Materials Research Bulletin 43 (2008) 447452 www.elsevier.

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Crystal structure and EPR study of Mn-doped b-tricalcium phosphate

I. Mayer a,*, S. Cohen a, S. Gdalya a, O. Burghaus b, D. Reinen b
b a Department of Inorganic and Analytical Chemistry, Hebrew University, Jerusalem 91904, Israel r Materialwissenschaften, Philipps Universita t, 35032 Marburg, Germany Fachbereich Chemie and Zentrum fu

Received 4 September 2006; received in revised form 27 December 2006; accepted 19 February 2007 Available online 23 February 2007

Abstract Mn-doped b-tricalcium phosphate was prepared by solid state reaction at 1100 8C. The crystal structure of Ca2.85Mn0.15(PO4)2, was determined by single crystal X-ray diffraction and found to be rhombohedral, R3c. Unit cell parameters are: a = 10.3419(3); (hexagonal setting), Z = 21. Structure renement data show that from the ve Ca positions the Ca(4) site is only half c = 37.025(3) A lled and that the Mn2+ ions occupy the hexacoordinated Ca(5) site solely. EPR spectroscopy reveals that manganese in solid solutions Ca3xMnx(PO4)2 (x = 0.1; 0.28; 0.6) is divalent and supports the structure renement results that Mn occupies the Ca(5) site with a geometry very near to a regular octahedron. # 2007 Elsevier Ltd. All rights reserved.
Keyword : A. Inorganic compounds; D. Crystal structure; D. Electronic paramagnetic resonance (EPR)

1. Introduction b-Tricalcium phosphate (TCP) is one of the most important biomaterials because it is an excellent biocompatible and osteoconductive compound. It is widely used in dentistry and orthopedics to repair bone defects and as coating material for metallic implants. TCP is found to be even more advantageous than HA [13]. TCP crystallizes in a rhombohedral structure and is isomorphous with the mineral whitlockite which contains small amounts of Mg and Fe and is also studied for this purpose when doped with monovalent Li, Na and K [4] and particularly divalent Mg, Zn and Cd ions [57]. Previously [8,9] HA and TCP samples containing Mn2+ were prepared and studied. The motivation for the addition of Mn2+ ions was due to the fact that divalent Mn2+ has been linked to the activation of integrins [10], a family of receptors which mediate cellular interactions with extracellular matrix and cell surface ligands. In the presence of Mn2+ ions the ligand afnity of integrin increases and cell adhesion is promoted. High temperature treatment of precipitated HA samples has shown that samples with low carbonate content transform partially or completely to TCP. TCP with Mn was also prepared by solid state reaction with the general composition Ca3xMnx(PO4)2. EPR spectroscopy has proved that manganese is divalent in the heated HA samples and was found to occupy Ca2+ sites in b-TCP as Mn2+ as well [9]. In a further study [11] human osteoblasts were cultured on the surfaces of Mn-doped HA

* Corresponding author. Tel.: +972 2 6585214; fax: +972 2 6585319. E-mail address: isaacm@vms.huji.ac.il (I. Mayer). 0025-5408/$ see front matter # 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.materresbull.2007.02.031

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thin lms deposited on etched Ti substrates. Biological tests demonstrated that the Mn-doped HA coatings favour osteoblasts proliferation, activation of their metabolism and differentiation. The crystal structure of TCP was determined in the past for Ca3(PO4)2 [12] and for Ca3(PO4)2 with Ca2+ partly substituted by Mg [13]. As was pointed out above, Mn-doped TCP might be of biological importance because of its advantage in use for coating metallic implants. The knowledge of the structural properties of Mn-doped TCP, not available until now, is therefore important for their full understanding and characterization. The present work was initiated to obtain such data by single crystal structural study and EPR characterization of Mn-doped b-TCP. 2. Experimental 2.1. Synthesis of b-TCP by high temperature solid state reaction Stoichiometric amounts of CaCO3, (NH4)2HPO4 and Mn(NO3)2 were thoroughly crushed and mixed in an agate mortar and heated in an alumina crucible at 300 8C for 3 h, recrushed, mixed and then heated at 1100 8C overnight. Following this, the samples were cooled slowly with a rate of 1 8C/min. In one of these processes several small single crystals were obtained. 2.2. Single crystal XRD A single crystal of Mn-doped b-TCP was attached to a glass ber, with epoxy glue, and transferred to a Bruker SMART APEX CCD X-ray diffractometer system equipped with a graphite monochromator. The system was controlled by a Pentium-based PC running the SMART software package [14]. Data were collected at room ). Immediately after collection, the raw data frames were temperature using Mo Ka radiation (l = 0.71073 A transferred to a second PC computer for integration and reduction by the SAINT program package [15]. The structure was solved and rened by the SHELXTL software package [16]. 2.3. EPR spectroscopy EPR measurements were performed at X-, Q- and V-band frequencies and 298 K with a Bruker ESP-300 spectrometer; the V-band accessory is self constructed. 3. Results Crystallographic structure renement data for Mn-doped b-TCP are presented in Table 1. The nal atomic coordinates, as well as selected bond distances and angles are listed in Tables 2 and 3, respectively. Further details of the crystal structure investigation can be obtained from: Fachinformationszentrum Karlsruhe, D76344 Eggenstein-Leopoldshafen (Germany), under the deposition No. CSD-416803. 4. Discussion b-Ca3(PO4)2 and Mg containing b-Ca3(PO4)2 crystallize in a rhomobohedral unit cell with space group R3c. In pure b-Ca3(PO4)2 [7] Ca2+ ions are distributed between ve crystallographic sites. Four of them are completely lled, the Ca(4) site is only half occupied. The environment of the cations is such that Ca(1), Ca(2) are seven and Ca(3) eight coordinated to oxygen atoms. Ca(4) is six coordinated, similar to Ca(5), whose environment is nearly octahedral, however, with only a small axial (trigonal) distortion component. As can be seen from Table 2, the substituted Mn2+ ions occupy the Ca(5) site only. Several trials of the occupancy factor of the Ca(4) and Ca(5) sites were made in order to prove this: (1) occupation of half of the Ca(4) and the Ca(5) sites by Ca (without Mn); (2) Mn only on the Ca(4) site; (3) Mn randomly distributed between the Ca(4) and Ca(5) sites; (4) Mn exclusively on the Ca(5) sites. Renement of the structure has shown that only in the last case the occupancy factor of the Ca(4) and Ca(5) sites as well as the R factor were obtained with reasonably good values. Mean CaO distances summarized in Table 4 show that the CaO bond lengths on the Ca(5) site of b-TCP are unusually

I. Mayer et al. / Materials Research Bulletin 43 (2008) 447452 Table 1 Crystal data and structure renement for Mn-doped b-TCP Empirical formula Formula weight Temperature Wavelength Crystal system Space group Unit cell dimensions Ca2.85 Mn0.15 O8 P2 312.30 295(1) K 0.71073 A Rhombohedral R3c , a = 908 a = 10.3419(3) A , b = 908 b = 10.3419 A , g = 1208 c = 37.025(3) A 3 3429.4(3) A 21 3.176 Mg/m3 3.182 mm1 3249 0.08 mm 0.07 mm 0.04 mm 2.5326.998 13 h 13, 13 k 13, 47 11775 1676 [R(int) = 0.0350] 100.0% None 0.8833 and 0.7849 Full-matrix least-squares on F2 1676/1/142 1.143 R1 = 0.0272, wR2 = 0.0665 R1 = 0.0277, wR2 = 0.0667 0.00(19) 3 0.399 and 0.394 e A

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Volume Z Density (calculated) Absorption coefcient F(0 0 0) Crystal size Theta range for data collection Index ranges Reections collected Independent reections Completeness to theta = 26.998 Absorption correction Max. and min. transmission Renement method Data/restraints/parameters Goodness-of-t on F2 Final R indices [I > 2sigma(I)] R indices (all data) Absolute structure parameter Largest diff. peak and hole

47

Table 2 2 103) for Mn-doped b-TCP Atomic coordinatesa and equivalent isotropic displacement parameters (A x Ca(1) Ca(2) Ca(3) Ca(4)b Ca[Mn](5) P(1) P(2) P(3) O(1) O(2) O(3) O(4) O(5) O(6) O(7) O(8) O(9) O(10) 0.7266(1) 0.6177(1) 0.7305(1) 1 1 1 0.6876(1) 0.6553(1) 0.7372(3) 0.7234(3) 0.7579(4) 0.5140(3) 0.6023(3) 0.5785(3) 0.8240(3) 0.6244(3) 1.1384(3) 1 y 0.8688(1) 0.7935(1) 0.8764(1) 1 1 1 0.8254(1) 0.8067(1) 0.8205(3) 0.7221(3) 0.9849(3) 0.7544(3) 0.6462(3) 0.8791(3) 0.9014(3) 0.8044(3) 0.9954(4) 1 z 1.1656(1) 0.9649(1) 1.0584(1) 0.9197(1) 0.7340(1) 0.9999(1) 0.8682(1) 0.7647(1) 0.9069(1) 0.8456(1) 0.8543(1) 0.8650(1) 0.7768(1) 0.7845(1) 0.7723(1) 0.7243(1) 0.9864(1) 1.0409(1) U(eq) 8(1) 9(1) 13(1) 31(1) 8(1) 8(1) 8(1) 8(1) 16(1) 11(1) 18(1) 15(1) 14(1) 17(1) 13(1) 12(1) 16(1) 15(1)

U(eq) is dened as one-third of the trace of the orthogonalized Uij tensor. a Point symmetries general, with the exception of Ca(4), Ca[Mn](5) and O(10) having trigonal symmetry. b Half occupied position.

450 Table 3 ) Selected bond distances and angles (A Ca(1)O(6)#1 Ca(1)O(9)#3 Ca(1)O(4)#1 Ca(1)O(4)#4 Ca(2)O(9)#6 Ca(2)O(7)#5 Ca(2)O(3)#7 Ca(2)O(5)#5 Ca(3)O(2)#5 Ca(3)O(10) Ca(3)O(8)#4 Ca(3)O(1)#5 Ca(4)O(1)#8 Ca(4)O(9) Ca(4)O(9)#8 Ca[Mn](5)O(4)#10 Ca[Mn](5)O(7) Ca[Mn](5)O(7)#8 P(1)O(9) P(1)O(9)#8 P(2)O(1) P(2)O(4) P(3)O(8) P(3)O(7) O(10)P(1)O(9)#8 O(9)P(1)O(9)#6 O(9)P(1)O(9)#8 O(3)P(2)O(1) O(1)P(2)O(2) O(1)P(2)O(4) O(6)P(3)O(8) O(8)P(3)O(5) O(8)P(3)O(7)

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2.307(3) 2.434(3) 2.467(3) 2.484(3) 2.348(3) 2.418(3) 2.438(3) 2.642(3) 2.403(3) 2.502(2) 2.554(3) 2.630(3) 2.452(3) 2.868(4) 2.868(4) 2.088(3) 2.124(3) 2.124(3) 1.539(3) 1.539(3) 1.531(3) 1.568(3) 1.529(3) 1.541(3) 108.9(1) 110.0(1) 110.0(1) 111.5(2) 106.6(2) 112.3(2) 108.9(2) 108.1(2) 110.5(2)

Ca(1)O(8)#2 Ca(1)O(5)#4 Ca(1)O(2)#4 Ca(1)O(3)#1 Ca(2)O(2)#5 Ca(2)O(1) Ca(2)O(7)#7 Ca(2)O(6)#7 Ca(3)O(5)#4 Ca(3)O(8)#1 Ca(3)O(3)#7 Ca(3)O(6)#1 Ca(4)O(1)#6 Ca(4)O(1) Ca(4)O(9)#6 Ca[Mn](5)O(4)#9 Ca[Mn](5)O(4)#11 Ca[Mn](5)O(7)#6 P(1)O(10) P(1)O(9)#6 P(2)O(3) P(2)O(2) P(3)O(6) P(3)O(5) O(10)P(1)O(9) O(10)P(1)O(9)#8 O(9)#6P(1)O(9)#8 O(3)P(2)O(2) O(3)P(2)O(4) O(2)P(2)O(4) O(6)P(3)O(5) O(6)P(3)O(7) O(5)P(3)O(7)

2.358(3) 2.456(3) 2.473(3) 2.838(3) 2.363(3) 2.422(3) 2.439(3) 2.697(3) 2.377(3) 2.482(3) 2.518(3) 2.617(3) 2.452(3) 2.452(3) 2.868(4) 2.088(3) 2.088(3) 2.124(3) 1.519(5) 1.539(3) 1.522(3) 1.541(3) 1.524(3) 1.532(3) 108.9(1) 108.9(1) 110.0(1) 114.7(2) 107.2(2) 104.4(2) 113.6(2) 107.6(2) 108.2(2)

Symmetry transformations used to generate equivalent atoms: (#1) y + 5/3, x y + 4/3, z + 1/3; (#2) x, x y + 1, z + 1/2; (#3) x 2/3, x y + 2/ 3, z + 1/6; (#4) x + y + 2/3, x + 4/3, z + 1/3; (#5) y + 4/3, x + 5/3, z + 1/6; (#6) x + y + 1, x + 2, z; (#7) x + y + 1/3, y 1/3, z + 1/6; (#8) y + 2, x y + 1, z; (#9) y + 5/3, x + 4/3, z 1/6; (#10) x + 2/3, x y + 4/3, z 1/6; (#11) x + y + 2/3, y + 1/3, z 1/6.

Table 4 ) in pure TCP and in Mg and Mn substituted TCP samples Mean CaO distances (A Mean x = 0a Ca(1) Ca(2) Ca(3) Ca(4) Ca(5)
a b c

x = 0.11b 2.437 2.479 2.526 2.709 2.184

x = 0.15c 2.426 2.472 2.493 2.660 2.106

x = 0.29b 2.435 2.471 2.509 2.620 2.077

2.435 2.487 2.537 2.790 2.263

Ref. [12]. Ref. [13]. Present work.

I. Mayer et al. / Materials Research Bulletin 43 (2008) 447452 Table 5 ) in pure TCP (a) and in Mg (b) and Mn (c) substituted TCP samples Minimum and maximum CaO distances (A Minimum x = 0a Ca(1) Ca(2) Ca(3) Ca(4) Ca(5)
a b c

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Maximum x = 0.11b 2.315 2.368 2.388 2.491 2.163 x = 0.15c 2.307 2.348 2.377 2.452 2.088 x = 0.29b 2.308 2.363 2.381 2.444 2.070 x = 0a 2.507 2.752 2.611 3.041 2.287 x = 0.11b 2.499 2.721 2.625 2.927 2.206 x = 0.15c 2.484 2.697 2.630 2.868 2.124 x = 0.29b 2.499 2.681 2.626 2.796 2.084

2.316 2.369 2.384 2.538 2.238

Ref. [12]. Ref. [13]. Present work.

Table 6 O Ca(5) O angles in pure TCP and in Mg and Mn substituted TCP samples O Ca(5) O (8) O(4)Ca(5)O(40 ) O(7)Ca(5)O(70 )
a b c

x = 0a 82.7 77.1

x = 0.11b 83.7 78.6

x = 0.15c 84.34 80.22

x = 0.29b 85.4 79.1

Ref. [12]. Ref. [13]. Present work.

) as compared to CaO (2.404 A ). The partial substitution (about 1/2) by Mn2+ induces a further short (2.263 A ). The full occupation (corresponding ) due to the smaller radius of Mn2+ (MnO in MnO = 2.222 A shrinking (2.106 A 2+ )as PO ) leads, in the case of Mg , to an even smaller bond length (2.077 A to the composition Ca2:714 MII 4 0:286 2 ). Simultaneously, the octahedra become more regular, as can be deduced when expected (MgO in MgO 2.107 A

Fig. 1. Q-band (33.95 GHz) and V-band (62.44 GHz, not calibrated) EPR spectrum of (for Ca2+) Mn2+ doped b-TCP, above the inset shows the half-eld signal and below, respectively (298 K). The six-line manganese hyperne splitting (A = 8.5 103 cm1) and the broad features due to the axial zero-eld splitting (D 4.5 102 cm1) are nicely seen (see Ref. [8] for details).

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Fig. 2. The X-band spectra (298 K) of b-Ca3xMnx(PO4)2 solid solutions, with (a) x = 0.1 (9.16 GHz), (b) x = 0.28 (9.14 GHz) the inset shows the second-derivative spectrum, indicating the six-line hyperne structure and (c) x = 0.6 (9.11 GHz).

looking at the distance and angle anisotropies collected in Tables 5 and 6. The mixed crystal with Mg0.11 behaves somewhat differently: here it is claimed that Mg2+ randomly distributes between the Ca(4) and Ca(5) sites. EPR spectroscopy strongly supports the structural result that Mn2+ enters the Ca(5) site of b-TCP exclusively. At lower concentrations (x 0.1) Q-band nicely reveals the six-line manganese hyperne structure in the central signal better resolved at the higher V-band frequency and the more extended broader features due to zero-eld splitting (Fig. 1). The latter is very small though, indicating that the host site geometry is very near to a regular octahedron. Furthermore the zero-eld has purely axial symmetryas has been discussed thoroughly elsewhere [10]. These results unambigously reveal, together with the bond length considerations above, that the Ca(5) position is the host site. The X-band spectra in Fig. 2 show that with increasing Mn2+ concentration dipolar interactions average out the hyperne splitting though still recognisable in the second-derivative spectrum but leaving the features due to the axial site distortion (though broadened) unchanged. This is obviously a long distance effect, because the MII(5)O6 polyhedra lie isolated in the lattice. Only, if x = 0.286 is distinctly exceeded, exchange narrowing occurs, with a collapse into one central signal. We think that this feature is brought about by direct MnOMn contacts and accordingly implies the additional occupation of Ca(1) and/or Ca(2) sites. Only these have oxygen ligand atoms with Ca(5) in common (Table 3). The EPR results are not compatible with the substitution into the Ca(4) position, however. The possibility of easy substitution of manganese(II) into b-TCP already at moderate temperatures should be the reason for the stabilization of this structure in the presence of Mn2+ with respect to the HA lattice, where smaller Ca sites with lower coordination numbers are not available. References
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