Supramolecular Nature of Multicomponent Crystals Formed from 2,2'-Thiodiacetic Acid with 2,6-Diaminopurine or N9-(2-Hydroxyethyl)adenine.

The synthesis and characterization of the multicomponent crystals formed by 2,2'-thiodiacetic acid (H2tda) and 2,6-diaminopurine (Hdap) or N9-(2-hydroxyethyl)adenine (9heade) are detailed in this report. These crystals exist in a salt rather than a co-crystal form, as confirmed by single crystal X-ray diffractometry, which reflects their ionic nature. This analysis confirmed proton transfer from the 2,2'-thiodiacetic acid to the basic groups of the coformers. The new multicomponent crystals have molecular formulas [(H9heade+)(Htda-)] 1 and [(H2dap+)2(tda2-)]·2H2O 2. These were also characterized using FTIR, 1H and 13C NMR and mass spectroscopies, elemental analysis, and thermogravimetric/differential scanning calorimetry (TG/DSC) analyses. In the crystal packing the ions interact with each other via O-H⋯N, O-H⋯O, N-H⋯O, and N-H⋯N hydrogen bonds, generating cyclic hydrogen-bonded motifs with graph-set notation of R22(16), R22(10), R32(10), R33(10), R22(9), R32(8), and R42(8), to form different supramolecular homo- and hetero-synthons. In addition, in the crystal packing of 2, pairs of diaminopurinium ions display a strong anti-parallel π,π-stacking interaction, characterized by short inter-centroids and interplanar distances (3.39 and 3.24 Å, respectively) and a fairly tight angle (17.5°). These assemblies were further analyzed energetically using DFT calculations, MEP surface analysis, and QTAIM characterization.

Enhanced NSAIDs Solubility in Drug-Drug Formulations with Ciprofloxacin.

Drug-drug salts are a kind of pharmaceutical multicomponent solid in which the two co-existing components are active pharmaceutical ingredients (APIs) in their ionized forms. This novel approach has attracted great interest in the pharmaceutical industry since it not only allows concomitant formulations but also has proved potential to improve the pharmacokinetics of the involved APIs. This is especially interesting for those APIs that have relevant dose-dependent secondary effects, such as non-steroidal anti-inflammatory drugs (NSAIDs). In this work, six multidrug salts involving six different NSAIDs and the antibiotic ciprofloxacin are reported. The novel solids were synthesized using mechanochemical methods and comprehensively characterized in the solid state. Moreover, solubility and stability studies, as well as bacterial inhibition assays, were performed. Our results suggest that our drug-drug formulations enhanced the solubility of NSAIDs without affecting the antibiotic efficacy.

Slow Magnetic Relaxation and Modulated Photoluminescent Emission of Coordination Polymer Based on 3-Amino-4-hydroxybenzoate Zn and Co Metal Ions.

As a starting point, a new 3D porous framework with the {[CoL]·0.5DMF·H2O}n chemical formula (where L = 3-amino-4-hydroxybenzoate) is described. Its performance as a single molecule magnet was explored. The study of magnetic properties reveals that Co-MOF shows no frequency-fdependant alternating current (ac) signals under zero direct current (dc) magnetic field, whereas single-molecule magnet behaviour is achieved when CoII ions are diluted in a ZnII based matrix. Interestingly, this strategy renders a bifunctional [CoxZn1-xL]n material that is also characterized by a strong photoluminescent emitting capacity.

The Copper(II)-Thiodiacetate (tda) Chelate as Efficient Receptor of N9-(2-Hydroxyethyl)Adenine (9heade): Synthesis, Molecular and Crystal Structures, Physical Properties and DFT Calculations of [Cu(tda)(9heade)(H2O)]·2H2O.

Considering that Cu(tda) chelate (tda: dithioacetate) is a receptor for adenine and related 6-aminopurines, this study reports on the synthesis, molecular and crystal structures, thermal stability, spectral properties and DFT calculations related to [Cu(tda)(9heade)(H2O)]·2H2O (1) [9heade: N9-(2-hydroxyethyl)adenine]. Concerning the molecular recognition of (metal chelate)-(adenine synthetic nucleoside), 1 represents an unprecedented metal binding pattern (MBP) for 9heade. However, unprecedentedly, the Cu(tda)-9heade molecular recognition in 1 is essentially featured in the Cu-N1(9heade) bond, without any N6-H⋯O(carboxyl tda) interligand interaction. Nevertheless, N1 being the most basic donor for N9-substituted adenines, this Cu-N1 bond is now assisted by an O2-water-mediated interaction (N6-H⋯O2 and O2⋯Cu weak contact). Also, in the crystal packing, the O-H(ol) of 9heade interacts with its own adenine moiety as a result of an O3-water-mediated interaction (O(ol)-H⋯O3 plus O3-H36⋯π(adenine moiety)). Both water-mediated interactions seem to be responsible for serious alterations in the physical properties of crystalline or grounded samples. Density functional theory calculations were used to evaluate the interactions energetically. Moreover, the quantum theory of atoms-in-molecules (QTAIM), in combination with the noncovalent interaction plot (NCIPlot), was used to analyze the interactions and rationalize the existence and relative importance of hydrogen bonding, chalcogen bonding and π-stacking interactions. The novelty of this work resides in the discovery of a novel binding mode for N9-(2-hydroxyethyl)adenine. Moreover, the investigation of the important role of water in the solid state of 1 is also relevant, along with the chalcogen bonding interactions demonstrated by the density functional theory (DFT) study.

H(N3)dap (Hdap = 2,6-Diaminopurine) Recognition by Cu2(EGTA): Structure, Physical Properties, and Density Functional Theory Calculations of [Cu4(µ-EGTA)2(µ-H(N3)dap)2(H2O)2]·7H2O.

Reactions in water between the Cu2(µ-EGTA) chelate (EGTA = ethylene-bis(oxyethyleneimino)tetraacetate(4-) ion) and Hdap in molar ratios 1:1 and 1:2 yield only blue crystals of the ternary compound [Cu4(µ-EGTA)2(µ-H(N3)dap)2(H2O)2]·7H2O (1), which has been studied via single-crystal X-ray diffraction and various physical methods (thermal stability, spectral and magnetic properties), as well as DFT theoretical calculations. In the crystal, uncoordinated water is disordered. The tetranuclear complex molecule also has some irrelevant disorder in an EGTA-ethylene moiety. In the complex molecule, both bridging organic molecules act as binucleating ligands. There are two distorted five- and two six-coordinated Cu(II) centers. Each half of EGTA acts as a tripodal tetradentate Cu(II) chelator, with a mer-NO2 + O(ether, distal) conformation. Hdap exhibits the tautomer H(N3)dap, with the dissociable H-atom on its less basic N-heterocyclic atom. These features favor the efficient cooperation between Cu-N7 or Cu-N9 bonds with appropriate O-EGTA atoms, as N6-H···O or N3-H···O interligand interactions, respectively. The bridging role of both organics determines the tetranuclear dimensionality of the complex. In this crystal, such molecules associate in zig-zag chains built by alternating π-π interactions between the five- or six-atom rings of Hdap ligands of adjacent molecules. DFT theoretical calculations (using two different theoretical models and characterized by the quantum theory of "atoms in molecules") reveal the importance of these π-π interactions between Hdap ligands, as well as those corresponding to the referred hydrogen bonds in the contributed tetranuclear molecule.

Multifunctional Lanthanide-Based Metal-Organic Frameworks Derived from 3-Amino-4-hydroxybenzoate: Single-Molecule Magnet Behavior, Luminescent Properties for Thermometry, and CO2 Adsorptive Capacity.

Herein, we describe and study a new family of isostructural multifunctional metal-organic frameworks (MOFs) with the formula {[Ln5L6(OH)3(DMF)3]·5H2O}n (where (H2L) is 3-amino-4-hydroxybenzoic acid ligand) for magnetism and photoluminescence. Interestingly, three of the materials (Dy-, Er-, and Yb-based MOFs) present single-molecule magnet (SMM) behavior derived from the magnetic anisotropy of the lanthanide ions as a consequence of the adequate electronic distribution of the coordination environment. Additionally, photoluminescence properties of the ligand in combination with Eu and Tb counterparts were studied, including the heterometallic Eu-Tb mixed MOF that shows potential as ratiometric luminescent thermometers. Finally, the porous nature of the framework allowed showing the CO2 sorption capacity.

Catalytic Performance and Electrophoretic Behavior of an Yttrium-Organic Framework Based on a Tricarboxylic Asymmetric Alkyne.

A new Y-based metal-organic framework (MOF) GR-MOF-6 with a chemical formula of {[YL(DMF)2]·(DMF)}n {H3L = 5-[(4-carboxyphenyl)ethynyl] isophthalic acid; DMF = N,N-dimethylformamide} has been prepared by a solvothermal route. Structural characterization reveals that this novel material is a three-dimensional MOF in which the coordination of the tritopic ligand to Y(III) metal ions leads to an intercrossing channel system extending over three dimensions. This material has proven to be a very efficient catalyst in the cyanosilylation of carbonyls, ranking second in catalytic activity among the reported rare earth metal-based MOFs described so far but with the lowest required catalyst loading. In addition, its electrophoretic behavior has been studied in depth, providing a zero-charge point between pH 4 and 5, a peak electrophoretic mobility of -1.553 µm cm V-1 s-1, and a ζ potential of -19.8 mV at pH 10.

Sensing Capacity in Dysprosium Metal-Organic Frameworks Based on 5-Aminoisophthalic Acid Ligand.

Two novel metal-organic frameworks (MOFs), based on dysprosium as the metal and the 5-aminoisophthalic acid (5aip) ligand, have been solvothermally synthesized, with the aim of studying and modulating their luminescence properties according to the variation of solvent in the structure. These materials display intense photo-luminescence properties in the solid state at room temperature. Interestingly, one fascinating sensory capacity of compound 2 regards obtaining a variation of the signal, depending on the solvent to which it is exposed. These results pave the way for a new generation of sensitive chemical sensors.

Selectivity of Relative Humidity Using a CP Based on S-Block Metal Ions.

Herein, we present the syntheses of a novel coordination polymer (CP) based on the perylene-3,4,9,10-tetracarboxylate (pery) linkers and sodium metal ions. We have chosen sodium metal center with the aim of surmising the effect that the modification of the metal ion may have on the relative humidity (RH) experimental measurements of the material. We confirm the role of the ions in the functionalization of the deposited layer by modifying their selectivity towards moisture content, paving the way to the generation of sensitive and selective chemical sensors.

Drug-Inclusive Inorganic-Organic Hybrid Systems for the Controlled Release of the Osteoporosis Drug Zoledronate.

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., Sr2+ and Ba2+) 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 Sr2+ or Ba2 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.

A Highly Water-Stable meta-Carborane-Based Copper Metal-Organic Framework for Efficient High-Temperature Butanol Separation.

Biofuels are considered sustainable and renewable alternatives to conventional fossil fuels. Biobutanol has recently emerged as an attractive option compared to bioethanol and biodiesel, but a significant challenge in its production lies in the separation stage. The current industrial process for the production of biobutanol includes the ABE (acetone-butanol-ethanol) fermentation process from biomass; the resulting fermentation broth has a butanol concentration of no more than 2 wt% (the rest is essentially water). Therefore, the development of a cost-effective process for separation of butanol from dilute aqueous solutions is highly desirable. The use of porous materials for the adsorptive separation of ABE mixtures is considered a highly promising route, as these materials can potentially have high affinities for alcohols and low affinities for water. To date, zeolites have been tested toward this separation, but their hydrophilic nature makes them highly incompetent for this application. The use of metal-organic frameworks (MOFs) is an apparent solution; however, their low hydrolytic stabilities hinder their implementation in this application. So far, a few nanoporous zeolitic imidazolate frameworks (ZIFs) have shown excellent potential for butanol separation due to their good hydrolytic and thermal stabilities. Herein, we present a novel, porous, and hydrophobic MOF based on copper ions and carborane-carboxylate ligands, mCB-MOF-1, for butanol recovery. mCB-MOF-1 exhibits excellent stability when immersed in organic solvents, water at 90 °C for at least two months, and acidic and basic aqueous solutions. We found that, like ZIF-8, mCB-MOF-1 is non-porous to water (type II isotherm), but it has higher affinity for ethanol, butanol, and acetone compared to ZIF-8, as suggested by the shape of the vapor isotherms at the crucial low-pressure region. This is reflected in the separation of a realistic ABE mixture in which mCB-MOF-1 recovers butanol more efficiently compared to ZIF-8 at 333 K.

Two Isostructural URJC-4 Materials: From Hydrogen Physisorption to Heterogeneous Reductive Amination through Hydrogen Molecule Activation at Low Pressure.

Herein, two novel isostructural metal-organic frameworks (MOFs) M-URJC-4 (M = Co, Ni; URJC = "Universidad Rey Juan Carlos") with open metal sites, permanent microposity, and large surface areas and pore volumes have been developed. These novel MOFs, with polyhedral morphology, crystallize in the monoclinic P21/c space group, exhibiting a three-dimensional structure with microporous channels along the c axis. Initially, they were fully characterized and tested in hydrogen (H2) adsorption at different conditions of temperature and pressure. The physisorption capacities of both materials surpassed the gravimetric H2 uptake shown by most MOF materials under the same conditions. On the basis of the outstanding adsorption properties, the Ni-URJC-4 material was used as a catalyst in a one-pot reductive amination reaction using various carbonyl compounds and primary amines. A possible chemical pathway to obtain secondary amines was proposed via imine formation, and remarkable performances were accomplished. This work evidences the dual ability of M-URJC-4 materials to be used as a H2 adsorbent and a catalyst in reductive amination reactions, activating molecular H2 at low pressures for the reduction of C═N double bonds and providing reference structural features for the design of new versatile heterogeneous materials for industrial application.

Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects.

We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6-37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest.

Novel and Versatile Cobalt Azobenzene-Based Metal-Organic Framework as Hydrogen Adsorbent.

A novel URJC-3 material based on cobalt and 5,5'-(diazene-1,2-diyl)diisophthalate ligand, containing Lewis acid and basic sites, has been synthesized under solvothermal conditions. Compound URJC-3, with polyhedral morphology, crystallizes in the tetragonal and P43 21 2 space group, exhibiting a three-dimensional structure with small channels along a and b axes. This material was fully characterized, and its hydrogen adsorption properties were estimated for a wide range of temperatures (77-298 K) and pressures (1-170 bar). The hydrogen storage capacity of URJC-3 is quite high in relation to its moderate surface area, which is probably due to the confinement effect of hydrogen molecules inside its reduced pores of 6 Å, which is close the ionic radii of hydrogen molecules. The storage capacity of this material is not only higher than that of active carbon and purified single-walled carbon nanotubes, but also surpasses the gravimetric hydrogen uptake of most MOF materials.

A Reversible Phase Transition of 2D Coordination Layers by B-H∙∙∙Cu(II) Interactions in a Coordination Polymer.

Materials that combine flexibility and open metal sites are crucial for myriad applications. In this article, we report a 2D coordination polymer (CP) assembled from CuII ions and a flexible meta-carborane-based linker [Cu2(L1)2(Solv)2]•xSolv (1-DMA, 1-DMF, and 1-MeOH; L1: 1,7-di(4-carboxyphenyl)-1,7-dicarba-closo-dodecaborane). 1-DMF undergoes an unusual example of reversible phase transition on solvent treatment (i.e., MeOH and CH2Cl2). Solvent exchange, followed by thermal activation provided a new porous phase that exhibits an estimated Brunauer-Emmett-Teller (BET) surface area of 301 m2 g-1 and is capable of a CO2 uptake of 41 cm3 g-1. The transformation is reversible and 1-DMF is reformed on addition of DMF to the porous phase. We provide evidence for the reversible process being the result of the formation/cleavage of weak but attractive B-H∙∙∙Cu interactions by a combination of single-crystal (SCXRD), powder (PXRD) X-ray diffraction, Raman spectroscopy, and DFT calculations.

Sulfoxide-Induced Homochiral Folding of ortho-Phenylene Ethynylenes (o-OPEs) by Silver(I) Templating: Structure and Chiroptical Properties.

A new family of homochiral silver complexes based on carbophilic interactions with ortho-phenylene ethynylene (o-OPE) scaffolds containing up to two silver atoms are described. These compounds represent a unique class of complexes with chirality at the metal. Chiral induction is based on the inclusion of chiral sulfoxides, which allow efficient transfer of chirality to the helically folded o-OPE, leading to circularly polarized luminescence (CPL)- and vibrational circular dichroism (VCD)-active compounds. In the presence of silver(I) cations, carbophilic interactions dominate, which promote helical structures with a defined helicity. This is one of the very scarce examples of the use of such interactions in the attractive field of abiotic foldamers. The switching event has been extensively studied by using different chiroptical techniques, including circular dichroism, CPL, and VCD, and represents one of the few CPL switches described in the literature.

Three-Component Copper-Phosphonate-Auxiliary Ligand Systems: Proton Conductors and Efficient Catalysts in Mild Oxidative Functionalization of Cycloalkanes.

The synthesis, structural characterization, topological analysis, proton conductivity, and catalytic properties are reported of two Cu(II)-based compounds, namely a dinuclear Cu(II) complex [Cu2(µ-VPA)2(phen)2(H2O)2]·8H2O (1) (H2VPA = vinylphosphonic acid, phen = 1,10-phenanthroline) and a 1D coordination polymer [Cu(µ-SO4)(phen)(H2O)2]∞ (2). Their structural features and H-bonding interactions were investigated in detail, showing that the metal-organic structures of 1 and 2 are extended by multiple hydrogen bonds to more complex 2D or 1D H-bonded architectures with the kgd [Shubnikov plane net (3.6.3.6)/dual] and SP 1-periodic net (4,4)(0,2) topology, respectively. These nets are primarily driven by the H-bonding interactions involving water ligands and H2O molecules of crystallization; besides, the (H2O)4/(H2O)5 clusters were identified in 1. Both 1 and 2 are moderate proton conductors, with proton conductivity values, σ = 3.65 × 10-6 and 3.94 × 10-6 S·cm-1, respectively (measured at 80 °C and 95% relative humidity). Compounds 1 and 2 are also efficient homogeneous catalysts for the mild oxidative functionalization of C5-C8 cycloalkanes (cyclopentane, cyclohexane, cycloheptane, and cyclooctane), namely for the oxidation by H2O2 to give cyclic alcohols and ketones and the hydrocarboxylation by CO/H2O and S2O82- to the corresponding cycloalkanecarboxylic acids as major products. The catalytic reactions proceed under mild conditions (50-60 °C) in aqueous acetonitrile medium, resulting in up to 34% product yields based on cycloalkane substrate.

A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections.

A rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC® strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1⁻32 µg/mL against Gram-positive ATCC® strains. The structure⁻activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16, were the MIC50/90 were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC50/90 was 256/512 µg/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.

Precipitation and Crystallization Kinetics in Silica Gardens.

Silica gardens are extraordinary plant-like structures resulting from the complex interplay of relatively simple inorganic components. Recent work has highlighted that macroscopic self-assembly is accompanied by the spontaneous formation of considerable chemical gradients, which induce a cascade of coupled dissolution, diffusion, and precipitation processes occurring over timescales as long as several days. In the present study, this dynamic behavior was investigated for silica gardens based on iron and cobalt chloride by means of two synchrotron-based techniques, which allow the determination of concentration profiles and time-resolved monitoring of diffraction patterns, thus giving direct insight into the progress of dissolution and crystallization phenomena in the system. On the basis of the collected data, a kinetic model is proposed to describe the relevant reactions on a fundamental physicochemical level. The results show that the choice of the metal cations (as well as their counterions) is crucial for the development of silica gardens in both the short and long term (i.e. during tube formation and upon subsequent slow equilibration), and provide important clues for understanding the properties of related structures in geochemical and industrial environments.

m-Carboranylphosphinate as Versatile Building Blocks To Design all Inorganic Coordination Polymers.

The first examples of coordination polymers of manganese(II) and a nickel(II) complex with a purely inorganic carboranylphosphinate ligand are reported, together with its exhaustive characterization. X-ray analysis revealed 1D polymeric chains with carboranylphosphinate ligands bridging two manganese(II) centers. The reactivity of polymer 1 with water and Lewis bases has also been studied.