University of Basra, Basra-Iraq Synthesis and thermal study of multi arms nano block copolymers via combination of ROP and thio-click chemistry Hadi Al-Lami University of Basra, Basra-Iraq hadi.abbas@uob.edu.iq hadisalman54@yahoo.com

Presentation Outline Applications scope of smart polymers. Definition of CRP, ROP, and Thio-Click Chemistry. Synthesis of nano multi arms block copolymers. Characterization by: FTIR, NMR (1H &13C), and GPC. Microstructure Studies. Swelling, biodegradability and drug release study. Thermal studies. Conclusions.

Methods used to prepare multi arms nano block copolymers CRP may defined as a polymerization reaction, where no unwanted side reactions such as transfer or termination take place, and where all polymer chains are initiated at the same time. ROP is a form of polymerization, in which the active terminal end can react by opening its ring and form a longer polymer chain. "Click Chemistry" is a term that was introduced by Sharpless in 2001 to describe reactions that are highly selective, yielding and wide in scope.

Preparation of (Pentaerythritol-lactide) polymer (PL10, PL25, PL50, and PL100)

(Pentaerythritol-Lactide Bromide)-(hydroxy ethyl acrylamide) copolymer

Preparation of Thiolate POSS by Thio-Click reaction of Octavinyl POSS with 2-Mercapto ethanol

(Thiolate POSS -Lactide Bromide)-(N-hydroxy ethyl acrylamide) copolymer

Characterization Characterization of (Pentaerythritol- lactide) polymers (PL10, PL25, PL50 and PL100) by FT-IR

Characterization of (Pentaerythritol-lactide) polymers (PL10, PL25, PL50 and PL100) by 1H NMR

Characterization of (Pentaerythritol-lactide) polymers (PL10, PL25, PL50 and PL100) by 13C NMR

Characterization of Thiolate POSS by FT-IR

Characterization of Thiolate POSS by 13C NMR

Characterization of (Thiolate POSS-lactide) polymers: (TL10, TL25, TL50, and TL100) by FT-IR

Characterization of (Thiolate POSS- lactide) polymers: (TL10, TL25, TL50, and TL100) by 1H NMR

Characterization of (Thiolate POSS- lactide) polymers: (TL10, TL25, TL50, and (TL100) 13C NMR

Gel Permeation Chromatography (GPC) No. Polymer Name Calculated Mn (Daltons) Found Mw Polydispersity Index (PDI) 1 PL10 3018 3063 3317 1.08 2 PL25 7342 7319 8351 1.14 3 PL50 14549 14563 15805 4 PL100 28962 28903 31102 1.07 5 TL10 7023 7094 8164 1.15 6 TL25 15671 15653 17364 1.10 7 TL50 30084 29995 32998 8 TL100 58911 58951 61130 1.03

No. Copolymer Name Value of (m) Mn (Daltons) Mw Polydispersity Index (PDI) 1 PL10BrNm 12 9126 10347 1.13 2 PL25BrNm 29 21264 23815 1.11 3 PL50BrNm 59 42266 43383 1.02 4 PL100BrNm 113 81502 87810 1.07 5 PL10BrDm 13 11725 12651 6 PL25BrDm 28 25475 27339 7 PL50BrDm 57 50947 58105 1.14 8 PL100BrDm 115 101795 110018 1.08 9 TL10BrNm 20138 21673 10 TL25BrNm 30 44496 50770 11 TL50BrNm 60 86484 93180 TL100BrNm 165933 176655 1.06 TL10BrDm 23257 25066 14 TL25BrDm 31 55860 59243 15 TL50BrDm 58 104177 121661 1.16 16 TL100BrDm 116 205861 284755 1.38

Scanning Electron Microscopy (SEM)

Biodegradability Studies Swelling Studies The swelling ratio for all prepared were studied as a function of time at three different pH, 1.2, 7 and 8.4. The obtained data showed that the swelling ratio decreasing as PLA chain length increases. Biodegradability Studies Hydrolytic degradation studies were followed as well at same pH (1.2, 7 and 8.4) for 7 weeks with 40% as maximum degradation. Hydrolytic degradation percent was decreased with increasing of PLA chain length.

Thermogravimetric Analysis TGA thermogram of of PL10

Polymer Ti (oC) Tf Rate of Decomposition % wt / min   Activation Energy KJ.mol-1 Weight Loss (%) T50 PL10 176.56 201.47 6.33 0.011 94.33 186.03 PL25 181.93 213.09 3.96 0.013 97.09 190.60 PL50 211.49 231.62 3.21 94.09 215.94 PL100 233.26 291.67 1.95 0.026 98.78 253.57

Polymer Ti (oC) Tf Rate of Decomposition % wt / min   Activation Energy KJ.mol-1 Weight Loss (%) T50 TL10 189.31 219.05 3.92 0.075 98.09 198 TL25 191.55 246.43 2.32 0.079 92.09 201 TL50 229.94 260.29 2.29 0.086 99.09 235 TL100 252.22 304.76 1.88 0.092 98.58 265

Copolymer Ti (oC) Tf Rate of Decomposition % wt/min Activation Energy   Activation Energy kJ.mol-1 Weight Loss (%) T50% PL10BrDm 1st. decomp. 145.82 216.80 0.38 0.015 27.77 294.05 2nd. decomp. 289.74 332.14 0.67 0.016 53.84 PL25BrDm 158.33 241.70 0.37 0.020 24.95 296.43 295.37 330.76 0.65 0.018 57.84 PL50BrDm 173.92 246.26 0.32 0.023 32.71 292.32 291.71 345.24 0.42 0.021 48.2 PL100BrDm 190.03 253.74 0.31 0.044 20.97 315.48 306.03 346.43 0.51 0.033 64.17

Conclusions The following conclusions can be withdrawn from the current work: 1. Combination of ROP with the Thio-click chemistry has been reached with successes using ATRP macroinitiator. 2. A series of block copolymers pentaerythritol-Lactide and thiolate POSS-Lactide multi arms nano block copolymers were obtained. 3. FT-IR, 1HNMR and 13CNMR were proved the structures for the prepared copolymers. 4. GPC results revealed that all the tested copolymers are of nearly monodisperse polymer.

5. Lactide polymer chains exhibited a nano structure as they examined by SEM. 6. The ability of the prepared polymer to degraded in vitro and in vivo, and they exhibited excellent biocompatibility with human plasma with no toxicity. 7. The release rate of insulin can be designed by choosing the suitable conditions and can be given orally. 8. Thermal studies showed better stability of the multi arms copolymers as lactide units increased and POSS is present.