed studies of the sporopollenin were undertaken to establish its chemical and physical stability, swelling, filtering and hydration characteristics. Results indicated that sporopollenin would make a good alternative to other solid supports as it showed little swelling in organic solvents, was easily filtered through grade 3-4 sinters and the size of the sporopollenin was constant. Also, it could be dried efficiently and showed good chemical and physical stability, e. g. it can be refluxed for several days in strong acid and base and a variety of organic solvents without decomposition. It also can be stirred for several days with little degradation. In contrast, a parallel study with a commercial PS-DVB resin showed it to be considerably less stable, e. g. stirring for one day resulted in severe degradation of the resin. Also, most of the commercially available resins are found to have a variable particle size and variable loadings.

An investigation into the types of functional groups present on the sporopollenin surface was undertaken to explain the types of functionalities present on sporopollenin and examine their reactivity. The objective was to assess the potential of sporopollenin for use as a solid phase support for synthesis and drug delivery. Studies indicated that ketone, acid and hydroxyl groups were present. Thus, in order to obtain uniformity of functionality sporopollenin was reduced with the objective of obtaining solely hydroxyl groups on its surface. Suprisingly the loading of hydroxyl groups varied between one batch to another (0.40-0.92 mmol/g). Attempts to halogenate the hydroxy groups with PCl5 and SOCl2 or condense them with amino acids to form ester linkages was only moderately successful. In contrast, chloromethylation of sporopollenin using dirnethoxymethane and SOCl2 with ZnCl2 as a catalyst gave consistent levels of
chloride loading from one batch to another (1.01-1.28 mmol/g). Such a form of chloromethylated sporopollenin could be compared to Merrifield resin. Preliminary attempts to substitute the chloride proved difficult due presumably to the attachment of chloromethyl groups to aliphatic sites rather than aromatic sites. Amination of different batches of sporopollenin with primary amines, e. g. n-butylamine gave loadings of around 1-2 mmol/g. An extensive study was undertaken to assess the stability of the amine attachment to acid, bases and organic solvents. In all of these a relatively robust attachment was found with no less than 70% of the amine still attached. This study encourages the use of diamines as linker groups with the intention that one primary amine would attach to the sporopollenin with the other being available for further substitution to attach either synthons or drugs.

Citation

Kettley, S. J. (2001). Novel derivatives of sporopollenin for potential applications in solid phase organic synthesis and drug delivery. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4212704

• Thesis Type: Thesis
• Deposit Date: Jul 24, 2012
• Publicly Available Date: Feb 22, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4212704
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: Sep 1, 2001