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. 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