Autocatalytic Self-sorting In Cystamine-based Biomimetic Polymer

Self-sorting is the capacity of mutual recognition and selective self-assembly of chemical species. In supramolecular system, self-sorting can be achieved by hydrogen bonding, metal coordination, geometrical and chiral recognition, etc. To date, only hydrogen bonding has been successfully used for the self-sorting in polymer systems in organic media. Self-sorting wide exist in biological systems, such as DNA replication, transcription and translation. On the other hand, NH3+-to-NH2 in protein, transition can balance physiological environment. Redox of thiol-disulfide residues plays important roles in the construction of hydrophobic centers, balance of physiological environment and peptide-folding in proteins. Moreover, the peptide thiol/amino residues participate in structural immobilization, enzymatic catalysis, substrate and information delivery, and hierarchical architectures via metal complexation. Disulfides exchange can proceed rapidly and reversibly under mild conditions. Accordingly, we synthesized poly(cystamine methacrylamide hydrochloride)(PCysMA) whose monomer units comprised lysine-mimetic alkyl ammonium ions and cystine-mimetic alkyl disulfide spacers, the self-sorting behaviors through dynamic disulfide exchange in the absence and presence of copper ions were studied in this thesis.Cystamine methacrylamide hydrochloride(CysMA) monomer was synthesized by means of amidation of acryloyl chloride with cystamine hydrochloride, a peptide-cystine metabolite. Poly(2-hydroypropylmethacrylamide)-block-poly(cystamine methacrylamide hydrochloride)(PHPMA-b-PCysMA) was synthesized by aqueous RAFT under visible light irradiation at 25 oC, in which the CysMA units comprise the disulfide bonds and primary amine groups. 1H NMR, UV-vis spectroscopy and elements analysis results indicated that the polymer was well-defined with intact RAFT terminal groups. SEC results revealed the narrow molecular weight distribution at a polydispersity index(PDI) of 1.10.Self-sorting behavior of this block copolymer in water was studied in this thesis. 1H NMR, UV-vis spectroscopy and elemental analysis results confirmed the perfect aqueous solubility and intactness of RAFT terminal groups in water at pH 3.0. Upon increase of solution pH, the amino groups underwent a NH3+-to-NH2 transition, leading to aminolysis of the RAFT chain-ends to afford catalytic amount of thiolates and thereby initiated the dynamic exchange of disulfide bonds. The polymeric disulfide bonds sorted into the cross-linked hydrophobic domains with synchronous release of water-soluble cystamine molecules into water medium. DLS and AFM results revealed irreversible evolution of swollen micelles to collapsed ones. This self-sorting reached a maximum of 65~67% at pH 10.5, indicating that residual CysMA units still existed. All these demonstrated that the self-sorting behavior led to the structural variation to hydrophobic disulfides with simultaneous release of water-soluble cystamine to aqueous media, which is an analogue to a metabolic process in biological systems.Furthermore, the effects of metal coordination on the self-sorting and self-assembly were examined in the present of stoichiometric copper ions([Cu(II)]0:[NH2]0=1:4). The acid-base titration results revealed that the coordination led to a decrease in the pKa parameter from pH 6.6 to 6.1. This block copolymer was stable and soluble in water at pH 3.0. UV-vis spectroscopy result indicated that Cu(II)-NH2 coordination took place rapidly at pH 7.0, with simultaneous aminolysis of the RAFT chain-ends into thiolates, leading to the dynamic exchange of PCysMA disulfide bonds and NH2-to-SH substitution at metal centers. The asgenerated Cu(I)-S intermediate complexes were oxidized into cupric ions and cystamine on exposure to air. 1H NMR, UV-vis spectroscopy, atomic absorption spectroscopy, elemental analysis results unveiled that the block copolymer underwent a serious of intermediate reactions, including Cu(II)-NH2 coordination, aminolysis, NH2-to-SH ligand substitution, and oxidation of intermediate complexes, and completely self-sorted into hydrophobic crosslinked domains with concomitant release of cystamine molecules and intermediate cuprous complexes into water at pH 8.8. Self-assembly proceeded in a programmed supramolecularto-supracolloidal assembly manner. All these demonstrated that an ideal metabolism-alike self-sorting can be achieved in this biomimetic polymer with the aid of copper incorporation.Therefore, a well-defined PHPMA107-b-PCysMA80 block copolymer that contained both disulfide bonds and amine groups was synthesized under mild conditions. The self-sorting behavior was achieved in this block copolymer through aminolysis of the RAFT chain-ends, dynamic exchange of disulfide bonds, and thereby the hydrophilic-hydrophobic conversion. Moreover, an ideal autocatalytic self-sorting was achieved with incorporation of copper ions, which promoted Cu(II)-NH2 coordination, aminolysis of the RAFT chain-ends, NH2-to-SH ligand substitution at metal centers and the oxidation of Cu(I)-S intermediate complexes in ambient air atomosphere. As such, a novel metabolism-alike ideal autocatalytic self-sorting was achieved in the as-synthesized biomimetic polymer in aqueous solution.