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.sup.2+, Zn.sup.2+, and Mg.sup.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.sub.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.

The present invention relates to conjugate compounds and methods of making and using same.

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.sup.2+, Zn.sup.2+, and Mg.sup.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. Dissolution profiles were conducted to investigate the release of BBPA from BBPA-based metal complexes under physiological conditions (phosphate-buffered saline, PBS). These results show that <50% of BBPA was released from the BBPA-based metal complexes after 72 h. Binding assays employing hydroxyapatite (HA) were conducted to explore the affinity of BBPA to the bone microenvironment. About 99% of the BBPA could bind to HA in 10 days, revealing that BBPA is capable of binding to the bone. 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.sub.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 no cytotoxic against these cell lines.

It is intended to provide a novel bisphosphonic acid compound or a salt thereof which shows a remarkable inhibitory effect on ectopic calcification, and a pharmaceutical composition comprising the same. The present invention provides a bisphosphonic acid compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof: ##STR00001##
wherein represents a single bond or a double bond; A represents a saturated cyclic hydrocarbon or a saturated heterocyclic ring comprising a sulfur atom or an oxygen atom; and R.sup.1 and R.sup.2 each independently represent an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryloxy group, a haloalkoxy group, a haloalkyl group, a halogen atom or a hydrogen atom.

It is intended to provide a novel bisphosphonic acid compound or a salt thereof which shows a remarkable inhibitory effect on ectopic calcification, and a pharmaceutical composition comprising the same. The present invention provides a bisphosphonic acid compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:

##STR00001##

wherein represents a single bond or a double bond; A represents a saturated cyclic hydrocarbon or a saturated heterocyclic ring comprising a sulfur atom or an oxygen atom; and R.sup.1 and R.sup.2 each independently represent an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryloxy group, a haloalkoxy group, a haloalkyl group, a halogen atom or a hydrogen atom.

The present application relates to metal-organic frameworks (MOFs). More specifically, the present application relates to process for their preparation and uses thereof. The present application includes a process for preparing a chromium (III) phosphonate metal-organic framework (MOF) comprising: a) dehydrating a hydrogen-bonded metal-organic framework (HMOF) comprising chromium (III) hydrogen bonded to one or more organic polyphosphonate molecule by heating the HMOF at a controlled rate; b) cooling the dehydrated HMOF from a) to provide the MOF.