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Amide derivatives of xanthene dyes such as rhodamine B are useful in a variety of sensing applications due to their colorimetric responses to stimuli such as acidity changes and UV light. The optical properties of these molecules can be influenced by intermolecular associations into dimeric structures, but the exact impact can be hard to predict. We have designed a covalently linked intramolecular dimer of the dye rhodamine B utilizing

Hybrid organic-inorganic metal-halide perovskites have emerged as versatile materials for enabling low-cost, mechanically flexible optoelectronic applications. The progress has been commendable; however, technological breakthroughs have outgrown the basic understanding of processes occurring in bulk and at device interfaces. Here, we investigated the photocurrent at perovskite/organic semiconductor interfaces in relation to the microstructure of electronically active layers. We found that the photocurrent response is significantly enhanced in the bilayer structure as a result of a more efficient dissociation of the photogenerated excitons and trions in the perovskite layer. The increase in the grain size within the organic semiconductor layer results in reduced trapping and further enhances the photocurrent by extending the photocarriers' lifetime. The photodetector responsivity and detectivity have improved by 1 order of magnitude in the optimized samples, reaching values of 6.1 ± 1.1 A W-1, and 1.5 × 1011 ± 4.7 × 1010 Jones, respectively, and the current-voltage hysteresis has been eliminated. Our results highlight the importance of fine-tuning film microstructure in reducing the loss processes in thin-film optoelectronics based on metal-halide semiconductors and provide a powerful interfacial design method to consistently achieve high-performance photodetectors.

Over the last three decades, the chemistry of zirconium has facilitated antibody development and the clinical management of disease in the precision medicine era. Scientists have harnessed its reactivity, coordination chemistry, and nuclear chemistry to develop antibody-based radiopharmaceuticals incorporating zirconium-89 (89Zr: t1/2 = 78.4 h, β+: 22.8%, Eβ+max = 901 keV; EC: 77%, Eγ = 909 keV) to improve disease detection, identify patients for individualized therapeutic interventions. and monitor their response to those interventions. However, release of the 89Zr4+ ion from the radiopharmaceutical remains a concern, since it may confound the interpretation of clinical imaging data, negatively affect dosimetric calculations, and hinder treatment planning. In this report, we relate our novel observations involving the use of polyazamacrocycles as zirconium-89 chelators. We describe the synthesis and complete characterization of zirconium 2,2',2″,2‴-(1,4,7,10-tetraazacyclotridecane-1,4,7,10-tetrayl)tetraacetic acid (Zr-TRITA), zirconium 3,6,9,15-Tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (Zr-PCTA), and zirconium 2,2',2″-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (Zr-NOTA). In addition, we elucidate the solid-state structure of each complex using single-crystal X-ray diffraction analysis. Finally, we found that [89Zr]Zr-PCTA and [89Zr]Zr-NOTA demonstrate excellent stability in vitro and in vivo and provide a rationale for these observations. These innovative findings have the potential to guide the development of safer and more robust immuno-PET agents to improve precision medicine applications.

A structure-activity relationship study was performed for a set of rigidified platinum-acridine anticancer agents containing linkers derived from chiral pyrrolidine and piperidine scaffolds. Screening a library of microscale reactions and selected resynthesized compounds in non-small-cell lung cancer (NSCLC) cells showed that cytotoxicities varied by more than three orders of magnitude. A potent hit compound was discovered containing a (R)-N-(piperidin-3-yl) linker (P2-6R), which killed NCI-H460 and A549 lung cancer cells 100 times more effectively than the S enantiomer (P2-6S). P2-6R accumulated in A549 cells significantly faster and produced 50-fold higher DNA adduct levels than P2-6S. Ligand similarity analysis suggests that only module 6R may be compatible with strainless monofunctional intercalative binding. NCI-60 screening and COMPARE analysis highlights the spectrum of activity and potential utility of P2-6R for treating NSCLC and other solid tumors.

This paper describes the synthesis and characterization of RP­(o-biphenyl)2 phosphine ligands (where R = PhO, Ph, and t-Bu), corresponding gold­(I) chloride precatalysts, gold­(I) triflate catalysts, and gold­(I) π-complexes. All ligands and gold chlorides and three π-complexes were characterized in the solid state. The most significant differences between complexes in the solid state were varying P–Au bond lengths, a consistent reflection of the different electronic character of each phosphine. NMR spectroscopic data on enol ether π-complexes is consistent with increasing cationic character in the alkene fragment, from R = t-Bu to R = Ph and OPh. The intermolecular alkene exchange process for [LAu­(methoxypropene)]­SbF6 (L = PhO­(o-biphenyl)2P) is faster than that of the analogous complex with t-Bu2(o-biphenyl)­P, presumably due to the higher electrophilicity of the former complex. Examination of a series of vinyl silane π-complexes with triaryl phosphine ligands reveals increasing stability and ease of preparation (Ph3P < Ph2P­(o-biphenyl) < PhP­(o-biphenyl)2). These results reveal that incorporation of a second biphenyl substituent into ligand architectures allows preparation of a series of gold π-complexes with increased stability over a range of phosphine donicity.

Three new derivatives of a platinum–acridine hybrid anticancer agent were synthesized using nitrile–amine coupling (amidination) chemistry. In the new structures, the nonleaving group propane-1,3-diamine (pn) of a previously optimized analogue (hybrid 1) was replaced with 2,2-dimethylpropane-1,3-diamine (Me2pn, hybrid 2), (1R,2R)-1,2-diaminocyclohexane (R,R-dach, hybrid 3), or (1S,2S)-1,2-diaminocyclohexane (S,S-dach, hybrid 4). The cytotoxicity of the four compounds was determined in two non-small cell lung cancer (NSCLC) cell lines, NCI-H460 and A549. The IC50 values extracted from cell proliferation assays span a range of two orders of magnitude, with the highest activity established for compound 1 in NCI-H460 (8 nM) and the lowest for compound 4 in A549 (825 nM). Partitioning coefficients (log D, based on compound distribution in 1-octanol/saline) and levels of cellular accumulation (by inductively coupled plasma mass spectrometry, ICP-MS) were determined for the hybrids. The results suggest that efficient cellular uptake by an active transport mechanism, which depends on the nature of the nonleaving group, is a modulator of chemosensitivity and a prerequisite for the high nanomolar cytotoxicity observed for the most active platinum–acridines.

Current treatment options for bacterial infections are dependent on antibiotics that inhibit microbial growth and viability. These approaches result in the evolution of drug-resistant strains of bacteria. An anti-infective strategy that is less likely to lead to the development of resistance is the disruption of quorum sensing mechanisms, which are involved in promoting virulence. The goal of this study was to identify fungal metabolites effective as quorum sensing inhibitors. Three new prenylated diresorcinols (1-3), along with two known compounds, (4 R) -regiolone and decarboxycitrinone, were isolated from a freshwater fungus (Helotiales sp.) from North Carolina. Their structures were assigned on the basis of HRESIMS and NMR experiments. The structure of compound 1 was confirmed via X-ray diffraction analysis, and its absolute configuration was established by TDDFT-ECD and optical rotation calculations. Compounds 1-3 suppressed quorum sensing in a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA), with IC

A new layered gallium phosphonate-oxalate hybrid material, [C2H10N2]0.5[Ga3(PO3CH3)4(C2O4)].H2O, denoted as MOP-1, was synthesized under mild hydrothermal conditions (150 °C) in the presence of ethylenediammonium ion (H2en)2+ as structure-directing agent. The compound was structurally characterized by single-crystal X-ray diffraction (SCXRD), Fourier transformed infra-red spectroscopy (FTIR), and thermogravimetric analysis (TGA). Its structure consists of gallium phosphonate double layers formed of GaO6 octahedra, GaO4 tetrahedra, and PO3CH3 groups sharing corners. The double layers are cross-linked by oxalate ligands to form a three-dimensional framework with intersecting channels where the ammonium ions and water molecules are located. The bridging oxalate ligand acts as a bidentate ligand to each Ga in octahedral coordination environment. Crystal data are as follows: Monoclinic P21/n (14), a = 8.7530(5) A; b = 16.3427(8) A; c = 14.7522(8) A; β = 93.284(1)°, V = 2106.8(2) A3 and Z = 4.

Over the last three decades, the chemistry of zirconium has facilitated antibody development and the clinical management of disease in the precision medicine era. Scientists have harnessed its reactivity, coordination chemistry and nuclear chemistry to develop antibody-based radiopharmaceuticals incorporating zirconium-89 ((89)Zr: t(½) = 78.4 h, β(+): 22.8%, E(β+max) = 901 keV; EC: 77%, E(γ) = 909 keV) to improve disease detection, identify patients for individualized therapeutic interventions and monitor their response to those interventions. However, release of the (89)Zr(4+) ion from the radiopharmaceutical remains a concern since it may confound the interpretation of clinical imaging data, negatively affect dosimetric calculations and hinder treatment planning. In this report we relate our novel observations involving the use of polyazamacrocycles as zirconium-89 chelators. We describe the synthesis and complete characterization of zirconium 2,2′,2”,2”’-(1,4,7,10-tetraazacyclotridecane-1,4,7,10-tetrayl)tetraacetic acid (Zr-TRITA), zirconium 3,6,9,15-Tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (Zr-PCTA) and zirconium 2,2’,2”-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (Zr-NOTA). Additionally, we elucidate the solid-state structure of each complex using single crystal x-ray diffraction analysis. Finally, we found that [(89)Zr]Zr-PCTA and [(89)Zr]Zr-NOTA demonstrate excellent stability in vitro and in vivo and provide a rationale for these observations. These innovative findings have the potential to guide the development of safer and more robust immuno-PET agents to improve precision medicine applications.

The single-crystal X-ray structures of the hexacoordinate Co(II), Ni(II), and Mn(II) complexes of thiophene-2-carboxamide are reported as the perchlorate salts. The Co(II) and Ni(II) complexes are isostructural and crystallize in a cubic habit which is not frequently observed for complexes of metal ions with organic ligands (Pa $$\overline 3$$ , Z = 4, Co complex, 2, a = 16.466(2) A, Ni complex, 3, a = 16.430(2) A). The Mn(II) complex, 4, is monoclinic and contains four t-butanol molecules in the unit cell (P21/n, Z = 2, a = 9.7796(4) A, b = 11.4847(4) A, c = 23.3062(9) A, β = 93.504(1)°). Hydrogen-bonding is a significant factor in all of these substances, especially for the Mn(II) complex. The structures and the infrared spectra of the compounds are discussed. Ellipsoid plots of the ions Co(C3H5NOS)6 2+ and Mn(C3H5NOS)6 2+

Di(2-thienyl)imide, 1, has been shown to chemically polymerize, and, if metal complexes of 1 could be synthesized, the polymer could have potential applications as an ion sensor and environmental remediation agent. As a first step towards this goal, di(2-thienyl)imide is shown to form complexes with Mn (II), Co (II), and Zn (II) perchlorates. The complexes of Mn2+ and Co2+ are isostructural with two di(2-thienyl)imide ligands in equatorial positions and two perchlorate ions axial. The Zn2+ complex has two water molecules in the axial positions and the thiophene rings in the two equatorial ligands are tilted in the same direction from the median plane due to intra- and intermolecular contacts. The crystal structures and infrared spectra, as well as an improved synthesis and polymerization of di(2-thienyl)imide, are reported and discussed.

Using a modular library format in conjunction with cell viability (MTS) and flow cytometry assays, 90 cationic complexes [AuPL]n+ (P = phosphine ligand; L = thiourea derivative or chloride) were studied for their antiproliferative activity in CD8+ T lymphocyte cells. The activity of the compounds correlates with the steric bulk of the phosphine ligands. Thiourea serves as a leaving group that is readily replaced by cysteine thiol (NMR, ESI-MS). Taking advantage of selective thiourea ligand exchange, the fragments [Au(PEt3)]+ and [Au(JohnPhos)]+ (JohnPhos = 1,1′-biphenyl-2-yl)di-tert-butylphosphine) in compounds 1 and 2 were transferred to recombinant human serum albumin (rHSA). PEt3 promoted efficient modification of Cys34 in HSA (HSA-1), whereas use of bulky JohnPhos as a carrier ligand led to serum protein nonspecifically modified with multiple gold adducts (HSA-2) (Ellman’s test, ESI-TOF MS). HSA-1, but not HSA-2, strongly inhibits T cell proliferation at nanomolar doses. The potential role of HSA as a...

The performance of organic field-effect transistors (OFETs) depends heavily upon the intrinsic properties and microstructure of the semiconducting layer, the processes taking place at the semiconductor/dielectric interface, and the quality of contacts. In this article, we report on 7,14-bis(trimethylsilylethynyl) benzo[k]tetraphene single crystal and thin-film OFETs and compare their properties. We find that the single crystals exhibit a pronounced anisotropy in electrical characteristics, with a maximum field-effect mobility of 0.3 cm2 V−1 s−1. Through density functional theory (DFT) calculations we identified the main direction for hole transport, which was confirmed by X-ray diffraction (XRD) measurements as parallel to the plane of the single crystal facet where the transport was probed. By processing the material as a thin-film semiconductor, the content of high-mobility direction probed within the transistor channel was enhanced. The control of film morphology, coupled with a different design of the device structure allowed us to obtain an order of magnitude higher charge-carrier mobilities and a very small spread in device performance.

It was found that methyl-2-thienylimide ( L 1 ), C 4 H 3 SC(O)NHC(O)CH 3 , could act as a ligand and combine with metal(II) perchlorates (Ni 2+ , Mn 2+ , and Co 2+ ) to produce complexes for potential use as metal ion uptake and release agents in polymer form. Methyl-3-thienylimide ( L 2 ) formed a similar complex with Co 2+ . The synthesis and structures obtained from single crystal X-ray diffraction data are reported. The carbonyl groups in the ligands are cis / trans with respect to the N-H group in the solid state but are necessarily trans-trans in the complex. The ligands are bidentate, forming bonds to the metal ions through the imide oxygen atoms; the imide ligands are protonated. The cobalt and nickel complexes have two bidentate ligands in the equatorial positions and two water molecules in the apical positions with the ligands cis to each other in the case of methyl-2-thienylimide while they are trans in the cobalt complex formed by methyl-3-thienylimide. The manganese complex is seven coordinate with three bidentate ligands and one water molecule. Significant hydrogen bonding is present in all of the complexes leading to the formation of 2D networks in two cases and an infinite chain in one. IR, and UV–Visible spectroscopy along with elemental analyses are also presented.

Previously, the generation of alkyl gold intermediates (B) from nucleophilic addition to inactivated alkenes was limited by the use of trigold oxo complexes (A) with arylphosphine ligands, [(Ar3PAu)3O]BF4, in the presence of amine base. In this mechanism study, we have found that the basicity of the gold complex is key to favoring alkyl gold complex formation. Kinetic and substrate studies have shown that the strongly Bronsted basic IPrAuOH also mediates alkyl gold complex formation. The observation of an intermediate gold amide complex suggests these processes are initiated by deprotonation of the nucleophile. Trigold oxo reactions in the absence of base reveal that the byproduct from the reaction of substrate with A is digold hydroxide complex, [(LAu)2OH]BF4 (C). This complex is catalytically active for urea hydroamination at room temperature to form pyrrolidine D; however, it does not catalyze the hydroalkoxylation of the alcohol substrate. Importantly, catalysis to D occurs faster than can be accounte...

During high power density operations, the performance of polymer electrolyte membrane fuel cells (PEMFCs) is limited by high water saturation levels in the cathode catalyst layer due to high wettability of the ionic polymer phase. A new heat treatment was used to create and permanently lock-in the surface structure of a biphasic membrane (Nafion® 212). Several surface characterization techniques were used to verify the engineered membrane’s surface after heat treatment, including contact angle, multi-mode atomic force microscopy (AFM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). We found that specific heat treatment conditions will lead to the formation of either a hydrophobic or hydrophilic surface layer. The results of this research will guide the design of a new class of PEMFC catalyst layers. Engineered PEMFC catalyst layers are expected to prevent electrode flooding, therefore leading to higher performance and efficiency during high power density operations.

Poly(glycerol sebacate) (PGS)/nanohydroxyapatite (nHA) composites were assessed to develop new materials for closure via tissue transport for nonhealing defects (e.g., cleft palate and large skin wounds). The elastic shape memory polymer, PGS, was reinforced with nHA at 3 and 5% loading to increase the mechanical properties compared with the undoped PGS. Differential scanning calorimetry (DSC) was utilized to identify a glass transition temperature (Tg ) of -25°C. X-ray diffraction demonstrated a reduction in the amorphous nature of the material. The Fourier transform infrared photoacoustic spectral (FTIR-PAS) data showed decreased CO bonding and increased hydrogen bonding with increased nHA incorporation. Composites exhibited Young's moduli in the range of 0.25-0.5 MPa and tensile strength of 1.5-3 N. No significant difference in extension to break (∼50 mm) with addition of nHA was observed. The elastic modulus significantly increased for 5% PGS/nHA compared to 0 and 3% PGS/nHA and tensile strength significantly increased for 3% PGS/nHA compared to 0 and 5% PGS/nHA. Degradation of 5% nHA/PGS significantly increased during the second week compared to PGS 0 and 3% PGS/nHA. The accelerated degradation for 5% PGS/nHA coupled with decreased flexibility and tensile strength implies an interruption in crosslinking. By maintaining flexibility and extension while increasing tensile strength, the 3% PGS/nHA doped satisfied the force range desired for closure of soft tissue defects. Based on this work, PGS with 3% nHA shape memory polymers should serve as a good candidate for closure of nonhealing soft tissues. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1366-1373, 2016.

In this work we have revisited the charge-transfer crystal system perylene–TCNQ and found that this complex can crystallize with a 2:1 stoichiometric ratio in addition to the 1:1 and 3:1 stoichiometries previously observed. The vibrational and electronic properties of these perylene–TCNQ charge-transfer crystals have been investigated by means of Raman scattering measurements and density functional theory calculations. Electrical measurements were also performed by preparing organic field-effect transistors (OFETs) from the crystals. The Raman spectra in the low-frequency range (below 200 cm–1) are found to be unique to the specific crystal structure and can therefore be used to determine the stoichiometry. The Raman data and the X-ray diffraction measurements indicate that at room temperature the amount of charge transferred to the TCNQ molecule is less than 0.2e for all three compounds, and is nearly the same in P1T1 and P2T1 but is slightly larger in P3T1. The electronic structure calculations suggest ...

Cationic gold(I) enamine complexes with the (t-Bu)2(o-biphenyl)phosphine ligand were isolated and characterized by NMR spectroscopy and X-ray crystallography. The complexes display highly distorted coordination modes that are consistent with characterization as α-metalated iminium ions. The barrier to rotation around the formal enamine C–C double bond has been measured in a geminally disubstituted enamine complex, and it is comparable to the barrier to C–C single-bond rotation in electronically restricted alkanes. With additional substitution on the enamine double bond, the complexes remain highly distorted, and the reaction of a mixture of E and Z enamines results in formation of a stereochemically pure gold complex. A survey of binding constants reveals enamines to be significantly stronger donors than any alkenes examined to date, and in the case of a geminally disubstituted enamine, the coordination is stronger even than that of triethylamine. The high stability drives the isomerization of an internal...

A thin film of a RuII(bpy)2(dcbpy)Cl2, RuDCBPY, doped metal–organic framework of Zr6O4(OH)4(bpdc)6, RuDCBPY-UiO67 (where bpy is 2,2′-bipyridine, dcbpy is 5,5′-dicarboxyphenyl-2,2′-bipyridine, and bpdc is 4,4′-biphenyldicarboxylic acid), has been prepared on fluorine-doped tin oxide and glass slides solvothermally. The film is shown to be isostructural with UiO-67 and similarly doped RuDCBPY-UiO67 powders. The photophysical properties of the film show significant line broadening of the diffuse reflectance spectra, a successive red shift of the emission maxima, and biphasic kinetics with increased RuDCBPY doping of UiO-67 films above 10 mm. The two lifetime components are consistent with a dual population of RuDCBPY within the UiO-67 material: a population of RuDCBPY incorporated into the framework of UiO-67 replacing a bpdc ligand and a second population of RuDCBPY encapsulated within the octahedral cavities. The RuDCBPY dopant within the UiO-67 films interact with each other and undergo self-quenching via...

Development of resorbable elastic composites as an alternative means to apply contractive forces for manipulating craniofacial bones is described herein. Composites made from the biodegradable elastomer, poly (1,8-octanediol co-citric acid) (POC), and hydroxyapatite (nHA) with a 200 nm diameter (0-20% loadings) were created to develop a material capable of applying continuous contractive forces. The composites were evaluated for variation in their mechanical properties, rate of degradation, and interaction of the hydroxyapatite nanoparticles with the polymer chains. First, an ex vivo porcine model of cleft palate was used to determine the rate of cleft closure with applied force. The closure rate was found to be 0.505 mm N(-1) . From this approximation, the ideal maximum load was calculated to be 19.82 N, and the elastic modulus calculated to be 1.98 MPa. The addition of nHA strengthens POC, but also reduces the degradation time by 45%, for 3% nHA loading, compared to POC without nHA. X-ray diffraction data indicates that the addition of nHA to amorphous POC results in the formation of a semicrystalline phase of the POC adjacent to the nHA crystals. Based on the data, we conclude that amongst the 0-20% nHA loadings, a 3% loading of nHA in POC may be an ideal material (1.21 MPa elastic modulus and 13.17 N maximum load) to induce contraction forces capable of facilitating osteogenesis and craniofacial bone repair.

As a result of explorations into the solution chemistry of silver/gold mixtures, a unique diphosphine trimetallic chloronium dication was discovered that incorporates silver-arene chelation and a triangular mixed gold/silver core in the solid state. Notably, it was isolated from a Celite prefiltered solution initially thought to be silver-free. The crystal structure also incorporates the coordination to silver of one fluorine atom of one SbF6(-) counterion. The structure was compared to two new, but well-precedented, phosphine digold chloride cations. DFT calculations supported significant silver-halide and silver-arene interactions in the mixed gold/silver complex and metallophilic interactions in all three complexes. Comparison of computed data revealed that the ωB97X-D functional, which has a long-range corrected hybrid with atom-atom dispersion corrections, gave a better fit to the experimental data compared with the PBE0 functional, which has previously failed to capture aurophilic interactions. Preliminary studies support the presence of the mixed gold/silver structure in solution.

The new crystalline compound, Li2PO2N, was synthesized using high temperature solid state methods starting with a stoichiometric mixture of Li2O, P2O5, and P3N5. Its crystal structure was determined ab initio from powder X-ray diffraction. The compound crystallizes in the orthorhombic space group Cmc21 (# 36) with lattice constants a = 9.0692(4) A, b = 5.3999(2) A, and c = 4.6856(2) A. The crystal structure of SD-Li2PO2N consists of parallel arrangements of anionic chains formed of corner sharing (PO2N2) tetrahedra. The chains are held together by Li+ cations. The structure of the synthesized material is similar to that predicted by Du and Holzwarth on the basis of first principles calculations (Phys. Rev. B 81, 184106 (2010)). The compound is chemically and structurally stable in air up to 600 °C and in vacuum up to 1050 °C. The Arrhenius activation energy of SD-Li2PO2N in pressed pellet form was determined from electrochemical impedance spectroscopy measurements to be 0.6 eV, comparable to that of the glassy electrolyte LiPON developed at Oak Ridge National Laboratory. The minimum activation energies for Li ion vacancy and interstitial migrations are computed to be 0.4 eV and 0.8 eV, respectively. First principles calculations estimate the band gap of SD-Li2PO2N to be larger than 6 eV.

Three bioactive compounds were isolated from an organic extract of an ascomycete fungus of the order Chaetothyriales (MSX 47445) using bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Of these, two were benzoquinones [betulinan A (1) and betulinan C (3)], and the third was a terphenyl compound, BTH-II0204-207:A (2). The structures were elucidated using a set of spectroscopic and spectrometric techniques; the structure of the new compound (3) was confirmed via single-crystal X-ray diffraction. Compounds 1-3 were evaluated for cytotoxicity against a human cancer cell panel, for antimicrobial activity against Staphylococcus aureus and Candida albicans, and for phosphodiesterase (PDE4B2) inhibitory activities. The putative binding mode of 1-3 with PDE4B2 was examined using a validated docking protocol, and the binding and enzyme inhibitory activities were correlated.

Large-pore mesoporous silica nanoparticles (MSN) were prepared and functionalized to serve as a highly robust and biocompatible delivery platform for platinum-acridine (PA) anticancer agents. The material showed a high loading capacity for the dicationic, hydrophilic hybrid agent [PtCl(en)(N-[acridin-9-ylaminoethyl]-N-methylpropionamidine)] dinitrate salt (P1A1) and virtually complete retention of payload at neutral pH in a high-chloride buffer. In acidic media mimicking the pH inside the cells' lysosomes, rapid, burst-like release of P1A1 from the nanoparticles is observed. Coating of the materials in phospholipid bilayers resulted in nanoparticles with greatly improved colloidal stability. The lipid and carboxylate-modified nanoparticles containing 40 wt.% drug caused S phase arrest and inhibited cell proliferation in pancreatic cancer cells at submicromolar concentrations similar to carrier-free P1A1. The most striking feature of nanoparticle-delivered P1A1 was that the payload did not escape from the acidified lysosomal vesicles into the cytoplasm, but was shuttled to the nuclear membrane and released into the nucleus.

Eighteen (1-18) and seven (1, 4, 6-8, 17 and 18) compounds were isolated from organic extracts of axenic cultures of two freshwater fungi Clohesyomyces sp. and Clohesyomyces aquaticus (Dothideomycetes, Ascomycota), respectively. Compounds 1-12 belong to the α-pyrone class of natural products, compounds 13 and 14 were tetrahydroxanthones, compounds 15 and 16 were hexahydroxanthones, while compounds 17 and 18 were cyclodepsipeptides. The structures were elucidated using a set of spectroscopic and spectrometric techniques. The absolute configurations of compounds 2, 3, 6, and 7 were assigned via a modified Mosher's ester method using 1H NMR data. The relative configurations of compounds 14-16 were determined through NOE data. Compounds 1, 2, 6, 8, 13, 14, and 15 were found to inhibit the essential enzyme bacterial peptidyl-tRNA hydrolase (Pth1), with (13; secalonic acid A) being the most potent. Compounds 1 and 4-18 were also evaluated for antimicrobial activity against an array of bacteria and fungi but were found to be inactive.

Cationic {[(t-Bu)2(o-biphenyl)P]Au(enol ether)}+SbF6– and {[(t-Bu)3P]Au(enol ether)}+SbF6– complexes were isolated and characterized by NMR spectroscopy and X-ray crystallography. For three of the four complexes characterized in the solid state, gold coordinates to the electron-rich bond in a η1 fashion, while a 2,3-dihydrofuran complex displays η2 coordination.

The formation of unusual seven-membered, sterically overloaded chelates [Pt(en)(L/L´)](NO(3))(2) (4a/4b) from the corresponding potent hybrid antitumor agents [PtCl(en)(LH/L´H)](NO(3))(2) (3a/3b) is described, where en is ethane-1,2-diamine and L(H) and L´(H) are (protonated) N-(2-(acridin-9-ylamino)ethyl)-N-methylpropionimidamide and N-(2-(acridin-9-ylamino)ethyl)-N-methylacetimidamide, respectively. Compounds 3a and 3b inhibit H460 lung cancer cell proliferation with IC(50) values of 12 ± 2 nM and 2.8 ± 0.3 nM, respectively. The new derivative 3b proves to be not only the most cytotoxic platinum-acridine hybrid of this kind, but also one of the most potent platinum-based anticancer agents described to date. The chelates 4a and 4b do not undergo ligand substitution reactions with nucleobase nitrogen and cysteine sulfur and do not intercalate into DNA. Despite their inertness, the two chelates appear to maintain micromolar activity in H460 cells. The results are discussed in the context of potential DNA-mediated and DNA-independent cell kill mechanisms and the potential use of the chelates as prodrugs.

Five new isostructural two-dimensional lanthanide-based coordination polymers with the formula Ln 2 (F 4 BDC) 3 (DEF) 2 (EtOH) 2 -2(DEF) (Ln = Tb, 1 ; Gd, 2 ; Eu, 3 ; La, 4 ; Nd, 5 ; F 4 BDC 2− = 2,3,5,6-tetrafluoro-1,4-benzenedicarboxylate ligands; DEF = N,N′-diethylformamide), have been synthesized by reaction of Ln(NO 3 ) 3 and F 4 BDC in a DEF/EtOH solvent mixture. The compounds were characterized by single-crystal and powder X-ray diffraction. In all cases, the metal ion is coordinated by nine oxygen atoms from two bidentate μ 2 -F 4 BDC 2− ligands, two bridging μ 2 -F 4 BDC 2− ligands, one μ 3 -F 4 BDC 2− ligand, one DEF molecule and one EtOH molecule forming a tri-capped trigonal prism. The Ln(1) metal ion is linked to an adjacent Ln(1) metal ion through the oxygen atoms of two bridging μ 2 -F 4 BDC 2− ligands and two μ 3 -F 4 BDC 2− bridging ligands to form a Ln 2 O 18 dimer. The Ln 2 O 18 polyhedra building units are linked to each other through four F 4 BDC 2− ligands to form 2D sheets that are held together by hydrogen bonding to form a 3D framework. Compounds 1–5 were further characterized using thermogravimetric analysis and infrared spectroscopy. Studies of the photoluminescence properties of compounds 1 and 3 , as well as the catalytic activity of compounds 3 – 5 in the Biginelli reaction, are presented.

Reactions between [Nb6Cl12(CN)6]4− and [Mn(salen)]+ in MeOH–H2O solvent mixture led to the formation of a new compound: {[(Mn2(salen)2)][[Mn(salen)(H2O)]0.67[Mn(salen)(MeOH)]1.33(Nb6Cl12(CN)6)]}·1.7H2O·2MeOH (1). Single crystal X-ray analysis has shown that 1 possesses 1D framework built of heterotrimeric supramolecular anions, {[Mn(salen)(s)]2[Nb6Cl12(CN)6]}2− and [Mn2(salen)2]2+ phenoxo bridged dimers linked to each other through two cyanide ligands located in axial positions. When 1 was left in a methanolic solution of (Me4N)+, its 1D framework was transformed into a 2D framework of the previously reported compound [Me4N]2[(Mn(salen))2(Nb6Cl12(CN)6))] (2) which has a 2D anionic 4,4-network built of [Nb6Cl12(CN)6]4− and [Mn(salen)]+ nodes linked by CN ligands (Zhou, Day and Lachgar, Chem. Mater., 2004, 16, 4870).1Magnetic susceptibility measurements indicate that 1 exhibits weak antiferromagnetic interactions due to the phenolate-bridged out-of-plane Mn(III) dimers with J = −1.50(5) cm−1. Thermal stability of 1 was studied.

An ene-yne cross methasis of silyl-substituted alkynes and alkenes has been developed as a route to 4-aryl- and 4-alkyl-2-silyl-substituted 1,3-dienes. The dienes prepared were used to affect highly diastereoselective Diels-Alder reactions and then the silicon-substituted Diels-Alder cycloadducts were used in Hiyama cross-coupling reactions. The cross-coupling reactions enable these silicon dienes to be used as synthons for a variety of other dienes one might prepare and need access to. Two of the silicon-substituted Diels-Alder cycloadducts and one of the Hiyama cross-coupling products were also characterized by X-ray crystallography.

A series of cationic gold(I) complexes containing 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea (1), [AuL(1)]n+ (where L is Cl−, Br-, SCN−, PEt3, PPh3, or 1), derived from a class of analogous platinum(II) antitumor agents, has been synthesized. Unlike platinum, gold does not form permanent adducts with DNA, and its complexes are two orders of magnitude less cytotoxic in non-small-cell lung cancer cells than the most active platinum-based agent. Instead, several gold analogues show submicromolar and selective antimicrobial activity against Mycobacterium tuberculosis.

Two new lanthanide thiophenedicarboxylate-based metal-organic frameworks with the formulas La2(2,5-TDC)3(DMF)2H2O DMF (1) and Gd2(2,5-TDC)3(DMF)2H2O (2) (2,5-TDC = 2,5-thiophenedicarboxylic acid; DMF = N,N′-dimethylformamide), have been synthesized by two different methods (solvothermal and reflux). The synthesis of these materials from metal nitrate hydrates with 2,5-TDC as the organic linker in DMF/n-propanol afforded two rigid non-interpenetrating frameworks with coordinated solvent molecules (DMF and H2O) occupying the channels. Compound (1) crystallizes in an orthorhombic space group Pna21 with Z = 4, a = 17.434(4) A, b = 11.227(3) A, c = 17.980(4) A and V = 3,519.0(15) A3. Compound (2) crystallizes in a monoclinic P21/n space group with Z = 4, a = 17.5387(17) A, b = 10.8038(11) A, c = 17.7283(18) A, β = 104.793(2) and V = 3,247.9(6) A3. Powder X-ray diffraction, thermogravimetric analysis and infrared spectroscopy of (1) and (2) are presented. Two new 3D lanthanide-thiophenedicarboxylate based coordination polymers with the formulas La2(2,5-TDC)3(DMF)2H2O-DMF (1) and Gd2(2,5-TDC)3(DMF)2H2O (2) (2,5-TDC = 2,5-thiophenedicarboxylic acid), have been synthesized by two different methods (solvothermal and reflux) and fully characterized.

N-(3-Thenoyl)fluorosulfonimide, (1), C4H3SC(O)N(H)SO2F, was prepared by the reaction of 3-thenoic acid with fluorosulfuryl isocyanate in acetonitrile solution. The new compound is a moderately strong nitrogen acid having a pKa of 2.4. Single-crystal X-ray structural analysis of (1) shows a pattern of strong intermolecular hydrogen-bonding, resulting in the formation of linear chains. (1) is electroinactive over a range of 2 V but undergoes hydrogen reduction ( E p / 2 c = − 0.28 V ). The salt of (1) with TBA+, 2, has been prepared and its crystal structure determined. The new dithienyl compound, bis(2-thienyl)imide, 3, has been prepared and crystallographically characterized. The polymers of 1, 3, and a polymer containing the fluorosulfonimide group formed from a copolymer of 3-methylthiophene/3-thiophene carboxylic acid are also reported.

A number of alkynols have been prepared by Sonogoshira coupling of propargyl alcohol to disubstituted aromatic halides. Chelation controlled addition of organometallic nucleophiles to these alkynols was then affected followed by the addition of sulfur dioxide. This methodology was used to prepare a number of oxathiolene oxides which have been screened as NQO1 (quinone oxidoreductase) inducers.

Reactions between (Me4N)4[Nb6Cl12(CN)6], [Mn(ACEN)Cl] (ACEN2- = bis(acetylacetonato)ethylenediamine), and dpyo (dpyo = 4,4′-dipyridyl-N,N′-dioxide) in different ratios led to the crystallization of two cluster-based metal-organic materials (CMOMs): {[Mn(ACEN)]2[Mn(ACEN)(MeOH)]2(Nb6Cl12(CN)6)(dpyo)}·2MeCN (1) and {[Mn(ACEN)]4(Nb6Cl12(CN)6)(dpyo)2}·MeCN·2MeOH·3.5H2O (2). Their crystal structures were determined by single-crystal X-ray diffraction. Both materials are built of neutral heteropentamers {[Mn(ACEN)]4[Nb6Cl12(CN)6]} in which the edge-bridged hexacyano octahedral metal cluster [Nb6Cl12(CN)6]4- is functionalized by four [Mn(III)(ACEN)]+ complexes. The supramolecular assemblies are connected to each other by the ditopic ligand, dpyo. In 1, each heteropentamer is trans-bridged by two dpyo linkers to give a neutral chain. Hydrogen bonds between nonbridging cyanides and coordinated methanol ligands further connect the chains into layers which are separated by solvent molecules. In 2 each heteropentamer ...

2-BF3-substituted 1,3-butadienes with potassium and tetrabutyl ammonium counterions have been prepared in gram quantities from chloroprene via a simple synthetic procedure. The potassium salt of this new main group element substituted diene has been characterized by 1H, 13C, 11B, and 19F NMR and the tetra n-butyl ammonium salt was also characterized by X-ray crystallography. Diels–Alder reactions of these dienes with dienophiles such as ethyl acrylate, methyl vinyl ketone, and N-phenylmaleimide are reported as well as subsequent Pd-catalyzed cross-coupling reactions of those Diels–Alder adducts. 4-Phenyl-2-BF3-substituted 1,3-diene was prepared by magnesium–halogen exchange from the corresponding 2-bromo and iodo dienes. The 4-phenyl-2-bromo-1,3-butadiene was also characterized by X-ray crystallography. 4-Phenyl-2-BF3-1,3-butadiene was used in Diels–Alder/cross-coupling reactions and the product of a Diels–Alder reaction with N-phenylmaleimide followed by cross-coupling with 4-bromo-benzonitrile was also characterized by X-ray crystallography.

The 9-aminoacridine chromophore is an important building block of DNA-targeted chemotherapeutic agents. The success of 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea as a carrier group in cytotoxic platinum-intercalator conjugates prompted us to explore the synthesis of an analogous guanidine-functionalized acridine. In a successful effort to generate such a derivative, various methods of guanidylation were employed, which demonstrate that the acridine C9-N9 linkage is highly susceptible to electrophilic and nucleophilic attack. The newly established reactivities provide efficient pathways to novel cyclic and spirocyclic acridine derivatives.

The following complexes of type [PtCl(R)(ACRAMTU)](NO3)2 (ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea)), derived from prototype 1 (with R = ethane-1,2-diamine), were synthesized: 2 (with R = (1R,2R)-1,2-diaminocyclohexane), 3 (with R = propane-1,3-diamine), 4 (with R = N1,N1,N2,N2-tetramethylethane-1,2-diamine), and 5 (with R = 2,2'-bipyridine). The DNA sequence specificity of the conjugates and their antiproliferative potential in HL-60 and H460 cells were investigated. Conjugate 3 showed the strongest non-cisplatin-type DNA damage in polymerase stop assays and superior cell kill efficacy in H460 lung cancer (IC50 = 70 nM).

The exploration of freshwater ascomycetes, which have undergone only limited investigation, may provide opportunities both to characterize new genera/species of fungi and to uncover new chemical diversity. In this study, seven acetophenone derivatives, madisone, 4'-methoxymadisone, dehydromadisone, 2″-methoxymadisone, dihydroallovisnaginone, dimadisone, and 4'-methoxydimadisone were characterized from an organic extract of a recently described Lindgomyces madisonensis (G416) culture, which was isolated from submerged wood collected in a stream in North Carolina. Madisone, dehydromadisone, 2″-methoxymadisone, dimadisone and 4'-demethoxydimadisone have not been reported previously, while 4'-methoxymadisone and dihydroallovisnaginone were previously unknown as natural products. Their structures were assigned on the basis of NMR and HRESIMS data, with the structure of madisone supported by X-ray crystallography. The antimicrobial activities of madisone, 4'-methoxymadisone and dihydroallovisnaginone were evaluated against a panel of bacteria and fungi. A heat map analysis of the surface of a G416 culture showed that most of the isolated compounds concentrated in the guttate compared with the vegetative mycelium of the fungus.

Chitosan films were synthesized with hexagonal silver nanoparticles (Ag NP). The unique shape and size of the Ag NP shift the optical absorption into the infrared. Stimulation of the nanoparticles with infrared light was used to generate heat and facilitate intracellular delivery of fluorescently-labeled dextran molecules. Chitosan films prepared with hexagonal or spherical Ag NP were characterized by optical and thermal analyses, and X-ray diffraction. There were found to be slight differences between how the chitosan molecular chains interface with the Ag NP depending upon shape of the nanoparticle. Viability of cells associated with dermal wound healing was evaluated on chitosan films prepared with hexagonal or spherical Ag NP, with both keratinocytes and fibroblasts having normal or moderately enhanced growth on films containing hexagonally-shaped nanoparticles.

1,3-Dien-2-yl(Rpyr)bis(dimethylglyoximato) cobalt(III) complexes (R = H, NMe2) have been shown to participate in cycloaddition reactions with a variety of tropones. In general, tropones that do not contain electron-withdrawing substituents react with dienyl complexes via [6 + 4] cycloaddition and tropones that are substituted with at least one additional electron-withdrawing group react via [4 + 2] cycloaddition. Both types of metal-substituted cycloadducts ([6 + 4] and [4 + 2]) presented here have also been characterized by X-ray crystallography.

Poly(glycerol sebacate) (PGS)/nanohydroxyapatite (nHA) composites were assessed to develop new materials for closure via tissue transport for nonhealing defects (e.g., cleft palate and large skin wounds). The elastic shape memory polymer, PGS, was reinforced with nHA at 3 and 5% loading to increase the mechanical properties compared with the undoped PGS. Differential scanning calorimetry (DSC) was utilized to identify a glass transition temperature (Tg ) of -25°C. X-ray diffraction demonstrated a reduction in the amorphous nature of the material. The Fourier transform infrared photoacoustic spectral (FTIR-PAS) data showed decreased CO bonding and increased hydrogen bonding with increased nHA incorporation. Composites exhibited Young's moduli in the range of 0.25-0.5 MPa and tensile strength of 1.5-3 N. No significant difference in extension to break (∼50 mm) with addition of nHA was observed. The elastic modulus significantly increased for 5% PGS/nHA compared to 0 and 3% PGS/nHA and tensile strength significantly increased for 3% PGS/nHA compared to 0 and 5% PGS/nHA. Degradation of 5% nHA/PGS significantly increased during the second week compared to PGS 0 and 3% PGS/nHA. The accelerated degradation for 5% PGS/nHA coupled with decreased flexibility and tensile strength implies an interruption in crosslinking. By maintaining flexibility and extension while increasing tensile strength, the 3% PGS/nHA doped satisfied the force range desired for closure of soft tissue defects. Based on this work, PGS with 3% nHA shape memory polymers should serve as a good candidate for closure of nonhealing soft tissues. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1366-1373, 2016.