Engineered Dual Antioxidant Enzyme Complexes Targeting ICAM-1 on Brain Endothelium Reduce Brain Injury-Associated Neuroinflammation.

The neuroinflammatory cascade triggered by traumatic brain injury (TBI) represents a clinically important point for therapeutic intervention. Neuroinflammation generates oxidative stress in the form of high-energy reactive oxygen and nitrogen species, which are key mediators of TBI pathology. The role of the blood-brain barrier (BBB) is essential for proper neuronal function and is vulnerable to oxidative stress. Results herein explore the notion that attenuating oxidative stress at the vasculature after TBI may result in improved BBB integrity and neuroprotection. Utilizing amino-chemistry, a biological construct (designated "dual conjugate" for short) was generated by covalently binding two antioxidant enzymes (superoxide dismutase 1 (SOD-1) and catalase (CAT)) to antibodies specific for ICAM-1. Bioengineering of the conjugate preserved its targeting and enzymatic functions, as evaluated by real-time bioenergetic measurements (via the Seahorse-XF platform), in brain endothelial cells exposed to increasing concentrations of hydrogen peroxide or a superoxide anion donor. Results showed that the dual conjugate effectively mitigated the mitochondrial stress due to oxidative damage. Furthermore, dual conjugate administration also improved BBB and endothelial protection under oxidative insult in an in vitro model of TBI utilizing a software-controlled stretching device that induces a 20% in mechanical strain on the endothelial cells. Additionally, the dual conjugate was also effective in reducing indices of neuroinflammation in a controlled cortical impact (CCI)-TBI animal model. Thus, these studies provide proof of concept that targeted dual antioxidant biologicals may offer a means to regulate oxidative stress-associated cellular damage during neurotrauma.

Threonine functionalized colloidal cadmium sulfide (CdS) quantum dots: The role of solvent and counterion in ligand induced chiroptical properties.

The functionalization of semiconductor nanocrystals, quantum dots (QDs), with small organic molecules has been studied extensively to gain better knowledge on how to tune the electronic, optical and chiroptical properties of QDs. Chiral QDs have progressively emerged as key materials in a vast range of applications including biosensing and biorecognition, imaging, asymmetric catalysis, optoelectronic devices, and spintronics. To engage the full potential of the unique properties of chiral nanomaterials and be able to prepare them with tailorable chiroptical characteristics, it is essential to understand how chirality is rendered from chiral molecular ligands at the surface of nanocrystals to the electronic states of QDs. Using a series of polar protic and aprotic solvents together with ammonium (NH4+), tetramethylammonium (TMA+), and tetrabutylammonium (TBA+) countercations in the preparation of threonine-functionalized cadmium sulfide (Thr-CdS) QDs by phase transfer ligand exchange approach, we demonstrated the significance of the role both the solvent and the countercations play in the transfer of chirality from chiral molecular ligand to achiral semiconductor QDs as apparent by the modulations of the signatures and anisotropy of the circular dichroism (CD) spectra. Moreover, we have utilized tetrabutylammonium countercation to successfully synthesize chiral QDs in nonpolar cyclohexane solvent for the first time. This study provides further insights into the origin of the ligand induced chirality of colloidal nanomaterials and facilitates the synthesis of tailormade chiral QDs.

Synthesis of Metastable Ternary Pd-W and Pd-Mo Transition Metal Carbide Nanomaterials.

Research and catalytic testing of platinum group transition metal carbides have been extremely limited due to a lack of reliable, simple synthetic approaches. Powder samples have been reported to phase separately above 1%, and only thin-film samples have been reported to have appreciable amounts of precious metal doping. Herein, we demonstrated, through the simple co-precipitation of Pd and W or Mo precursors and their subsequent annealing, the possibility to readily form ternary carbide powders. During the investigation of the Pd-W ternary system, we discovered a new hexagonal phase, (PdW)2C, which represents the first non-cubic Pd ternary carbide. Additionally, the solubility of Pd in the Pd-W-C and Pd-Mo-C systems was increased to 24 and 32%, respectively. As a potential application, these new materials show an enhanced activity for the methanol oxidation reaction (MOR) compared to industrial Pd/C.

Multistep Fractionation of Coal and Application for Graphene Synthesis.

Despite its complex structure, coal has shown to be a promising precursor for graphene synthesis by chemical vapor deposition (CVD). However, the presence of heteroatoms and aliphatic chains in coal can lead to defects in the graphene lattice, preventing the formation of pristine graphene layers. Therefore, the goal of this study was to formulate a multistep coal fractionation scheme to extract and characterize the most aromatic fractions and explore their potential as graphene precursors. The scheme consisted of direct coal liquefaction under different conditions, Soxhlet extraction with heptane then toluene, and preparative liquid chromatography on silica gel using heptol solutions with different heptane/toluene ratios. The fractions obtained by this process were analyzed by proton nuclear magnetic resonance, thermogravimetric and elemental analyses, and automated SAR-AD (saturates, aromatics, resins-asphaltene determinator) separations. This characterization allowed the identification of two aromatic fractions with and without heteroatoms, which were subsequently used for graphene synthesis by CVD on nickel and copper foils. Raman spectrometry revealed that both fractions primarily formed defect-free multilayered graphene with approximately 11 layers on nickel due to the high solubility of carbon and the defect-healing effect of nickel. On the other hand, these fractions generated amorphous carbon on copper due to the high solubility of hydrogen in copper, which competed with carbon. Molecules in the more aromatic heteroatom-free fraction still contained alkyl pendant substituents and did not share the same planarity and symmetry to form defect-free graphene on copper. Thus, the quality of graphene was governed by the substrate on nickel and by the precursor quality on copper. When deposited directly on lacey carbon-coated copper grids of a transmission electron microscope, the heteroatom-free fraction gave rise to much larger graphene domains. The presence of heteroatoms promoted the formation of small self-assembled agglomerates of amorphous carbon.

CdSe Quantum Dots Functionalized with Chiral, Thiol-Free Carboxylic Acids: Unraveling Structural Requirements for Ligand-Induced Chirality.

Functionalization of colloidal quantum dots (QDs) with chiral cysteine derivatives by phase-transfer ligand exchange proved to be a simple yet powerful method for the synthesis of chiral, optically active QDs regardless of their size and chemical composition. Here, we present induction of chirality in CdSe by thiol-free chiral carboxylic acid capping ligands (l- and d-malic and tartaric acids). Our circular dichroism (CD) and infrared experimental data showed how the presence of a chiral carboxylic acid capping ligand on the surface of CdSe QDs was necessary but not sufficient for the induction of optical activity in QDs. A chiral bis-carboxylic acid capping ligand needed to have three oxygen-donor groups during the phase-transfer ligand exchange to successfully induce chirality in CdSe. Intrinsic chirality of CdSe nanocrystals was not observed as evidenced by transmission electron microscopy and reverse phase-transfer ligand exchange with achiral 1-dodecanethiol. Density functional theory geometry optimizations and CD spectra simulations suggest an explanation for these observations. The tridentate binding via three oxygen-donor groups had an energetic preference for one of the two possible binding orientations on the QD (111) surface, leading to the CD signal. By contrast, bidentate binding was nearly equienergetic, leading to cancellation of approximately oppositely signed corresponding CD signals. The resulting induced CD of CdSe functionalized with chiral carboxylic acid capping ligands was the result of hybridization of the (achiral) QD and (chiral) ligand electronic states controlled by the ligand's absolute configuration and the ligand's geometrical arrangement on the QD surface.

Synthesis of metastable chromium carbide nanomaterials and their electrocatalytic activity for the hydrogen evolution reaction.

Transition metal carbides including chromium, molybdenum, and tungsten are of particular interest as renewable energy catalysts due to their low cost and abundance. While several single metal carbide systems form multiple phases with different compositions and crystal structures, most of these materials are not as well studied due to their limited synthetic approaches and instability. By taking advantage of a low temperature salt flux synthetic method, these unique phases can be more easily synthesized and separated as phase pure materials. As an example, Chromium carbide forms five different crystal structures including three common phases, Cr3C2, Cr7C3, and Cr23C6, and two less studied phases, Cr2C and CrC. All five compounds were synthesized using the salt flux method and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and electrocatalytic testing for the hydrogen evolution reaction (HER). This low temperature method allows for routine access to multiple compounds in complex phase diagrams and separation of each phase synthetically. This represents a significant step forward in synthesizing rare phases like rocksalt CrC and hexagonal Cr2C and allows for investigation into their potential catalytic properties and future applications.

Chirality Inversion of CdSe and CdS Quantum Dots without Changing the Stereochemistry of the Capping Ligand.

L-cysteine derivatives induce and modulate the optical activity of achiral cadmium selenide (CdSe) and cadmium sulfide (CdS) quantum dots (QDs). Remarkably, N-acetyl-L-cysteine-CdSe and L-homocysteine-CdSe as well as N-acetyl-L-cysteine-CdS and L-cysteine-CdS showed "mirror-image" circular dichroism (CD) spectra regardless of the diameter of the QDs. This is an example of the inversion of the CD signal of QDs by alteration of the ligand's structure, rather than inversion of the ligand's absolute configuration. Non-empirical quantum chemical simulations of the CD spectra were able to reproduce the experimentally observed sign patterns and demonstrate that the inversion of chirality originated from different binding arrangements of N-acetyl-L-cysteine and L-homocysteine-CdSe to the QD surface. These efforts may allow the prediction of the ligand-induced chiroptical activity of QDs by calculating the specific binding modes of the chiral capping ligands. Combined with the large pool of available chiral ligands, our work opens a robust approach to the rational design of chiral semiconducting nanomaterials.

Formation mechanism of nanostructured metal carbides via salt-flux synthesis.

Nanostructured metal carbides are of particular interest because of their potential as high surface area, low-cost catalysts. By taking advantage of a salt-flux synthesis method, multiple carbide compounds were synthesized at low temperatures providing a pathway to nanosized materials. To better understand the reaction mechanism, vanadium carbide (V8C7) synthesis was monitored by quenching samples at 100 °C intervals and analyzed by multiple spectroscopic methods. The reaction was determined to occur through the formation of metal halide and acetylide carbide intermediates, which were repeatedly observed by X-ray diffraction and further supported by IR and Raman spectroscopies. Control experiments were also employed to further verify this mechanism of formation by using different salt compositions and a solid-state metathesis reaction. The reaction mechanism was also verified by applying these techniques to other metal carbide systems, which produced similar intermediate compounds.

Multiple phases of molybdenum carbide as electrocatalysts for the hydrogen evolution reaction.

Molybdenum carbide has been proposed as a possible alternative to platinum for catalyzing the hydrogen evolution reaction (HER). Previous studies were limited to only one phase, ß-Mo2C with an Fe2N structure. Here, four phases of Mo-C were synthesized and investigated for their electrocatalytic activity and stability for HER in acidic solution. All four phases were synthesized from a unique amine-metal oxide composite material including γ-MoC with a WC type structure which was stabilized for the first time as a phase pure nanomaterial. X-ray photoelectron spectroscopy (XPS) and valence band studies were also used for the first time on γ-MoC. γ-MoC exhibits the second highest HER activity among all four phases of molybdenum carbide, and is exceedingly stable in acidic solution.

Supramolecular ssDNA templated porphyrin and metalloporphyrin nanoassemblies with tunable helicity.

Free-base and nickel porphyrin-diaminopurine conjugates were formed by hydrogen-bond directed assembly on single-stranded oligothymidine templates of different lengths into helical multiporphyrin nanoassemblies with highly modular structural and chiroptical properties. Large red-shifts of the Soret band in the UV/Vis spectroscopy confirmed strong electronic coupling among assembled porphyrin-diaminopurine units. Slow annealing rates yielded preferentially right-handed nanostructures, whereas fast annealing yielded left-handed nanostructures. Time-dependent DFT simulations of UV/Vis and CD spectra for model porphyrin clusters templated on the canonical B-DNA and its enantiomeric form, were employed to confirm the origin of observed chiroptical properties and to assign the helicity of porphyrin nanoassemblies. Molar CD and CD anisotropy g factors of dialyzed templated porphyrin nanoassemblies showed very high chiroptical anisotropy. The DNA-templated porphyrin nanoassemblies displayed high thermal and pH stability. The structure and handedness of all assemblies was preserved at temperatures up to +85 °C and pH between 3 and 12. High-resolution transition electron microscopy confirmed formation of DNA-templated nickel(II) porphyrin nanoassemblies and their self-assembly into helical fibrils with micrometer lengths.

Ligand induced circular dichroism and circularly polarized luminescence in CdSe quantum dots.

Chiral thiol capping ligands L- and D-cysteines induced modular chiroptical properties in achiral cadmium selenide quantum dots (CdSe QDs). Cys-CdSe prepared from achiral oleic acid capped CdSe by postsynthetic ligand exchange displayed size-dependent electronic circular dichroism (CD) and circularly polarized luminescence (CPL). Opposite CPL signals were measured for the CdSe QDs capped with D- and L-cysteine. The CD profile and CD anisotropy varied with size of CdSe nanocrystals with largest anisotropy observed for CdSe nanoparticles of 4.4 nm. Magic angle spinning solid state NMR (MAS ssNMR) experiments suggested bidentate interaction between cysteine and the surface of CdSe. Time Dependent Density Functional Theory (TDDFT) calculations verified that attachment of L- and D-cysteine to the surface of model (CdSe)13 nanoclusters induces measurable opposite CD signals for the exitonic band of the nanocluster. The origin of the induced chirality is consistent with the hybridization of highest occupied CdSe molecular orbitals with those of the chiral ligand.

Crystal structure and morphology control of molybdenum carbide nanomaterials synthesized from an amine-metal oxide composite.

Multiple phases of molybdenum carbide have been synthesized using a unique amine-metal oxide composite material. By combining molybdenum oxide and an amine, a templated precursor is formed which can be thermally decomposed to form molybdenum carbide with control over the structure and morphology of the nano-sized products.

Orthogonal reactivity of metal and multimetal nanostructures for selective, stepwise, and spatially-controlled solid-state modification.

Chemists rely on a toolbox of robust chemical transformations for selectively modifying molecules with spatial and functional precision to make them more complex in a controllable and predictable manner. This manuscript describes proof-of-principle experiments for a conceptually analogous strategy involving the selective, stepwise, and spatially controlled modification of inorganic nanostructures. The key concept is orthogonal reactivity: one component of a multicomponent system reacts with a particular reagent under a specific set of conditions while the others do not, even though they are all present together in the same reaction vessel. Using the chemical conversion of metal nanoparticles into intermetallic, sulfide, and phosphide nanoparticles as representative examples, the concept of orthogonal reactivity is defined and demonstrated for a variety of two- and three-component nanoscale systems. First, solution-phase reactivity data are presented and collectively analyzed for the reaction of metal nanoparticles (Ni, Cu, Rh, Pd, Ag, Pt, Au, Sn) with several metal salt and elemental reagents (Bi, Pb, Sb, Sn, S). From these data, several two- and three-component orthogonal systems are identified. Finally, these results are applied to the spatially selective chemical modification of lithographically patterned surfaces and striped template-grown metal nanowires.

Multistep solution-mediated formation of AuCuSn2: mechanistic insights for the guided design of intermetallic solid-state materials and complex multimetal nanocrystals.

Understanding how solids form is a challenging task, and few strategies allow for the elucidation of reaction pathways that are useful for designing new solids. Here, we describe an unusual multistep reaction pathway that leads to the formation of AuCuSn(2), a new ternary intermetallic compound that was discovered as nanocrystals using a low-temperature solution route. The formation of AuCuSn(2) using a modified polyol process occurs through a multistep pathway that was elucidated by taking aliquots throughout the course of the reaction and studying the products using a variety of techniques. The reaction proceeds through four distinct steps: (a) formation of Au nanoparticles at or near room temperature, mediated by a galvanic reaction between Au(3+) and Sn(2+) (forming Au(0) and Sn(4+), precipitated as SnO(2) that forms a shell around the nanoparticles), (b) formation of NiAs-type AuSn nanoparticles, along with Cu and Sn, upon addition of NaBH(4), (c) aggregation and thermal interdiffusion to form AuCu(x)Sn(y) alloy nanoparticles, and (d) nucleation of intermetallic AuCuSn(2), which has an ordered NiAs-derived structure. The proposed mechanism was tested by starting the reaction with the AuSn intermediate. AuSn nanoparticles were synthesized separately and reacted with Cu and Sn nanoparticles, and ordered AuCuSn(2) formed as expected. Elucidation of this reaction pathway has important implications for guiding the design of new intermetallic solids, as well as for controlling the synthesis of complex multimetal nanocrystals.

Low-temperature polyol synthesis of AuCuSn2 and AuNiSn2: using solution chemistry to access ternary intermetallic compounds as nanocrystals.

Ternary intermetallic compounds, which possess a wide variety of important properties with both academic and technological relevance, are typically synthesized using traditional high-temperature methods. Here, we demonstrate that the polyol method, which is used extensively to synthesize nanocrystals and nanocrystalline powders of metals and simple binary compounds, serves as an effective low-temperature exploratory medium for synthesizing new ordered ternary intermetallics as nanocrystals. Accordingly, we describe the synthesis and structural characterization of AuCuSn2 and AuNiSn2, which adopt an ordered NiAs-type superstructure that is not observed using equilibrium synthetic methods. AuCuSn2 forms in solution of 120 degrees C as well-formed nanocrystals, and the ordered phase is stable up to 450 degrees C. AuNiSn2 behaves similarly to AuCuSn2.

Metallurgy in a beaker: nanoparticle toolkit for the rapid low-temperature solution synthesis of functional multimetallic solid-state materials.

Intermetallic compounds and alloys are traditionally synthesized by heating mixtures of metal powders to high temperatures for long periods of time. A low-temperature solution-based alternative has been developed, and this strategy exploits the enhanced reactivity of nanoparticles and the nanometer diffusion distances afforded by binary nanocomposite precursors. Prereduced metal nanoparticles are combined in known ratios, and they form nanomodulated composites that rapidly transform into intermetallics and alloys upon heating at low temperatures. The approach is general in terms of accessible compositions, structures, and morphologies. Multiple compounds in the same binary system can be readily accessed; e.g., AuCu, AuCu3, Au3Cu, and the AuCu-II superlattice are all accessible in the Au-Cu system. This concept can be extended to other binary systems, including the intermetallics FePt3, CoPt, CuPt, and Cu3Pt and the alloys Ag-Pt, Au-Pd, and Ni-Pt. The ternary intermetallic Ag2Pd3S can also be rapidly synthesized at low temperatures from a nanocomposite precursor comprised of Ag2S and Pd nanoparticles. Using this low-temperature solution-based approach, a variety of morphologically diverse nanomaterials are accessible: surface-confined thin films (planar and nonplanar supports), free-standing monoliths, nanomesh materials, inverse opals, and dense gram-scale nanocrystalline powders of intermetallic AuCu. Importantly, the multimetallic materials synthesized using this approach are functional, yielding a room-temperature Fe-Pt ferromagnet, a superconducting sample of Ag2Pd3S (Tc = 1.10 K), and a AuPd4 alloy that selectively catalyzes the formation of H2O2 from H2 and O2. Such flexibility in the synthesis and processing of functional intermetallic and alloy materials is unprecedented.

Colloidal crystal microarrays and two-dimensional superstructures: a versatile approach for patterned surface assembly.

A simple, fast, and robust approach to colloidal assembly on patterned surfaces was developed. The approach involves the rapid settling and dewetting of suspensions of spherical colloids on lithographically templated surfaces. Using this method, we can quickly and easily fabricate close-packed colloidal crystal microarrays of both silica and polystyrene spheres that range in size from 500 nm to 4.5 microm. The microarrays tend to induce the formation of monolayer colloidal crystals, which can be interconnected and removed from the templates as free-standing colloidal crystal slabs. The same approach can also be used to assemble two-dimensional colloidal crystal superlattices that can adopt a variety of structures. Graphite, kagome, body-centered cubic, open hexagonal, tetragonal, and linear chain structures can all be quickly accessed by adjusting the ratio of the sphere diameter to the template diameter.