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Free Radical Polymerization

Inhibition of Anionic PolymerizationBatch Anionic Polymerization Reaction (0 ˚C)Solvent: Dichloromethane (DCM)Initiator: Triethylamine (TEA) (1% of monomer)Monomer concentration 0.03 mol/LThe anionic polymerization was inhibited using amixture of DCM with Dichloroacetic acid (DCAA)(50 ppm)

IntroductionAlkyl CyanoAcrylates are highly reactive acrylic functional monomers undergoing very fast anionic polymerization inthe presence of weak bases.Poly-Alkyl Cyano Acrylates are FDA approved materials for biomedical applications such as tissue adhesives andraw material for the syntesis of nanoparticles (NPs) aiming to drug delivery. However, the high reactivity and the fastdegradation rates limit their use.Recently, the possibility to copolymerize Alkyl CyanoAcrylates with MethAcrylates by free radical polymerizationprocesses disclosed new opportunities towards the uses of such polymers.

Aim of the workThe first objective of this work was to control the anionic polymerization of Butyl CyanoAcrylate (BCA).The reactivity of the copolymerization system has been investigated through ab initio simulations in order to guide the further experiments.Free radical copolymerization of Butyl CyanoAcrylate with Methyl MethAcrylate (MMA) was carried out and the obtained co-polymers have beencharacterized.The produced co-polymers were used to prepare nanoparticles (NPs) through nanoprecipitation NPs characterizationFinally, the biocompatibility of these NPs have been studied in in vitro experiments using human fetal amniotic fluid derived stem cells.

Various mixtures of monomers without addition of initiatorInhibitor: mixture of DCM and DCAA (100:1) 5% v/vTemperature: 50 °CResidence time: 30 minResults for the conversion were obtained by gravimetric analysis using moisture analyzer at 120 °C

NMR analysis of the sample with highest conversion

Absence of polymer peak in the NMR spectrum Same NMR spectra for all the samples GPC and MALDI-TOF analysis confirm the absence of polymer Assumption that the solid residue is product of side reactions at

120 °C during the drying process DCAA can inhibit the anionic polymerization under conditions

suitable for FRP

GPC analysis Presence of monomer peak after monomer

addition The area of monomer peak decreases

progressively over time while the polymer peak increases its area and moves to higher molecular weights

Gravimetric analysis Monomer Addition starts the polymerization

(living process) Higher reaction rate after the monomer

addition

Poly CyanoAcrylate-based Biodegradable Copolymers

Evangelos Mavroudakis1, Valentina Diana2, Giuseppe Storti3, Davide Moscatelli11Department of Chemistry, Materials and Chemical Engineering ‘‘Giulio Natta’’ Politecnico di Milano, via Mancinelli 7, 20131 Milan Italy

2Istituto Auxologico Italiano, Milan Italy 3Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland

Conclusions

NanoprecipitationNPs prepared by using the copolymer obtained through FRP

Biocompatibility test Human fetal amniotic fluid derived stem cells were cultured in stem cells culture medium supplemented with Poly Butyl CyanoAcrylate based nanoparticles at dilutions of 1:1 and 1:100

Computational study: Thermodynamic and kinetic

parameters determined by a Density Functional Theory (B3LYP/6-31 G(d,p))

Calculations performed with Gaussian 03

Copolymer reactivity ratios determined according to the Terminal Model

GPC analysis (sample 3) GPC analysis (sample 4)

Monomer ratioMMA - BCA

solvent Size (nm) PDI

1 10% - 90% THF 203,5 0,230

2 30% - 70% THF 202,7 0,194

3 50% - 50% THF 157,6 0,113

4 70% - 30% THF 204,3 0,242

5 90% - 10% THF 192,3 0,175

DCAA proved a good inhibiton of anionic polymerization even under conditions suitable for free radical polymerization(high temperature, bulk reactors)

The anionic polymerization of BCA confirmed to be a living process Copolymers of BCA with MMA were synthesized through bulk free radical polymerization and then characterized NPs prepared through a nanoprecipitation process with size suitable for biological applications The biocompatibility of the nanoparticles has been proved in in vitro experiments on stem cell

Copolymerization of BCA with MMA could lead to polymers with controlled degradation rates. The biocompatibility of these copolymers and the relative nanoparticles confirms their possible use in biomedical applications.

NPs TEM picture(sample 4)

All the experimental efforts sustain the possible use of BCA - MMA copolymers for stem cell housing/culture

1) 2) 3) 4) 5)

MALDI TOF analysis (sample 4)

Experiments : Butch reactors without strirring Initiator: AIBN (1% w/w) Temperature: 50 °C Inhibitor: DCAA (1% v/v)

Copolymer composition according to the Terminal Model

* Polymer characterization by GPC (standard styrene)** Data for copolymer composition obtained by MALDI TOF

Monomer ratios Mn* (100% conversion)(Da)

PDI* Polymer compositionfor low conversion**

(MMA%)

1 10MMA/90BCA 3,44 x 104 1,93 21 ± 102 30MMA/70BCA 1,44 x 105 1,97 23 ± 103 50MMA/50BCA 2,11 x 105 1,93 30 ± 104 70MMA/30BCA 2,41 x 105 1,99 36 ± 155 90MMA/10BCA 3,04 x 105 1,96 40 ± 15

Monomer units 4 MMA 5MMAFMMA Intensity FMMA Intensity

4BCA 50% 67 55% 215BCA 44% 86 50% 356BCA 40% 98 45% 427BCA 36% 100 42% 478BCA 33% 100 38% 539BCA 31% 96 35% 5010BCA 29% 87 33% 41

The presence of the NPs does not significantly induce cell toxicity.

High concentration of MMA (sample 5) reduces cell metabolism (long terms - 4 days).

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Time (s)

The living characteristic of the anionic polymerization of BCA has been confirmed

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% BCA in monomer mixture