Convenient synthesis of zwitterionic calcium(II)-carboxylate metal organic frameworks with efficient activities for the treatment of osteoporosis

Calcium supplementation is effective in alleviating the process of osteoporosis and the occurrence of osteoporotic fractures for people with long-term calcium deficiency. Herein, five water-stable calcium carboxylate compounds, that is, mononuclear coordination compound [Ca(Cbdcp)(H2O)6]·0.5H2O (1, H3CbdcpBr = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium bromide), and metal organic frameworks (MOFs) {[Ca3(Dcbdcp)2(H2O)12]·2H2O}n (2, H4DcbdcpBr = N-(3,5-dicarboxybenzyl)-(3,5-dicarboxyl)pyridinium bromide), {[Ca(Cmdcp)(H2O)4]·3H2O}n (3, H3CmdcpBr = N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide), {[Ca(Cdcbp)]·2H2O}n (4, H3CdcbpBr = 3-carboxyl-(3,5-dicarboxybenzyl)-pyridinium bromide) and {[Ca0.5(Cmcp)]·2H2O}n (5, H2CmcpBr = N-carboxymethyl-(3-carboxyl)pyridinium bromide), were synthesized from the reaction of CaCl2 with five different kinds of zwitterionic carboxylate ligands in the presence of NaOH, respectively. Compounds 1–5 were characterized by Fourier-transform infrared (FTIR) spectroscopy, elemental analyses, single-crystal X-ray crystallography, and inductively coupled plasma mass spectrometry (ICP-MS). Compound 1 features a mononuclear structure and MOF 2 with a one-dimensional (1D) structure while MOFs 3 and 5 with 2D layer structures and MOF 4 showing a 3D structure. Compounds 1–5 exhibited good water stability and possessed considerable biocompatibility with primary mice osteoblasts. The in vitro ability of compounds 1–5 in regulating osteoblastic differentiation was studied via alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, and quantitative real-time polymerase chain reaction (qPCR). Among these 5 compounds, MOF 4 showed the overall best in vitro osteogenic effects. Then, we administrated MOF 4 intragastrically to bilaterally ovariectomized mice for 8 weeks and found that bone loss caused by ovariectomy (OVX) was significantly alleviated. Besides, MOF 4 administration showed no toxic effects in the main organs of the mice. Altogether, zwitterionic carboxylate ligands-based calcium compounds provide a new strategy for calcium agents development.