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The chemistry of metal-organic frameworks (MOFs) continues to expand rapidly, providing materials with diverse structures and properties. The reticular chemistry approach, where well-defined structural building blocks are combined together to form crystalline open framework solids, has greatly accelerated the discovery of new and important materials. However, its full potential toward the rational design of MOFs relies on the availability of highly connected building blocks because these greatly reduce the number of possible structures. Toward this, building blocks with connectivity greater than 12 are highly desirable but extremely rare. We report here the discovery of novel 18-connected, trigonal prismatic, ternary building blocks ( tbb 's) and their assembly into unique MOFs, denoted as Fe- tbb -MOF- x ( x : 1, 2, 3), with hierarchical micro- and mesoporosity. The remarkable tbb is an 18-c supertrigonal prism, with three points of extension at each corner, consisting of triangular (3-c) and rectangular (4-c) carboxylate-based organic linkers and trigonal prismatic [Fe 3 (μ 3 -Ο)(-COO) 6 ] + clusters. The tbb 's are linked together by an 18-c cluster made of 4-c ligands and a crystallographically distinct Fe 3 (μ 3 -Ο) trimer, forming overall a 3-D (3,4,4,6,6)-c five nodal net. The hierarchical, highly porous nature of Fe- tbb -MOF- x ( x : 1, 2, 3) was confirmed by recording detailed sorption isotherms of Ar, CH 4 , and CO 2 at 87, 112, and 195 K, respectively, revealing an ultrahigh BET area (4263-4847 m 2 g -1 ) and pore volume (1.95-2.29 cm 3 g -1 ). Because of the observed ultrahigh porosities, the H 2 and CH 4 storage properties of Fe- tbb -MOF- x were investigated, revealing well-balanced high gravimetric and volumetric deliverable capacities for cryoadsorptive H 2 storage (11.6 wt %/41.4 g L -1 , 77 K/100 bar-160 K/5 bar), as well as CH 4 storage at near ambient temperatures (367 mg g -1 /160 cm 3 STP cm -3 , 5-100 bar at 298 K), placing these materials among the top performing MOFs. The present work opens new directions to apply reticular chemistry for the construction of novel MOFs with tunable porosities based on contracted or expanded tbb analogues.

Bisphosphonate (BP)-based treatments have been extensively prescribed for bone-related conditions, particularly for osteoporosis. Their low bioavailability creates the need for prescribed dosage increase to reach therapeutic levels but generates a plethora of undesirable side effects. A viable approach to alleviating these issues is to design and exploit controlled release strategies. Herein, the controlled release profiles of 15 structurally characterized BPs (actual drugs and structural analogs) were thoroughly studied from tablets containing three (cellulose, lactose, and silica) or two (cellulose, and silica) excipients in human stomach-simulated pH conditions. The BPs were of two types, alkyl-BPs and amino-BPs. Alkyl-BPs included four derivatives of etidronate (acid, disodium, tetra-sodium, and monopotassium forms), medronic acid, and three analogs of etidronate, in which the -CH 3 group was replaced by the moieties -H, -CH 2 CH 2 CH 3 , and -CH 2 CH 2 CH 2 CH 2 CH 3 . Amino-BPs included the commercial drugs pamidronate, alendronate, neridronate, and ibandronate, as well as three analog compounds. Release curves were constructed based on data taken from 1 H NMR peak integration and were expressed as "% BP release" vs time. The controlled release profiles (initial release rate, plateau value, etc.) were correlated with certain structural features (number of hydrogen and metal-oxygen bonds), showing that the molecular and crystal lattice features of each BP profoundly influence its release characteristics. It was concluded that for all BPs, in general, the initial rate became lower as the total number of lattice interactions increased. For the alkyl-BPs elongation of the alkyl side chain seems to decelerate the release. Amino-BPs, in general, show slower release than the alkyl-BPs. No adverse effects of alkyl- and amino-BP drugs on NIH3T3 cell viability were noted.

In drug research and development, knowledge of the precise structure of an active ingredient is crucial. However, it is equally important to know the water content of the drug molecule, particularly the number of crystal waters present in its structure. Such knowledge ensures the avoidance of drug dosage and formulation errors since the number of water molecules affects the physicochemical and pharmaceutical properties of the molecule. Several methods have been used for crystal water measurements of organic compounds, of which thermogravimetry and crystallography may be the most common ones. To the best of our knowledge, solution-state NMR spectroscopy has not been used for crystal water determination in deuterium oxide. Quantitative NMR (qNMR) method will be presented in the paper with a comparison of single-crystal X-ray diffraction and thermogravimetric analysis results. The qNMR method for water content measurement is straightforward, reproducible, and accurate, including measurement of 1 H NMR spectrum before and after the addition of the analyte compound, and the result can be calculated after integration of the reference compound, analyte, and HDO signals using the given equation. In practical terms, there is no need for weighing the samples under study, which makes it simple and is a clear advantage to the current determination methods. In addition, the crystal structures of two model bisphosphonates used herein are reported: that of monopotassium etidronate dihydrate and monosodium zoledronate trihydrate.

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 (Ca 2+ and Cu 2+ ), 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.

Bisphosphonates (BPs) are common pharmaceutical treatments used for calcium- and bone-related disorders, the principal one being osteoporosis. Their antiresorptive action is related to their high affinity for hydroxyapatite, the main inorganic substituent of bone. On the other hand, the phosphonate groups on their backbone make them excellent ligands for metal ions. The combination of these properties finds potential application in the utilization of such systems as controlled drug release systems (CRSs). In this work, the third generation BP drug zoledronate (ZOL) was combined with alkaline earth metal ions (e.g., Sr 2+ and Ba 2+ ) in an effort to synthesize new materials. These metal-ZOL compounds can operate as CRSs when exposed to appropriate experimental conditions, such as the low pH of the human stomach, thus releasing the active drug ZOL. CRS networks containing Sr 2+ or Ba 2 and ZOL were physicochemically and structurally characterized and were evaluated for their ability to release the free ZOL drug during an acid-driven hydrolysis process. Various release and kinetic parameters were determined, such as initial rates and release plateau values. Based on the drug release results of this study, there was an attempt to correlate the ZOL release efficiency with the structural features of these CRSs.

In this paper we report drug delivery systems that are based on phosphonate MOFs. These employ biologically-acceptable metal ions (e.g. Ca 2+ and Mg 2+ ) and several anti-osteoporosis bisphosphonate drugs (etidronate, pamidronate, alendronate and neridronate), as the organic linkers. These materials have been synthesized, structurally characterized, and studied for the self-sacrificial release (by pH-driven dissolution) of the bisphosphonate active ingredient. They exhibit variable release rates and final % release, depending on the actual structure of the metal-bisphosphonate material. Their cytotoxicity profiles match those of the active ingredients.