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Synthesis of Anticoagulant Glycopolymers and Lactose-Containing Hydrogels

Huang, Yongshun
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1468337467

Abstract Details

2016, PhD, University of Cincinnati, Arts and Sciences: Chemistry.
The design of the sulfated polyurea glycopolymers is based on the concept to introduce hydrophilic/thromboresistance functional groups onto the backbones, i.e. polyurea, by polymerizing sugar-containing diamines with diisocyanates. Four different sugars, including glucose, mannose, glucosamine and lactose, were selected to investigate their performance in in intro blood compatibilities (Chapter 2). Glucose and mannose were chosen because they are monosaccharides with different stereochemistry. Lactose was used to compare monosaccharide versus disaccharide pendant groups. The glucosamine unit provided an amino group for N-sulfonation, which has been reported to enhance anticoagulant activities over O-sulfation. The sulfated polyurea glycopolymers were obtained using step-growth polymerization techniques between sugar-containing diamines with hexamethylene diisocyanate (HDI), followed with deprotection by MeOH/NaOMe, and sulfation with a SO3/pyridine complex. The average degree of sulfation was calculated from elemental analysis and found to be between three and four sulfate groups per saccharide unit. The blood compatibilities of the sulfated polyurea glycopolymers were measured using platelet adhesion assay, activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT), exhibiting two highest anticoagulant activities to be mannose and lactose dimer based glycopolymers. The mechanism of anticoagulant activities was measured by anti-IIa and anti-Xa assays with a preference of an anti-IIa pathway rather than an anti-Xa pathway. After screening different sugar monomers, the influence of diisocyante effect and degree of sulfation on blood compatibilities of sulfated polyurea glycopolymers were studied (Chapter 3). Sulfated polyurea glycopolymers were synthesized from mannose or lactose dimer based diamines (M-D or L-D) with different diisocyanates, HDI, toluene 2,4-diisocyanate (TDI), isophorone diisocyanate (IPDI) and methylene bis(4-cyclohexyl isocyanate) (HMDI). The influence of degree of sulfation was investigated by synthesizing sulfated polyurea glycopolymers from HMDI and L-D with sulfur contents ranging from ~3% to 15.4%. The influence of diisocyanate effect was probed by measuring aPTT, PT and TT of the sulfated polyurea glycopolymers. Sulf(HMDI-L-D) and sulf(IPDI-M-D) exhibited higher prolongation of aPTT values than the other diisocyanate-containing sulfated polyurea glycopolymers. aPTT indicated that higher degrees of sulfation result in prolonged clotting times. The purpose to synthesize lactose-containing hydrogels was to stabilize papain against higher temperature denaturation (Chapter 4). Lactose containing monomers, sulfated and nonsulfated N-(2-lactosylethyl)acrylamides, were synthesized and polymerized with N-hydroxyethyl acrylamide to produce hydrogels. 1 wt% of N,N'-methylenebis(acrylamide) and potassium persulfate was used as a crosslinker and an initiator, respectively. The weight percent of lactose-containing monomer was increased from 0 to 100 % in increments of 10%. Hydrogels were successfully produced with up to 90 wt% of N-(2-lactosylethyl)acrylamide, and 70 wt% of sulfated N-(2-lactosylethyl)acrylamide. Gelation was confirmed by inverting the hydrogel vials and rheology measurements. The rheological measurement of sulfated hydrogels was responsive to the ionic strengths, but independent to pH values. The nonsulfated hydrogels were used for papain stabilization against heat burden for pelleting. Papain that was loaded into hydrogels showed 45% more activity after heating as compared to papain that was heated without hydrogel stabilization. This hydrogel stabilization technique has potential applications in preserving enzyme activity in animal feed.
Neil Ayres, Ph.D. (Committee Chair)
David Smithrud, Ph.D. (Committee Member)
Pearl Tsang, Ph.D. (Committee Member)
232 p.
Chemistry
glycopolymer; anticoagulant; hydrogel

Recommended Citations

Citations

  • Huang, Y. (2016). Synthesis of Anticoagulant Glycopolymers and Lactose-Containing Hydrogels [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1468337467

    APA Style (7th edition)

  • Huang, Yongshun. Synthesis of Anticoagulant Glycopolymers and Lactose-Containing Hydrogels. 2016. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1468337467.

    MLA Style (8th edition)

  • Huang, Yongshun. "Synthesis of Anticoagulant Glycopolymers and Lactose-Containing Hydrogels." Doctoral dissertation, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1468337467

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Cincinnati and OhioLINK.