Methanetriol─Formation of an Impossible Molecule.

Orthocarboxylic acids─organic molecules carrying three hydroxyl groups at the same carbon atom─have been distinguished as vital reactive intermediates by the atmospheric science and physical (organic) chemistry communities as transients in the atmospheric aerosol cycle. Predicted short lifetimes and their tendency to dehydrate to a carboxylic acid, free orthocarboxylic acids, signify one of the most elusive classes of organic reactive intermediates, with even the simplest representative methanetriol (CH(OH)3)─historically known as orthoformic acid─not previously been detected experimentally. Here, we report the first synthesis of the previously elusive methanetriol molecule in low-temperature mixed methanol (CH3OH) and molecular oxygen (O2) ices subjected to energetic irradiation. Supported by electronic structure calculations, methanetriol was identified in the gas phase upon sublimation via isomer-selective photoionization reflectron time-of-flight mass spectrometry combined with isotopic substitution studies and the detection of photoionization fragments. The first synthesis and detection of methanetriol (CH(OH)3) reveals its gas-phase stability as supported by a significant barrier hindering unimolecular decomposition. These findings progress our fundamental understanding of the chemistry and chemical bonding of methanetriol, hydroxyperoxymethane (CH3OOOH), and hydroxyperoxymethanol (CH2(OH)OOH), which are all prototype molecules in the oxidation chemistry of the atmosphere.

The investigation of the ultrafast excited state deactivation mechanisms for coumarin 307 in different solvents.

The intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT) processes of coumarin 307 (C307) in different solvents were investigated by performing steady-state/time-resolved transient absorption spectroscopic and steady-state photoluminescence spectroscopic characterizations in combination with time-dependent density functional theoretical calculation (TDDFT). The study unveiled the remarkable influence of solvent polarity and the strength of intermolecular hydrogen bonds formed between the solutes and solvents on the relaxation dynamics of the electronic excited state. Significantly, the emergence of the TICT state was observed in polar solvents, specifically dimethylformamide (DMF) and dimethyl sulfoxidemethanol (DMSO), owing to their inherent polarity as well as the enhanced intermolecular hydrogen bonding interactions. Interestingly, even in a weak polar solvent such as methanol (MeOH), the TICT state was also observed due to the intensified hydrogen bonding effects. Conversely, nonpolar solvents, exemplified by 1,4-dioxane (Diox), resulted in the stabilization of the ICT state due to the augmented N-H⋯O hydrogen bonding interactions. The experimental findings were corroborated by the computational calculations, thus ensuring the reliability of the conclusions drawn. Furthermore, schematic diagrams were presented to illustrate the mechanisms underlying the excited-state deactivation. Overall, this investigation contributes valuable mechanistic insights and provides a comprehensive understanding of the photochemical and photophysical properties exhibited by coumarin dyes.

High resolution electronic spectroscopy of uranium mononitride, UN.

The isoelectronic molecules UN and UO+ are known to have Ω = 3.5 and Ω = 4.5 ground states, respectively (where Ω is the unsigned projection of the electronic angular momentum along the internuclear axis). A ligand field theory model has been proposed to account for the difference [Matthew and Morse, J. Chem. Phys. 138, 184303 (2013)]. The ground state of UO+ arises from the U3+(5f3(4I4.5))O2- configuration. Owing to the higher nominal charge of the N3- ligand, the U3+ ion in UN is stabilized by promoting one of the 5f electrons to the more polarizable 7s orbital, reducing the repulsive interaction with the ligand and rendering U3+(5f27s(4H3.5))N3- the lowest energy configuration. In the present work, we have advanced the characterization of the UN ground state through studies of two electronic transitions, [18.35]4.5-X(1)3.5 and [18.63]4.5-X(1)3.5, using sub-Doppler laser excitation techniques with fluorescence detection. Spectra were recorded under field-free conditions and in the presence of static electric or magnetic fields. The ground state electric dipole moment [µ = 4.30(2) D] and magnetic ge-factor [2.160(9)] were determined from these data. These values were both consistent with the 5f27s configurational assignment. Dispersed fluorescence measurements were used to determine vibrational constants for the ground and first electronically excited states. Electric dipole moments and magnetic ge-factors are also reported for the higher-energy electronically excited states.

Unraveling the effect of solvents on the excited state dynamics of C540A by experimental and theoretical study.

In this work, the excited-state dynamics including intramolecular charge transfer (ICT) and the redshift of C540A have been investigated in a series of solvents on the basis of the Kamlet-Taft solvatochromic parameters (π*, α, ß) using femtosecond transient absorption spectra and systematic theoretical calculation. We demonstrate that the redshift of the emission peak has a linear relationship with the α and π* scales and the effect of the π* scale is slightly stronger than that of the α scale. Meanwhile, the ICT rates can be suggested as relevant to not only the α scale but also the π* scale. Additionally, C540A-AN has proved that the excited state molecules have a unique inactivation mechanism because of the dark feature of the S1 (CT) state. The valuable mechanistic information gleaned from the excited-state dynamics by the experimental and theoretical study would facilitate the design of organic materials for prospective applications in photochemistry and photobiology.

Mechano-bioconjugation Strategy Empowering Fusion Protein Therapeutics with Aggregation Resistance, Prolonged Circulation, and Enhanced Antitumor Efficacy.

Bioconjugation is a powerful protein modification strategy to improve protein properties. Herein, we report mechano-bioconjugation as a novel approach to empower fusion protein therapeutics and demonstrate its utility by a protein heterocatenane (cat-IFN-ABD) containing interferon-α2b (IFN) mechanically interlocked with a consensus albumin-binding domain (ABD). The conjugate was selectively synthesized in cellulo following a cascade of post-translational events using a pair of heterodimerizing p53dim variants and two orthogonal split-intein reactions. The catenane topology was proven by combined techniques of LC-MS, SDS-PAGE, SEC, and controlled proteolytic digestion. Not only did cat-IFN-ABD retain activities comparable to those of the wild-type IFN and ABD, the conjugate also exhibited enhanced aggregation resistance and prolonged circulation time over the simple linear and cyclic fusions. Consequently, cat-IFN-ABD potently inhibited tumor growth in the mouse xenograft model. Therefore, mechano-bioconjugation by catenation accomplishes function integration with additional benefits, providing an alternative pathway for developing advanced protein therapeutics.

Higher Order Protein Catenation Leads to an Artificial Antibody with Enhanced Affinity and In Vivo Stability.

The chemical topology is a unique dimension for protein engineering, yet the topological diversity and architectural complexity of proteins remain largely untapped. Herein, we report the biosynthesis of complex topological proteins using a rationally engineered, cross-entwining peptide heterodimer motif derived from p53dim (an entangled homodimeric mutant of the tetramerization domain of the tumor suppressor protein p53). The incorporation of an electrostatic interaction at specific sites converts the p53dim homodimer motif into a pair of heterodimer motifs with high specificity for directing chain entanglement upon folding. Its combination with split-intein-mediated ligation and/or SpyTag/SpyCatcher chemistry facilitates the programmed synthesis of protein heterocatenane or [n]catenanes in cells, leading to a general and modular approach to complex protein catenanes containing various proteins of interest. Concatenation enhances not only the target protein's affinity but also the in vivo stability as shown by its prolonged circulation time in blood. As a proof of concept, artificial antibodies have been developed by embedding a human epidermal growth factor receptor 2-specific affibody onto the [n]catenane scaffolds and shown to exhibit a higher affinity and a better pharmacokinetic profile than the wild-type affibody. These results suggest that topology engineering holds great promise in the development of therapeutic proteins.

Capillary liquid bridge soft lithography for micro-patterning preparation based on SU-8 photoresist templates with special wettability.

Patterned micro-nano arrays have shown great potential in the fields of optics, electronics and optoelectronics. In this study, a strategy of interface-induced dewetting assembly based on capillary liquid bridges and SU-8 photoresist templates is proposed for patterning organic molecules and nanoparticles. First, photoresist templates with chemical stability were prepared via a simplified lithography method. Then the interface wettability and the contact angle hysteresis of water droplets on the fluorosilane modified templates were adequately studied and discussed. Subsequently, a sandwich structure, composed of a superhydrophilic target substrate, a hydrophobic high adhesive photoresist template and a growth solution were introduced for the confined space dewetting assembly. The related mechanism was investigated and revealed, with the assistance of in situ observation via a fluorescence microscope. Finally, the patterned arrays of water-soluble organic small molecules and aqueous dispersed nanoparticles were successfully obtained on the target substrates. This method is simple and easy, and the SU-8 photoresist templates possess a series of advantages such as low processing cost, short preparation periods and reusable performance, which endow this strategy with potential for application in molecular functional devices.

Colorimetric paper sensor for sensitive detection of explosive nitroaromatics based on Au@Ag nanoparticles.

Rapid, reliable, onsite approaches for detection trace level of trinitrotoluene (TNT) is a pressing necessity for both homeland security and environmental protection. To this end, hydrophilic amine(-NH2) protected Au@Ag nanoparticles (NPs) were developed and fabricated as colorimetric paper sensor for delicate detection of TNT. The as-developed nanoprobe selectively reacts with TNT through classic Meisenheimer complex formation by means of charge transfer process from an electron-rich NH2 group of ß-cysteamine to an electron-deficient nitro group on TNT. Due to the absence of this particular interaction of other nitroaromatics, the proposed probe is highly selective for TNT detection with a better linear range (0-20 µg/mL) and limit of detection (LOD) of 0.35 µg/mL. The present work provides a novel and facile strategy to fabricate colorimetric paper sensors with rapid and selective recognition ability for label free analysis of TNT.

Fluorine Grafted Cu7S4-Au Heterodimers for Multimodal Imaging Guided Photothermal Therapy with High Penetration Depth.

We report the multifunctional nanocomposites (NCs) consisting of 19F-moieties grafted Cu7S4-Au nanoparticles (NPs) for negligible background 19F-magnetic resonance imaging (19F-MRI) and computed tomography (CT) imaging guided photothermal therapy. The localized surface plasmon resonance (LSPR) absorption can be reasonably tuned to the in vivo transparent window (800-900 nm) by coupling Au (<10 nm, LSPR ∼530 nm) with Cu7S4 (<15 nm, LSPR ∼1500 nm) into Cu7S4-Au heterodimers. The in vivo photothermal tests show that Cu7S4-Au show deeper light penetration with 808 nm irradiation, better photothermal efficacy, and less damage to normal tissues than Cu7S4 with 1500 nm irradiation. Moreover, compared to traditional 1H-MRI, the 19F-MRI based on these NCs demonstrates much better sensitivity due to the negligible background. This work offers a promising strategy for multimodal imaging guided photothermal therapy of deep tissue with good efficacy.

Full-Range pH Stable Au-Clusters in Nanogel for Confinement-Enhanced Emission and Improved Sulfide Sensing in Living Cells.

The sensitive and selective detection of hydrogen sulfide is of great importance due to its crucial role in pathological and physiological processes. Herein, we report a novel fluorescent platform, AuNCs@GC, for selective detection of hydrogen sulfide in living cells by impregnating the Au nanoclusters (AuNCs) into a biocompatible cationic polymer matrix, glycol-chitosan (GC) nanogel. The confinement effect significantly increased the emissive Au(I) units, resulting in a 6-fold enhancement of quantum yield (from 6.38% to 36.42%). In addition, the prepared positively charged AuNCs@GC nanogel exhibits excellent selectivity and improved sensitivity to aqueous sulfides. Moreover, the as-fabricated AuNCs@GC showed very good biocompatibility and super fluorescence stability across the full pH range and good salt tolerance, which demonstrated excellent adaptability toward intracellular sulfide imaging.

Note: Ultraviolet photodissociation dynamics of o-bromofluorobenzene in 234-267 nm.

Photodissociation dynamics of o-bromofluorobenzene in the 234-267 nm range has been experimentally investigated using the DC-slice velocity map imaging technique. It is found that Br(2P3/2) atoms produced from repulsive singlet state surfaces via excitation of one or more 1ππ* excited states dominate the Br photofragments. The quantum yield of spin-orbit excited Br(2P1/2) atoms was found to be only ∼0.02, indicating weak spin-orbit couplings in the low-lying electronic states of o-bromofluorobenzene.

Photodissociation dynamics of OCS at ∼210 nm: The role of c(23A″) state.

Photodissociation dynamics of carbonyl sulfide (OCS) in the deep ultraviolet region is investigated using a time-sliced ion velocity map imaging technique. The measured total kinetic energy release spectra from the photodissociation of OCS at ∼210 nm shows three dissociation channels to the fragment S(1D2), corresponding to low, medium, and high kinetic energy release (ET), respectively. The high ET channel is found to be a new dissociation channel opening with photolysis wavelength at ∼210 nm. Based on the aq(k)(p) polarization parameters as well as the anisotropy parameters ß determined from the images of S(1D2), the dissociation of OCS to S(1D2) + CO at 210 nm is concluded to involve a direct vertical excitation of the triplet c(23A″) state from the ground state, followed by processes as: the low ET component arises from a non-adiabatic transition from the repulsive A(21A') state to the electronic ground state X(11A'); the medium ET component arises from a simultaneous excitation to two repulsive excited states; and the high ET component arises from the intersystem crossing from the triplet c(23A″) state to the repulsive A(21A') state. The present study shows that, due to the strong spin-orbit coupling between the triplet c(23A″) state and the repulsive A(21A') state, a direct excitation to c(23A″) significantly contributes to the photodissociation dynamics of OCS in the deep-UV region.

Ultrasmall Organic Nanoparticles with Aggregation-Induced Emission and Enhanced Quantum Yield for Fluorescence Cell Imaging.

The use of fluorescence probes for biomedical imaging has attracted significant attention over recent years owing to their high resolution at cellular level. The probes are available in many formats including small particle size based imaging agents which are considered to be promising candidates, due to their excellent stabilities. Yet, concerns over the potential cytotoxicity effects of inorganic luminescent particles have led to questions about their suitability for imaging applications. Exploration of alternatives inspired us to use organic fluorophores with aggregation-induced emission (AIE), prepared by functionalizing the amine group on tetraphenylethene with 3,5-bis(trifluoromethyl)phenyl isocyanate. The as-synthesized novel AIE fluorophore (TPE-F) display enhanced quantum yield and longer lifetime as compared with its counterparts (4,4',4″,4‴-(ethene-1,1,2,2-tetrayl)tetraaniline, TPE-AM). Furthermore, the TPE-F was encapsulated into small-size organic nanoparticles (NPs; dynamic light scattering size, ∼10 nm) with polysuccinimide (PSI). The biocompatibility, excellent stability, bright fluorescence, and selective cell targeting of these NPs enable the as-prepared TPE-F NPs to be suitable for specific fluorescence cell imaging.

Upconversion luminescence tracking of gene delivery via multifunctional nanocapsules.

The real-time fluorescence tracking of gene delivery is very important as it helps to figure out how a vector enters a cell and also to follow its fate within the cell interior. Lanthanide-doped upconversion nanoparticles (UCNPs) have shown great potential in biomedical applications in virtue of their unique optical and biological properties. Herein, we report a simple and versatile strategy to fabricate a multifunctional nanocapsule for effective gene delivery and real-time luminescence tracking. The hydrophobic UCNPs were modified by positively charged amphiphilic polymer together with polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) polymer, affording biocompatible nanocapsules with high gene loading capacity and good stability. Red UC luminescence of UCNPs are able to track the delivery of nanocapsules in cells without background fluorescence interference, in the meantime, the green fluorescence of green fluorescence protein (GFP) expressed by the pDNA could subtly monitor the gene transfection efficacy. The results demonstrated that our nanocapsule has ideal biocompatibility, satisfactory gene loading capacity and great bioimaging ability, which is promising for imaging guided cell therapy and gene engineering.

A Fluorescent Chemodosimeter for Live-Cell Monitoring of Aqueous Sulfides.

Aqueous sulfides are emerging signaling agents implicated in various pathological and physiological processes. The development of sensitive and selective methods for the sensing of these sulfides is therefore very important. Herein, we report that the as-synthesized 1-oxo-1H-phenalene-2,3-dicarbonitrile (OPD) compound provides promising fluorescent properties and unique reactive properties toward aqueous sulfides. It was found that OPD showed high selectivity and sensitivity toward Na2S over thiols and other inorganic sulfur compounds through a sulfide involved reaction which was confirmed by high-resolution mass spectroscopy (HRMS) and nuclear magnetic resonance (NMR) results. The fluorescence intensity increases linearly with sulfide concentration in the range of 1.0-30 µM with a limit of detection of 52 nM. This novel fluorescent probe was further exploited for the fluorescence imaging sensing of aqueous sulfide in HeLa cells.

Real-time fluorescence tracking of gene delivery via multifunctional nanocomposites.

Fluorescence imaging of transduced cells and tissues is valuable in the development of gene vectors and the evaluation of gene therapy efficacy. We report here the simple and rational design of multifunctional nanocomposites (NCs) for simultaneous gene delivery and fluorescence tracking based on ZnS:Mn(2+) quantum dots (QDs) and positively charged polymer coating. The positively charged imidazole in the as-synthesized amphiphilic copolymer can be used for gene loading via electrostatic interaction. While the introduced poly(ethylene glycol) (PEG) can be used to reduce the binding of plasma proteins to nanovectors and minimize clearance by the reticuloendothelial system after intravenous administration. Most importantly, these multifunctional nanovectors showed much lower cellular toxicity than the commercial polyethylenimine (PEI) transfection vectors. On the basis of the red fluorescence of QDs, we can real-time track the gene delivery in cells, and the transfection efficacy of pDNA encoding enhanced green fluorescence protein (pEGFP) was monitored via the green fluorescence of the GFP expressed by the pDNA delivered into the nuclei. Fluorescence imaging analysis confirmed that the QDs-based nanovectors delivered pDNA into HepG2 cells efficiently. These new insights and capabilities pave a new way toward nanocomposite engineering for fluorescence imaging tracking of gene therapy.

Note: Vibrationally mediated photodissociation of carbon dioxide cation.

The photodissociation dynamics of carbon dioxide cation, CO2(+), mediated by its different Ã(2)Πu,1/2(υ1,υ2,0) vibronic states has been investigated by means of time-sliced velocity map imaging. Through analysis of the recorded translational energy release spectra of photofragment CO(+), we found that the photodissociation of CO2(+) exhibits drastic change in a rather narrow energy region. A conformational barrier in the CO2(+)(Ã(2)A1) state is suggested to be ∼5600 cm(-1) relative to the CO2(+)(Ã(2)Πu,1/2(0,0,0)) state, in reasonable agreement with previous prediction.

Note: Observation of a new electronically excited state of cobalt monoxide.

The laser-induced fluorescence excitation spectra of jet-cooled CoO molecules have been recorded in the energy region of 21,800-25,000 cm(-1). Apart from the seven vibronic bands assigned to the known G(4)Φ(9∕2)(υ(')) - X(4)Δ(7∕2)(υ(") = 0) progression [M. Barnes, D. J. Clouthier, P. G. Hajigeorgiou, G. Huang, C. T. Kingston, A. J. Merer, G. F. Metha, J. R. D. Peers, and S. J. Rixon, J. Mol. Spectrosc. 186, 374 (1997)], we observed a new band system assignable to the [22.95](4)Δ(7∕2)(υ(') = 0 - 4) - X(4)Δ(7∕2)(υ(") = 0) progression. Extensive perturbations among these vibronic bands have been revealed by means of reduced energy plots. The new electronically excited (4)Δ state has been determined to be most likely of an electronic configuration (2pπ)(3)(4sσ)(2)(3dδ)(3)(3dπ)(3) based on the charge-transferred promotion model.