Influence of ionic additives on triclinic calcium pyrophosphate dihydrate precipitation

Abstract

Triclinic calcium pyrophosphate dihydrate (t- CPPD) crystals are one of the two polymorphs of microcrystals that have been found in the joints of patients suffering from pseudogout. However, there is currently no treatment for inhibiting the formation of these crystals, which present a high inflammatory potential. In this context we studied in vitro the precipitation of t-CPPD in a stirred reactor under pH- and temperature-controlled conditions and determined the effect of selected biologically relevant ionic additives (Mg2+, Cu2+, Fe3+, Zn2+, S2O3 2−) on its formation. The results showed that 1 mM Fe3+, Zn2+, or Cu2+ induced the most significant changes by partly inhibiting the crystallization of t-CPPD and favoring the formation of an amorphous-CPP phase (98 wt %) in the presence of Fe3+ or a monoclinic-CPPD phase (78 or 71 wt %, respectively) in the presence of Zn2+ or Cu2+. Correlations between 31P solid-state NMR, XRD, and elemental analyses showed that the additive cations are inserted into the monoclinic-CPPD and/or amorphous-CPP phases. This study, which combines structural, morphological, and elemental analyses, paves the way toward a deeper comprehension of the role of ionic additives in preventing the formation of CPPD crystalline phases, and is a key step in long-term development of an effective therapeutic treatment