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Herein, we report mechanistic investigations into the Cu-catalyzed three-component carboamination of alkenes with α-halo carbonyls and aryl amines via an oxocarbenium intermediate. Monitoring the reaction reveals the formation of transient atom transfer radical addition (ATRA) intermediates with both electron-neutral and deficient vinyl arenes as well as unactivated alkenes. Based on our experimental studies and density functional theory calculations, the oxocarbenium is generated through atom transfer and subsequent intramolecular substitution. Further, mechanistic factors that dictate the regioselectivity of the nucleophilic attack onto the oxocarbenium to afford the γ-amino ester, γ-iminolactone, or γ-lactone are discussed. A strategy to overcome scope limitation with respect to unactivated alkenes is developed using the mechanistic insights gained herein. Finally, we demonstrate that under modified conditions, our Cu catalyst enables the ATRA reaction between a variety of alkyl halides and vinyl arenes/α-olefins, and we present a one-pot, two-step carbofunctionalization with an array of nucleophiles through ATRA/SN2.

Although chemical methods for the selective derivatization of amino acid (AA) side chains in peptides and proteins are available, selective N-terminal labeling is challenging, especially for glycine, which has no side chain at the α-carbon position. We report here a double activation at glycine’s α-methylene group that allows this AA to be differentiated from the other 19 AAs. A condensation reaction of dibenzoylmethane with glycine results in the formation of an imine, and subsequent tautomerization is followed by intramolecular cyclization, leading to the formation of a fluorescent pyrrole ring. Additionally, the approach exhibits compatibility with AAs possessing reactive side chains. Further, the method allows for selective pull-down assays of N-terminal glycine peptides from mixtures without prior knowledge of the N-terminal peptide distribution.

A nanographene-fused expanded carbaporphyrin (5) and its BF2complex (6) were synthesized. Single-crystal X-ray structures revealed that 5and 6are connected by two hexa-peri-hexabenzocoronene (HBC) units and two dipyrromethene or BODIPY units, respectively. As prepared, 5and 6both show nonaromatic character with figure-of-eight carbaoctaphyrin (1.1.1.0.1.1.1.0) cores and adopt tweezers-like conformations characterized by a partially confined space between the two constituent HBC units. The distance between the HBC centers is >10 Å, while the dihedral angles between the two HBC planes are 30.5 and 35.2° for 5and 6, respectively. The interactions between 5and 6and fullerene C60were studied both in organic media and in the solid state. Proton NMR spectral titrations of 5and 6with C60revealed a 1:1 binding mode for both macrocycles. In toluene-d8, the corresponding binding constants were determined to be 1141 ± 17 and 994 ± 10 M–1for 5and 6, respectively. Single-crystal X-ray diffraction structural analyses confirmed the formation of 1:1 fullerene inclusion complexes in the solid state. The C60guests in both complexes are found within triangular pockets composed of two HBC units from the tweezers-like receptor most closely associated with the bound fullerene, as well as an HBC unit from an adjacent host. Femtosecond transient absorption measurements revealed subpicosecond ultrafast charge separation between 5(and 6) and C60in the complexes. To the best of our knowledge, the present report provides the first example wherein a nanographene building block is incorporated into the core of a porphyrinic framework.

Deferasirox is an FDA-approved iron chelator used in the treatment of iron toxicity. In this work, we report the use of several deferasirox derivatives as lanthanide chelators. Solid-state structural studies of three representative trivalent lanthanide cations, La(III), Eu(III), and Lu(III), revealed the formation of 2:2 complexes in the solid state. A 1:1 stoichiometry dominates in DMSO solution, with Kavalues of 472 ± 14, 477 ± 11, and 496 ± 15 M–1being obtained in the case of these three cations, respectively. Under the conditions of competitive precipitation in the presence of triethylamine, high selectivity (up to 80%) for lutetium(III) was observed in competition with La(III), Ce(III), and Eu(III). Theoretical calculations provided support for the observed selective crystallization.

A key challenge to the effective utilization of solar energy is to promote efficient photoinduced charge transfer, specifically avoiding unproductive, circuitous electron-transfer pathways and optimizing the kinetics of charge separation and recombination. We hypothesize that one way to address this challenge is to develop a fundamental understanding of how to initiate and control directional photoinduced charge transfer, particularly for earth-abundant first-row transition-metal coordination complexes, which typically suffer from relatively short excited-state lifetimes. Here, we report a series of functionalized heteroleptic copper(I)bis(phenanthroline) complexes, which have allowed us to investigate the directionality of intramolecular photoinduced metal-to-ligand charge transfer (MLCT) as a function of the substituent Hammett parameter. Ultrafast transient absorption suggests a complicated interplay of MLCT localization and solvent interaction with the Cu(II) center of the MLCT state. This work provides a set of design principles for directional charge transfer in earth-abundant complexes and can be used to efficiently design pathways for connecting the molecular modules to catalysts or electrodes and integration into systems for light-driven catalysis.

Described in this work are calix[4]pyrrole-based ion-pair receptors, cis/trans-1and cis/trans-2, designed for the extraction of sodium hydroxide. An X-ray diffraction analysis of a single crystal of the cis-1·NaOH isomer isolated from a mixture of cis/trans-1revealed a unique dimeric supramolecular structure. An average dimer in toluene-d8solution was inferred on the basis of diffusion-ordered spectroscopy (DOSY). Support for the proposed stoichiometry came from density functional theory (DFT) calculations. The structural stability of the dimeric cis-1·NaOH complex in toluene solution was further confirmed by ab initio molecular dynamics (AIMD) simulation with explicit representation of solvent. Under conditions of liquid–liquid extraction (LLE), purified receptors cis- and trans-2were both found to remove NaOH from a pH 11.01 aqueous source phase into toluene with extraction efficiencies (E%) of 50–60% when used equimolar to NaOH. However, in all cases, precipitation was observed. Complexities associated with precipitation could be avoided by immobilization of the receptors onto a chemically inert poly(styrene) resin by means of solvent impregnation. The use of solvent-impregnated resins (SIRs) eliminated precipitation in solution while retaining the extraction efficiency toward NaOH. This allowed both the pH and salinity of the alkaline source phase to be lowered.

Two cyclic carbaporphyrin arrays (trimer 6and tetramer 7) were synthesized from a dibrominated carbaporphyrin precursor (5) via a one-pot Yamamoto-type coupling. Single-crystal X-ray diffraction analyses revealed that 6and 7contain three and four covalently linked carbaporphyrin (formally dicarbacorrole) units, respectively. Trimer 6adopts a roughly planar conformation and tetramer 7adopts an up-and-down zig-zag conformation. Both 6and 7contain a [n]cyclo-meta-phenylene ([n]CMP) core, namely, [6]- and [8]CMP for 6and 7, respectively. Transient absorption (TA) anisotropy and pump-power-dependent excited-state decay studies provided evidence for excitation energy transfer (EET) within both trimer 6and tetramer 7. The exciton energy hopping (EEH) times were estimated to be 18 and 35 ps for 6and 7, respectively, as inferred from pump-power-dependent TA measurements. Since the center-to-center distances between adjacent carbaporphyrin units are similar in 6and 7, the different EEH times are attributed to differences in the orientation of the transition dipoles in these two congeneric arrays. The orientation factor κ2, the key parameter defining the Förster resonance energy transfer efficiency, was calculated to be 2.15 and 1.03 for 6and 7, respectively, a finding that supports the shorter excitation energy hopping time seen in the case of trimer 6. To our knowledge, this is the first time that covalently linked cyclic carbaporphyrin arrays were synthesized using a single carbaporphyrin as the starting point and that EET between carbaporphyrin subunits constrained within a well-defined polycyclic framework has been correlated with structural differences.

We report here a nanosized “buckytrap”, 1, constructed from two bis-zinc(II) expanded-TTF (exTTF) porphyrin subunits. Two forms, 1aand 1b, differing in the axial ligands, H2O vs tetrahydrofuran (THF), were isolated and characterized. Discrete host–guest inclusion complexes are formed upon treatment with fullerenes as inferred from a single-crystal X-ray structural analyses of 1awith C70. The fullerene is found to be encapsulated within the inner pseudohexagonal cavity of 1a. In contrast, the corresponding free-base derivative (2) was found to form infinite ball-and-socket type supramolecular organic frameworks (3D-SOFs) with fullerenes, (2•C60)nor (2•C70)n. This difference is ascribed to the fact that in 1aand 1bthe axial positions are blocked by a H2O or THF ligand. Emission spectroscopic studies supported a 1:1 host–guest binding stoichiometry, allowing association constants of (2.0 ± 0.5) × 104M–1and (4.3 ± 0.9) × 104M–1to be calculated for C60and C70, respectively. Flash-photolysis time-resolved microwave conductivity (FP-TRMC) studies of solid films of the Zn-complex 1arevealed that the intrinsic charge carrier transport, i.e., pseudo-photoconductivity (ϕ∑μ), increases upon fullerene inclusion (e.g., ϕ∑μ = 1.53 × 10–4cm2V–1s–1for C60⊂(1a)2and ϕ∑μ = 1.45 × 10–4cm2V–1s–1for C70⊂(1a)2vs ϕ∑μ = 2.49 × 10–5cm2V–1s–1for 1a) at 298 K. These findings provide support for the notion that controlling the nature of self-assembly supramolecular constructs formed from exTTF-porphyrin dimers through metalation or choice of fullerene can be used to regulate key functional features, including photoconductivity.

We have been investigating monoalkoxynaphthalene–naphthalimide (MAN–NI) donor–acceptor dyads that undergo a unique and dramatic orange-to-yellow thermochromic transition in the solid state. This study reports a new series of these stimuli-responsive solids, based on dyads with symmetric and relatively long alkyl side chains, as well as asymmetric derivatives. The length of the alkyl side chains influenced the structures, properties, and dynamic behavior of the resulting solids. All of the symmetric alkyl side chain derivatives can crystallize with identical packing (allowing for alkyl chain length differences) in a lasagna-like fashion with alternating alkyl and stacked aromatic layers. The fully extended alkyl side chains are aligned in an interdigitated, “cork and bottle” fashion. The aromatic layers feature head-to-head stacking geometries of the aromatic dyad cores. The crystalline solids derived from each of these derivatives undergo dramatic thermochromic orange-to-yellow transition in the solid state. Crystal structures were obtained for three of the four asymmetric dyad derivatives. In each case, layered structures were observed, although the mismatch in alkyl side chain lengths results in a unique hybrid alkyl/aromatic layer. Two of the asymmetric derivatives exhibit almost identical head-to-head dyad core stacking geometries, while one exhibits a head-to-tail dyad core stacking geometry. Of the four asymmetric dyads studied, only two asymmetric derivatives with the longer alkyl side chains exhibit dynamic solid-state behavior. Overall, our results demonstrate the relatively general nature of the thermochromic orange-to-yellow color-changing mechanism of the MAN–NI dyads and verify the link between the alkyl side chain interactions and this interesting stimuli-responsive behavior in the solid-state.

The environmentally benign metal-organic framework (MOF) CUK-1 based on 2,4-pyridine dicarboxylate has been prepared for the first time using Mn(II) as the inorganic node and water as the only solvent. Mn-CUK-1 shows reversible and efficient capture of H2O, SO2, and H2S. Compared to previously studied Co(II) and Mg(II) versions of the same MOF, Mn-CUK-1 also exhibited unique temperature-induced structural flexibility due to organic linker torsion, as detailed by variable-temperature single-crystal X-ray diffraction studies. Owing to this inherent solid-state flexibility, Mn-CUK-1 showed stepwise adsorption for polar gases, which induce structural deformations upon adsorption, while the nonpolar guest adsorbates were reversibly sorbed in a more classical manner. Notably, Mn-CUK-1 demonstrates the highest reported H2S capacity-to-surface area ratio among MOFs that are chemically stable toward this reactive acidic molecule. Moreover, Mn-CUK-1 displays exceptional structural stability in the presence of high relative humidity and corrosive gases and shows soft crystalline behavior triggered by changes in both the adsorption temperature and guest molecule identity.

One hundred eighty million years ago, a small, hairy animal resembling a shrew or a vole evolved a new way to care for her developing offspring. Instead of laying eggs [...]

Deferasirox, an FDA-approved iron chelator, has gained increasing attention for use in anticancer and antimicrobial applications. Recent efforts by our group led to the identification of this core as an easy-to-visualize aggregation-induced emission platform, or AIEgen, that provides a therapeutic effect equivalent to deferasirox (J. Am. Chem. Soc.2021, 143, 3, 1278–1283). However, the emission wavelength of the first-generation system overlapped with that of Syto9, a green emissive dye used to indicate live cells. Here, we report a library of deferasirox derivatives with various fluorescence emission profiles designed to overcome this limitation. We propose referring to systems that show promise as both therapeutic and optical imaging agents as “illuminoceuticals”. The color differences between the derivatives were observable to the unaided eye (solid- and solution-state) and were in accord with the Commission Internationale de L’Eclairage (CIE) chromaticity diagram 1913. Each fluorescent derivative successfully imaged the respective spherical and rod shapes of methicillin-resistant Staphylococcus aureus(MRSA) and Pseudomonas aeruginosa. They also displayed iron-dependent antibiotic activity. Three derivatives, ExNMe2(3), ExTrisT(11), and ExDCM(13), display emission features that are sufficiently distinct so as to permit the multiplex (triplex) imaging of both MRSA and P. aeruginosaviastimulated emission depletion microscopy. The present deferasirox derivatives allowed for the construction of a multi-fluorophore sensor array. This array enabled the successful discrimination between Gram-positive/Gram-negative and drug-sensitive/drug-resistant bacteria. Antibiotic sensitivity and drug-resistant mutants from clinically isolated strains could also be identified and differentiated.

Reported herein are two functionalized crown ether strapped calix[4]pyrroles, H1and H2. As inferred from competitive salt binding experiments carried out in nitrobenzene-d5and acetonitrile-d3, these hosts capture LiCl selectively over four other test salts, viz. NaCl, KCl, MgCl2, and CaCl2. Support for the selectivity came from density functional theory (DFT) calculations carried out in a solvent continuum. These theoretical analyses revealed a higher innate affinity for LiCl in the case of H1, but a greater selectivity relative to NaCl in the case of H2, recapitulating that observed experimentally. Receptors H1and H2were outfitted with methacrylate handles and subject to copolymerization with acrylate monomers and cross-linkers to yield gels, G1and G2, respectively. These two gels were found to adsorb lithium chloride preferentially from an acetonitrile solution containing a mixture of LiCl, NaCl, KCl, MgCl2, and CaCl2and then release the lithium chloride in methanol. The gels could then be recycled for reuse in the selective adsorption of LiCl. As such, the present study highlights the use of solvent polarity switching to drive separations with potential applications in lithium purification and recycling.

Television series like Location, Location, Location are making more and more people think about property as an investment or even as a pension alternative. But there are some long term [...]

Deferasirox, ExJade, is an FDA-approved iron chelator used for the treatment of iron overload. In this work, we report several fluorescent deferasirox derivatives that display unique photophysical properties, i.e., aggregation-induced emission (AIE), excited state intramolecular proton transfer, charge transfer, and through-bond and through-space conjugation characteristics in aqueous media. Functionalization of the phenol units on the deferasirox scaffold afforded the fluorescent responsive pro-chelator ExPhos, which enabled the detection of the disease-based biomarker alkaline phosphatase (ALP). The diagnostic potential of these deferasirox derivatives was supported by bacterial biofilm studies.

Immunogenic cell death (ICD) is a way of reengaging the tumor-specific immune system. ICD can be induced by treatment with chemotherapeutics. However, only a limited number of drugs and other treatment modalities have been shown to elicit the biomarker responses characteristic of ICD and to provide an anticancer benefit in vivo. Here, we report a rationally designed redox-active Au(I) bis-N-heterocyclic carbene that induces ICD both in vitro and in vivo. This work benefits from a synthetic pathway that allows for the facile preparation of asymmetric redox-active Au(I) bis-N-heterocyclic carbenes.

There is growing interest in creating solids that are responsive to various stimuli. Herein we report the first molecular-level mechanistic picture of the thermochromic polymorphic transition in a series of MAN-NI dyad crystals that turn from orange to yellow upon heating with minimal changes to the microscopic morphology following the transition. Detailed structural analyses revealed that the dyads assemble to create an alternating bilayer type structure, with horizontal alternating alkyl and stacked aromatic layers in both the orange and yellow forms. The observed dynamic behavior in the solid state moves as a yellow wavefront through the orange crystal. The overall process is critically dependent on a complex interplay between the layered structure of the starting crystal, the thermodynamics of the two differently colored forms, and similar densities of the two polymorphs. Upon heating, the orange form alkyl chain layers become disordered, allowing for some lateral diffusion of dyads within their own layer. Moving to either adjacent stack in the same layer allows a dyad to exchange a head-to-head stacking geometry (orange) for a head-to-tail stacking geometry (yellow). This transition is unique in that it involves a nucleation and growth mechanism that converts to a faster cooperative wavefront mechanism during the transition. The fastest moving of the wavefronts have an approximately 38° angle with respect to the long axis of the crystal, corresponding to a nonconventional C–H···O hydrogen bond network of dyad molecules in adjacent stacks that enables a transition with cooperative character to proceed within layers of orange crystals. The orange-to-yellow transition is triggered at a temperature that is very close to the temperature at which the orange and yellow forms exchange as the more stable, while being lower than the melting temperature of the original orange, or final yellow, solids.

We report here a new extended tetrathiafulvalene (exTTF)-porphyrin scaffold, 2, that acts as a ball-and-socket receptor for C60and C70. Supramolecular interactions between 2and these fullerenes serve to stabilize 3D supramolecular organic frameworks (SOFs) in the solid state formally comprising peapod-like linear assemblies. The SOFs prepared via self-assembly in this way act as “tunable functional materials”, wherein the complementary geometry of the components and the choice of fullerene play crucial roles in defining the conductance properties. The highest electrical conductivity (σ = 1.3 × 10–8S cm–1at 298 K) was observed in the case of the C70-based SOF. In contrast, low conductivity was seen for the SOF based on pristine 2(σ = 5.9 × 10–11S cm–1at 298 K). The conductivity seen for the C70-based SOF approaches that seen for other TTF- and fullerene-based supramolecular materials despite the fact that the present systems are metal-free and constructed entirely from neutral building blocks. Transient absorption spectroscopic measurements corroborated the formation of charge-transfer states (i.e., 2δ+/C60δ−and 2δ+/C70δ−, respectively) rather than fully charge separated states (i.e., 2•+/C60•–and 2•+/C70•–, respectively) both in solution (toluene and benzonitrile) and in the solid state at 298 K. Such findings are considered consistent with an ability to transfer charges effectively over long distances within the present SOFs, rather than, for example, the formation of energetically trapped ionic species.

The chelating 2-pyridone ligand (E)-6-(1-((2-(methylthio)phenyl)imino)ethyl)pyridin-2(1H)-one (1) has been used to synthesize five nickel(II) complexes that have been characterized by single-crystal X-ray diffraction, UV/vis and IR spectroscopies, and benchtop magnetometry. Reaction of NiX2(X = BF4, Cl) with 1yielded the C2-symmetric halide-bridged Ni dimers [(μ-F)Ni2(κN,N,O-1–)2(κN,N-1)2](BF4) (2) and [(μ-Cl)Ni2(κN,N,O-1–)2(κN,N-1–)(κN,N-1)] (3), where 2is formed via a rare example of fluoride abstraction from BF4–by a transition metal. Remarkably, the reaction of Ni(OAc)2with 1followed by different methods of crystallization yielded three different products: the dimer[(μ-OH2)Ni2(κN,N,O-1–)(κN,N-1–)(κN,N-1)(OAc)2] (4), as well as the monomers[Ni(κN,N-1–)2(MeOH)2] (5) and [Ni(κN,N-1–)(κN,N-1)(OAc)(OH2)] (6). This observation is emblematic of the soft energy landscape of coordination motifs and nuclearity that pyridone ligands provide with late 3d transition metals. To better understand the solution versus solid-state speciation, solid-state UV/vis reflectance and solution-state UV/vis absorbance spectra were obtained. Surprisingly, the solution-state UV/vis spectra of 4and 6each provided nearly identical absorption spectra (λmax≈ 360 nm), which matched neither of the solid-state reflectance spectra of 4or 6(λ ≈ 590, 790, 970 nm; 3A2g→ 3T1g, 3A2g→1E2g, and 3A2g→ 3T2g, respectively). Rather, the solution spectra are consistent only with the spectroscopic features (MLCT) of a conventional square-planar Ni(II) species.

There is a recognized need in the area of explosives detection for fluorescence-based sensing systems that are capable of not only producing a turn-on response but also generating a distinctive spectral signature for a given analyte. Here, we report several supramolecular ensembles displaying efficient fluorophore displacement that give rise to an increase in fluorescence intensity upon exposure to various nitroaromatic compounds. The synthetic supramolecular constructs in question consist of a tetrathiafulvalene (TTF)-based pyrrolic macrocycle, benzo-TTF-calix[4]pyrrole (Bz-TTF-C4P), and fluorescent dyes, monomeric or dimeric naphthalenediimide (NDI) and perylenediimide (PDI) derivatives, as well as chloride or hexafluorophosphate (PF6–) salts of rhodamine 6G (Rh-6G). In chloroform solution, these assemblies exist in the form of discrete supramolecular complexes or oligomeric aggregates depending on the specific dye combinations in question. Each ensemble was tested as a potential explosive-responsive fluorescence indicator displacement assay (FIDA) by challenging it with a series of di- and trinitroaromatic compounds and examining the change in fluorescence spectral characteristics. Upon addition of nitroaromatic compounds (NACs), either a “turn-on” or a “turn-off” fluorescent response was observed depending on the nature of the constituent fluorophore and, where applicable, the counteranion. The FIDAs based on the PDI derivatives were found to display not only a ratiometric fluorescence enhancement but also analyte-dependent spectral changes when treated with NACs. The NAC-induced fluorescence spectral response of each ensemble was rationalized on the basis of various solution-phase spectroscopic studies, as well as single-crystal X-ray diffraction analyses.

Here we report the first series of in-plane thorium(IV), uranium(IV), and neptunium(IV) expanded porphyrin complexes. These actinide (An) complexes were synthesized using a hexa-aza porphyrin analogue, termed dipyriamethyrin, and the nonaqueous An(IV) precursors, ThCl4(DME)2, UCl4, and NpCl4(DME)2. The molecular and electronic structures of the ligand, each An(IV) complex, and a corresponding uranyl(VI) complex were characterized using nuclear magnetic resonance (NMR) and UV–vis spectroscopies as well as single-crystal X-ray diffraction analysis. Computational analyses of these complexes, coupled to their structural features, provide support for the conclusion that a greater degree of covalency in the ligand–cation orbital interactions arises as the early actinide series is traversed from Th(IV) to U(IV) and Np(IV). The axial ligands in the present An(IV) complexes proved labile, allowing for the electronic features of these complexes to be further modified.

We demonstrate a simple and generalizable method for the one pot, in situ formation of bimetallic metal–organic framework (MOF) materials decorated with crystallographically defined, low-valent metal sites. Solvothermal reactions between poly(carboxylated) aryl(phosphine) ligands and mixtures of higher- and lower-valent metal precursors achieves concomitant P–M complexation and MOF formation via metal–carboxylate network bonding. This method is demonstrated in the preparation of two new phosphine coordination materials, PCM-107 and PCM-74, which feature Ar3P–AuX (X = Cl, Br) and chelated PN̂–Cu2I2–PN̂units as the MOF building blocks, respectively. PCM-107 is an active catalyst for alkyne hydroaddition, while PCM-74 shows promise for the crystallization of MOFs bearing kinetically favored isomers.

We report here the fluorescent sensing of both aromatic and linear saturated dicarboxylate anions (DC2–) (as their tetrabutylammonium salts) with different lengths and shapes in acetonitrile using a single fluorescent probe, i.e., the bis-calix[4]pyrrole-appended 9,14-diphenyl-9,14-dihydrodibenzo[a,c]phenazine (DPAC-bisC4P) incorporating a vibration-induced emission (VIE) phenazine core. Fluorescence titration studies revealed that treating DPAC-bisC4Pwith dicarboxylate guests capable of forming pseudomacrocyclic host–guest complexes via multiple hydrogen-bonding interactions between the dicarboxylates and calix[4]pyrrole moieties led to a blue-shift in the emission of the phenazine core. The binding-based fluorescence-tuning features of DPAC-bisC4Pallow the underlying binding events and inferred structural changes to be monitored in the form of different chromaticity outputs. The analyte-induced differences in the fluorescence response to DC2–cover a wide range within the chromaticity diagram and can be visualized readily. The present system thus functions as a rudimentary dicarboxylate anion sensor. It highlights the potential benefits associated with combining a tunable VIE core with noncovalent binding interactions and thus sets the stage for the development of new fluorescent chemosensors where a single chemical entity responds to different analytes with a high level of tunability.

Reported here are new platinum(IV) (Pt(IV)) complexes bearing ferrocene (Fc) moieties. These systems differ from one another only by the nature of the functional group (ester vs amide) connecting the linker to the Fc subunits. This minor structural variation (one atom difference) leads to major differences in solubility, stability, and antiproliferative activity against lung (A549) cancer cells. The host–guest chemistry of these complexes was investigated in an aqueous medium in the presence of β-cyclodextrins (β-CD), either free or in the form of a covalently linked Fc-Pt-β-CD hybrid. An inclusion complex between Fc and β-CD is formed in aqueous media, presumably as a result of hydrophobic interactions involving the Fc and the inner β-CD cavity. Consequently, it proved possible to use a β-CD-based strategy to purify the Pt-Fc conjugates in this study under aqueous conditions (by means of C18 silica gel columns). The use of a β-CD adjuvant also allowed dimethyl sulfoxide (DMSO) to be avoided as an organic cosolvent in cell studies. The amide version reported here (2) proved to be more soluble, more stable, and more active than the ester analogue (11) in A549 cells. The use of a β-CD functionalized with a fluorescent probe allowed intracellular Pt-Fc localization to be visualized by confocal fluorescence microscopy.

Tetranuclear organopalladium(II) complexes 1–3and mononuclear complex 4have been synthesized by the complexation of 3-acetyl-7-methoxy-2H-chromen-2-one derived Schiff bases with potassium tetrachloropalladate K2[PdCl4]. Structural confirmation for the complexes (1–3) has been achieved by single-crystal X-ray diffraction analysis. The ligands are found to bind with the palladium ion through its azomethine nitrogen, thiolate sulfur, and C4 carbon atom of the coumarin moiety subsequent to C–H activation. The monomeric nature of complex 4was confirmed from its mass spectroscopic data. In complex 4, coordination occurred via the lactone oxygen, azomethine nitrogen, and thiolate sulfur atoms. Computational study has been used to determine the optimized molecular structures of the complexes. An explanation on the energies of their highest occupied and lowest unoccupied molecular orbital levels and their electronic spectra has also been provided on the basis of the theoretical calculations. A systematic study of the application of these complexes as catalysts in Suzuki–Miyaura coupling (SMC) has been done with different aryl halides and phenyl boronic acid in an aqueous medium. Optimization of the reaction indicated that complex 2exhibits greater efficiency than other complexes. An appreciable yield of the coupled products was observed with the minimum use of catalyst (μmol), and the C–C coupling has been confirmed by GC/GC-MS. An interesting result of our catalyst is the coupling of four different chloroquinolines with phenyl boronic acid to afford the coupled products in good yields.

A molecular cage, macrobicycle 2, containing amide and pyrrole groups as hydrogen-bonding donors and imine groups as hydrogen-bonding acceptors has been synthesized. Compound 2was found to recognize tetrahedral oxyanions with high affinities, such as H2PO4–, HSO4–, SO42–, and HP2O73–, as well as the spherical halide anions, in chloroform. A single-crystal X-ray diffraction analysis revealed that compound 2formed a 1:1 complex with H2PO4–in the solid state.

We report an expanded “Texas-sized” molecular box (AzoTxSB) that incorporates photoresponsive azobenzene bridging subunits and anion recognition motifs. The shape of this box can be switched through light induced E ↔ Z photoisomerization of the constituent azobenzenes. This allows various anionic substrates to be bound and released by using different forms of the box. Control can also be achieved using other environmental stimuli, such as pH and anion competition.

Different pyridine dipyrrolate cages including cage-based dimers and polymers may be fabricated in a controlled manner from the same two starting materials, namely, an angular ligand 1 and Zn(acac)2, by changing the counter cation source. With tetrabutylammonium (TBA+) and dimethyl viologen (DMV2+), Cage-3and Cage-5are produced. In these cages, two ligands act as bridges and serve to connect together two cage subunits to produce higher order ensembles. In Cage-3and Cage-5, the TBA+and DMV2+counter cations lie outside the cavities of the respective cages. This stands in contrast to what is seen with a previously reported system, Cage-1, wherein dimethylammonium (DMA+) counter cations reside within the cage cavity. When the counter cations are tetraethylammonium (TEA+) and bis(cyclopentadienyl) cobalt(III) (Cp2Co+), polymeric cage materials, PC-1and PC-2, are formed, respectively. The counter cations thus serve not only to balance charge but also to tune the structural features as a whole. The organic cations used in the present study also act to modulate the further assembly of individual cages. The present cation-based tuning emerges as a new method for a fine-tuning of the multidimensional morphology of self-assembled inorganic materials.

Using naphthobipyrrole as a functional building block, a new expanded porphyrin, naphthoisoamethyrin, was prepared in 85% yield under acid-catalyzed [4 + 2] MacDonald coupling conditions. Treatment of naphthoisoamethyrin with the nonaqueous uranyl silylamide salt [UO2[N(SiMe3)2]2·2THF] yielded the corresponding uranyl complex. Upon metalation, naphthoisoamethyrin undergoes a two-electron oxidation to yield a formal 22 π-electron aromatic species, as inferred from 1H NMR and UV–vis spectroscopy, as well as cyclic voltammetry.

A fully conjugated three-dimensional (3D) expanded carbaporphyrin (2) was prepared in a one-pot procedure that involves a [2+4] condensation reaction between a dibenzo[g,p]chrysene-bearing tetrapyrrole precursor (1) and pentafluorobenzaldehyde, followed by oxidation. Single crystal X-ray diffraction analysis revealed that 2possesses a cage-like structure consisting of four dipyrromethenes and two bridging dibenzo[g,p]chrysene units. As prepared, 2is nonaromatic as inferred from UV–vis-NIR and 1H NMR spectroscopy and a near-zero (−1.75) nucleus-independent chemical shift (NICS) value. In contrast, after protonation with trifluoroacetic acid (TFA), the cage gains global aromatic character as inferred from the large negative NICS value (−11.63) and diatropic ring current observed in the anisotropy of the induced current density (ACID) plot, as well as the ca. 8-fold increase in the excited state lifetime. In addition, the size of the cavity increases to ca. 143 Å3upon protonation as deduced from a single crystal X-ray diffraction analysis. To our knowledge, this is the largest carbaporphyrin prepared to date and the first with a fully conjugated 3D cage structure whose size and electronic features may be tuned through protonation.

A diblock copolymer containing a strapped calix[4]pyrrole-based ion pair recognition subunit has been synthesized via RAFT polymerization. As prepared, the polymer is hydrophobic and devoid of any particular morphological form. However, upon ion pair complexation, the copolymer self-assembles to generate reverse micelles in organic media. The reverse micelles formed in this way may be used to extract alkali cation and cesium halide anion salts from an aqueous source into an organic receiving phase. The polymer proved more effective as an extractant than the corresponding free ion pair receptor.

Proton-coupled electron transfer (PCET) is an important chemical and biological phenomenon. It is attractive as an on–off switching mechanism for redox-active synthetic systems but has not been extensively exploited for this purpose. Here we report a core-modified planar weakly antiaromatic/nonaromatic octaphyrin, namely, a [32]octaphyrin(1.0.1.0.1.0.1.0) (1) derived from rigid naphthobipyrrole and dithienothiophene (DTT) precursors, that undergoes proton-coupled two-electron reduction to produce its aromatic congener in the presence of HCl and other hydrogen halides. Evidence for the production of a [4n+ 1] π-electron intermediate radical state is seen in the presence of trifluoroacetic acid. Electrochemical analyses provide support for the notion that protonation causes a dramatic anodic shift in the reduction potentials of octaphyrin 1, thereby facilitating electron transfer from halide anions (viz. I–, Br–, and, Cl–). Electron-rich molecules, such as tetrathiafulvene (TTF), phenothiazine (PTZ), and catechol, were also found to induce PCET in the case of 1. Both the oxidized and two-electron reduced forms of 1were characterized by X-ray diffraction analyses in the solid state and in solution via spectroscopic means.

Anion receptor 1, a pyrene-functionalized tetrakis-(1H-pyrrole-2-carbaldehyde), binds tetrabutylammonium dihydrogen phosphate in chloroform with high affinity over other test salts. Fluorescence quenching is seen upon the addition of H2PO4–to 1. The limit of detection (LOD) is ca. 46 nM. Anion binding in the solid state was confirmed via X-ray diffraction analysis, which revealed a sandwich-type complex, [1·3TBAH2PO4]2, wherein two separate molecules of 1are linked via six dihydrogen phosphate anions bound in an S-like fashion.

Large-bodied organisms have more cells that can potentially turn cancerous than small-bodied organisms, imposing an increased risk of developing cancer. This expectation predicts a positive correlation between body size and cancer risk; however, there is no correlation between body size and cancer risk across species (“Peto’s paradox”). Here, we show that elephants and their extinct relatives (proboscideans) may have resolved Peto’s paradox in part through refunctionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro-apoptotic functions. LIF6is transcriptionally upregulated by TP53 in response to DNA damage and translocates to the mitochondria where it induces apoptosis. Phylogenetic analyses of living and extinct proboscidean LIF6genes indicates that its TP53 response element evolved coincident with the evolution of large body sizes in the proboscidean stem lineage. These results suggest that refunctionalizing of a pro-apoptotic LIF pseudogene may have been permissive (although not sufficient) for the evolution of large body sizes in proboscideans.

Light-emitting electrochemical cells (LEECs) from ionic transition-metal complexes (iTMCs) offer the potential for high-efficiency electroluminescence in a simple, single-layer device. However, LEECs typically rely on the use of rare metal complexes. This has limited their cost effectiveness and put constraints on their applicability. With a view to leveraging the efficient emission of these complexes while mitigating costs, we describe here a host/guest LEEC strategy that relies on the use of carbazole (Cz)-based organic small-molecule hosts and iTMC guests. Three cationic host molecules were prepared via the coupling of 1-(4-bromophenyl)-2-phenylbenzimidazole (PBI-Br) with Cz. This has allowed a comparison between the hosts bearing methoxy (PBI-CzOMe) and tert-butyl (PBI-CztBu) substituents, as well as an unsubstituted analogue (PBI-CzH). Cyclic voltammetry and UV–visible absorption revealed that all three host materials have wide band gaps characterized by reversible oxidation and irreversible reduction events. On the basis of electronic structure calculations, the host highest occupied molecular orbital (HOMO) resides primarily on the Cz moiety, whereas the lowest unoccupied molecular orbital (LUMO) is located primarily on the phenyl-benzimidazolium unit. Photoluminescence analysis of thin-film blends of PBI-CzH with iTMC guests confirmed that the emission was blue-shifted relative to pristine iTMC films, which is consistent with what was seen in dilute dichloromethane solution. LEEC devices were prepared based on thin films of the pristine hosts, pristine guests, and 90%/10% (w/w) host/guest blends. Among these host/guest blends, LEECs based on PBI-CzH displayed the best performance, particularly when an iridium complex was used as the guest. The system in question yielded a luminance maximum of 624 cd/m2at an external quantum efficiency of 3.80%. This result stands in contrast to what is seen with typical organic light-emitting diode host studies, where tert-butyl substitution of the host generally leads to a better performance. To rationalize the present observations, the host materials were subject to single-crystal X-ray diffraction analysis. The resulting structures revealed clear head-to-tail interactions in the case of both PBI-CzH and PBI-CzOMe. No such interactions were evident in the case of PBI-CztBu. Furthermore, PBI-CzH showed a relatively smaller spacing between the successive HOMO and successive LUMO levels relative to PBI-CzOMe and PBI-CztBu, a finding consistent with more favorable charge transport and energy transfer. The results presented here can help inform the design and preparation of host materials suitable for use in single-layer iTMC LEECs.

We report here a metal complexation-based strategy that permits access to a highly stable expanded porphyrin-type quinoidal polycyclic aromatic hydrocarbons (PAH). Specifically, double insertion of Pd(II) ions into a dibenzo[g,p]chrysene-fused bis-dicarbacorrole (bis-H3) gives rise to a bis-metalated species (bis-Pd) that undergoes a facile benzenoid-quinonoid transformation. In contrast to what is true for the corresponding mono-Pd(II) complex, which has organic radical character, well resolved 1H NMR and 19F NMR spectra are seen for bis-Pd. This complex is also electron paramagnetic resonance (EPR) silent over a range of temperatures. On the basis of crystallographic analyses, Raman spectroscopic studies, harmonic oscillator model of aromaticity (HOMA), and nucleus-independent chemical shift (NICS) calculations, we suggest that the dibenzo[g, p]chrysene bridge in bis-Pdhas quinoidal character and that the system as a whole is a closed shell species. As expected for a quinoidal system, bis-Pdis characterized by a lowest energy absorption band that is shifted into the NIR (λmax= ca. 1420 nm (ε > 1.5 × 105M–1cm–1) for bis-Pdvs 780 nm (ε < 5.0 × 103M–1cm–1) for bis-H3). On the other hand, bis-Pddisplays solvent dependent ground state and transient absorption spectral features. Such findings provide support for a zwitterionic resonance contribution to what is a predominantly a quinonoid-type ground state. The use of specific metalation to fine-tune the electronic features of polytopic ligands, as reported here, opens the door to what might be a potentially generalizable approach to the design of quinoidal PAH structures with long wavelength solvatochromic absorption features.

Novel polymers bearing pendant picolinic acid functionalities have been synthesized by ring-opening metathesis polymerization (ROMP) for applications in separations-based purification protocols. These polymers and their corresponding monomer were shown to be selective for Cu2+over a variety of other divalent metal cations as inferred from pH dependent studies carried out under both liquid–liquid and solid–liquid extraction conditions. The polymer system of this study also showed high selectivity for Cu2+over Ni2+in mock protocols that could be relevant to the purification of Cu radioisotopes. Separation factors as high as 290 were achieved for extractions from solutions containing a 100-fold excess of Ni2+relative to Cu2+.

Herein we report the synthesis, X-ray structure, and characterization of the title pentairon (molybdo)carbido cluster. The reaction of the pentairon (μ5-carbido) dianion [Fe5(μ6-C)(μ2-CO)2(CO)12]2–(1) with [Mo(CO)3(chpt)] (chpt = cycloheptatriene) forms the heterohexanuclear cluster [K(benzo-18-crown-6)]2[Fe5Mo(μ6-C)(μ2-CO)3(CO)14] (2). The dianion exhibits a Fe5Mo(μ6-C) core structure supported by three bridging (νCO= 1788 cm–1) and terminal (νCO= 1943 cm–1) CO ligands. Cluster 2provides the selective reduction of diphenylacetylene to cis-diphenylethylene via a spectroscopically observed cluster-hydride intermediate (1H NMR: δ −26).

Classic formulations of aromaticity have long been associated with topologically planar conjugated macrocyclic systems. The theoretical possibility of so-called bicycloaromaticity was noted early on. However, it has yet to be demonstrated by experiment in a simple synthetic organic molecule. Conjugated organic systems are attractive for studying the effect of structure on electronic features. This is because, in principle, they can be modified readily through dedicated synthesis. As such, they can provide useful frameworks for testing by experiment with fundamental insights provided by theory. Here we detail the synthesis and characterization of two purely organic non-planar dithienothiophene-bridged [34]octaphyrins that permit access to two different aromatic forms as a function of the oxidation state. In their neutral forms, these congeneric systems contain competing 26 and 34 π-electronic circuits. When subject to two-electron oxidation, electronically mixed [4n+1]/[4n+1] triplet biradical species in the ground state are obtained that display global aromaticity in accord with Baird's rule.

Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC).

The syntheses, interconversions, and spectroscopic properties of a set of iron carbonyl clusters containing an interstitial carbide are reported. This includes the low temperature X-ray structures of the six-iron clusters (Y)2[Fe6(μ6-C)(μ2-CO)4(CO)12] (1a–c; where Y = NMe4, NEt4, PPh4); the five-iron cluster [Fe5(μ5-C)(CO)15] (3); and the novel formulation of the five-iron cluster (NMe4)2[Fe5(μ5-C)(μ2-CO)(CO)13] (4). Also included in this set is the novel charge-neutral cluster, [Fe6(μ6-C)(CO)18] (2), for which we were unable to obtain a crystallographic structure. As synthetic proof for the identity of 2, we performed a closed loop of interconversions within a family of crystallographically defined species (1, 3, and 4): [Fe6]2–→ [Fe6]0→ [Fe5]0→ [Fe5]2–→ [Fe6]2–. The structural, spectroscopic, and electronic properties of this “missing link” cluster 2were investigated by IR, Raman, XPS, and Mössbauer spectroscopiesas well as by DFT calculations. A single νCOfeature (1965 cm–1) in the IR spectrum of 2, as well as a prominent Raman feature (νsymm= 1550 cm–1), are consistent with the presence of terminal carbonyls and a {(μ6-C)Fe6} arrangement of iron centers around the central carbide. The XPS of 2exhibits a higher energy Fe 2p3/2feature (707.4 eV) as compared to that of 1(705.5 eV), consistent with the two-electron oxidation induced by treatment of 1with two equivalents of [Fc](PF6) under CO atmosphere (for the two added CO ligands). DFT calculations indicate two axial and four equatorial Fe sites in 1, all of which have the same or similar oxidation states, for example, two Fe(0) and four Fe(+0.5). These assignments are supported by Mössbauer spectra for 1, which exhibit two closely spaced quadrupole doublets with δ = 0.076 and 0.064 mm s–1. The high-field Mössbauer spectrum of 2(4.2 K) exhibits three prominent quadrupole doublets with δ = −0.18, −0.11, and +0.41 mm s−1. This indicates three pairs of chemically equivalent Fe sites. The first two pairs arise from irons of a similar oxidation state, while the last pair arises from irons in a different oxidation state, indicating a mixed-valent cluster. Variable field Mössbauer spectra for 2were simulated assuming these two groups and a diamagnetic ground state. Taken together, the Mössbauer results and DFT calculations for 2indicate two axial Fe(II) sites and four equatorial sites of lower valence, probably Fe(0). In the DFT optimized pentagonal bipyramidal structure for 2, the Fe(II)–Ccarbidedistances are compressed (∼1.84 Å), while the Fe(0)–Ccarbidedistances are elongated (∼2.05 Å). Analysis of the formulations for 1(closo-square bipyramid) and 2(nido-pentagonal bipyramid) is considered in the context of the textbook electron-counting rules of 14n+2 and 14n+4 for closoand nidoclusters, respectively. This redox-dependent intracluster disproportionation of Fe oxidation states is concluded to arise from changes in bonding to the central carbide. A similar phenomenon may be promoted by the central carbide of the FeMoco cluster of nitrogenase, which may in turn stimulate N2reduction.

Gene regulation shapes the evolution of phenotypic diversity. We investigated the evolution of liver promoters and enhancers in six primate species using ChIP-seq (H3K27ac and H3K4me1) to profile cis-regulatory elements (CREs) and using RNA-seq to characterize gene expression in the same individuals. To quantify regulatory divergence, we compared CRE activity across species by testing differential ChIP-seq read depths directly measured for orthologous sequences. We show that the primate regulatory landscape is largely conserved across the lineage, with 63% of the tested human liver CREs showing similar activity across species. Conserved CRE function is associated with sequence conservation, proximity to coding genes, cell-type specificity, and transcription factor binding. Newly evolved CREs are enriched in immune response and neurodevelopmental functions. We further demonstrate that conserved CREs bind master regulators, suggesting that while CREs contribute to species adaptation to the environment, core functions remain intact. Newly evolved CREs are enriched in young transposable elements (TEs), including Long-Terminal-Repeats (LTRs) and SINE-VNTR-Alus (SVAs), that significantly affect gene expression. Conversely, only 16% of conserved CREs overlap TEs. We tested the cis-regulatory activity of 69 TE subfamilies by luciferase reporter assays, spanning all major TE classes, and showed that 95.6% of tested TEs can function as either transcriptional activators or repressors. In conclusion, we demonstrated the critical role of TEs in primate gene regulation and illustrated potential mechanisms underlying evolutionary divergence among the primate species through the noncoding genome.

Three Fe(II) bis(terpyridine)-based complexes with thiophene (Fe(L1)2), bithiophene (Fe(L2)2), and 3,4-ethylenedioxythiophene (Fe(L3)2) side chains were designed and synthesized for the purpose of providing two terminal active sites for electrochemical polymerization. The corresponding metallopolymers (poly-Fe(Ln)2, n= 2 or 3) were synthesized on indium tin oxide (ITO)-coated glass substrates via oxidative electropolymerization of the thiophene-substituted monomers and characterized using electrochemistry, X-ray photoelectron spectroscopy, UV–vis spectroscopy, and atomic force microscopy. The film poly-Fe(L2)2was further studied for electrochromic (EC) color-switching properties and fabricated into a solid-state EC device. Poly-Fe(L2)2films exhibit an intense MLCT absorption band at 596 nm (ε = 4.7 × 104M–1cm–1) in the UV–vis spectra without any applied voltage. Upon application of low potentials (between 1.1 and 0.4 V vs Fc+/Fc), the obtained electropolymerized film exhibited great contrast with a change of transmittance percentage (ΔT%) of 40% and a high coloration efficiency of 3823 cm2C–1with a switching time of 1 s. The film demonstrates commonplace stability and reversibility with a 10% loss in peak current intensity after 200 cyclic voltammetry cycles and almost no loss in change of transmittance (ΔT%) after 900 potential switches between 1.1 and 0.4 V (vs Fc+/Fc) with a time interval of 0.75 s. The electropolymerization of Fe(L2)2provides convenient and controllable film fabrication. Electrochromic behavior was also achieved in a solid-state device composed of a poly-Fe(L2)2film and a polymer-supported electrolyte sandwiched between two ITO-coated glass electrodes.

Transcription factors (TFs) play multiple roles in development. Given this multifunctionality, it has been assumed that TFs are evolutionarily highly constrained. Here, we investigate the molecular mechanisms for the origin of a derived functional interaction between two TFs, HOXA11 and FOXO1. We have previously shown that the regulatory role of HOXA11 in mammalian endometrial stromal cells requires interaction with FOXO1, and that the physical interaction between these proteins evolved before their functional cooperativity. Here, we demonstrate that the derived functional cooperativity between HOXA11 and FOXO1 is due to derived allosteric regulation of HOXA11 by FOXO1. This study shows that TF function can evolve through changes affecting the functional output of a pre-existing protein complex.

The controlled preparation of higher order oligopyrrolic species holds broad utility across the chemical and material sciences. Here, we describe the gram-scale synthesis of a bench-stable 5,5″-unsubstituted terpyrrole in excellent yield via a tandem Suzuki cross-coupling with in situdeprotection. The solution and solid-state stability as well as UV–vis, fluorescence, and single crystal X-ray diffraction structure are also detailed.

Woolly mammoths and living elephants are characterized by major phenotypic differences that have allowed them to live in very different environments. To identify the genetic changes that underlie the suite of woolly mammoth adaptations to extreme cold, we sequenced the nuclear genome from three Asian elephants and two woolly mammoths, and we identified and functionally annotated genetic changes unique to woolly mammoths. We found that genes with mammoth-specific amino acid changes are enriched in functions related to circadian biology, skin and hair development and physiology, lipid metabolism, adipose development and physiology, and temperature sensation. Finally, we resurrected and functionally tested the mammoth and ancestral elephant TRPV3 gene, which encodes a temperature-sensitive transient receptor potential (thermoTRP) channel involved in thermal sensation and hair growth, and we show that a single mammoth-specific amino acid substitution in an otherwise highly conserved region of the TRPV3 channel strongly affects its temperature sensitivity.

A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs). Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs co-opted into hormone-responsive regulatory elements distributed throughout the genome.

Serum profiling using mass spectrometry-based proteomic techniques has great potential to detect biomarkers that might improve the management for advanced breast cancer patients. The albuminome has previously been investigated as a tool in biomarker discovery, however other high abundant blood proteins are also likely to sequester potentially interesting molecules.

Most people are attracted to T'ai Chi Ch'uan because of the grace and fluidity of the exercise form. These external movements, however, represent only a small part of what is [...]