title: Modulating the self-assembly of amphiphilic X-shaped block copolymers with cyclodextrins: structure and mechanisms.
abstract: Inclusion complexes between cyclodextrins and polymers-so-called pseudopolyrotaxanes (PPR)-are at the origin of fascinating supramolecular structures, which are finding increasing uses in biomedical and technological fields. Here we explore the impact of both native and a range of modified cyclodextrins (CD) on the self-assembly of X-shaped poly(ethylene oxide)-poly(propylene oxide) block copolymers, so-called Tetronics or poloxamines, by focusing on Tetronic 904 (T904, Mw 6700). The effects are markedly dependent on the type and arrangement of the substituents on the macrocycle. While native CDs drive the formation of a solid PPR, most substituted CDs induce micellar breakup, with dimethylated β-CD (DIMEB) having the strongest impact and randomly substituted CDs a much weaker disruptive effect. Using native α-CD as a "molecular trap", we perform competitive binding experiments-where two types of CDs thread together onto the polymer chains-to establish that DIMEB indeed has the highest propensity to form an inclusion complex with the polymer, while hydroxypropylated CDs do not thread. 1D (1)H NMR and ROESY experiments confirm the formation of a soluble PPR with DIMEB in which the CD binds preferentially to the PO units, thus providing the drive for the observed demicellization. A combination of dynamic light scattering (DLS) and small-angle neutron scattering (SANS) is used to extract detailed structural parameters on the micelles. A binding model is proposed, which exploits the chemical shifts of selected protons from the CD in conjunction with the Hill equation, to prove that the formation of the PPR is a negatively cooperative process, in which threaded DIMEBs hamper the entrance of subsequent macrocycles.
authors.affiliation: †Departamento de Química y Edafología, Facultad de Ciencias, Universidad de Navarra, 31080 Pamplona, Spain.
authors.forename: Gustavo
authors.initials: G
authors.lastname: González-Gaitano
authors.affiliation: ‡Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, U.K.
authors.forename: Céline
authors.initials: C
authors.lastname: Müller
authors.affiliation: §Jülich Center for Neutron Science, JCNS Outstation at MLZ, Forschungszentrum Jülich GmbH, Lichtenbergstraße 1,85747 Garching, Germany.
authors.forename: Aurel
authors.initials: A
authors.lastname: Radulescu
authors.affiliation: ‡Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, U.K.
authors.forename: Cécile A
authors.initials: CA
authors.lastname: Dreiss
mesh_terms: D003505:Cyclodextrins / Q000737:chemistry*; D005029:Ethylenediamines / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008745:Methylation; D008823:Micelles; D011095:Polyethylenes / Q000737:chemistry*; D011126:Polypropylenes / Q000737:chemistry*
chemical_list: D003505:Cyclodextrins; D005029:Ethylenediamines; D008823:Micelles; D011095:Polyethylenes; D011126:Polypropylenes; C525597:Tetronic 904; C078661:UCON 50-HB-5100