Benzene 1,4-bis(bisphosphonic acid)-based metal complexes, method of synthesis and applications thereof
The invention provides extended bisphosphonate-based metal complexes using benzene1,4-bis(bisphosphonic acid) (BBPA), an analog of benzene 1,4-dicarboxylic acid (BDC). Hydrothermal synthesis of BBPA with the bioactive metals Ca 2+ , Zn 2+ , and Mg 2+ leads to four crystals phases, namely, BBPA-Ca forms I and II, BBPA-Zn form I, and BBPA-Mg form I. Out of the three structures, BBPA-Ca form II presents large channels (8 Å×12 Å), potentiating the use of this framework to load drugs. Cytotoxicity effects of BBPA was elucidated in a human breast cancer MDA-MB-231 and a normal osteoblast hFOB 1.19 cell lines. The half-maximal inhibitory concentration (IC 50 ) for BBPA used to treat both cell lines were >200 μM at 24, 48, and 72 h of treatment. The BBPA in the range of concentration employed (0-200 μM) was not cytotoxic against these cell lines.
1. A bisphosphonate-based coordination complex comprising: a mixture of benzene 1,4-bis(bisphosphonic acid) (BBPA) and a bioactive metal selected from the group consisting of: Ca 2+ , Zn 2+ , and Mg 2+ .
2. The bisphosphonate-based coordination complex according to claim 1 , wherein said metal is Ca 2+ and a single crystal form is characterized by major x-ray powder diffraction peaks at 2.theta. angles of 8.42, 12.04, 14.79, 16.87, 18.68 and 27.70.
3. The bisphosphonate-based coordination complex according to claim 1 , wherein said metal is Ca 2+ and a single crystal form is characterized by major x-ray powder diffraction peaks at 2.theta. angles of 10.05, 10.98, 14.45, 15.18, 23.04 and 29.36.
4. The bisphosphonate-based coordination complex according to claim 1 , wherein said metal is Zn 2+ and a single crystal form is characterized by major x-ray powder diffraction peaks at 2.theta. angles of 9.25, 14.73, 14.77, 21.63, 26.42 and 32.75.
5. The bisphosphonate-based coordination complex according to claim 1 , wherein said metal is Mg 2+ and a single crystal form is characterized by major x-ray powder diffraction peaks at 2.theta. angles of 8.36, 10.69, 11.96, 12.89, 16.84 and 25.27.
6. The bisphosphonate-based coordination complex of claim 1 , having an empirical formula of: Ca 2 C 8 H 14 O 17 P 4 , 3(H 2 O).
7. The bisphosphonate-based coordination complex of claim 1 , having an empirical formula of: 2(CaC 4 H 9 O 9 P 2 ), 9(H 2 O).
8. The bisphosphonate-based coordination complex of claim 1 , having an empirical formula of: ZnC 4 H 5 O 8 P 2 , 2(H 2 O).
9. The bisphosphonate-based coordination complex of claim 1 , having an empirical formula of: Mg 3 C 8 H 22 O 11 P 4 , 8(H 2 O).
10. The bisphosphonate-based coordination complex of claim 2 , wherein the single crystal form is characterized by X-ray powder diffraction pattern of FIG. 16 .
11. The bisphosphonate-based coordination complex of claim 3 , wherein the single crystal form is characterized by X-ray powder diffraction pattern of FIG. 17 .
12. The bisphosphonate-based coordination complex of claim 4 , wherein the single crystal form is characterized by X-ray powder diffraction pattern of FIG. 18 .
13. The bisphosphonate-based coordination complex of claim 5 , wherein the single crystal form is characterized by X-ray powder diffraction pattern of FIG. 19 .
14. The bisphosphonate-based coordination complex of claim 2 , wherein the single crystal form has a monoclinic unit cell with cell parameters: a=11.65839 Å, b=12.35838 Å, c=21.9782 Å and β=138.112°.
15. The bisphosphonate-based coordination complex of claim 3 , wherein the single crystal form has a monoclinic unit cell with cell parameters: a=13.1217 Å, b=10.0502 Å, c=21.74.61 Å and β=95.844°.
16. The bisphosphonate-based coordination complex of claim 4 , wherein the single crystal form has a monoclinic unit cell with cell parameters: a=6.8687 Å, b=19.1708 Å, c=8.3853 Å and β=105.689°.
17. The bisphosphonate-based coordination complex of claim 5 , wherein the single crystal form has a monoclinic unit cell with cell parameters: a=10.60620 Å, b=10.39300 Å, c=13.9383 Å and β=97.8330°.
18. The bisphosphonate-based coordination complex of claim 2 , wherein the single crystal form has monoclinic space group of P2 1 /c.
19. The bisphosphonate-based coordination complex of claim 3 , wherein the single crystal form has monoclinic space group of I2/a.
20. The bisphosphonate-based coordination complex of claim 4 , wherein the single crystal form has monoclinic space group of P2 1 /n.
21. The bisphosphonate-based coordination complex of claim 5 , wherein the single crystal form has monoclinic space group of P2 1 /c.