A crystallographically characterized nine-coordinate calcium-phosphocitrate complex as calcification inhibitor in vivo.

Calcium-containing crystal deposition diseases represent a group of clinically heterogeneous calcific diseases that are a significant source of morbidity.1 Phosphorylated carboxylic acids are powerful inhibitors of biological crystallization as it relates to those diseases.2 Phosphocitrate (PC), a naturally occurring compound (Chart 1),3 is particularly potent. It has been demonstrated to inhibit the transformation of calcium phosphate to hydroxyapatite (Ca5(PO4)3(OH)), the deposition of calcium oxalates,5 the crystallization of octacalcium phosphate (Ca8(HPO4)2(PO4)4‚5H2O), and calcium pyrophosphate (Ca2P2O7‚ 2H2O), and the formation of struvite (Mg(NH4)(PO4)‚6H2O) in vivo.8 PC has also expressed inhibitory activity against the formation of scaling Ca salts, such as calcite (CaCO3) and gypsum (CaSO4‚2H2O), related to industrial water treatment.9 In addition, allied to these later actions, PC has been noted to prevent corrosion of carbon steel surfaces.9 Overall then, the compound attracts keen interest from the viewpoint of its nontoxic nature10 and potential to influence biomineralization in many diverse biological fields. In this paper we describe the preparation and crystal and molecular structure of a polymeric mixed salt of PC, namely [CaNa(PC)2(H2O)]n (CaNaPC), and its improved calcification inhibition properties compared to its precursor, NaPC.11 CaNaPC forms by the reaction of NaPC and Ca2+ at pH ∼2 according to the balanced equation (protons on PC also shown): The structure of CaNaPC12 (Figure 1) can be described as polymeric in nature with Ca(PC)2(H2O) “monomers” linked through Na+ bridges.