Volume 106, Number 6, November–December 2001 Journal of Research of the National Institute of Standards and Technology [J. Res. Natl. Inst. Stand. Technol. 106, 1035–1044 (2001)] Structures of Biological Minerals in Dental Research Volume 106 Number 6 November–December 2001 Mathai Mathew and Shozo Takagi Structural features of some calcium phos- for the epitaxial, interlayered mixtures phates of biological interest are de- formed by these compounds and the in situ American Dental Association scribed. Structure of hydroxyapatite conversion of OCP to OHAp. Possible Health Foundation, (OHAp), considered as the prototype for roles of OCP in biological mineralization Paffenbarger Research Center, the inorganic component of bones and teeth are discussed. is discussed with respect to the kinds and National Institute of Standards and locations of ionic substitutions. Octacalcium Key words: biominerals; calcium phos- Technology, phosphate (OCP), is a probable precursor phates; crystal structure; fluorapatite; Gaithersburg, MD 20899-0001 in biological mineralization. OCP has a glaserite; hydroxyapatite; octacalcium USA layer type structure, with one layer quite phosphate. similar to that of OHAp and the other, a hydrated layer consisting of more widely Accepted: August 22, 2001 [email protected] spaced Ca, and PO4 ions and the water [email protected] molecules. The closeness of fit in the ap- atitic layers of OCP and OHAp accounts Available online: http://www.nist.gov/jres 1. Introduction The crystallography program at the American Dental found under physiological conditions, but are commer- Association Health Foundation, Paffenbarger Research cially important as components in fertilizers. Center, was initiated in the early 1970s. The program was designed to investigate the crystal structures of bio- logical minerals and related compounds associated with 2. Discussion—Calcium Phosphates or with potential bearing in mineralization processes. Since calcium phosphates comprise the largest group of The known pure calcium phosphates have been clas- biominerals in vertebrate animals, most of the work sified into three major structural types [1]: (i) the apatite carried out, was centered on or around calcium phos- type, Ca10(PO4)6X2, which includes the derivatives of phates or related materials. Crystal structures of a num- hydroxyapatite (X = OHϪ) and fluorapatite (X = FϪ)as ber of pyrophosphates, carbonates, bisphosphonates, well as those related to apatite-type structures such as and highly hydrated phosphates and arsenates of cal- octacalcium phosphate (OCP), [Octacalcium bis(hydro- cium, magnesium and strontium were also investigated. genphosphate) tetrakis(phosphate) pentahydrate], This review will summarize the structural features of Ca8(HPO4)2(PO4)4и5H2O and tetracalcium phosphate calcium phosphates relevant to biomineralization. The (TTCP), Ca4(PO4)2O; (ii) the glaserite type, which can 2Ϫ 3Ϫ phosphates containing HPO4 and PO4 generally con- be considered to include all polymorphs of tricalcium stitute the biologically relevant calcium phosphates. phosphates (TCP), Ca3(PO4)2; and (iii) the Ca-PO4 Ϫ Phosphates with only H2PO4 ions are not normally sheet-containing compounds, which include dicalcium 1035 Volume 106, Number 6, November–December 2001 Journal of Research of the National Institute of Standards and Technology phosphate dihydrate (DCPD), CaHPO4и2H2O, dical- cium phosphate anhydrous (DCPA), CaHPO4,and monocalcium phosphates, Ca(H2PO4)2иH2Oand Ca(H2PO4)2. A number of highly hydrated phosphatic compounds have been included as a new type of calcium phosphate [1], struvite-type structures, after the biomin- eral struvite, Mg(NH4)PO4и6H2O, although these com- pounds do not represent pure calcium phosphates. Amorphous calcium phosphate (ACP), a possible pre- cursor to bioapatite, may be related to one or more of the structural types discussed above. 2.1 Apatite Type Structures Apatites are a structural type for compounds of the general formula M10(XO4)6Y2 rather than specific com- pounds. In general, they are known to be capable of accommodating a wide variety of modifications and combinations of substitutions of ions and groups within Fig. 1. Crystal structure of FAp or hexagonal OHAp projected down the c-axis. The corners of the unit cell (marked by shaded circles) are the apatitic lattice. However, the term “apatite” has been occupied by FϪ in FAp and by OHϪ in OHAp. An alternate choice of extensively and synonymously used to represent the cal- unit cell is identified as a' and b'. Ϫ Ϫ cium phosphates, Ca10(PO4)6X2, where X = F ,OH ,or Ϫ Cl and this concept will be followed in this review. occupy 6h positions similar to the Ca2 ions, in expanded Apatites are thermodynamically the most stable phases triangular positions. Adjacent Ca1 and Ca2 polyhedra 3Ϫ among the calcium phosphates and, therefore, can be are linked through oxygen atoms of the PO4 tetrahe- considered as the probable end product in many reac- dra. Because of the crystallographic mirror symmetry tions. imposed by the space group, each OHϪ ion has to be considered at statistically disordered positions (4e) both 2.1.1 Hydroxyapatite above and below the mirror planes at z = 1/4 and 3/4. It has been shown by neutron diffraction studies [2] that Hydroxyapatite (OHAp), Ca10(PO4)6(OH)2, is used as the oxygen atoms in hydroxide ions are 0.34 Å away a model for inorganic component of bones and teeth. from the mirror plane with the OHϪ direction pointing However, apatites as they occur in biological tissues, away from the mirror planes. An averaged structure mineral formations and laboratory products can incor- could imply that in approximately half the unit cells the porate a wide variety of impurities and are seldom found OHϪ ions are pointed upward from the mirror plane and in pure stoichiometric form. in the remaining unit cells they are pointed downward. The most common form is hexagonal and the crystal However, this statistical disordering need not be com- structure has been described in the space group P63/m pletely random. At least some short range ordering is to (No. 176) with lattice parameters a = b = 9.432 Å and be invoked such as OH-OH-OH...HO-HO. The reversal c = 6.881 Å, Z = 1 [2]. The structure is depicted in Fig. of the OHϪ direction can be achieved by replacement of 1. The 10 Ca2+ ions occupy two crystallographically an OHϪ by FϪ or ClϪ etc. or by a vacancy. Thus, the different symmetry sites, 4f and 6h.FourCa2+ ions (4f) hexagonal OHAp is probably never strictly stoichiomet- are located in columns along the three-fold axes at 1/3, ric. 2/3, 0 and 2/3, 1/3, 0 separated by approximately one- Stoichiometric OHAp has been described as mono- half of the c-axis. These are commonly referred to as clinic, space group P21/b having cell parameters Ca1 (or column Ca). Ca1 is coordinated to nine O a = 9.4214(8) Å, b =2a, c = 6.8814(7) Å, ␥ = 120Њ, atoms, with six shorter bonds that define an approxi- with twice as many formula units per unit cell as in the mate trigonal prism and three longer bonds capping the hexagonal unit [3]. The structure is closely related to prism faces. The Ca-O9 polyhedra share the trigonal that of the hexagonal form, but with no restrictions 2+ 3Ϫ faces to form chains parallel to the c-axis. The remain- imposed by the mirror symmetry. The Ca and PO4 ing six Ca2+ ions (6h sites, referred to as Ca2 or triangu- ions occupy similar positions as in the hexagonal form. lar Ca) form two triangular sets at z = 1/4 and 3/4 on the However, the OHϪ ions are located in two different mirror planes. The Ca2 ions are seven-coordinated, with columns. Within each column all the OHϪ ions have the Ϫ 3Ϫ six O atoms and one OH ion. The six PO4 ions same direction of displacements from z = 1/4 as in the 1036 Volume 106, Number 6, November–December 2001 Journal of Research of the National Institute of Standards and Technology Ϫ 2Ϫ hexagonal form. All the OH ions in one column point stitially. Both HPO4 , and structurally incorporated wa- upward, while those in the other column point down- ter occur in some synthetic and biological apatites, but ward. Thus, there is no disordering of the OHϪ ions in their structural locations are not known. the monoclinic form. The monoclinic form is formed only under favorable thermal conditions. ؊ 2.1.4.1 X Ion Substitution The XϪ ion positions in apatites or the “X ion chan- 2.1.2 Fluorapatite nels”, as they are often referred to, appear to be the sites Ϫ Fluorapatite (FAp), Ca10(PO4)6F2, is the most stable of a great deal of interesting activity in apatites. The X among the apatites. FAp is hexagonal with the space ion positions in apatites are substituted by a variety of Ϫ Ϫ Ϫ 2Ϫ group P63/m and lattice parameters, a = b = 9.367(1) Å ions, frequently by OH ,F ,andCl , but also by CO3 and c = 6.884(1) Å, Z = 1 [4]. The positions of the two and O2Ϫ, or by vacancies or any combination of these. In 2+ 3Ϫ Ϫ sets of Ca ions and the PO4 ions are nearly identical pure form each X ion takes up its own particular loca- to those of OHAp. However, the FϪ ions occupy the tion, as noted above. However, when two or more of center of the Ca2 triangles (6h positions), on the mirror these ions are present at the same time, they interact planes at z = 1/4 and 3/4. with each other to produce effects not predicted from the knowledge of the structures of the end-member alone [5,7,8]. The positional z-parameters of the XϪ 2.1.3 Chlorapatite ions are shifted from their normal positions in the pure Chlorapatite (ClAp), Ca10(PO4)6(Cl)2, has been de- form, but the effects are more pronounced when the Ϫ scribed in the hexagonal space group P63/m, with cell larger Cl ions are involved.