Photochemical C-F Activation Enables Defluorinative Alkylation of Trifluoroacetates and -Acetamides.

The installation of gem-difluoromethylene groups into organic structures remains a daunting synthetic challenge despite their attractive structural, physical, and biochemical properties. A very efficient retrosynthetic approach would be the functionalization of a single C-F bond from a trifluoromethyl group. Recent advances in this line of attack have enabled the C-F activation of trifluoromethylarenes, but limit the accessible motifs to only benzylic gem-difluorinated scaffolds. In contrast, the C-F activation of trifluoroacetates would enable their use as a bifunctional gem-difluoromethylene synthon. Herein, we report a photochemically mediated method for the defluorinative alkylation of a commodity feedstock: ethyl trifluoroacetate. A novel mechanistic approach was identified using our previously developed diaryl ketone HAT catalyst to enable the hydroalkylation of a diverse suite of alkenes. Furthermore, electrochemical studies revealed that more challenging radical precursors, namely trifluoroacetamides, could also be functionalized via synergistic Lewis acid/photochemical activation. Finally, this method enabled a concise synthetic approach to novel gem-difluoro analogs of FDA-approved pharmaceutical compounds.

Photoreduction of CO2 with a Formate Dehydrogenase Driven by Photosystem II Using a Semi-artificial Z-Scheme Architecture.

Solar-driven coupling of water oxidation with CO2 reduction sustains life on our planet and is of high priority in contemporary energy research. Here, we report a photoelectrochemical tandem device that performs photocatalytic reduction of CO2 to formate. We employ a semi-artificial design, which wires a W-dependent formate dehydrogenase (FDH) cathode to a photoanode containing the photosynthetic water oxidation enzyme, Photosystem II, via a synthetic dye with complementary light absorption. From a biological perspective, the system achieves a metabolically inaccessible pathway of light-driven CO2 fixation to formate. From a synthetic point of view, it represents a proof-of-principle system utilizing precious-metal-free catalysts for selective CO2-to-formate conversion using water as an electron donor. This hybrid platform demonstrates the translatability and versatility of coupling abiotic and biotic components to create challenging models for solar fuel and chemical synthesis.

Visible-Light-Activated Asymmetric ß-C-H Functionalization of Acceptor-Substituted Ketones with 1,2-Dicarbonyl Compounds.

We report a visible-light-activated asymmetric ß-C(sp3)-H functionalization of 2-acyl imidazoles and 2-acylpyridines with 1,2-dicarbonyl compounds (typically α-ketoesters) catalyzed by a tailored stereogenic-at-rhodium Lewis acid catalyst. The C-C bond formation products are obtained in high yields (up to 99%) and with excellent stereoselectivities (up to >20:1 dr and up to >99% ee). Experimental and computational studies support a mechanism in which a photoactivated Rh-enolate transfers a single electron to the 1,2-dicarbonyl compound followed by proton transfer and a subsequent stereocontrolled radical-radical recombination.

Photo-physical, theoretical and photo-cytotoxic evaluation of a new class of lanthanide(iii)-curcumin/diketone complexes for PDT application.

Herein we report the synthesis, characterization, photophysical and photocytotoxicity studies of a new class of curcumin-based lanthanide(iii) complexes of general molecular formula [La(1,10-phen)2(L)(NO3)2] (1-4), where L = 1-phenylbutane-1,3-dione (L1, 1), 1-(anthracen-9-yl)butane-1,3-dione (L2, 2), 1-(3a1,5a1-dihydropyren-1-yl)butane-1,3-dione (L3, 3) and curcumin (L4, 4). Complex 1 was characterized by single-crystal X-ray crystallography and it exhibited the N4O6 coordination of La(iii). The presence of the low-lying and long-lived triplet excited state enabled the luminescent complexes (2-4) to generate singlet oxygen (1O2) in high yield when the complex was activated with visible light (400-700 nm, 10 J cm-2), which could be responsible for the photo-ablation of cancer cells. Complexes (2-4) exhibited remarkable photocytotoxicity in HeLa and MCF-7 cells with photocytotoxicity index 4-50 in the presence of visible light (400-700 nm, 10 J cm-2), while they were non-toxic in the dark with an IC50 value of >100 µM. The significantly lower toxicity (IC50 > 100 µM in the dark; IC50 in visible light ∼60 µM) of the complexes in MCF-10A (normal cells) in the dark and in visible light suggested their potential for targeting anticancer activity. Further studies showed that complex 4 induced caspase-dependent apoptosis through mitochondrial damage, mitochondrial respiration inhibition and reactive oxygen species (ROS) elevation. The cytosolic localization of complex 4 in HeLa cells, having a curcumin moiety as a fluorophore, was proved from the confocal microscopic studies. The photocytotoxicity of the complexes (1-4) was directly correlated to the efficacy of the complexes to generate singlet oxygen, which resulted in the photocytotoxicity order of 4 > 3>2 ≫ 1. Photo-physical studies revealed that the chelation of curcumin by La(iii) facilitated intersystem crossing in curcumin by reducing the energy gap of the singlet to triplet excited state. Therefore, the presence of low-lying and long-lived triplet excited state was responsible for increasing the generation of singlet oxygen and, thereby, photo-cytotoxicity in HeLa and MCF-7 cells. The present study has given an overall (Chemistry to Biology) perspective on the effect of La(iii) on the photo-cytotoxicity of selected photo-active curcumin-based ß-diketonate ligands.

Conducting Polyetheretherketone Nanocomposites with an Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multimodal Therapeutic Applications.

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades because of its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue toward its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Because of the formation of an electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved 12 orders of magnitude enhancement in their electrical conductivity and thereby enabled electrophoretic deposition of a bioactive/antibacterial coating consisting of stearyltrimethylammonium chloride-modified hydroxyapatite. The coated composite implant shows significant boosting of bone marrow mesenchymal stem cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers has enabled laser-induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 °C in 150 s. The unique multifunctionality of the implant has also been demonstrated for photothermal applications such as enhancing bacterial eradication and tumor cell inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multifunctional implant in bone repair applications as well as multimodal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis.

Microwave-assisted Wolff rearrangement of cyclic 2-diazo-1,3-diketones: an eco-compatible route to alpha-carbonylated cycloalkanones.

The microwave-assisted Wolff rearrangement of cyclic 2-diazo-1,3-diketones performed in the presence of a stoichiometric amount of alcohol, amine, or thiol is an efficient, user, and environmentally friendly synthetic protocol for the synthesis of alpha-carbonylated cycloalkanones. This approach proves superior to existing protocols in scope and eco-compatibility.

Enhanced osteogenic activity of phosphorylated polyetheretherketone via surface-initiated grafting polymerization of vinylphosphonic acid.

Polyetheretherketone (PEEK) is considered to be a prime candidate with the potential to replace biomedical metallic materials as an orthopedic and dental implant on account of its elastic modulus similar to that of human cortical bone. Unfortunately, its biomedical application is impeded by the bioinert surface property and inferior osteogenic activity. In this work, phosphate groups were incorporated onto the PEEK surface through a single-step UV-initiated graft polymerization of vinylphosphonic acid. Diffuse reflectance Fourier transform infrared spectroscopy (DRFTIR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) revealed that phosphate groups were successfully introduced onto the PEEK surface without apparently altering its surface topographical feature and roughness. Water contact angle measurements diclosed the increasing hydrophilia after surface phosphonation. In vitro cell adhesion, spreading, proliferation, alkaline phosphatase activity, extracellular matrix mineralization, and real-time PCR analyses showed enhanced adhesion, spreading, proliferation and osteogenic differentiation of MC3T3-E1 osteoblast on the surface-phosphorylated PEEK. An in vivo biological evaluation in the rabbit tibiae proximal defect model by means of a histological analysis confirmed that the surface-phosphorylated PEEK had improved bone-implant contact. The obtained results indicate that enhanced osteogenic activity to surface-phosphorylated PEEK, which gives positive information of its potential applications in orthopedic and dental implants.

Photolysis of dibenzyl ketones sorbed on MFI zeolites in the presence of spectator molecules: cage effects, kinetics, and external surface sites characterization.

Over the past two decades, the photolytic reactions of dibenzyl ketones sorbed on zeolites have been investigated. The reported results are consistent with a supramolecular model that takes into account the physical and chemical nature of the structure of the zeolites and their effect on the reactive radical intermediates produced by photolysis of adsorbed molecules. The model incorporates various phenomena such as surface coverage, external and internal sorption, surface diffusion, radical sieving, and the resulting product distributions. This account reports direct evidence for the validation of the model through FT-IR spectroscopy and through a new method for "titrating" the binding sites via EPR spectroscopy. It is shown that it is possible to adjust and modulate the photolytic product distribution by varying the parameters of the system. The effects of co-adsorbed spectator molecules with different polarities, namely water, pyridine, and benzene, on the photolysis of o-methyldibenzyl ketone and dibenzyl ketone sorbed on MFI zeolites is examined. This study provides insights into a displacement mechanism caused by spectator molecules and further demonstrates how the product distribution of photolysis of sorbed ketones can be controlled. The kinetics of persistent radicals formed by photolysis of ketones sorbed on zeolites is directly monitored over time by EPR, providing a measure of the lifetime of these reactive organic intermediates. Finally, measurement of Langmuir isotherms was employed to provide classical evidence for the model.

Templation of the excited-state chemistry of alpha-(n-alkyl) dibenzyl ketones: how guest packing within a nanoscale supramolecular capsule influences photochemistry.

Excited-state behavior of eight alpha-alkyl dibenzyl ketones (alkyl = CH3 through n-C8H17) that are capable of undergoing type II and/or type I photoreactions has been explored in isotropic solution and within a water-soluble capsule. The study consisted of two parts: photochemistry that explored the excited-state chemistry and an NMR analysis that revealed the packing of each guest within the capsule. The NMR data (COSY, NOESY, and TOCSY experiments) revealed that ternary complexes between alpha-alkyl dibenzyl ketones and the capsule formed by two cavitands are kinetically stable, and the guests fall into three packing motifs modulated by the length of the alpha-alkyl chain. In essence, the host is acting as an external template to promote the formation of distinct guest conformers. The major products from all eight guests upon irradiation either in hexane or in buffer solution resulted from the well-known Norrish type I reaction. However, within the capsule the excited-state chemistry of the eight ketones was dependent on the alkyl chain length. The first group consisted of alpha-hexyl, alpha-heptyl, and alpha-octyl dibenzyl ketones that yielded large amounts of Norrish type II products within the host, while in solution the major products were from Norrish type I reaction. The second group consists of alpha-butyl and alpha-pentyl dibenzyl ketones that yield equimolar amounts of two rearranged starting ketones within the capsule (combined yield of ca 60%), while in solution no such products were formed. The third group consisted of alpha-methyl, alpha-ethyl, and alpha-propyl dibenzyl ketones that within the capsule yielded only one (not two) rearranged starting ketone in larger amounts (21-35%) while in solution no rearrangement product was obtained. Variation in the photochemistry of the guest within the capsule, with respect to the alpha-alkyl chain length of the guest, highlights the importance of how a small variation in supramolecular structure can influence the selectivity within a confined nanoscale reactor.

Ultrasound promoted asymmetric transfer hydrogenation of ketones using Ru(II)arene/amino alcohol catalyst system.

Asymmetric transfer hydrogenation of ketones using Ru(II)arene/amino alcohol catalyst system proceeds with significant rate enhancement by ultrasound promotion. Comparison of the silent reactions carried out at 25 degrees C with reactions under sonochemical activation at 25 degrees C clearly showed enhancement in catalytic activity by 5-10 times without significantly affecting the enantioselectivity.

Stable photoinduced charge separation in heptacene.

Heptacene, generated in inert gas matrices by photobisdecarbonylation of a bridged alpha-diketone precursor, undergoes ionization into radical anion and radical cation upon UV irradiation.

Degradation mechanisms of geosmin and 2-MIB during UV photolysis and UV/chlorine reactions.

We conducted chlorination, UV photolysis, and UV/chlorin reactions to investigate the intermediate formation and degradation mechanisms of geosmin and 2-methylisoborneol (2-MIB) in water. Chlorination hardly removed geosmin and 2-MIB, while the UV/chlorine reaction at 254 nm completely removed geosmin and 2-MIB within 40 min and 1 h, respectively, with lesser removals of both compounds during UV photolysis. The kinetics during both UV photolysis and UV/chlorine reactions followed a pseudo first-order reaction. Chloroform was found as a chlorinated intermediate during the UV/chlorine reaction of both geosmin and 2-MIB. The pH affected both the degradation and chloroform production during the UV/chlorine reaction. The open ring and dehydration intermediates identified during UV/chlorine reactions were 1,4-dimethyl-adamantane, and 1,3-dimethyl-adamantane from geosmin, 2-methylenebornane, and 2-methyl-2-bornene from 2-MIB, respectively. Additionally, 2-methyl-3-pentanol, 2,4-dimethyl-1-heptene, 4-methyl-2-heptanone, and 1,1-dichloro-2,4-dimethyl-1-heptane were newly identified intermediates from UV/chlorine reactions of both geosmin and 2-MIB. These intermediates were degraded as the reaction progressed. We proposed possible degradation pathways during the UV photolysis and UV/chlorine reactions of both compounds using the identified intermediates.

Microwave-assisted direct transformation of amines to ketones using water as an oxygen source.

Retro-reductive aminations, direct transformations of amines to ketones, were catalyzed by Pd/C in water under microwave irradiation.

Enhancement of bioactivity on medical polymer surface using high power impulse magnetron sputtered titanium dioxide film.

This study utilizes a novel technique, high power impulse magnetron sputtering (HIPIMS), which provides a higher ionization rate and ion bombardment energy than direct current magnetron sputtering (DCMS), to deposit high osteoblast compatible titanium dioxide (TiO2) coatings with anatase (A-TiO2) and rutile (R-TiO2) phases onto the biomedical polyetheretherketone (PEEK) polymer substrates at low temperature. The adhesions of TiO2 coatings that were fabricated using HIPIMS and DCMS were compared. The in vitro biocompatibility of these coatings was confirmed. The results reveal that HIPIMS can be used to prepare crystallinic columnar A-TiO2 and R-TiO2 coatings on PEEK substrate if the ratio of oxygen to argon is properly controlled. According to a tape adhesion test, the HIPIMS-TiO2 coatings had an adhesion grade of 5B even after they were immersed in simulated body fluid (SBF) environments for 28days. Scratch tests proved that HIPIMS-TiO2 coatings undergo cohesive failure. These results demonstrate that the adhesive force between HIPIMS-TiO2 coating/PEEK is stronger than that between DCMS-TiO2 coating/PEEK. After a long period (28days) of immersion in SBF, a bone-like crystallinic hydroxyapatite layer with a corresponding Ca/P stoichiometry was formed on both HIPIMS-TiO2. The osteoblast compatibility of HIPIMS-TiO2 exceeded that of the bare PEEK substrate. It is also noticeable that the R-TiO2 performed better in vitro than the A-TiO2 due to the formation of many negatively charged hydroxyl groups (-OH(-)) groups on R-TiO2 (110) surface. In summary, the HIPIMS-TiO2 coatings satisfied the requirements for osseointegration, suggesting the possibility of using HIPIMS to modify the PEEK surface with TiO2 for spinal implants.

Rapid prototyping of polymer microsystems via excimer laser ablation of polymeric moulds.

This study presents a novel method for rapid prototyping of polymer microsystems. The method is based on excimer laser ablation of a thermally and mechanically stable polymer, such as PEEK (poly-ether-ether-ketone). A negative of the desired microsystem is laser machined in PEEK, which can then be used directly for hot embossing or injection moulding of a series of prototypes. This approach is very rapid and considerably cheaper than more traditional approaches to toolmaking, while still performing well in terms of reproduction of tool dimensions. The reduction in time and cost for a master tool using this method opens up new possibilities for testing small series in the R&D phase of a microsystem. Finally, two particular applications of the technique are presented.

Scaffold development using selective laser sintering of polyetheretherketone-hydroxyapatite biocomposite blends.

In tissue engineering (TE), temporary three-dimensional scaffolds are essential to guide cell proliferation and to maintain native phenotypes in regenerating biologic tissues or organs. To create the scaffolds, rapid prototyping (RP) techniques are emerging as fabrication techniques of choice as they are capable of overcoming many of the limitations encountered with conventional manual-based fabrication processes. In this research, RP fabrication of solvent free porous polymeric and composite scaffolds was investigated. Biomaterials such as polyetheretherketone (PEEK) and hydroxyapatite (HA) were experimentally processed on a commercial selective laser sintering (SLS) RP system. The SLS technique is highly advantageous as it provides good user control over the microstructures of created scaffolds by adjusting the SLS process parameters. Different weight percentage (wt%) compositions of physically mixed PEEK/HA powder blends were sintered to assess their suitability for SLS processing. Microstructural assessments of the scaffolds were conducted using electron microscopy. The results ascertained the potential of SLS-fabricated TE scaffolds.

Efficient synthesis of imidazoles from aldehydes and 1,2-diketones using microwave irradiation.

[reaction: see text] A simple, high-yielding synthesis of 2,4,5-trisubstituted imidazoles from 1,2-diketones and aldehydes in the presence of NH(4)OAc is described. Under microwave irradiation, alkyl-, aryl-, and heteroaryl-substituted imidazoles are formed in yields ranging from 80 to 99%. Short syntheses of lepidiline B and trifenagrel illustrate the utility of this approach.

[Spectroscopic and chromatographic studies on photochemical isomerism of alpha, beta-diunsaturated ketones]. / Spektroskopische und chromatographische untersuchungen zur photochemischen isomerisierung von alpha,beta-diungesättigten ketonen.

Spectroscopic (UV, IR, NMR, MS) and chromatographic (HPLC, GC) investigations show for alpha,beta-diunsaturated ketones with one double bond fixed in a cyclohexene-, furan- or thiophene ring in most examples a photochemical Z/E-isomerization in solution by the influence of light. Investigations of conformers by IR and NMR however are not influenced during usual operations and light protection is not nessessary.

Safety of retained microcatheters: an evaluation of radiofrequency heating in endovascular microcatheters with nitinol, tungsten, and polyetheretherketone braiding at 1.5 T and 3 T.

BACKGROUND: The use of ethylene-vinyl alcohol copolymer for liquid embolization of cranial vascular lesions has resulted in microcatheter fragments entrapped in patients following endovascular procedures. Undergoing subsequent diagnostic MRI examinations poses a safety concern due to the possibility of radiofrequency heating of the metallic braid incorporated into the microcatheter. Heating of nitinol, tungsten, and polyetheretherketone (PEEK) braided microcatheters was assessed and compared using a phantom model. METHODS: Microcatheters coupled with fluoroptic temperature probes were embedded in a polyacrylamide gel within a head and torso phantom. Experiments were performed at 1.5 T and 3 T, analyzing the effects of different catheter immersion lengths, specific absorption rate (SAR) levels, short clinical scans, long clinical scans, and microcatheter fragment lengths. RESULTS: The maximal increase in temperature for the nitinol braided microcatheter during a 15 min scan was 3.06°C using the T1 fast spin echo sequence at 1.5 T and 0.45°C using the balanced steady state free precession sequence at 3 T. The same scans for fragment lengths of 9, 18, 36, and 72 cm produced maximal temperature rises of 0.68, 0.80, 1.70, and 1.07°C at 1.5 T, respectively. The temperature changes at 3 T for these fragment lengths were 0.66, 0.83, 1.07, and 0.72°C, respectively. The tungsten and PEEK braided microcatheters did not demonstrate heating. CONCLUSIONS: Substantial heating of nitinol braided microcatheters occurred and was a function of SAR level and geometric considerations. SAR and time limitations on MR scanning are proposed for patients with this microcatheter entrapped in their vasculature. In contrast, tungsten and PEEK braided microcatheters showed potential safe use in MRI.

A simple strategy for in situ fabrication of a smart hydrogel microvalve within microchannels for thermostatic control.

Self-regulation of temperature in microchip systems is crucial for their applications in biomedical fields such as cell culture and biomolecule synthesis as well as those cases that require constant temperature conditions. Here we report on a simple and versatile approach for in situ fabrication of a smart hydrogel microvalve within a microchip for thermostatic control. The thermo-responsive hydrogel microvalve enables the "on-off" switch by sensing temperature fluctuations to control the fluid flux as well as the fluid heat exchange for self-regulation of the temperature at a constant range. Such temperature self-regulation is demonstrated by integrating the microvalve-incorporated microchip into the flow circulation loop of a micro-heat-exchanging system for thermostatic control. Moreover, the microvalve-incorporated microchip is employed for culturing cells under temperature self-regulation. The smart microvalve shows great potential as a temperature controller for applications that require thermostatic conditions. This approach offers a facile and flexible strategy for in situ fabricating hydrogel microvalves within microchips as chemostats and microreactors for biomedical applications.