(Poly)phosphonic acids constitute an exciting family of phosphorus compounds. One of the attractive attributes of these molecules is the rich chemistry of the phosphonate moiety, and, in particular, its high affinity for metal ions and mineral surfaces. Whether the phosphonate group belongs to a “small” molecule or to a polymeric matrix, phosphonate-containing compounds have found a phalanx of real-life applications. Herein, we address a special category of phosphorus compounds called bisphosphonates (BPs, a.k.a. “-dronates”) and also phosphonate containing polymers. The success of BPs in mitigating osteoporosis notwithstanding, these “-dronate” drugs present a number of challenges. Nevertheless, the main drawback of BPs is their limited oral bioavailability. It is, therefore, imperative to design and fabricate “smart” systems that allow controlled delivery of the active BP agent. Here, easy-to-prepare drug delivery systems are presented based on silica gels. These have been synthesized, characterized, and studied as hosts in the control release of several BP drugs. They exhibit variable release rates and final % release, depending on the nature of bisphosphonate (side-chain length, hydro-philicity/-phobicity, water-solubility), cations present, pH and temperature. These gels are robust, injectable, re-loadable and re-usable. Furthermore, alternative drug delivery systems are presented that are based on metal-organic frameworks (MOFs). In these biologically acceptable inorganic metal ions have been incorporated, together with BPs as the organic portion. These materials have been synthesized, characterized, and studied for the self-sacrificial release (by pH-driven dissolution) of the BP active ingredient. Several such materials were prepared with a variety of bisphosphonate drugs. They exhibit variable release rates and final % release, depending on the actual structure of the metal-bisphosphonate material. Lastly, we will present the use of phosphonate-grafted polymers as scale inhibitors for water treatment applications.

Bisphosphonate drugs constitute the primary treatment for bone diseases such as Paget’s disease and osteoporosis. Despite their effectiveness, they also exhibit severe drawbacks, such as rapid excretion and limited oral bioavailability. High doses are usually administered to counterbalance these drawbacks. Subsequently, side effects are triggered, such as osteonecrosis of the lower jaw and esophageal cancer. Controlled drug release systems may be viable candidates to overcome those issues. Herein, we present novel functionalized silica-based hydrogels loaded with the osteoporosis drug etidronate (1,1-hydroxyethylidene-diphosphonate) used to control the release profile of the drug. Various methodologies were evaluated to control the initial release rate and the final released concentration of the drug. These included the gel density, by systematically increasing the initial concentration of silicate used to prepare the hydrogels, the presence of metal cations (Ca2+ and Cu2+), and the internal surface functionalization of the gel with silane-based grafting agents (with anionic, cationic, and neutral groups). This study also contributes to our continuous effort to develop new a priori programmable drug-loaded gels for the controlled release of osteoporosis drugs.

A series of 11 compounds, including alkali (Li, Na, K, Rb, Cs) and alkaline-earth (Mg, Ca, Sr, Ba) coordination polymers, transition-metal (Cu, Cd) complexes, and the ammonium salt of 3,5-dimethylpyrazole-4-sulfonic acid (HL), were synthesized. Single crystals of HL, and CdL 2 (H 2 O) 3 •2H 2 O were obtained from aqueous solutions either by evaporation or acetone vapor diffusion. Characterization by single-crystal X-ray diffraction reveals that the coordination compounds of L − (except Cu) possess alternating inorganic−organic layered structures, in which L − engages in extensive charge-assisted networks of H-bonding and aromatic interactions as well as metal coordination through the pyrazole N atom and/or the sulfonate O atom. A topological analysis and classification of underlying metal−organic or hydrogen-bonded networks uncover a number of distinct topological nets (3,5L2, hcb, 6,6L1, 3,5C1, 3,8L28, hex, and pcu). A thermogravimetric analysis shows that HL and NH 4 L are stable up to 285 and 90 °C, respectively, whereas the anhydrous metal compounds decompose above 200−230 °C. The pK a values of 3,5-dimethylpyrazole-4-sulfonic acid (HL) and pyrazole-4-sulfonic acid were determined by 1 H NMR titrations with H 2 SO 4 . Copper corrosion experiments indicate that 3,5-dimethylpyrazole-4sulfonic acid (HL) is a better anticorrosion agent than the parent pyrazole-4-sulfonic acid at pH 4, whereas the coordination polymers of L − offer weaker corrosion protection in comparison to the corresponding pyrazole-4-sulfonate complexes. The latter result is corroborated by the less compact and less robust thin films formed by metal−L compounds, as indicated by scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS) measurements, and the weaker acidity of HL, which allows for easier protonation of the conjugate base L − in metal−L compounds.

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