FellowCristian Peptu
Project NameFUNCTIONAL STAR ARCHITECTURES BASED ON CYCLODEXTRIN CORES AND BIOINSPIRED SYNTHETIC ARMS FOR VERSATILE DRUG DELIVERY SYSTEMS
Host organisationPolymer Institute
Duration of the project01.01.2016 - 31.12.2018

Abstract
Project's general objective is to provide a method for preparation of alkene functional star polymers, starting from cyclodextrin (CD) core. These complex macromolecular architectures will be prepared through a core first approach, by ring opening polymerization (ROP) of cyclic carbonates and/or esters initiated by cyclodextrins. In a first approach, ROP will be performed by a green chemistry route, only in presence of CD and, subsequently, organocatalysts will be employed. The monomers taken into consideration are α‐methylene‐γ‐butyrolactone or Tulipaline A (found in tulips ), 5-Methyl-5-allyloxycarbonyl-1,3-dioxan-2-one, ε-caprolactone and D,L-lactide. The structural characterization of the star polymers will be performed by mass spectrometry, NMR and chromatographic methods. The star polymers will have a controllable (through co-monomer feed in ROP) amount of pendant alkene functions along the polymer chain, which will be further exploited through post-polymerization modification. The envisaged goal is to prepare covalently crosslinked nanoparticles and hydrogels through A) thiol-ene addition/radical coupling between thio-functional chitosan and cyclodextrin-alkene functional oligoester/oligocarbonate and through B) radical copolymerization with acrylic and methacrylic derivatives.

Project Summary with Interim Results

Project's general objective is to provide a method for preparation of complex functional oligocarbonate/oligoester architectures, star polymers, starting from cyclodextrin (CD) core (Scheme 1). The way to prepare these complex macromolecular architectures includes the use of green chemistry monomers such as αmethyleneγbutyrolactone (MBL), known also as Tulipalin A, and/or environmentally friendly cyclic carbonates as 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC).


Scheme 1. Synthesis of cyclodextrin based alkene functional star copolymers

So far, materials with similar structure were prepared by ring opening polymerization (ROP) employing usually various potentially toxic heavy metal catalysts. This project proposes different approach based on green chemistry method applying the lately demonstrated catalytic potential of cyclodextrins in ROP of cyclic esters. Therefore, this approach will contribute to the development of new functional materials without necessity of using any toxic catalyst. The prepared star polymers will contain a controllable amount of pendant alkene functions along the polymer chain obtained by simple comonomers feed ratios. Such alkene functional groups can be further exploited through post-modification. The envisaged goal is to prepare covalently crosslinked nanoparticles and hydrogels through A) thiol-ene addition/radical coupling between chitosan functionalized with thiol groups and alkene groups of oligoester/oligocarbonate-cyclodextrin, and B) radical copolymerization with acrylic and methacrylic derivatives.

Particularly, the most important achievement of the first year activities consists in finding an appropriate synthetic method, which allows designing cyclodextrins functionalized with 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one and L-lactide. The cyclodextrin was used as both initiator and catalyst which can be beneficial for the further use of such materials in medical field. The clear cut characterization of the products by mass spectrometry methods supported the structural assignment of the products. Another important feature derived from the first year activity concerns the study of the ROP of cyclic esters through used green methods at a fundamental level. The structural assignment of the cyclodextrin derivatives presented previously in literature claimed that the bucket shaped cyclodextrin molecule was functionalized preferentially on the larger rim. However, mass spectrometry and NMR spectroscopy characterization performed within the first year of project implementation showed that functionalization takes place on the smaller rim of cyclodextrin. This finding is particularly important in establishing the catalytic activity of cyclodextrin in ROP of cyclic esters.