Poly(glycidyl methacrylate): a

versatile polymeric building

block for functional materials*

*Polymer Chemistry, 2013, 4, 124-132 / Patent Filed

M. Benaglia, A. Alberti, F. Magnoni, S. Tozzi

ISOF - Bologna

Coffee talk@ISOF 6 November 2012

L. Giorgini - Bologna University

A

B

M

n

Results achieved with the advent of controlled

polymerization techniques

Controlled MW with narrow distribution

Control of the chemical composition of the polymer by selecting the appropriate monomer

Introduction of functional groups at the chain ends

Moreover

Unprecedented control on the polymer architecture

Spatial self-organization

R

S Z

S

M

The RAFT technique in particular…

The RAFT group permits conjugation reactions that involve either the dithio carbonyl group or the forming thiol function

Introduction of special functionalities by choosing the appropriate RAFT agent

R

S

M

n

Z

S

Disadvantage:

polymerization conditions must be optimized for each monomer

•Hetero Diels-Alder reaction •Thiol-ene click reaction •Disulfide bridge formation •Thiol anchoring

Poly(glycidyl methacrylate)

Reactive epoxy function

Hydrogels Methacrylic epoxy resins as coatings and adhesives

Glycidyl methacrylate

industrially widely employed

Radical Polymerization

Poly(glycidyl methacrylate) by RAFT

Ring-opening reactions induced by nucleophiles

PGMA obtained with:

•controlled MW •determined architecture •functionalized ends

The treatment investigated enables maximum control of the chemical composition for a pre-synthesized polymer

Nucleophilic ring-opening of the epoxy groups

A

B

n

OO

O

A

B

n

OO

OH

Nu

:Nu

Nucleophiles:

•Amines •Thiols •Phenols •Azide

Treatment with amines

Cross-linked polymer

Linear polymer

Primary amines

Secondary amines

Easy access to a library of polymers

Morpholine

N-methylpiperazine

Piperidine

4-Hydroxypiperidine

3-Hydroxypiperidine

Diethylamine

Diethanolamine

Methylethanolamine

Imidazole

Benzimidazole

pH tunable sensitive materials

and the

solubility can be varied from

hydrophilic to lipophilic

Materials obtained with amines as nucleophiles are:

R

S*

OO

n

OH

N

O

By NMR the ring-opening reaction is quantitative

00.511.522.533.544.55

ppm

H2O

DMSO

R

SC(S)Z

OO

n

O

2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5

GPC analysis: the linearity of the PGMA is maintained

mL THF

R

SC(S)Z

OO

n

O

Mn 10900 g mol-1

PDI 1.14

2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5

R

S*

OO

n

OH

N

OMn 14000 g mol-1

PDI 1.15

molecular weight <50 KDa for renal excretion

Possible cross-linking mechanisms

2,5 3 3,5 4 4,5 5 5,5 6 6,5 7 7,5

PGMA Treatment in aprotic polar solvents like:

DMSO or

N-Methylpyrrolidone

-speeds up the process

-cross-linking is avoided

mL

Trans-esterification

Other class of nucleophiles

Thiols

OO

n

OH

S

HO

SH

OH

0123456

ppm

DMSO

H2O

OH

OO

n

O

OH

Aromatic alcohols

Other class of nucleophiles

012345678

ppm

DMSO

H2O

pH insensitive

and

can be

hydrophilic or lipophilic materials

Materials obtained with mercaptanes or

aromatic alcohols as nucleophiles are:

Treatment with sodium azide

C=O

O

O

C=O

n

O

HO

N

m

C=O

O

O

n+m

O

NHO C=O

O

C=O

n

O

HO

N

HO

N3

NaN3

m

O

-N3

2104 cm-1

Azide functionalized polymers

for click reactions with

alkynyl-substrates

Amphiphilic block-copolymer

PHMPMA-b-PMMA PHMPMA-b-PSt PHMPMA-b-PBA

Spatial self-organization into micelles

Polymeric micelles

CO CO CO

O O O

OH

N

O

CO

O

OH

N

O

OH

N

O

OH

N

O

Lipophilic block

Hydrophilic block Hydrated shell

H2O Self-assembling

Amphiphilic block-copolymer

= Nile Red

Loaded core

Intracellular Delivery of

Lipophilic Substances

Cellular uptake of polymeric micelles

Human colon carcinoma cells LS-174T

Post post-polymerization processes enables for

further chemical and structural modifications

012345678910

ppm

H2O DMSO

Pre post-polymerization functionalizations

Maleimide-functionalized substrates

R = Amino-terminated polymers

Fluorescent dyes

Maleimide - Not Reversible Linking

Pre post-polymerization functionalizations

Suitable for (bio-)conjugation with thiol substrates

Suitable for conjugation with amine substrates

Disulfide Bridge - Reversible Linking

Conclusions

The treatment of PGMA with nucleophilic reagents

enables a multitude of different materials specifically

functionalized to be synthesized from the same polymer.

This process provides polymeric materials for:

Diagnostic agents delivery

Therapeutic agents delivery

Gene delivery

Active and/or passive targeting

Anti non-specific protein absorption properties

} Theranostic approach

> Plasmids, siRNA

Moreover, photoactive as well as electron and proton conductive

materials are also accessible

Acknowledgements

ISOF

Dr. Angelo Alberti

Dr. Francesco Magnoni

Dr. Silvia Tozzi

Students

Dr. Tommaso Tabanelli

Alice Cognigni

Cristiano Luciani

Gaia Tombari

Emilio Iacoli

Thank you for your kind attention

University of Bologna

Dr. Loris Giorgini

DR. Enzo Spisni