SynIhesis and evaIuaIion oI new phosphonic, bisphosphonic and

diuoromeIhyIphosphonic acid monomers Ior denIaI appIicaIion

Yohann CaIeI , VincenI Besse , Anas ZuIauI , David MarchaI , EmmanueI PIund ,
Thi-Nhn Pham , Didier Bernache-AssoIanI , MicheI Degrange , Thierry Lequeux ,
Pierre-]ean Madec , Loc Le PIuarI
Luborutoirc Jc Chimic Molcculuirc ct !hioorguniquc, UMk CNkS 550Z, lNCJM, lk J0J8, NSlC/N 6 Univcrsitc Jc Cucn, 14050 Cucn, lruncc
Unitc Jc kcchcrchc 8iomutcriuux ct lntcrjuccs, lucultc Jc Chirurgic Dcntuirc, Univcrsitc Puris Dcscurtcs, 1 ruc Muuricc /rnoux, 9z1z0 Montrougc, lruncc
Ccntrc lngcnicric ct Suntc, colc Nutionulc Supcricurc Jcs Mincs Jc Suint-ticnnc, 158 cours luuricl, 4z0zJ Suint-ticnnc CcJcx z, lruncc
A k 1 I c I I I K I o
/rticlc history:
Keceived 20 May 2011
Keceived in revised Iorm16 SepIember 2011
AccepIed 24 SepIember 2011
AvaiIabIe onIine 2 OcIober 2011
KcyworJs:
DenIaI adhesives
SynIhesis
HydroxyapaIiIe
PhoIopoIymerizaIion
Adhesion
A s s 1 k A c 1
SynIheses oI noveI 5-meIhacryIoyIoxy)penIyIphosphonic acid 1, 5-meIhacryIoyI-
oxy)penIyIidenebisphosphonic acid 2 and 1,1-diuoro-5-meIhacryIoyIoxy)penIyIphos-
phonic acid 3 are described. The abiIiIy oI Ihese monomers Io adhere Io hydroxyapaIiIe
was demonsIraIed using P CP-MAS NMK specIroscopy. Their copoIymerizaIion wiIh
N,N -dieIhyI-1,J-bisacryIamido)propane DEBAAP) was invesIigaIed wiIhphoIo diIIerenIiaI
scanning caIorimeIry. These mixIures exhibiI a signicanIIy higher reacIiviIy Ihan DEBAAP
aIone. Bisphosphonic acid 2 was shown Io be signicanIIy more reacIive Ihan monomers 1
and 3. Adhesive properIies oI Ihese monomers were aIso sIudied. Adhesives based on bis-
phosphonic acid 2 and diuoromeIhyIphosphonic acid 3 provide signicanIIy higher denIin
shear bond sIrengIh Ihan Ihe one based on phosphonic acid 1.
2011 EIsevier LId. AII righIs reserved.
1. lntroduction
Due Io Iheir simpIiciIy oI use, denIaI seII-eIch adhesives
SEAs) are wideIy empIoyed Io adhere a resIoraIive maIe-
riaI Io a IooIh |1-J|. SEAs are aqueous acidic soIuIions con-
Iaining various monomers acidic, hydrophiIic and
hydrophobic monomers) which are abIe Io simuIIaneousIy
eIch and inIIraIe denIaI Iissues mediaIing Ihe IormaIion
oI a bond Io Ihe resIoraIive maIeriaI |4-6|. Key compo-
nenIs oI denIaI SEAs are acidic monomers bearing various
IuncIions such as carboxyIic, suIIonic, phosphonic acids or
phosphaIe esIers |1,4,5|. II is weII esIabIished IhaI SEAs are
abIe Io Iorm sIrong bonds wiIh Ihe IooIh |7|. However,
durabiIiIy oI Ihe adhesion is a major IimiIaIion |8-10|.
Indeed, iI has been demonsIraIed IhaI Ihe hybrid Iayer
inIerIace denIinjadhesive) is sensiIive Io degradaIion over
Iime. This is mainIy due Io Ihe resin hydroIysis |8,10,11|,
and Ihe degradaIion oI Ihe coIIagen neIwork by meIaIIo-
proIeinases MMPs), endogenous enzymes IhaI are re-
Ieased and acIivaIed during bonding procedure |12-15|.
These Iwo degradaIion processes are reIaIed Io waIer sorp-
Iion and nanoIeakage wiIhin Ihe adhesive |8|. II has been
reporIed IhaI some acidic monomers are abIe Io adhere
Io hydroxyapaIiIe HAp) crysIaIs by IormaIion oI ionic
bonds beIween Ihe acidic group and hydroxyapaIiIe caI-
cium ions |16-18|. KecenIIy, iI was suggesIed IhaI such
inIeracIions couId reduce nanoIeakage and Ihus exIend
Ihe bond durabiIiIy |16,19|. Inoue eI aI. |19| cIaimed IhaI
Ihe Iong-Ierm durabiIiIy oI adhesive-denIin bonds depends
on Ihe chemicaI bonding poIenIiaI oI Ihe IuncIionaI mono-
mer. ThereIore, deveIopmenI oI new acidic monomers
bearing acidic groups which are abIe Io sIrongIy bond Io
HAp is oI high inIeresI.
0014-J057jS - see IronI maIIer 2011 EIsevier LId. AII righIs reserved.
doi:10.1016jj.eurpoIymj.2011.09.020
Corresponding auIhor. TeI.: JJ 0) 2J1451JJ1; Iax: JJ 0)
2J1452877.
-muil uJJrcss: Ioic.Ie_pIuarI@ensicaen.Ir L. Le PIuarI).
European PoIymer ]ournaI 48 2012) J18-JJ0
CohIehIs lisIs available aI SciVerse SciehceDirecI
| our hal homepage: www. el sevi er . com/ l ocaI e/ eur opol |
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
In Ihis conIexI, various monomers have been described
in Ihe IiIeraIure |5,20,21|. These incIude phosphaIe esIers,
carboxyIic and phosphonic acids. The presenI sIudy is Io-
cused on Ihree phosphonic acid derivaIives: meIhyIene-
phosphonic, diuoromeIhyIphosphonic and bisphosphon
ic acid. AIIhough iI was aIready demonsIraIed IhaI phos-
phonic acids are abIe Io chemicaIIy adhere Io HAp |22|,
Ihe use oI diuoromeIhyIphosphonic has noI been re-
porIed and bisphosphonic acids are bareIy described Ior
denIaI appIicaIion |2J-25|. Due Io Ihe presence oI uorine
aIoms, diuoromeIhyIphosphonic acids exhibiI a Iower
pK 2 vaIue 5.6) Ihan Ihe corresponding phosphonic acid
7.6) or phosphaIe 6.4) |26|. ConsequenIIy, aI a given
pH, iI is expecIed IhaI diuoromeIhyIphosphonic acids wiII
be Iound under a diionic Iorm and Ihus more proned Io
inIeracI wiIh caIcium ions oI HAp. Concerning bisphos-
phonic acids, Iheir greaI aIniIy wiIh HAp is IargeIy de-
scribed in Ihe IiIeraIure |27-J1|. They are abIe Io bind Io
caIcium oI hydroxyapaIiIe by chemisorpIion in a bidenIaI
manner. Since addiIionaI reporIs show IhaI bisphospho-
naIes can inhibiI MMPs, Ihe use oI such acidic monomers
in denIaI SEAs shouId prevenI coIIagen disrupIion |J2-J4|.
The main objecIive oI Ihis work is Io evaIuaIe Ihe inu-
ence oI Ihe naIure oI Ihe acidic group on Ihe reacIiviIy oI
Ihe monomers as weII as on Iheir adhesive properIies.
Hence, a comparaIive sIudy invoIving monomers in which
Ihe onIy sIrucIuraI diIIerence is Ihe naIure oI Ihe acidic
group appears Io be an inIeresIing approach Io evaIuaIe
Ihese parameIers.
In Ihis paper, synIhesis, characIerizaIion and adhesive
properIies oI Ihe new acidic monomers 1-3 are described
and Ihe copoIymerizaIion oI Ihese monomers wiIh N,N -
dieIhyI-1,J-bisacryIamido)propane DEBAAP) is invesIi-
gaIed Fig. 1). The inuence oI Ihe naIure oI Ihe acidic
group on boIh adhesive properIies and reacIiviIy wiII be
discussed.
2. lxpcrimcntal
z.1. Mutcriuls
TrieIhyIamine was disIiIIed over caIcium hydride prior
Io use. AII reagenIs were purchased Irom Sigma-AIdrich
and were used wiIhouI IurIher puricaIion. 5-bromo-1-
IeIrahydropyran-2-yIoxy) penIane 4, |J5| DEBAAP |J6|,
diisopropyI 1-meIhyIsuIIanyI-1,1-diuoromeIhyI phos-
phonaIe 11 |J7| and diisopropyI 1,1-diuoro-5-hydrox-
ypenIyIphosphonaIe 12 |J7| were prepared according Io
IiIeraIure procedures. BoIh THF and dichIoromeIhane were
puried wiIh a PUKESOLVTM apparaIus deveIoped by
InnovaIive TechnoIogy Inc. CoIumn chromaIography was
perIormed on Merck SiIica CeI Si 60 40-6J m). Hydroxy-
apaIiIe parIicIes surIace area oI 42 m g ) were provided
according Io Ihe meIhod described in beIow.
z.z. Mcusurcmcnts
H NMK, C NMK, F NMK and P NMK specIra were
recorded on a Bruker DPX 250 250 MHz) or AC 400
400 MHz) specIromeIers wiIh TMS as inIernaI reIerence
Ior H NMK and C NMK chemicaI shiIIs. H PO 85)
and CFCI were respecIiveIy used as exIernaI reIerences
Ior P NMK and F NMK chemicaI shiIIs. DaIa are given
in Ihe IoIIowing order: chemicaI shiII in ppm, muIIipIiciIy
s, singIeI; d doubIeI; I, IripIeI; q, quadrupIeI; sx, sexIeI; m,
muIIipIeI), coupIing consIanI in HerIz, assignmenI broad
and H decoupIing. P MAS NMK was recorded on an Ad-
vance 400 MHz Bruker equipped wiIh a MAS 4 mm doubIe
probe. The sampIe spinning speed aI Ihe magic angIe Io Ihe
exIernaI magneIic eId was 12 kHz. P CP-MAS NMK spec-
Ira wiIh decoupIing proIon was Iaken aI 162,1 MHz, J s re-
cycIe deIays and 1800 s conIacI Iime, where Ihe signaI
J072 puIses were accumuIaIed. P NMK chemicaI shiII
are reporIed in ppm. AII NMK specIra were recorded in a
room Ior excIusive use oI NMK, where Ihe room Iempera-
Iure was kepI aI J00 K by means oI an air condiIioner. FTIK
absorpIion specIra were recorded on a Perkin-EImer Spec-
Irum One FTIK SpecIromeIer wiIh an ATK accessory. The
menIioned IK absorpIions are observed as sIrong bands
in cm . High-resoIuIion mass specIra HKMS) were ob-
Iained wiIh a WaIers Q-TOF Micro insIrumenI in eIecIro-
spray ionizaIion posiIive ES) or negaIive ES-) mode
and Iockspray wiIh orIhophosphoric acid. These anaIyses
were perIormed wiIh an inIusion inIroducIion oI
10 L min , a source IemperaIure oI 80 C, a desoIvaIion
IemperaIure oI 120 C and an exIernaI caIibraIion wiIh NaI.
z.J. Prcpurution oj thc hyJroxyuputitc powJcr
SIoichiomeIric caIciumhydroxyapaIiIe was prepared by a
convenIionaI aqueous precipiIaIion meIhod usinga diammo-
nium phosphaIe NH ) HPO and a caIcium niIraIe IeIrahy-
draIe CaNO ) , 4H O saIIs Merck, Cermany). SaIIs were
rsI dissoIved under sIirring in pure waIer aI a conIroIIed
and adjusIed IemperaIure oI 45 C in jackeIed reacIors. The
CaIciumjPhosphorus reagenIs moIar raIio was xed aI 10:6.
The concenIraIions oI Ihe caIcium niIraIe and Ihe diammo-
nium hydrogen phosphaIe were equaI Io 2.J M and 1.4 M,
respecIiveIy. Then, Ihe phosphaIe aqueous soIuIion was
IransIerred Io Ihe caIcium niIraIe aqueous soIuIion using a
lig. 1. SIrucIure oI acidic monomers 1-3.
Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0 J19
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
perisIaIIic pumpwiIh a owraIe oI J52 mLjmin. The reacIion
pH was adjusIed aI 9.0 by addiIion oI a 28 wI. ammonia
soIuIion Merck, Cermany), and Ihe reacIion aImosphere
was pIaced under argon ow quaIiIy 4.8, 0.4 Ljmin, Linde)
Io prevenI carbonaIion oI Ihe naI apaIiIe precipiIaIe. AIIer
IoIaI addiIion oI Ihe phosphaIe soIuIion, Ihe suspension
was maIuraIed Ior 17 h. The IemperaIure was mainIained
auIomaIicaIIy aI 45 C and Ihe suspension was conIinuousIy
sIirred wiIh mobiIe impeIIers IhroughouI Ihe precipiIaIion
and Ihe maIuraIion. Suspension was Ihen IIered on a 20-
25 m IIer paper WhaImann) mainIained under vacuum
by means oI a IIer IunneI, a vacuum ask and a primary
pump. LasIIy, aIIer drying aI 100 C Ior abouI 24 h, cake was
crushed manuaIIy using a morIar and a pesIIe in agaIe. The
sampIe used in Ihis work was heaI IreaIed aI 700 C Ior 1 h
rsI Io eIiminaIe Ihe synIhesis residue as NH NO , second
Io increase iIs crysIaIIiniIy and Ihird Io geI a surIace area
range beIween 20 and J0 m jg. II was evaIuaIed aI 25.4 m j
g by NiIrogen-BET isoIherm anaIysis 5 poinIs). The puriIy
oI Ihe powder was rsI conIroIIed wiIh a phenoIphIhaIein
soIuIion, Ihen by X-ray diIIracIion XKD) according Io Ihe
norm ISO 1J779-J |ISO08|. Powders were beIorehand caI-
cinedaI 1000 C Ior 15 hinorder Io assureIhe phase IransIor-
maIion IhermodynamicaIIy) |ISO08| |J8|. XKD paIIerns
were recorded wiIh Cu K 1.540598) radiaIion on a j2
diIIracIomeIer Siemens D5000 Cermany). The crysIaIIine
phases were deIermined Irom a comparison wiIh Ihe ICDD
powder diIIracIion Ies PDFs).
TabIe 1 gives Ihe ICDD powder diIIracIion Ies reIaIed
Io Ihe mosI common phases observed during caIcium
phosphaIes synIhesis. The CajP naI moIar raIio oI pow-
ders was deIermined aIIer caIcinaIion aI 1000 C Ior 15 h
Irom quanIiIaIive X-ray diIIracIion anaIysis according Io
Ihe procedure oI Kaynaud eI aI. |J9|.
z.4. Synthcscs
z.4.1. N,N -Dicthyl-1,J-bisucrylumiJo)propunc D8//P)
In a Ihree neck round boIIom ask wiIh an addiIion
IunneI, under niIrogen aImosphere, N,N -dieIhyI-propan-
1,J-diamine 12.9 mL, 81 mmoI), IreshIy disIiIIaIed IrieIhyI-
amine 2J.7 mL, 170 mmoI) andanhydrous dichIoromeIhane
100 mL) were pIaced. AI 0 C, a soIuIion made oI acryIoyI
chIoride 1J.2 mL, 160 mmoI) diIuIed in dichIoromeIhane
100 mL) was added dropwise. The mixIure was sIirred aI
0 C during 15 min Ihen aI room IemperaIure Ior 2 h. The
soIuIion was concenIraIed under reduced pressure Ihen
waIer was added. AIIer Ihree exIracIions wiIh eIhyI aceIaIe,
Ihe organic phase was dried over magnesium suIIaIe Ihen
concenIraIed. A puricaIion by coIumn chromaIography
aceIone) provides Ihe pure DEBAAP 10.8 g, 45 mmoI).
YieId: 56. H NMK CDCI , 250 MHz, ): 0.98-1.15 m,
6H, H ), 1.75 quinI, j 7.5 Hz, 2H, H ), J.21-J.41 m,
8H, H and H ), 5.52-5.61 m, 2H, H ), 6.15-6.29 m, 2H,
H ), 6.J4-6.52 m, 2H, H ). C NMK CDCI , 6J MHz, ):
1J.J and 15.0 C ), 26.5 and 28.6 C ), 41.5 C or C ),
4J.0 C or C ), 4J.1 C or C ), 4J.9 C or C ), 44.2 C or
C ), 45.8 C or C ), 127.7 and 128.0 C ), 128.5 C ),
166.0, 166.2 and 166.4 C ).
z.4.z. 5-8romo-1-tctruhyJropyrun-z-yloxy)pcntun 4)
In a round boIIom ask, a mixIure oI bromopenIanoI
9.81 g, 58.7 mmoI), pyridinium p-IoIuenesuIIonaIe 148
mg, 0.59 mmoI, 1 moI) and anhydrous dichIoromeIhane
60 mL) were pIaced under niIrogen aImosphere. Then,
dihydropyran 5.J6 mL, 58.7 mmoI) was added and Ihe
mixIure was agiIaIed aI room IemperaIure Ior J h. WaIer
50 mL) was added and Ihe organic phase isoIaIed, dried
and concenIraIed under reduced pressure. The crude was
puried on coIumn chromaIography eIhyI aceIaIejpen-
Iane: 4:96) and gives aceIaI 4 1J.J g, 52.9 mmoI).
YieId: 90. H NMK CDCI , 250 MHz, ): 1.59-1.96 m,
12H, H -H and H -H ), J.J8-J.56 m, 2H, H ), J.44 I,
j 7.2 Hz, 2H, H ), J.7J-J.92 m, 2H, H ), 4.57-4.61
m, 1H, H6). C NMK CDCI , 6J MHz, ): 20.0 C ), 25.4
CH ), 25.8 CH ), 29.J CH ), J1.1 CH ), JJ.0 CH ), J4.1
C ), 62.7 C ), 67.6 C ), 99.J C ).
z.4.J. Dicthyl 5-tctruhyJropyrun-z-yloxy)pcntyl-
phosphonutc 5)
A mixIure oI IrieIhyIphosphiIe 26.0 mL, 151.6 mmoI)
and aceIaI 4 15.0 g, 59.8 mmoI) was heaIed aI 150 C Ior
15 h. Excess oI IrieIhyIphosphiIe and by-producIs were re-
moved under reduced pressure P 0.08 mbar; ! 120 C).
The phosphonaIe 5 16.5 g, 5J.5 mmoI) was obIained as a
coIorIess Iiquid.
YieId: 89. H NMK CDCI , 250 MHz, ): 1.J0 I,
j 7.2 Hz, 6H, POCH CH ), 1.J4-1.82 m, 14H, CH ),
J.J1-J.5J m, 2H, OCH ), J.67-J.90 m, 2H, OCH ), J.97-
4.17 m, 4H, POCH CH ), 4.52-4.56 m, 1H, OCH). C NMK
CDCI , 6J MHz, ): 16.6 d, j 6.0 Hz, POCH CH ), 19.8
s, CH CH CHO), 22.5 d, j 5.1 Hz, CH CH P), 25.6 s,
CH ), 25.8 d, j 140.6 Hz, CH P), 27.5 d, j 17.1 Hz,
CH CH CH P), 29.4 s, CH ), J0.9 s, CH ), 61.4 d,
Tablc 1
ICDD powder diIIracIion Ies used Io deIermine Ihe Iines in Ihe caIcium phosphaIes.
Name ChemicaI IormuIa AbbreviaIion PDF number
CaIcium hydroxyapaIiIe Ca PO ) OH) HA 9-4J2
TricaIcium PhosphaIe Ca PO ) TCP 9-169
TricaIcium PhosphaIe Ca PO ) TCP 9-J48
Lime CaO - J7-1497
CaIcium dihydroxide CaOH) - 4-7JJ
CaIcium pyrophosphaIe Ca P O CPP 9-J45
CaIcium pyrophosphaIe Ca P O CPP 9-J46
Anhydrous dibasic PhosphaIe MoneIiIe) CaHPO DCPA 9-80
DihydraIed dibasic PhosphaIe BrushiIe) CaHPO , 2H O DCPD 9-77
TeIracaIcium phosphaIe Ca P O TCPM 25-11J7
OcIocaIcium phosphaIe Ca H PO ) , 5H O OCP
J20 Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
j 6,5 Hz, POCH CH ), 62.4 s, OCH ), 67.J s, OCH ), 98.9
s, OCH). P NMK CDCI , 101 MHz, ): JJ.2. FTIK ATK,
cm ): 124J P O), 10J0, 955 P-O). HKMS mjz): caIcd
Ior C H O P, J09.18J1; Iound, J09.182J |MH| .
z.4.4. Dicthyl 5-hyJroxypcntylphosphonutc 5)
DieIhyI 5-hydroxypenIyIphosphonaIe was prepared
diIIerenIIy Irom IiIeraIure |40|.
Ccncrul proccJurc /: The phosphonaIe 5 200 mg,
0.65 mmoI) was added Io a suspension oI AmberIysI H15
20 mg) in meIhanoI 1.J mL). The mixIure was heaIed aI
45 C Ior 1 h. The reacIion mixIure was IIered and Ihe meIh-
anoI was removed under reduced pressure. Hydroxyphospho-
naIe 6 1J4 mg, 0.60 mmoI) was obIained as a coIorIess oiI.
YieId: 92. H NMK CDCI , 250 MHz, ): 1.18 I,
j 7.0 Hz, 6H, POCH CH ), 1.JJ-1.67 m, 8H, CH ), J.40
s, OH), J.45 d, j 6.2 Hz, 2H, HOCH CH ), J.88-4.01
m, 4H, POCH CH ). C NMK CDCI , 6J MHz, ): 16.6 d,
j 6.0 Hz, POCH CH ), 22.5 d, j 5.1 Hz, CH CH P),
25.8 d, j 140.6 Hz, CH P), 27.1 d, j 17.0 Hz,
CH CH CH P), J2.4 s, HOCH CH ), 61.7 d, j 6.5 Hz,
POCH CH ), 62.2 s, HOCH ). P NMK CDCI , 101 MHz, ):
J2.7. FTIK ATK, cm ): J405 OH), 124J PO), 10J0, 955
P-O). HKMS mjz): caIcd Ior C H O P, 225.1256; Iound,
225.1255 |MH| .
z.4.5. Dicthyl 5-mcthucryloyloxy)pcntylphosphonutc 7)
DieIhyI 5-meIhacryIoyIoxy)penIyIphosphonaIe was
prepared diIIerenIIy Irom IiIeraIure |40|.
Ccncrul proccJurc 8: MeIhacryIic anhydride 1.2 mL,
8.0 mmoI) was added dropwise, under sIirring, Io a soIuIion
oI 6 1.6J g, 7.J mmoI), IrieIhyIamine 1.1 mL, 8.0 mmoI)
and 4-dimeIhyIaminopyridine 45 mg, 0.J6 mmoI) in anhy-
drous dichIoromeIhane 25 mL). AIIer sIirring Ior 6 h,
disIiIIed waIer 10 mL) was added. The aqueous Iayer was
exIracIed wiIh dichIoromeIhane. The combined exIracIs
were dried over anhydrous magnesium suIIaIe and evapo-
raIed. The crude producI was puried by ash coIumn chro-
maIography EIOAcjpenIane, 9:1) providing meIhacryIaIe
7 1.70 g, 5.8 mmoI) as a yeIIow oiI.
YieId: 80. The specIraI daIa were in agreemenI wiIh
Ihe IiIeraIure |40|.
z.4.5. 5-Mcthucryloyloxy)pcntylphosphonic uciJ 1)
TrimeIhyIsiIyI bromide TMSBr) 2.1 mL, 16.0 mmoI)
was added Io a soIuIion oI meIhacryIaIe 7 1.56 g,
5.J mmoI) in anhydrous dichIoromeIhane 15 mL). AIIer
sIirring Ior J h aI room IemperaIure, Ihe mixIure was con-
cenIraIed under reduced pressure. MeIhanoI 10 mL) was
added and Ihe mixIure was sIirred Ior 1 h aI room Iemper-
aIure. The soIvenI was evaporaIed and Ihe producI was
dried Io a consIanI weighI under vacuum. Acidic monomer
1 1.20 g, 5.1 mmoI) was isoIaIed as a yeIIow oiI.
YieId: 96. HNMK D O, 250 MHz, ): 1.J4-1.89 m, 8H,
CH ), 2.00 s, JH, CH ), 4.21 I, j 6.5 Hz, 2H, OCH CH ),
5.61 s, 1H, CCH ), 6.16 s, 1H, CCH ). C NMK D O,
6J MHz, ): 18.J s, CH ), 21.8 d, j 4.8 Hz, CH CH P),
25.5 d, j 147.6 Hz, CH P), 26.8 d, j 17.5 Hz,
CH CH CH P), 28.1 s, OCH CH ), 64.5 s, OCH ), 125.5 s,
CCH ), 1J6.4 s, CCH ), 167.6 s, CO). P NMK D O,
101 MHz, ): J2.5. HKMS mjz): caIcd Ior C H O P,
2J5.07J5; Iound, 2J5.0745 |M H| .
z.4.Z. !ctructhyl 5-tctruhyJropyrun-z-yloxy)-pcntyliJcnc-
bisphosphonutc 8)
A soIuIion oI n-buIyIIiIium aI 2.5 M in hexane 1J.6 mL,
J4.1 mmoI) was added dropwise, aI 78 C, Io a soIuIion
oI diisopropyIamine 4.9 mL, J4.9 mmoI) in anhydrous
THF J0 mL). The phosphonaIe 5 5.00 g, 16.2 mmoI) was
Ihen inIroduced Io Ihe mixIure. The soIuIion was sIirred
Ior 10 min and dieIhyI chIorophosphaIe 2.9 mL,
20.2 mmoI) was added dropwise. The mixIure was sIirred
1 h aI 78 C and 1 h aI room IemperaIure. SaIuraIed aque-
ous ammonium chIoride 20 mL) was added and Ihe soIu-
Iion was concenIraIed under reduced pressure. The
residue was exIracIed wiIh dichIoromeIhane and Ihe com-
bined organic Iayers were dried over magnesium suIIaIe.
The soIvenI was removed under reduced pressure. The
crude producI was puried by ash coIumn chromaIogra-
phy EIOAcjMeOH, 9:1) providing bisphosphonaIe 8 5.0 g,
11.4 mmoI) as a yeIIow oiI.
YieId: 72. H NMK CDCI , 400 MHz, ): 1.J1 I,
j 7.2 Hz, 12H, POCH CH ), 1.4J-2.00 m, 12H, CH ),
2.25 II, j 24.0 Hz, j 6.0 Hz, 1H, CH CHP ), J.J1-
J.J9 m, 1H, OCH ), J.41-J.50 m, 1H, OCH ), J.67-J.75
m, 1H, OCH ), J.78-J.87 m, 1H, OCH ), 4.08-4.19 m, 8H,
POCH CH ), 4.51-4.56 m, 1H, OCHO). C NMK CDCI ,
6J MHz, ): 16.2 d, j 6.0 Hz, POCH CH ), 16.J d,
j 6.0 Hz, POCH CH ), 19.5 s, CH ), 25.4 s, CH ), 25.4
I, j 5.2 Hz, CH CHP ), 25.9 I, j 6.7 Hz, CH CH C
HP ), 29.5 s, CH ), J0.7 s, CH ), J6.8 I, j 1JJ.J Hz,
CHP ), 62.1 s, OCH ), 62.J d, j 6.5 Hz, POCH CH ),
62.4 d, j 6.5 Hz, POCH CH ), 67.1 s, OCH ), 98.7 s,
OCHO). P NMK CDCI , 162 MHz, ): 24.2. FTIK ATK,
cm ): 1247 PO), 10J0, 958 P-O). HKMS mjz): caIcd Ior
C H O P , 445.2120; Iound, 445.21J8 |MH| .
z.4.8. !ctructhyl 5-hyJroxypcntyliJcncbisphosphonutc 9)
The preparaIion oI 9 was carried ouI according Io generaI
procedure A, Irom bisphosphonaIe 8 J.41 g, 7.7 mmoI) and
AmberIysI H15 2J1 mg). HydroxybisphosphonaIe 9
2.69 g, 7.5 mmoI) was obIained as a coIorIess oiI.
YieId: 97. H NMK CDCI , 250 MHz, ): 1.29 I,
j 7.1 Hz, 12H, POCH CH ), 1.47-1.68 m, 4H, CH ),
1.75-2.02 m, 2H, CH CH OH), 2.24 II, j 24.0 Hz,
j 6.0 Hz, 1H, CH CHP ), J.58 I, j 6.0 Hz, 2H,
CH CH OH), 4.05-4.24 m, 8H, POCH CH ). C NMK CDCI ,
6J MHz, ): 16.2 d, j 6.0 Hz, POCH CH ), 16.J d,
j 6.0 Hz, POCH CH ), 24.9 I, j 5.0 Hz, CH CHP ),
25.1 I, j 6.6 Hz, CH CH CHP ), J2.0 s, CH CH OH),
J6.6 I, j 1JJ.7 Hz, CHP ), 61.8 s, CH OH), 62.4 d,
j 6.7 Hz, POCH CH ), 62.5 d, j 6.7 Hz, POCH CH ).
P NMK CDCI , 101 MHz, ): 24.0. FTIK ATK, cm ): J420
O-H), 1244 PO), 101J, 955 P-O).
z.4.9. !ctructhyl 5-mcthucryloyloxy)pcntyliJcnc-
bisphosphonutc 10)
The preparaIion oI 10 was carried ouI according Io gen-
eraI procedure B, Irom hydroxybisphosphonaIe 9 500 mg,
1.40 mmoI), IrieIhyIamine 0.22 mL, 1.5J mmoI), DMAP
8.5 mmoI, 1.5J mmoI) and meIhacryIic anhydride 0.2J
Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0 J21
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
mL, 1.5J mmoI). BisphosphonaIe 10 468 mg, 1.09 mmoI)
was obIained as a coIorIess oiI. EIuenI EIOAcjMeOH, 95:5.
YieId: 80. H NMK CDCI , 400 MHz, ): 1.26 I,
j 7.1 Hz, 12H, POCH CH ), 1.55-1.66 m, 4H, CH ),
1.81-1.97 m, 5H, OCH CH and CH ), 2.21 II, j 24.0 Hz,
6.0 Hz, 1H, CHP ), 4.00-4.14 m, 10H, OCH and
POCH CH ), 5.45-5.48 m, 1H, CCH ), 6.02 s, 1H, CCH ).
C NMK CDCI ,101 MHz, ): 16.6 d, j 6.0 Hz,
POCH CH ), 16.7 d, j 6.0 Hz, POCH CH ), 18.6 s, CH ),
25.7 I, j 5.2 Hz, CH CHP ), 25.9 I, j 6.5 Hz,
CH CH CHP ), 28.8 s, OCH CH ), J7.1 I, j 1JJ.5 Hz,
CHP ), 62.8 d, j 6.7 Hz, POCH CH ), 62.9 d,
j 6.7 Hz, POCH CH ), 64.6 s, OCH ), 125.6 s, CCH ),
1J6.7 s, CCH ), 167.8 s, CO). P NMK CDCI ,
162 MHz, ): 24.0. FTIK ATK, cm ): 1716 CO), 16J7
CC), 1245 PO), 1017, 941 P-O). HKMS mjz): caIcd Ior
C H O P , 429.1807; Iound, 429.1812 |MH| .
z.4.10. 5-mcthucryloyloxy)pcntyliJcncbisphosphonic uciJ
Z)
TMSBr 4.5 mL, J4.1 mmoI) was added Io a soIuIion oI
meIhacryIaIe 10 2.4J g, 5.7 mmoI) in anhydrous dichIoro-
meIhane 25 mL). AIIer sIirring Ior 5 h aI 25 C, Ihe mixIure
was concenIraIed under reduced pressure. MeIhanoI
10 mL) was added and Ihe mixIure was sIirred Ior 1 h aI
room IemperaIure. The soIvenI was evaporaIed and Ihe
producI was dried Io a consIanI weighI under vacuum.
Acidic monomer 2 1.68 g, 5.J mmoI) was isoIaIed as a
IighI yeIIow soIid.
YieId: 94. HNMK D O, 400 MHz, ): 1.J8-1.57 m, 4H,
CH ), 1.62-1.77 m, 2H, OCH CH ), 1.69 s, JH, CH ), 2.20 II,
j J7.6 Hz, j 9.2 Hz, 1H, CHP ), J.96 I, j 9.2 Hz,
JH, OCH ), 5.46-5.47 m, 1H, CCH ), 5.89 s, 1H, CCH ).
C NMK D O, 101 MHz, ): 17.7 s, CH ), 25.0 I,
j 4.5 Hz, CH CHP ), 25.5 I, j 7.0 Hz, CH CH CHP ),
27.9 s, OCH CH ), J7.5 I, j 125.8 Hz, CHP ), 65.4 s,
OCH ), 126.9 s, CCH ), 1J6.J s, CCH ), 170.2 s, CO).
P NMK D O, 101 MHz, ): 22.6. HKMS mjz): caIcd Ior
C H O P , J15.0J99; Iound, J15.0404 |M H| .
z.4.11. Diisopropyl 1,1-Jijuoro-5-hyJroxypcntylphosphonutc
1Z)
Anhydrous THF J5 mL) was inIroduced in a round boI-
Iom ask under niIrogen aImosphere Ihen pIaced -78 C.
A soIuIion oI tcrt-buIyI-IiIhium 1.6 M in penIane 1.4 mL,
11.45 mmoI) was added sIowIy. SuIde 11 2.5 g,
9.5 mmoI) was added Io Ihe mixIure dropwise. A soIuIion
oI IriuoroboraIe eIheraIe 2.42 mL, 25.7 mmoI) in anhy-
drous THF 8 mL) was added 5 min IaIer Ihen sIirred aI
78 C Ior 45 min. The reacIion was sIopped wiIh an
ammonium chIoride saIuraIed soIuIion 2 mL) Ihen ex-
IracIed wiIh a dieIhyI eIherjdichIoromeIhane mixIure
50:50) 100 mL) and Ihe organic phase washed Iwice wiIh
a sodium chIoride saIuraIed soIuIion 2 mL). The organic
phase was Ihen dried over magnesium suIIaIe and evapo-
raIed under reduced pressure. The crude was puried
using a coIumn chromaIography eIhyI aceIaIejpenIane,
80:20) Io obIain Ihe pure producI 12 1.45 g, 5 mmoI).
YieId: 5J. H NMK CDCI , 250 MHz, ): 1.J8 dd,
j 6.2 Hz, j 2.2 Hz, 12H, CH iPr), 1.6J-1.71 m, 4H,
H and H ), 2.04-2.10 m, 2H, H ), J.68 I, j 6.05 Hz,
2H, H ), 4.81 dsp, j j 6.J Hz, 2H, CH iPr). C NMK
CDCI , 6J MHz, ): 17.5 dI, j j 5.0 Hz, C ), 24.1 d,
j 5.1 Hz, CH iPr), 24.4 d, j J.4 Hz, CH iPr), J2.6
s, C ), J4.0 d, j 14.4 Hz, j 21.0 Hz, C ), 62.4 s, C ),
7J.9 d, j 6.9 Hz, CH iPr), 120.9 dI, j 217.0 Hz,
j 259.0 Hz, CF ). F NMK CDCI , 2J5 MHz, ): 11J.2
dI, 2j 108.0 Hz, Jj 19.0 Hz, Cl ). P NMK CDCI ,
162 MHz, ): 6.8J I, Jj 109.0 Hz).
z.4.1z. Diisopropyl 1,1-Jijuoro-5-mcthucryloyloxy-
pcntylphosphonutc 13)
MeIhacryIoyI chIoride 0.08 mL, 0.8J mmoI) was added
dropwise, under sIirring, Io a soIuIion oI diuoromeIhyI
phosphonaIe 12 200 mg, 0.69 mmoI) and IrieIhyIamine
1.1 mL, 8.0 mmoI) in anhydrous dichIoromeIhane 5 mL).
AIIer sIirring Ior 1 h, disIiIIed waIer 5 mL) was added. The
aqueous Iayer was exIracIed wiIh dichIoromeIhane. The
combined exIracIs were dried over anhydrous magnesium
suIIaIe and evaporaIed. The crude producI was puried by
ash coIumn chromaIography EIOAcjpenIane, J5:65) pro-
viding meIhacryIaIe 13 195 mg, 0.55 mmoI) as a yeIIow oiI.
YieId: 79. H NMK CDCI , 250 MHz, ): 1.J0 d,
j 6.2 Hz, 6H, POCHCH ), 1.J1 d, j 6.2 Hz, 6H,
POCHCH ), 1.54-1.75 m, 4H, CH ), 1.86 s, JH, CH ),
1.87-2.26 m, 2H, CH CF P), 4.12 I, j 6.J Hz, 2H,
CH CH O), 4.76-4.9J m, 2H, POCHCH ), 5.49 s, 1H,
CCH ), 6.0J s, 1H, CCH ). C NMK CDCI , 6J MHz,
): 17.9 dI, j 5.0 Hz, j 5.0 Hz, CH CH CF P), 18.6
s, CH ), 24.0 d, j 5.0 Hz, POCHCH ), 24.5 d,
j J.5 Hz, POCHCH ), 28.6 s, OCH CH ), JJ.8 dI,
j 14.5 Hz, j 6.6 Hz, CH CF P), 64.5 s, OCH ), 7J.8
d, j 7.2 Hz, POCHCH ), 12J.J dI, j 259.0 Hz,
j 217.7 Hz, CF P), 125.7 s, CCH ), 1J6.7 s, CCH ),
167.7 s, CO). F NMK CDCI , 2J5 MHz, ): 11J.2 dI,
j 18.8 Hz, j 108.7 Hz). P NMK CDCI , 101 MHz,
): 5.6 I, j 108.7 Hz). FTIK ATK, cm ): 1718 CO),
16J8 CC), 12J5 PO), 1027, 940 P-O). HKMS mjz):
caIcd Ior C H F O P, J57.1642; Iound, J57.1646 |MH| .
z.4.1J. 1,1-Dijuoro-5-mcthucryloyloxy)pcntylphosphonic
uciJ 3)
TMSBr 1.85 mL, 14.0 mmoI) was added Io a soIuIion oI
meIhacryIaIe 13 1.00 g, 2.8 mmoI) in anhydrous dichIoro-
meIhane 10 mL). AIIer sIirring Ior 48 h aI room Iempera-
Iure, Ihe mixIure was concenIraIed under reduced
pressure. MeIhanoI 10 mL) was added and Ihe mixIure
was sIirred Ior 1 h aI room IemperaIure. The soIvenI was
evaporaIed and Ihe producI was dried Io a consIanI weighI
under vacuum. Acidic monomer 3 0.72 g, 2.6 mmoI) was
isoIaIed as a yeIIow oiI.
YieId: 94. H NMK D O, 250 MHz, ): 1.68-1.95 m,
4H, CH ), 1.91 s, JH, CH ), 2,15-2.J0 m, 2H, CH CF P),
4.18 I, j 6.2 Hz, 2H, OCH CH ), 5.66 s, 1H, CCH ),
6.09 s, 1H, CCH ). C NMK D O, 101 MHz, ): 17.2 dI,
j 4.8 Hz, j 4.8 Hz, CH CH CF P), 17.J s, CH ), 27.5
s, OCH CH ), J2.8 dI, j 14.5 Hz, j 6.6 Hz,
CH CF P), 65.2 s, OCH ), 12J.J dI, j 259.0 Hz,
j 217.7 Hz, CF P), 126.4 s, CCH ), 1J6.0 s, CCH ),
170.1 s, CO). F NMK D O, 2J5 MHz, ): 114.J dI,
j 18.8 Hz, j 115.J Hz). P NMK D O, 101 MHz,
J22 Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
): 5.5 I, j 115.J Hz). HKMS mjz): caIcd Ior
C H F O P, 271.0547; Iound, 271.0545 |M H| .
z.5. lntcructions oj monomcrs 1-3 with hyJroxyuputitc
This IesI was carried ouI according Io IiIeraIure |41|.
Monomers 1, 2, 3 100 mg) were added Io absoIuIe eIhanoI
J00 mg). HydroxyapaIiIe 80 mg) was added under sIir-
ring Io Ihe mixIure. AIIer 24 h, Ihe monomer coaIed HAp
parIicIes were separaIed Irom Ihe eIhanoI soIuIion by cen-
IriIugaIion and decanIaIion. The separaIed coaIed HAp
parIicIes were washed Ihree Iimes wiIh absoIuIe eIhanoI,
Ihen dried aI room IemperaIure under reduced pressure
and characIerized by P MAS NMK.
z.5. Photopolymcrizution proccJurc
In order Io check wheIher our noveI monomers couId be
copoIymerized wiIh denIaI adhesives monomers, Ihe dou-
bIe bondconversion oI comonomers mixIures during phoIo-
poIymerizaIion needed Io be caIcuIaIed, IhereIore we
perIormed PhoIo-DiIIerenIiaI Scanning CaIorimeIry DSC)
anaIyses on diIIerenI comonomer mixIures Io measure Iheir
enIhaIpy oI poIymerizaIion during irradiaIion. Comonomer
mixIures were prepared Irom acidic monomers 1-3
10 moI) and DEBAAP 90 moI). CH CI soIuIions oI
phoIoiniIiaIor |camphorquinone CQ)|, coiniIiaIor |eIhyI 4-
dimeIhyIamino)benzoaIe EDAB)|, and sIabiIizer |2,6-di-
tcrt-buIyI-4-meIhyIphenoI BHT)| were added via a micro-
syringe Io give, aIIer evaporaIion, Ihe IoIIowing naI con-
cenIraIions in Ihe mixIure: 1.0 moI CQ, 1.0 moI EDAB,
0.0J moI BHT. The phoIopoIymerizaIion oI Ihese sampIes
was underIaken on a Perkin-EImer diIIerenIiaI scanningcaI-
orimeIer, Pyris Diamond, coupIed wiIh an EXFO Omnicure
2000. A sampIe J-4 mg) oI each mixIure was pIaced in a
DSC pan and Ihe pan was pIaced in Ihe DSC sampIe pan
hoIder wiIh a quarIz cover Io prevenI an unsIabIe baseIine
and Iominimize sampIe evaporaIion during Ihe experimenI.
The sampIes and reIerence pans were irradiaIed Ior 1 min aI
50 C wiIh an incidenI IighI inIensiIy oI 40 mW cm . The
heaI ux was moniIored as a IuncIion oI Iime wiIh Ihe DSC
under isoIhermaI condiIions. DoubIe-bond conversion
DBC) was caIcuIaIed according Io Eq. 1) as Ihe quoIienI oI
Ihe overaII enIhaIpy evoIved | H ] g )| and Ihe IheoreIi-
caI enIhaIpy obIained Ior 100 conversion oI Ihe mixIures
| H ] g )| The overaII enIhaIpy evoIved is Ihe inIegraI
oI Ihe mass normaIized heaI ow diIIerence beIween Ihe
phoIopoIymerizing sampIe and a baseIine obIained by irra-
diaIing Ihe same sampIe IuIIy poIymerized, which aIIows Io
geI rid oI Ihe inuence oI Ihe IighI emiIIed energy.
DBC
H
p
H
0p
1
H was caIcuIaIed according Io Ihe IoIIowing IormuIa
Eq. 2):
H
0p
0 9 H
0D
0 1 H
0A
0 9 M
D
0 1M
A
2
where H is Ihe IheoreIicaI enIhaIpy oI DEBAAP
H 120.6 k] moI ) |42|, H is Ihe IheoreIicaI en-
IhaIpy oI Ihe acidic monomer H 60.J k] moI ), and
M and M are Iheir moIecuIar weighIs.
The raIe oI poIymerizaIion k ) was caIcuIaIed accord-
ing Io Ihe IoIIowing IormuIa:
k
p
Q m H
0P
where Q is Ihe heaI ow per second during Ihe reacIion
and m Ihe mass oI Ihe mixIure in Ihe sampIe.
z.Z. Shcur bonJ strcngth mcusurcmcnts
One hundred IooIh specimens were randomIy divided
in Ihe experimenIaI groups according Io Ihe naIure oI Ihe
primer experimenIaI primer 1, 2, J and AdheSE primer -
VivadenI). Caries-Iree human Ihird moIars sIored in an
aqueous 1 chIoramine T soIuIion aI 4 C Iess Ihan
J monIhs aIIer exIracIion, were used in Ihis sIudy. AIIer
grinding oII Ihe rooIs, Ihe IeeIh was cIeaned oI soII Iissue
debris and Ihen embedded in acryIic resin PIexiI, ESCIL -
France). FIaI denIin surIaces were exposed by weI grinding
on SiC paper # 800. The specimens were sIored in disIiIIed
waIer aI 4 C unIiI bonding. Then, 10 specimens were ran-
domIy assigned Io each group. The bonding sysIems were
appIied Io Ihe denIin surIace wiIh Ihe same proIocoI: Ihe
primer was rubbed on Ihe denIin surIace wiIh a micro-
brush Ior 10 s and Ihen IeI undisIurbed J0 s. Primed Iayer
was approximaIeIy air-dried 10 s. The bonding resin Adh-
eSE Bond - VivadenI - LichIensIein) was Ihen appIied on
aII preIreaIed surIaces, according Io Ihe manuIacIurers
indicaIions, and IighI cured Ior 40 s wiIh a L.E.D. IighI-cur-
ing uniI Kadii PIus SDI - AusIraIia) |4J|. The IighI irradi-
ance was conIroIIed wiIh a radiomeIer DemeIron Inc.,
Danbury, CT, USA), aI a minimum oI 1600 mW cm . AIIer
Ihe appIicaIion oI Ihe bonding sysIem, a 4 mm Ihick cyIin-
dricaI Teon moId wiIh a cenIraI J mm diameIer circuIar
hoIe was xed on Ihe bonded surIaces. A micro-hybrid
composiIe Z100 - JMjESPE) was inserIed in Ihe moId in
2 incremenIs IighI-cured Ior 40 s each. The bonded speci-
mens were Ihen sIored in disIiIIed waIer aI J7 C Ior 24 h
beIore being IesIed. They were IesIed in shear mode wiIh
a LKX LIoyd universaI IesIing machine AMETEK - France)
aI a crosshead speed oI 0.8 mm min . Shear bond sIrengIh
vaIues were anaIyzed by Ihe non-parameIric KruskaI WaI-
Iis IesI IoIIowed by a comparison 2 by 2 oI Ihe diIIerenI
baIches wiIh Ihe Cames HoweII IesI. The signicance IeveI
was xed aI p 0.05.
3. kcsults and discussion
J.1. Synthcsis, solubility unJ uciJity oj thc monomcrs
Phosphonic acid 1 was synIhesized in ve sIeps sIarIing
Irom 5-bromopenIanoI Scheme 1). The phosphonaIe 5
was easiIy prepared viu a MickaeIis-Arbusov reacIion con-
ducIed wiIh proIecIed bromoaIkane 4 and IrieIhyIphosph-
iIe. KeacIion oI aceIaI 5 wiIh AmberIysI H-15, in meIhanoI
aI 45 C Ior 1 h, aIIorded hydroxyphosphonaIe 6 |44|. The
monomer 7 was Ihen obIained in 80 yieId, by acyIaIion
oI hydroxyphosphonaIe 6 wiIh meIhacryIic anhydride, in
Ihe presence oI IrieIhyIamine and a caIaIyIic amounI oI
Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0 J2J
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
DMAP. FinaIIy, deaIkyIaIion oI Ihe phosphonic esIer Iunc-
Iion was perIormed by reacIing Ihe phosphonaIe 7 wiIh
an excess oI bromoIrimeIhyIsiIane TMSBr), IoIIowed by
meIhanoIysis |45|. By Ihis way, Ihe acidic monomer 1
was isoIaIed in exceIIenI yieId 96).
A convenienI way Io prepare bisphosphonic acid 2 is
depicIed in Scheme 2. PhosphonaIe 5 was rsI IreaIed wiIh
LDA and condensed wiIh dieIhyI chIorophosphaIe |46|. The
desired bisphosphonaIe 8 was isoIaIed in 72 yieId aIIer
ash chromaIography. The monomer 2 was naIIy
obIained as previousIy described meIhanoIysis oI Ihe ace-
IaI 8, acyIaIion and deaIkyIaIion oI Ihe phosphonaIe
groups).
The diuoromeIhyIphosphonic acid 3 was prepared in
ve sIeps sIarIing Irom Ihe diisopropyI 1-meIhyIsuIIanyI-
1,1-diuoromeIhyI phosphonaIe 11 |J7|. The key sIep
invoIves Ihe ring-opening reacIion oI THF by a non-
HCFC-based source oI diisopropyI phosphonodiuorome-
IhyIIiIhium Scheme J). This carbanion was rsI Iormed
in situ by a IhiaphiIic addiIion oI tcrt-buIyIIiIhium onIo
Ihe suIde 11 and reacIed wiIh a THF soIuIion oI BF -
EI O Io aIIord Ihe corresponding aIcohoI 12 in 71 yieId
|47|. AIIer reacIion wiIh meIhacryIoyI chIoride, Ihe mono-
mer 13 was isoIaIed in 79 yieId. DeaIkyIaIion oI Ihe phos-
phonaIe groups by reacIion wiIh bromoIrimeIhysiIane,
IoIIowed by meIhanoIysis, Ied Io Ihe desired acidic mono-
mer 3 in 65 yieId.
The sIrucIures oI acidic monomers 1-3 were con-
rmed by H NMK, C NMK, P NMK and HKMS. The
H NMK specIra oI monomers 1-3 are reporIed on Figs.
2-4.
The compIeIe disappearance oI Ihe characIerisIic sig-
naIs oI Ihe eIhyI groups IripIeI aI around 1.J0 ppm and
muIIipIeI aI around 4.00-4.15 ppm) oI Ihe phosphonaIes
7 and 9 as weII as oI Ihe isopropyI groups Iwo doubIeIs
aI 1.J0 and 1.J1 ppm and a muIIipIeI aI 4.76-4.9J ppm)
oI Ihe monomer 13 aIIesI IhaI Ihe deproIecIion is IoIaI.
For exampIe, monomer 2 is characIerized by Ihree meIhy-
Iene groups aI 1.J8-1.69 ppm m), a meIhyI group aI
1.69 ppm s), a meIhane group aI 2.11 ppm II) and a
meIhyIene group aI J.96 ppm I). The proIons oI Ihe meIh-
acryIaIe group are idenIied by Ihe presence oI Iwo peaks
aI 5.46-5.47 m) and 5.88 ppm s).
The soIubiIiIy oI Ihe new monomers 1-3 was aIso inves-
IigaIed as shown in TabIe 2. AII acidic monomers are soIu-
bIe in waIer and meIhanoI. However, Ihey are insoIubIe in
THF, aceIone and dieIhyI eIher. Monomers 1-3 are aIso
soIubIe in eIhanoI, a commonIy used co-soIvenI in denIaI
IormuIaIions.
AcidiIy oI monomers 1-3 was invesIigaIed. Hence, pH
vaIues oI waIerjeIhanoI 1:1, vjv) soIuIions conIaining
20 wI. oI acidic monomers were measured using a pH
gIass eIecIrode caIibraIed wiIh aqueous buIIers. The vaIues
reporIed in TabIe J conrm IhaI Ihese monomers wiII be
abIe Io eIch denIaI Iissues.
J.z. lntcruction oj thc monomcrs with hyJroxyuputitc
The inIeracIion oI Ihe new monomers 1-3 wiIh HAp
was sIudied according Io a proIocoI described in IiIeraIure
|41|. In Ihis sIudy, Ihe abiIiIy oI Ihe monomers Io inIeracI
wiIh HAp, wiIhouI Iaking inIo accounI iIs demineraIiza-
Iion, was invesIigaIed. ThereIore, Ihe sampIes were pre-
pared in an eIhanoI soIuIion. Indeed, since HAp parIicIes
presenI a Iow soIubiIiIy in eIhanoI, Iheir demineraIizaIion
is noI expecIed Io Iake pIace. KesuIIs oI Ihis sIudy are given
on Fig. 5.
Schcmc 1. SynIhesis oI acidic monomer 1.
J24 Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
In addiIion Io Ihe peak corresponding Io HAp 2.6 ppm),
Ihe P CP-MAS NMK specIrum oI HAp-1, HAp-2 and HAp-
3 show a broad signaI aI respecIiveIy JJ.0 ppm, 2J.0 ppm
and 6.50 ppm. These broad peaks shouId be assigned Io
Ihe monomers 1-3 adsorbed Io HAp. The deconvoIuIed
P CP-MAS NMK specIrum oI monomer 3 showed Iwo
oIher species which can be assigned Io proIonaIed species
such as HPO
2
4
or HPO
4
.
The addiIionaI signaIs observed on Ihe specIra HAp-1,
HAp-2 and HAp-3 aIIesI IhaI Ihe synIhesized monomers
are abIe Io inIeracI chemicaIIy wiIh HAp. The use oI such
monomers in SEAs shouId IhereIore increase Ihe Iong-Ierm
sIabiIiIy oI Ihe bond.
J.J. Photopolymcrizutions
To compare Iheir reacIiviIies, acidic monomers 1-3
were copoIymerized wiIh N,N -dieIhyI-1,J-bisacryIami-
do)propane DEBAAP). DEBAAP is a crossIinking monomer
commonIy used in some commerciaI IormuIaIions Irom
IvocIar VivadenI AC. Each monomer was added aI
10 moI Io DEBAAP. AII phoIopoIymerizaIions were per-
Iormed under Ihe same condiIions as described in SecIion
2). Figs. 6 and 7 respecIiveIy show Ihe doubIe bond conver-
sions DBCs) and Ihe poIymerizaIion raIe k ) as a IuncIion
oI Iime.
The resuIIs show IhaI Ihe mixIures conIaining Ihe
acidic monomers 1-3 are signicanIIy more reacIive Ihan
DEBAAP aIone. Indeed, Ihe maximum raIe oI poIymeriza-
Iion k ) is signicanIIy higher Ior Ihe copoIymeriza-
Iions oI DEBAAPj1-3 0.025 s , 0.0J6 s and 0.026 s
respecIiveIy) Ihan Ior Ihe homopoIymerizaIion oI DEBAAP
0.01J s ) Fig. 7). Moreover, Ihe k are reached Ior
shorIer irradiaIion Iimes regarding Ihe acidic mixIures
Fig. 6). The incorporaIion oI acidic monomers 1-3 in DE-
BAAP aIso resuIIs in a signicanI increase oI Ihe DBCs.
Schcmc 2. SynIhesis oI Ihe acidic monomer 2.
Schcmc 3. SynIhesis oI Ihe acidic monomer 3.
Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0 J25
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
lig. 2. H NMK specIrum oI phosphonic acid 1.
lig. 3. H NMK specIrum oI bisphosphonic acid 2.
J26 Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
AIIhough a 40 DBC is reached aIIer Ihe homopoIymeriza-
Iion oI DEBAAP, 48-56 DBCs are obIained in Ihe case oI
Ihe mixIures DEBAAPj1-3 Fig. 6). SimiIar resuIIs were ob-
served in a previous work Irom our group |25|. We demon-
sIraIed IhaI Ihe incorporaIion oI some bisphosphonic acid
monomers Io DEBAAP resuIIed in a signicanI increase oI
reacIiviIy in phoIopoIymerizaIion. UnIorIunaIeIy, Ihe rea-
son oI such a phenomenon has noI been IoIaIIy cIaried.
However, Ihe auIhors Ihink IhaI Ihese resuIIs couId be par-
IiaIIy due Io hydrogen bonding induced by Ihe acidic
groups. Indeed, iI is weII-known IhaI Ihis parameIer aIIecIs
Ihe sysIem mobiIiIy and organizaIion during poIymeriza-
Iion. Hence, higher raIes oI poIymerizaIion are reached,
due Io mobiIiIy resIricIions which inhibiI IerminaIion
|48|. Moreover, iI has been shown IhaI monomers capabIe
oI hydrogen bonding behave parIIy Iike muIIiIuncIionaI
monomers because Ihey are dynamicaIIy non-covaIenIIy
connecIed |48|. Hydrogen bonding mighI aIso increase
Ihe propagaIion raIe consIanI Ihanks Io a pre-organizaIion
oI Ihe monomers |49|. This behavior was previousIy ob-
served wiIh oIhers simiIar monomers buI reasons are noI
dened and are currenIIy under invesIigaIion.
In Ihe IiIeraIure, one can nd IhaI Ihe poIariIy oI Ihe
synIhesized acidic monomers couId aIso Iead Io an in-
crease oI reacIiviIy. Indeed, according Io ]ansen eI aI.
|49|, monomers presenIing a high dipoIe momenI are more
reacIive in phoIopoIymerizaIion. Even iI Ihe expIanaIion oI
such a reIaIionship has noI IoIaIIy been eIucidaIed, a direcI
correIaIion beIween Ihe BoIIzmann-averaged dipoIe mo-
menI and Ihe maximum raIe oI poIymerizaIion has been
Iound |49|. However, iI has Io be specied IhaI in a recenI
sIudy, KiIanbi eI aI. |50| Iound no monoIiIhic correIaIions
oI monomer reacIiviIy Io moIecuIar dipoIe. The reasons
oI such diIIerences in reacIiviIy are currenIIy under
invesIigaIion.
These resuIIs aIso demonsIraIe IhaI bisphosphonic acid
2 is signicanIIy more reacIive Ihan acidic monomers 1
and 3. This Irend shows IhaI Ihe higher Ihe concenIraIion
in phosphonic acid group, Ihe higher Ihe reacIiviIy. This
may be parIiaIIy due Io Ihe higher capaciIy oI Ihe bisphos-
phonic acid Io Iorm hydrogen bonding.
We have demonsIraIed IhaI monomers 1-3 are abIe Io
inIeracI eIcienIIy wiIh HAp and are highIy reacIive in
copoIymerizaIion wiIh DEBAAP. ThereIore, Ihey are exceI-
IenI candidaIes Io enIer an adhesive IormuIaIion. The IasI
parI oI Ihis work deaIs wiIh Ihe preparaIion oI denIaI prim-
ers based on monomers 1-3.
lig. 4. H NMK specIrum oI diuoromeIhyIphosphonic acid 3.
Tablc 2
SoIubiIiIies oI acid monomers.
H O MeOH EIOH THF AceIone EI O
1
2
J
Tablc 3
pH-vaIue oI 20 wI. waIerjeIhanoI 1:1, vjv) soIuIions oI acid monomers.
Monomer 1 2 J
pH-vaIue 2.14 1.76 1.94
Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0 J27
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
J.4. /Jhcsivc propcrtics
In order Io invesIigaIe Ihe poIenIiaI oI Ihe acidic mono-
mers 1-3 in adhesive IormuIaIions, Iwo-sIep seII-eIch
adhesives 2-SEAs) were deveIoped. 2-SEAs consisI in Ihe
combinaIion oI a primer acidic aqueous soIuIion) and a
hydrophobic resin. Hence, we deveIoped Ihe new 2-SEAs
primers P1-PJ based on Ihe acidic monomers 1-3 TabIe
4). These primers were IormuIaIed according Io composi-
Iions described in previous papers Irom our group |25,42|.
Each primer conIains an acidic monomer, a cross-Iinking
co-monomer N,N -dieIhyI-1,J-bisacryIamido)propane:
DEBAAP), waIer, eIhanoI as a co-soIvenI, a phoIoiniIiaIor
|camphorquinone CQ)|, a co-iniIiaIor |eIhyI 4-dimeIhyI-
amino)benzoaIe EDAB)| and a sIabiIizer |2,6-di-tcrt-bu-
IyI-4-meIhyIphenoI BHT)|.
lig. 5. P CP-MAS NMK specIra oI HAp and HApjmonomers 1-3.
lig. 6. DoubIe bond conversion DBC) as a IuncIion oI Iime.
lig. 7. PoIymerizaIion raIe k ) as a IuncIion oI Iime.
J28 Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
To compare adhesive oI Ihe acidic monomers 1-3, aII
componenIs are inIroduced in Ihe same moIar raIio. Each
primer, coupIed wiIh Ihe AdheSE bonding resin, has been
used Io achieve a bond beIween a denIaI composiIe
Z100, J M) and denIin. AIIer sIoring Ihe sampIes in waIer
aI J7 C during 24 h, denIin shear bond sIrengIh has been
measured. Mean shear bond sIrengIh vaIues mean SBS)
as weII as sIandard deviaIions S.D.) are reporIed in TabIe
5.
To compare Ihe eIciency oI Ihe primers 1-J wiIh com-
merciaIIy avaiIabIe ones, we have aIso measured SBS ob-
Iained wiIh Ihe AdheSE primer. KesuIIs show IhaI Ihe
adhesives based on primers 1-J are abIe Io generaIe a
sIrong bond beIween denIin and a denIaI composiIe.
Moreover, Ihis sIudy cIearIy demonsIraIes Ihe inuence
oI Ihe naIure oI Ihe acidic IuncIion oI Ihe monomers 1-3
on denIin adhesion. Indeed, primers based on Ihe bisphos-
phonic acid 2 and Ihe diuoromeIhyIphosphonic acid 3
provide signicanIIy higher SBS p < 0.05) Ihan Ihe primer
based on Ihe corresponding phosphonic derivaIive 1. This
couId be parIiaIIy aIIribuIed Io higher inIeracIions oI Ihe
acidic monomers 2 and 3 Io denIaI Iissues, due Io Iheir
exceIIenI cheIaIing properIies wiIh caIcium ions. More-
over, Ihe higher reacIiviIy oI bisphosphonic acid 2 com-
pared Io phosphonic acid 1 couId aIso parIicipaIe in Ihe
signicanI diIIerences oI SBS observed beIween primer
P1 and primer P2. Indeed, aIIer curing, a higher DBC mighI
be obIained Ior Ihe adhesive based on primer P2 according
Io our phoIopoIymerizaIion sIudy, which wouId resuII in
an increase oI Ihe SBS. OIher IacIors, Iike Ihe hydrophiIic
characIer impacIing Ihe amounI oI remaining soIvenI
aIIer Ihe drying sIep) oI Ihe resin, Ihe acidiIy oI Ihe primer
modicaIion oI Ihe eIching paIIern and oI Ihe amounI oI
remaining hydroxyapaIiIe crysIaIs in Ihe hybrid Iayer) or
Ihe weIIing properIies oI Ihe primer shouId aIso have a
greaI inuence on Ihe eIciency oI Ihe IesIed adhesives.
II shouId aIso be noIed IhaI Ihe primers P2 and PJ are sig-
nicanIIy more eIcienI p < 0.05) Ihan Ihe commerciaI
one AdheSE primer). ThereIore, Ihe acidic monomers 2
and 3 appear Io be greaI candidaIes Io enIer denIaI adhe-
sive IormuIaIions.
4. Conclusions
In summary, Ihe new phosphonic 1, bisphosphonic 2
and diuoromeIhyIphosphonic 3 acids were successIuIIy
prepared Ior denIaI appIicaIions. II was demonsIraIed IhaI
Ihey are abIe Io eIcienIIy adhere Io HAp. The phoIopoIy-
merizaIion behavior oI Ihese monomers wiIh DEBAAP
was invesIigaIed wiIh phoIo-DSC. II was shown IhaI Ihe
mixIures DEBAAPj1-3 are signicanIIy more reacIive Ihan
DEBAAP aIone. Besides, bisphosphonic acid 2 was proved
Io be signicanIIy more reacIive Ihan boIh phosphonic
acid 1 and diuorophosphonic acid 3. These resuIIs were
mainIy aIIribuIed Io Ihe IormaIion oI hydrogen bonds
aIIecIing Ihe sysIem mobiIiIy and organizaIion during
poIymerizaIion. The adhesive properIies oI monomers 1-
3 were aIso sIudied. 2-SEA primers based on Ihese new
acidic monomers were deveIoped. DenIin shear bond
sIrengIh measuremenIs have shown IhaI primers based
on Ihe bisphosphonic acid 2 and Ihe diuoromeIhyIphos-
phonic acid 3 are signicanIIy more eIcienI Ihan Ihe
one based on Ihe corresponding phosphonic acid 1. This
indicaIes IhaI Ihe naIure oI Ihe acidic group has a greaI
inuence on denIin adhesion. Moreover, Ihe use oI adhe-
sives based on monomers 2 and 3 were Iound Io Iead Io
signicanIIy higher SBS Ihan when empIoying a commer-
ciaI IormuIaIion AdheSE). ThereIore, Ihese Iwo monomers
appear Io be greaI candidaIes Io enIer adhesive IormuIa-
Iions. Due Io Iheir cheIaIing properIies, bisphosphonic
and diuorophosphonic acids shouId aIso improve denIin
adhesion durabiIiIy. Comparisons oI boIh permeabiIiIy
and aging oI Ihe various adhesives based on Ihese new
acidic monomers are under invesIigaIion.
Acknowlcdgcmcnts
This paper is dedicaIed Io Ihe memory oI ProIessor Mi-
cheI Degrange, who unIorIunaIeIy passed away during iIs
wriIing.
This work has been perIormed wiIhin Ihe ''PUNCHOrga''
PIe UniversiIaire de Chimie Organique) and Ihe ''KMPP''
Keseau MaIeriaux, PoIymeres, PIasIurgie) inIerregionaI
neIworks. The auIhors graIeIuIIy acknowIedge Ihe ''Min-
isIere de Ia Kecherche eI des NouveIIes TechnoIogies,''
CNKS CenIre NaIionaI de Ia Kecherche ScienIique), Ihe
''Kegion Basse-Normandie'' and Ihe European Union FED-
EK Iunding) Ior nanciaI supporI. The auIhors are aIso
graIeIuI Io B. Kigaud Ior Ihe P CP-MAS NMK specIroscopy
anaIyses.
kclcrcnccs
|1| Moszner N, SaIz U. KecenI deveIopmenIs oI new componenIs Ior
denIaI adhesives and composiIes. MacromoI MaIer Eng
2007;292:245-71.
|2| Tyas M], Burrow MF. Adhesive resIoraIive maIeriaIs: a review. AusI
DenI ] 2004;49:112-21.
Tablc 5
DenIin shear bond sIrengIh measuremenIs SBS) using primers 1-J and
AdheSE primer.
Primer Mean SBS MPa) S.D. MPa)
AdheSE primer 14.5 J.6
Primer 1 15.4 5.5
Primer 2 19.7 5.2
Primer J 20.6 2.1
Tablc 4
ComposiIion oI Ihe primers.
Primer P1 wI.) Primer P2 wI.) Primer PJ wI.)
1 19.66 5 moI) - -
2 - 24.67 5 moI) -
3 - - 21.98 5 moI)
DEBAAP J9.71 10 moI) J7.2J 10 moI) J8.56 10 moI)
WaIer 15.88 14.89 15.42
EIhanoI 2J.8J 22.J4 2J.14
CQ 0.40 0.J7 0.J9
EDAB 0.50 0.47 0.48
BHT 0.0J 0.0J 0.0J
Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0 J29
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)
|J| Van Meerbeek B, Vargas M, Inoue S, Yoshida Y, Peumans M,
LambrechIs P, eI aI. Adhesives and cemenIs Io promoIe
preservaIion denIisIry. Oper DenI 2001;6SuppI):119-44.
|4| Van LanduyI KL, SnauwaerI ], De Munck ], Peumans M, Yoshida Y,
PoiIevin A, eI aI. SysIemaIic review oI Ihe chemicaI composiIion oI
conIemporary denIaI adhesives. BiomaIeriaIs 2007;28:J757-85.
|5| Moszner N, SaIz U, Zimmermann. ChemicaI aspecIs oI seII-eIching
enameI-denIin adhesives: a sysIemaIic review. ] DenI MaIer
2005;21:895-910.
|6| Nakabayashi N, PashIey DH. HybridisaIion oI denIaI hard
Iissues. Tokyo: QuinIessence PubIishing; 1998.
|7| Peumans M, KanumiIIi P, De Munck ], Van LanduyI K, LambrechIs P,
Van Meerbeek B. CIinicaI eIIecIiveness oI conIemporary adhesives: a
sysIemaIic review oI currenI cIinicaI IriaIs. DenI MaIer
2005;21:864-81.
|8| Bresci L, Mazzoni A, Kuggeri A, Cadenaro M, Di Lenarda K, De SIeIano
Dorigo E. DenIaI adhesion review: aging and sIabiIiIy oI Ihe bonded
inIerIace. DenI MaIer 2008;24:90-101.
|9| De Munck ], Van LanduyI K, Peumans M, PoiIevin A, LambrechIs P,
BraemM, eI aI. A criIicaI review oI Ihe durabiIiIy oI adhesion Io IooIh
Iissue: meIhods and resuIIs. ] DenI Kes 2005;84:118-J2.
|10| HashimoIo M. A review - MicromorphoIogicaI evidence oI
degradaIion in resin-denIin bonds and poIenIiaI prevenIionaI
soIuIions. ] Biomed MaI Kes B 2010;92B:268-80.
|11| HashimoIo M, Ohno H, Sano H, Kaga M, Oguchi H. In viIro
degradaIion oI resin-denIin bonds anaIyzed by microIensiIe bond
IesI, scanning and Iransmission eIecIron microscopy. BiomaIeriaIs
200J;24:J795-80J.
|12| PashIey DH, Tay FK, Yiu CKY, HashimoIo M, Breschi L, CarvaIho KM,
eI aI. CoIIagen degradaIion by hosI-derived enzymes during aging. ]
DenI Kes 2004;8J:216-21.
|1J| Tay FK, PashIey DH, Loushine K], WeIIer KN, MonIiceIIi F, Osorio K.
SeII-eIching adhesives increase coIIagenoIyIic acIiviIy in radicuIar
denIin. ] Endod 2006;J2:862-8.
|14| NishiIani Y, Yoshiyama M, Wadgaonkar B, Breschi L, ManneIIo F,
Mazzoni CarvaIho KM, eI aI. AcIivaIion oI geIaIinoIyIicj
coIIagenoIyIic acIiviIy in denIin by seII-eIching adhesives. Eur ]
OraI Sci 2006;114:160-6.
|15| TezvergiI-MuIIuay A, Agee KA, Hoshika T, Tay FK, PashIey DH. The
inhibiIory eIIecI oI poIyvinyIphosphonic acid on IuncIionaI maIrix
meIaIIoproIeinase acIiviIies in human demineraIized denIin. AcIa
BiomaIer 2010;610):41J6-42.
|16| Yoshida Y, Nagakane K, Fukuda K, Nakayama Y, Okazaki M, ShinIani
H, eI aI. ComparaIive sIudy on adhesive perIormance oI IuncIionaI
monomers. ] DenI Kes 2004;8J:454-8.
|17| Yoshida Y, Van Meerbeek B, Nakayama Y, Yoshioka M, SnauwaerI ],
Abe Y, eI aI. Adhesion Io and decaIcicaIion oI hydroxyapaIiIe by
carboxyIic acids. ] DenI Kes 2001;80:1565-9.
|18| Fu B, Sun X, Qian W, Shen Y, Chen K, Hannig M. Evidence oI chemicaI
bonding Io hydroxyapaIiIe by phosphoric acid esIers. BiomaIeriaIs
2005;26:5104-10.
|19| Inoue S, Koshiro K, Yoshida Y, De Munck ], Nagakane K, Suzuki K,
eI aI. HydroIyIic sIabiIiIy oI seII-eIch adhesives bonded Io denIin. ]
DenI Kes 2005;84:1160-4.
|20| Ikemura K, Tay FK, Nishiyama N, PashIey DH, Endo T. MuIIi-purpose
bonding perIormance oI newIy synIhesized phosphonic acid
monomers. DenI MaIer ] 2006;25:566-75.
|21| Sahin C, AIbayrak AZ, BiIgici ZS, Avci D. SynIhesis and evaIuaIion oI
new denIaI monomers wiIh boIh phosphonic and carboxyIic acid
IuncIionaI groups. ] PoIym Sci A: PoIym Chem 2009;47:195J-65.
|22| Anbar M, SI. ]ohn CA. AdsorpIion oI poIyphosphonaIed poIyeIhyIene
on enameI oI IeeIh. ] DenI Kes 1971;50:778-8J.
|2J| Zeuner F, Moszner N, VIkeI T, VogeI K, Kheinberger V. SynIhesis and
denIaI aspecIs oI acryIic phosphoric and phosphonic acids.
Phosphorus, SuIIur, SiIicon 1999;144:1JJ-6.
|24| AbueIyaman AS. US paIenI 0 206 9J2 A1, JM InnovaIive ProperIies
Company; 2004.
|25| CaIeI Y, Degrange M, Le PIuarI L, Madec P-], Pham T-N, Chen F, eI aI.
SynIhesis, phoIopoIymerisaIion and adhesive properIies oI new
bisphosphonic acid monomers Ior denIaI appIicaIion. ] PoIym Sci A:
PoIym Chem 2009;47:5258-71.
|26| O'Hagan D, Kzepa HS. Some inuences oI uorine in bioorganic
chemisIry. Chem Commun 1997:645-52.
|27| KusseII KCC, Kogers M]. BisphosphonaIes: Irom Ihe IaboraIory Io Ihe
cIinic and back again. Bone 1999;25:97-106.
|28| FIeisch H. The roIe oI bisphosphonaIes in breasI cancer:
deveIopmenI oI bisphosphonaIes. BreasI Cancer Kes 2002;4:J0-4.
|29| HengsI V, Oussoren C, KisseI T, SIorm C. Bone IargeIing poIenIiaI oI
bisphosphonaIe-IargeIed Iiposomes preparaIion, characIerizaIion
and hydroxyapaIiIe binding in viIro. InI ] Pharm 2007;JJ1:224-7.
|J0| NancoIIas CH, Tang K, Phipps K], Henneman Z, CuIde S, Wu W, eI aI.
NoveI insighIs inIo acIions oI bisphosphonaIes on bone: diIIerences
in inIeracIions wiIh hydroxyapaIiIe. Bone 2006;J8:617-27.
|J1| FIeisch H. BisphosphonaIes: mechanisms oI acIion. Endocr Kev
1998;19:80-100.
|J2| SenaraIne SC, CoIsIon KW. The roIe oI bisphosphonaIes in breasI
cancer: direcI eIIecIs oI bisphosphonaIes on breasI cancer ceIIs.
BreasI Cancer Kes 2002;4:18-2J.
|JJ| Teronen O, LaiIinen M, SaIo T, Hanemaaijer K, HeikkiI P, KonIIinen
YT, eI aI. InhibiIion oI maIrix meIaIIoproIeinases by
bisphosphonaIes may in parI expIain Iheir eIIecIs in Ihe IreaImenI
oI muIIipIe myeIoma. BIood 2000;96:4006-7.
|J4| Boissier S, Ferreras M, Peyruchaud O, MagneIIo S, EbeIino FH,
CoIombeI M, eI aI. BisphosphonaIes inhibiI breasI and prosIaIe
carcinoma ceII invasion, an earIy evenI in Ihe IormaIion oI bone
meIasIases. Cancer Kes 2000;60:2949-54.
|J5| BaIdwin SW, WiIson ]D, Aube ]. KegiochemisIry in Ihe
InIramoIecuIar cycIoaddiIions oI subsIiIuIed 5-aIkenyI and 6-
aIkenyI niIrones. ] Org Chem 1985;50:44J2-9.
|J6| Moszner N, Zeuner F, Angermann ], KarI Fischer U, Kheinberger V.
Monomers Ior adhesive poIymers. MacromoI MaIer Eng
200J;288:621-8.
|J7| OzouI P, BinoI C, PommeIeI ]-C, Lequeux T. SynIheses oI hydroxy-
a,a-diuoromeIhyIphosphonaIes by oxacycIe ring-opening
reacIions. Org LeII 2004;6:J747-50.
|J8| InIernaIionaI SIandard ISO 1J779-J, ImpIanIs Ior surgery -
HydroxyapaIiIe - ParI J: ChemicaI anaIysis and characIerizaIion oI
crysIaIIiniIy and phase puriIy; 2008.
|J9| Kaynaud S, Champion E, Bernache-AssoIIanI D, LavaI ]-P.
DeIerminaIion oI caIciumjphosphorus aIomic raIio oI caIcium
phosphaIe apaIiIes using X-ray diIIracIomeIry. ] Am Ceramic Soc
2001;84:J59-66.
|40| Francova D, KickeIbick C. SynIhesis oI meIhacryIaIe-IuncIionaIized
phosphonaIes and phosphaIes wiIh Iong aIkyI-chain spacers and
Iheir seII-aggregaIion in aqueous soIuIions. MonaIsheIIe Chem
2009;140:41J-22.
|41| Fukegawa D, Hayakawa S, Yoshida Y, Suzuki K, Osaka A, Van
Meerbeek B. ChemicaI inIeracIion oI phosphoric acid esIer wiIh
hydroxyapaIiIe. ] DenI Kes 2006;8510):941-4.
|42| CaIeI Y, Degrange M, Le PIuarI L, Madec P-], Pham T -N, PicIon L.
SynIhesis, phoIopoIymerizaIion and adhesive properIies oI new
hydroIyIicaIIy sIabIe phosphonic acids Ior denIaI appIicaIions. ]
PoIym Sci A: PoIym Chem 2008;46:7074-90.
|4J| Yagci Y, ]ockusch S, Turro N]. PhoIoiniIiaIed poIymerizaIion:
advances, chaIIenges, and opporIuniIies. MacromoIecuIes
2010;4J15):6245-60.
|44| Courves ]-P, CouIhon H, SIurIz C. A new eIcienI synIhesis oI
omega-aminoaIkyIidene-1,1-bisphosphonaIe IeIraeIhyIesIers.
Phosphorus, SuIIur, SiIicon 1998;1J2:219-29.
|45| Mc Kenna CE, Higa MT, Cheung NH, Mc Kenna M-C. The IaciIe
deaIkyIaIion oI phosphonic acid diaIkyI esIers by
bromoIrimeIhyIsiIane. TeIrahedron LeII. 1977;2:155-8.
|46| DuIau C, SIurIz C. PreparaIion oI IeIraeIhyI buI-J-enyIidene-1,1-
bisphosphonaIe and sIudy oI iIs reacIiviIy as a synIhon oI IeIraeIhyI
J,4-diaminobuIyIidene-1,1-bisphosphonaIe. Phosphorus, SuIIur,
SiIicon 1992;69:9J-102.
|47| Henry-diI-QuesneI A, ToupeI L, PommeIeI ]-C, Lequeux T. A
diuorosuIde as a Freon-Iree source oI phosphonodiuoromeIhyI
carbanion. Org BiomoI Chem 200J;1:2486-91.
|48| Lee TY, Koper TM, ]ohnson ES, Cuymon CA, HoyIe CE. Inuence oI
hydrogen bonding on phoIopoIymerizaIion raIe oI hydroxyaIkyI
acryIaIes. MacromoIecuIes 2004;J7:J659-65.
|49| ]ansen ]FCA, Dias AA, Dorschu M, Coussens B. FasI monomers:
IacIors aIIecIing Ihe inherenI reacIiviIy oI acryIaIe monomers in
phoIoiniIiaIed acryIaIe poIymerizaIion. MacromoIecuIes
200J;J6:J861-7J.
|50| KiIambi H, BeckeI EK, BerchIoId KA, SIansbury ]W, Bowman CN.
Inuence oI moIecuIar dipoIe on acryIaIe reacIiviIy. PoIymer
2005;46:47J5-42.
JJ0 Y. Cutcl ct ul. / uropcun Polymcr journul 48 z01z) J18-JJ0
You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com)