Readily Accessible and Brightly Fluorogenic BODIPY/NBD-Tetrazines via SNAr Reactions.

We describe SNAr reactions of some commercial amino-tetrazines and halo-dyes, which give efficiently quenched BODIPY/NBD-tetrazines (ΦFl < 0.01) in high yields and, importantly, with high purities affordable via simple silica gel chromatography only. The dyes exhibit large Stokes shifts, moderate environmental sensitivity, and emission enhancements (up to 193-fold) upon Tz ligation with BCN─a strained dienophile. They successfully serve as labels for HSA protein premodified with BCN, resulting in bright blue-green emission upon ligation.

A boron dipyrromethene chiral at boron and carbon with a bent geometry: synthesis, resolution and chiroptical properties.

We report a boron dipyrromethene that is chiral at boron and carbon (B*C*-BODIPY) and accessible through a two-pot, one-step synthesis-an interrupted Knoevenagel condensation. The electronic circular dichroism spectra of chiral high performance liquid chromatography-resolved enantiomers show clear Cotton effects (∣gabs∣ ∼ 2.0 × 10-4) in the visible region, suggesting efficient chirality induction to the otherwise achiral BODIPY. The dye's unusually weak fluorescence (Φfl < 0.01) is attributed partly to vibrational relaxations, as revealed by viscosity experiments, and partly to probable intersystem crossing that may be facilitated by the reduced symmetry of the bent-shaped molecular geometry.

Titanium-Silicon on CoCr Alloy for Load-Bearing Implants Using Directed Energy Deposition-Based Additive Manufacturing.

Cobalt-chromium (CoCr) alloys offer outstanding wear resistance when compared to other biocompatible metallic materials and are extensively used in articulating surfaces of total hip and knee arthroplasty. However, CoCr alloys' biocompatibility is known to be inferior to titanium (Ti). Wear- and corrosion-induced metal-ion release from CoCr alloys has been reported to cause cancer and negative physiological impacts. In this study, CoCr alloy was coated with commercially pure Ti (CpTi) and CpTi-Silicon (CoCrTi-Si) with the specific objective of reducing Co and Cr ion release during articulation, without degrading the excellent wear resistance of the CoCr alloy. Directed energy deposition (DED), a blown powder-based laser additive manufacturing technique, was utilized to process CpTi- and CpTi-Si-based coatings on Stellite 6B commercial CoCr alloy. Scanning electron microscopy (SEM), X-ray diffraction (XRD) analyses, and hardness testing found that refined carbides and titanium silicides increased the hardness from 321 ± 13 to 758 ± 48 HV0.5. Tribological studies determined a comparable wear rate between Stellite 6B alloy and CoCrTi-Si in DI water but a statistically significant reduction in Dulbecco's Modified Eagle Medium (DMEM). The wear rates for Stellite 6B were 8.5 ± 0.8 × 10-5 and 12.9 ± 0.4 × 10-5 mm3/Nm in DI water and DMEM, respectively. While the wear rates for CoCrTi-Si were 9.1 ± 0.5 × 10-5 and 8.9 ± 0.8 × 10-5 mm3/Nm in DI water and DMEM, respectively. Contact resistance acquisition displayed the presence of a passive film formation during tribological testing. ICP-MS results for Stellite 6B and CoCrTi-Si concluded a reduction of Co ions release in DI water from 149.8 ± 66.7 to 17.5 ± 0.7 ppb and a reduction in Cr ions release from 66.7 ± 32.4 to 18.0 ± 0.5 ppb, respectively. In DMEM media, Co ion release for Stellite 6B and CoCrTi-Si reduced from 10.1 ± 1.4 to 4.1 ± 0.2 ppb and Cr ion release for Stellite 6B and CoCrTi-Si reduced from 8.7 ± 0.2 to 5.0 ± 0.7 ppb, respectively. The current study revealed a new mode of manufacturing for CoCr alloy-based load-bearing implants that can reduce toxic metal ions release due to wear- and corrosion-induced damages.

Alumina and tricalcium phosphate added CoCr alloy for load-bearing implants.

Cobalt-chromium (CoCr) alloys are used in load-bearing implants due to their excellent wear resistance. However, poor tissue-material interactions can originate due to the release of wear and corrosion-induced Co and Cr ions, motivating the use of surface modification to reduce such phenomena. Premixed feedstock powders of CoCrMo + 2 wt.% tricalcium phosphate (TCP, CoCrTCP) and CoCrMo + 2 wt.% tricalcium phosphate + 4 wt.% Al2O3 (CoCrTCP+Al) were used to surface coat CoCr alloy via Laser Engineered Net Shaping (LENS™) with the objective of increasing CoCr alloy's wear resistance. Electron micrographs of the microstructure revealed the dissociation of intergranular globular carbide phases and reprecipitation into a finer network-like microstructure with homogeneous distribution of Co and Cr. X-ray diffraction (XRD) spectra revealed texturing or preferential crystallographic orientation amongst the LENS™ processed materials, with the TCP added CoCr displaying some ε-phase stabilization. Tribological testing resulted in an 82.3% and 71.6% decrease in wear rate and wear coefficient, respectively, for CoCrTCP when compared to commercially available CoCr alloy. Additionally, in situ tribofilm development was observed for the fabricated samples via an increase in contact resistance. The current study resulted in not only a decrease in wear volume but also a decrease in the overall degradation of the coated CoCr alloy.

Additively manufactured calcium phosphate reinforced CoCrMo alloy: Bio-tribological and biocompatibility evaluation for load-bearing implants.

Cobalt-chromium-molybdenum (CoCrMo) alloys are widely used in load-bearing implants; specifically, in hip, knee, and spinal applications due to their excellent wear resistance. However, due to in vivo corrosion and mechanically assisted corrosion, metal ion release occurs and accounts for poor biocompatibility. Therefore, a significant interest to find an alternative to CoCrMo alloy exists. In the present work we hypothesize that calcium phosphate (CaP) will behave as a solid lubricant in CoCrMo alloy under tribological testing, thereby minimizing wear and metal ion release concerns associated with CoCrMo alloy. CoCrMo-CaP composite coatings were processed using laser engineered net shaping (LENS™) system. After LENS™ processing, CoCrMo alloy was subjected to laser surface melting (LSM) using the same LENS™ set-up. Samples were investigated for microstructural features, phase identification, and biocompatibility. It was found that LSM treated CoCrMo improved wear resistance by 5 times. CoCrMo-CaP composites displayed the formation of a phosphorus-based tribofilm. In vitro cell-material interactions study showed no cytotoxic effect. Sprague-Dawley rat and rabbit in vivo study displayed increased osteoid formation for CoCrMo-CaP composites, up to 2 wt.% CaP. Our results show that careful surface modification treatments can simultaneously improve wear resistance and in vivo biocompatibility of CoCrMo alloy, which can correlate to a reduction of metal ion release in vivo.

Microstructural evolution and mechanical properties of biomedical Co-Cr-Mo alloy subjected to high-pressure torsion.

The effects of severe plastic deformation through high-pressure torsion (HPT) on the microstructure and tensile properties of a biomedical Co-Cr-Mo (CCM) alloy were investigated. The microstructure was examined as a function of torsional rotation number, N and equivalent strain, εeq in the HPT processing. Electron backscatter diffraction analysis (EBSD) shows that a strain-induced martensitic transformation occurs by the HPT processing. Grain diameter decreases with increasing εeq, and the HPT-processed alloy (CCMHPT) for εeq=45 exhibits an average grain diameter of 47nm, compared to 70µm for the CCM alloy before HPT processing. Blurred and wavy grain boundaries with low-angle of misorientation in the CCMHPT sample for εeq<45 become better-defined grain boundaries with high-angle of misorientation after HPT processing for εeq=45. Kernel average misorientation (KAM) maps from EBSD indicate that KAM inside grains increases with εeq for εeq<45, and then decreases for εeq=45. The volume fraction of the ε (hcp) phase in the CCMHPT samples slightly increases at εeq=9, and decreases at εeq=45. In addition, the strength of the CCMHPT samples increases at εeq=9, and then decrease at εeq=45. The decrease in the strength is attributed to the decrease in the volume fraction of ε phase, annihilation of dislocations, and decrease in strain in the CCMHPT sample processed at εeq=45 by HPT.

Intracellular modulation of excited-state dynamics in a chromophore dyad: differential enhancement of photocytotoxicity targeting cancer cells.

The photosensitized generation of reactive oxygen species, and particularly of singlet oxygen [O2 (a(1) Δg )], is the essence of photodynamic action exploited in photodynamic therapy. The ability to switch singlet oxygen generation on/off would be highly valuable, especially when it is linked to a cancer-related cellular parameter. Building on recent findings related to intersystem crossing efficiency, we designed a dimeric BODIPY dye with reduced symmetry, which is ineffective as a photosensitizer unless it is activated by a reaction with intracellular glutathione (GSH). The reaction alters the properties of both the ground and excited states, consequently enabling the efficient generation of singlet oxygen. Remarkably, the designed photosensitizer can discriminate between different concentrations of GSH in normal and cancer cells and thus remains inefficient as a photosensitizer inside a normal cell while being transformed into a lethal singlet oxygen source in cancer cells. This is the first demonstration of such a difference in the intracellular activity of a photosensitizer.

Modularly evolved 2-aminoDMAP/squaramides as highly active bifunctional organocatalysts in Michael addition.

We report a new family of chiral bifunctional acid/base type organocatalysts, 2-aminoDMAP/Squaramides, which are proved to be highly active (1 mol % cat. loading) promoters in conjugate addition of dibenzoylmethane to various trans-ß-nitroalkenes. Steric demand of the catalysts was clearly seen by a set-by-set modulation of the squaramide unit through electronic and steric factors. The synergistic cooperation of 2-aminoDMAP "superbase" and sterically encumbered squaramide (H-bond donor) enabled complete conversion of a range of reactants into corresponding Michael adducts in a couple of hours with exquisite selectivities (up to 98% ee).

Designing an intracellular fluorescent probe for glutathione: two modulation sites for selective signal transduction.

A selective probe for glutathione was designed and synthesized. The design incorporates spatial and photophysical constraints for the maximal emission signal. Thus, pHs, as well as the intracellular thiol concentrations, determine the emission signal intensity through a tight control of charge-transfer and PeT processes. The probe works satisfactorily inside the human breast adenocarcinoma cells, highlighting GSH distribution in the cytosol.

Anesthesia mumps resulting in temporary facial nerve paralysis after the auditory brainstem implantation in a 3-year-old child.

An acute transient sialadenitis of the major salivary glands in the early postoperative period is called 'anesthesia mumps'. It has been reported in different surgical procedures especially in neurosurgical procedures. Anesthesia mumps develops very fast after the extubation period but it usually regresses with no sequelae within a few hours. However, sometimes serious complication can occur such as respiratory distress. In this report, we present a 3-year-old girl with an anesthesia mumps and facial palsy occurring after successful auditory brainstem implantation and we discuss the cause and the management of this rare complication in this report.

Cu-catalyzed selective mono-N-pyridylation: direct access to 2-aminoDMAP/sulfonamides as bifunctional organocatalysts.

Direct and selective mono-N-pyridylation of trans-(R,R)-cyclohexane-1,2-diamine is described here. Facile preparation of a novel chiral 2-aminoDMAP core catalaphore via Cu catalysis has led to the development of various sulfonamide/2-aminoDMAPs as bifunctional acid/base organocatalysts (most in two steps overall), which have been shown to very effectively promote asymmetric conjugate addition of acetylacetone to trans-ß-nitroolefins with good to excellent yields (87-93%) and enantioselectivites (up to 99%).

Chromogenic and fluorogenic sensing of biological thiols in aqueous solutions using BODIPY-based reagents.

Judicious design of BODIPY dyes carrying nitroethenyl substituents in conjugation with the BODIPY core yields dyes that respond to biological thiols by both absorbance and emission changes. Incorporation of solubilizing ethyleneglycol units ensures water solubility. The result is bright signaling of biologically relevant thiols in the longer wavelength region of the visible spectrum and in aqueous solutions.

The value of site-specific information and the environment: technology adoption and pesticide use under uncertainty.

Remote sensing technology offers an opportunity to significantly increase the amount of site-specific information about field characteristics such as pest populations. Coupled with variable rate application technologies, this added information has the potential to provide environmental benefits through reduced pesticide applications. However, producers face a complicated adoption decision because output prices and crop yields are uncertain. A model is developed to examine the potential value of remote sensing information to pesticide applications in an option-value framework under uncertainty. Simulations suggest that remote sensing information could decrease pesticide use, but uncertainty and irreversibility are likely to limit technological adoption by farmers. Potential cost-share subsidies are discussed.