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Macromolecular
Chemistry and Physics
DOI: 10.1002/macp.201300381
Novel Bisphosphonated Methacrylates:
Synthesis, Polymerizations, and Interactions
with Hydroxyapatite
Zeynep Sarayli Bilgici, Sebnem Begum Turker, Duygu Avci*
Five novel methacrylates containing either bisphosphonate (1 and 2), bisphosphonic acid (3),
carboxylic acid (4), or both bisphosphonic and carboxylic acid together (5), are synthesized.
The monomers 1 and 2 are synthesized by the reactions of tetraethyl 1-hydroxyethane-1,1-
diyldiphosphonate with ethyl α-bromomethacrylate and tert-
butyl α-bromomethacrylate; the same procedure fails with
tetraethyl hydroxy(phenyl)methylenediphosphonate. 1 is con-
verted to 3 by hydrolysis with trimethylsilyl bromide (TMSBr),
and 2 is converted to 4 by hydrolysis with trifluoroacetic acid
(TFA). Monomer 5 is obtained by hydrolysis of 2 first with
TMSBr and then with TFA. The hydrolytic stability, the proper-
ties of the copolymerizations with commercial dental mono-
mers, and HAP interactions make these monomers promising
candidates for dental adhesives.
Z. S. Bilgici, Prof. D. Avci
Department of Chemistry, Bogazici University,
34342, Bebek, Istanbul, Turkey
E-mail: avcid@boun.edu.tr
Dr. S. B. Turker
Faculty of Dentistry, Marmara, University,
34365, Nisantasi, Istanbul, Turkey
fulfilled using variously designed methacrylates and
methacrylamides with sufficient reactivity. The adhesion
of monomers on tooth tissue is mainly due to chemical
bonds, such as covalent or ionic bonds, resulting from
reaction of acidic and chelating groups with hydroxyapa-
tite (HAP) and physical bonds due to van der Waals
forces, London dispersion forces, hydrogen bonding, or
charge-transfer complexes.
[5]
According to the “adhesion–
decalcification” concept of Yoshida et al.,
[6,9]
the bonding
performance of the adhesives depends on the chemical
stability of the monomer-Ca salts formed with the inter-
action of the acid monomer and HAP. Therefore, the struc-
ture of the acid monomer is very important and small
differences such as polarity in the monomer structures
cause significant differences in their adhesive perfor-
mance. For example, while 4-META and Phenyl-P deposit
unstable calcium salts due to dissolution, MDP forms
hydrolysis-resistant calcium salts due to its hydrophobic
decyl group. Therefore, extensive research has been con-
ducted to develop new monomers with acid functional
groups, which may strongly bond to HAP. For example, bis-
phosphonates, structural analogues of naturally existing
pyrophosphate with increased chemical and enzymatic
stability and strong affinity for HAP, can be incorporated
1. Introduction
Monomers functionalized with acid groups such as
dihydrogen phosphates, carboxylic and phosphonic
acids can be utilized in dental materials such as self-
adhesive resin cements and self-etching adhesives.
[1–4]
The currently used examples of acid monomers are
4-methacryloxyethyl trimellitic anhydride (4-META),
2-methacryloxyethyl phenyl hydrogen phosphate (Phenyl-P),
10-methacryloxydecyl dihydrogen phosphate (MDP), and
2,4,6-trimethylphenyl 2-[4-(dihydroxyphosphoryl)-2-oxa-
butyl]acrylate (MAEPA)]. Some of the properties desired
for adhesive monomers are: i) high rate of free-radical
homopolymerization or copolymerization with the other
monomers in the adhesive, ii) ability to form strong
bonds with tooth tissue, iii) sufficient stability both in
storage and in the mouth. The first requirement can be
Macromol. Chem. Phys. 2013, 214, 2324−2335
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim