Imaging of Proteins in Tissue Samples Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

Chemical maps of tissue samples provide important information on biological processes therein. Recently, advances in tissue imaging have been achieved using ambient ionization techniques, such as desorption electrospray ionization mass spectrometry (DESI-MS), but such techniques have been almost exclusively confined to the mapping of lipids and metabolites. We report here the use of nanospray desorption electrospray ionization (nanoDESI) that allows us to image proteins in tissue samples in a label-free manner at atmospheric pressure with only minimum sample preparation. Multiply charged proteins with masses up to 15 kDa were successfully detected by nanoDESI using an LTQ Orbitrap mass spectrometer. In an adult mice brain section, expression of proteins including ubiquitin, β-thymosin, myelin basic protein, and hemoglobin were spatially mapped and characterized. We also determined the location of methylation on myelin basic protein. This imaging modality was further implemented to MYC-induced lymphomas. We observed an array of truncated proteins in the region where normal thymus cells were infiltrated by tumor cells, in contrast to healthy tissue

Excited-State Proton Transfer in 3‑Cyano-7-azaindole: From Aqueous Solution to Ice

We investigated the excited-state proton transfer (ESPT) reaction for 3-cyano-7-azaindole (<b>3CAI</b>) in aqueous solution and in ice. <b>3CAI</b> undergoes water-catalyzed ESPT in the aqueous solution, giving normal (355 nm) and proton transfer tautomer (∼472 nm) emission bands. Detailed temperature-dependent studies showed that the values of activation free energy (Δ<i>G</i>^‡) were similar between N–H and N–D isotopes. Therefore, water-catalyzed ESPT involves a stepwise mechanism incorporating solvation equilibrium (<i>K</i>_eq) to form a 1:1 (molar ratio) water:<b>3CAI</b> cyclic hydrogen-bonded complex as an intermediate, followed by perhaps proton tunneling reaction. In sharp contrast, <b>3CAI</b> in ice undergoes entirely different photophysical properties, in which <b>3CAI</b> self-organizes to form a double-hydrogen-bonded dimers at the grain boundary of the polycrystalline. Upon excitation, the dimer proceeds with a fast excited-state double proton transfer reaction, giving rise to solely a tautomer emission (∼450 nm). The distinct difference in ESPT properties between water and ice makes azaindoles feasible for the investigation of water–ice interface property

Modulation of Metallophilic Bonds: Solvent-Induced Isomerization and Luminescence Vapochromism of a Polymorphic Au–Cu Cluster

We report a homoleptic Au–Cu alkynyl cluster that represents an unexplored class of luminescent materials with stimuli-responsive photophysical properties. The bimetallic complex formulated as [Au₂Cu₂(C₂OHC₅H₈)₄]_<i>n</i> efficiently self-assembles from Au­(SC₄H₈)­Cl, Cu­(NCMe)₄PF₆, and 1-ethynylcyclopentanol in the presence of NEt₃. This compound shows remarkably diverse polymorphism arising from the modulation of metallophilic interactions by organic solvents. Four crystalline forms, obtained from methanol (<b>1a</b>); ethanol, acetone, or choloroform (<b>1b</b>); toluene (<b>1c</b>); and diethyl ether or ethyl acetate (<b>1d</b>), demonstrate different photoluminescent characteristics. The solid-state quantum yields of phosphorescence (Φ) vary from 0.1% (<b>1a</b>) to 25% (<b>1d</b>), depending on the character of intermetallic bonding. The structures of <b>1b</b>–<b>d</b> were determined by single-crystal X-ray diffraction. The ethanol (<b>1b</b>, Φ = 2%) and toluene (<b>1c</b>, Φ = 10%) solvates of [Au₂Cu₂(C₂OHC₅H₈)₄]_<i>n</i> adopt octanuclear isomeric structures (<i>n</i> = 2), while <b>1d</b> (Φ = 25%) is a solvent-free chain polymer built from two types of Au₄Cu₄ units. Electronic structure calculations show that the dramatic enhancement of the emission intensity is correlated with the increasing role of metal–metal bonding. The latter makes the emission progressively more metal-centered in the order <b>1b</b> < <b>1c</b> < <b>1d</b>. The metallophilic contacts in <b>1a</b>–<b>d</b> show high sensitivity to the vapors of certain solvents, which effectively induce unusual solid-state isomerization and switching of the absorption and luminescence properties via non-covalent interactions. The reported polymorphic material is the first example of a gold­(I) alkynyl compound demonstrating vapochromic behavior

Prominent Short-Circuit Currents of Fluorinated Quinoxaline-Based Copolymer Solar Cells with a Power Conversion Efficiency of 8.0%

A tailor-made medium-band gap fluorinated quinoxaline-based conjugated polymer of <b>PBDT-TFQ</b> was designed and synthesized as a donor material for bulk-heterojunction (BHJ) solar cells. This polymer is possessed of an intrachain donor–acceptor architecture and exhibits a broad and strong absorption spectrum across the entire UV–vis region. The introduction of F atoms with high electron affinity to the quinoxaline moiety is effective in further lowering both the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels of <b>PBDT-TFQ</b> to attain higher open-circuit voltage (<i>V</i>_oc). With an optimized blend ratio of <b>PBDT-TFQ</b>:PC₇₁BM (1:1, w/w), a high power conversion efficiency (PCE) of 8.0% was obtained, with a <i>V</i>_oc of 0.76 V, a short-circuit current density (<i>J</i>_sc) of 18.2 mA cm^–2, and a fill factor (FF) of 58.1% under AM 1.5G irradiation. The resulting copolymer reveals an outstanding <i>J</i>_sc value, arising from the higher hole mobility of <b>PBDT-TFQ</b>, together with the better continuous percolation pathways within the polymer blend for efficient exciton dissociation and charge transport

A Versatile Theranostic Delivery Platform Integrating Magnetic Resonance Imaging/Computed Tomography, pH/<i>cis</i>-Diol Controlled Release, and Targeted Therapy

The functions of biomedical imaging, cancer targeting, and controlled release of therapeutic agents were integrated into a drug delivery platform to proof its diagnostic and therapeutic capabilities. This versatile nanocomposite is based on the strategic design of wormlike mesoporous silica nanocarriers that are decorated with extremely small iron oxide nanoparticles, having a prominent T₁-weighted Magnetic Resonance Imaging (MRI) signal. The controlled release function was then achieved through the grafting of polyalcohol saccharide derivative ligands onto the surfaces of mesoporous silica nanoparticles to conjugate with boronic acid functionalized gold nanoparticles, which acted as the gate and the source of computed tomography (CT) signals. This versatile platform thus exhibited a MRI/CT dual imaging property drawing on the strong points to offset the weaknesses of each, rendering more accurate diagnosis. The capping of gold nanoparticles controlled with the hydrolysis of boronate ester bonds provides the reversible opening/closing process, avoiding further release of drug once the nanocomposite leaves the cell or tissue. To endow this platform with targeting ability, protocatechuic acid was utilized as a linker to connect folic acid with the boronic acid of the gold nanoparticles. The anchor of targeting moiety, folic acid, enriched this platform and enhanced the specific cellular uptake toward cells with folate receptor. This integrated drug delivery platform was then loaded with the antitumor agent doxorubicin, demonstrating its power for targeted delivery, bioimaging, and controlled release chemotherapy to reduce the undesired side effects of chemotherapy

Hybrid Inorganic–Organic Complexes of Zn, Cd, and Pb with a Cationic Phenanthro-diimine Ligand

The phosphonium-decorated phenanthro-imidazolyl pyridine ligand, LP+Br, readily reacts with zinc(II) and cadmium(II) bromides to give inorganic–organic zero-dimensional compounds [LP+ZnBr2]2[ZnBr4] (1) and [(LP+)2Cd2Br4][CdBr4] (2), respectively, upon crystallization. These salts are moderately fluorescent in the solid state under ambient conditions (λem = 458 nm, Φem = 0.11 for 1; λem = 460 nm, Φem = 0.13 for 2). Their emission results from spin-allowed electronic transitions localized on the organic component with the negligible effect of [MBr4]2– and MBr2 units. Contrary to ionic species 1 and 2, lead(II) bromide affords a neutral and water-stable complex [(LP+)2Pb3Br8] (3), showing weak room-temperature phosphorescence arising from spin–orbit coupling due to the heavy atom effect. The emission, which is substantially enhanced for the amorphous sample of 3 (λem = 575 nm, Φem = 0.06), is assigned to the intraligand triplet excited state, which is a rare phenomenon among Pb(II) molecular materials

Modulation of Metallophilic Bonds: Solvent-Induced Isomerization and Luminescence Vapochromism of a Polymorphic Au–Cu Cluster

We report a homoleptic Au–Cu alkynyl cluster that represents an unexplored class of luminescent materials with stimuli-responsive photophysical properties. The bimetallic complex formulated as [Au₂Cu₂(C₂OHC₅H₈)₄]_<i>n</i> efficiently self-assembles from Au­(SC₄H₈)­Cl, Cu­(NCMe)₄PF₆, and 1-ethynylcyclopentanol in the presence of NEt₃. This compound shows remarkably diverse polymorphism arising from the modulation of metallophilic interactions by organic solvents. Four crystalline forms, obtained from methanol (<b>1a</b>); ethanol, acetone, or choloroform (<b>1b</b>); toluene (<b>1c</b>); and diethyl ether or ethyl acetate (<b>1d</b>), demonstrate different photoluminescent characteristics. The solid-state quantum yields of phosphorescence (Φ) vary from 0.1% (<b>1a</b>) to 25% (<b>1d</b>), depending on the character of intermetallic bonding. The structures of <b>1b</b>–<b>d</b> were determined by single-crystal X-ray diffraction. The ethanol (<b>1b</b>, Φ = 2%) and toluene (<b>1c</b>, Φ = 10%) solvates of [Au₂Cu₂(C₂OHC₅H₈)₄]_<i>n</i> adopt octanuclear isomeric structures (<i>n</i> = 2), while <b>1d</b> (Φ = 25%) is a solvent-free chain polymer built from two types of Au₄Cu₄ units. Electronic structure calculations show that the dramatic enhancement of the emission intensity is correlated with the increasing role of metal–metal bonding. The latter makes the emission progressively more metal-centered in the order <b>1b</b> < <b>1c</b> < <b>1d</b>. The metallophilic contacts in <b>1a</b>–<b>d</b> show high sensitivity to the vapors of certain solvents, which effectively induce unusual solid-state isomerization and switching of the absorption and luminescence properties via non-covalent interactions. The reported polymorphic material is the first example of a gold­(I) alkynyl compound demonstrating vapochromic behavior

Probing Ligand Binding to Thromboxane Synthase

Various fluorescence experiments and computer simulations were utilized to gain further understanding of thromboxane A₂ synthase (TXAS), which catalyzes an isomerization of prostaglandins H₂ to give rise to thromboxane A₂ along with a fragmentation reaction to 12-l-hydroxy-5,8,10-heptadecatrienoic acid and malondialdehyde. In this study, 2-<i>p</i>-toluidinylnaphthalene-6-sulfonic acid (TNS) was utilized as a probe to assess the spatial relationship and binding dynamics of ligand–TXAS interactions by steady-state and time-resolved fluorescence spectroscopy. The proximity between TNS and each of the five tryptophan (Trp) residues in TXAS was examined through the fluorescence quenching of Trp by TNS via an energy transfer process. The fluorescence quenching of Trp by TNS was abolished in the W65F mutant, indicating that Trp65 is the major contributor to account for energy transfer with TNS. Furthermore, both competitive binding experiments and the computer-simulated TXAS structure with clotrimazole as a heme ligand strongly suggest that TXAS has a large active site that can simultaneously accommodate TNS and clotrimazole without mutual interaction between TNS and heme. Displacement of TNS by Nile Red, a fluorescence dye sensitive to environmental polarity, indicates that the TNS binding site in TXAS is likely to be hydrophobic. The Phe cluster packing near the binding site of TNS may be involved in facilitating the binding of multiple ligands to the large active site of TXAS

Interplay of Molecular Orientation, Film Formation, and Optoelectronic Properties on Isoindigo- and Thienoisoindigo-Based Copolymers for Organic Field Effect Transistor and Organic Photovoltaic Applications

A systematic study on the effects of heteroarenes on the solid state structure and optoelectronic properties of isoindigo analogues, namely, PBDT-IIG and PBDT-TIIG, used in solution-processed organic field effect transistors (OFETs) and organic photovoltaics (OPVs) is reported. We discover that the optical absorption, frontier orbitals, backbone coplanarity, molecular orientation, solubility, film morphology, charge carrier mobility, and solar cell performance are critically influenced by the heteroarenes in the acceptor subunits. PBDT-IIG exhibits good p-type OFET performance with mobility up to 1.03 × 10^–1 cm² V^–1 s^–1, whereas PBDT-TIIG displays ambipolar mobilities of μ_h = 7.06 × 10^–2 cm² V^–1 s^–1 and μ_e = 2.81 × 10^–4 cm² V^–1 s^–1. PBDT-IIG and PBDT-TIIG blended with [6,6]-phenyl-C₇₁-butyric acid methyl ester (PC₇₁BM) yield promising power conversion efficiencies (PCEs) of 5.86% and 2.55%, respectively. The excellent mobility of PBDT-IIG can be attributable to the growing fraction of edge-on packing by the interfacial surface treatment. Although PBDT-TIIG could construct a long-range face-on packing alignment to meliorate its photocurrent in OPV applications, the low open-circuit voltage caused by its high-lying HOMO energy level and greater recombination demonstrates the trade-off between light absorption and solar cell performance. Nevertheless, PBDT-TIIG with a PCE of 2.55% is the highest reported PCE to date for the TIIG-based systems

Studies of Excited-State Properties of Multibranched Triarylamine End-Capped Triazines

Electron donor–acceptor types of multibranched triarylamine end-capped triazines have been systematically investigated by steady-state electronic spectroscopy, electrochemistry, femtosecond fluorescence anisotropy and solvent relaxation dynamics. The results, together with computational approach, have gained in-depth insight into their excited-state properties, especially the interactions between branches. Among different branched triarylamines of one, two and three arms, the interbranch interaction between each arm is weak, as evidenced by their nearly identical absorption spectral profile and frontier orbitals analyses. Upon S₀ → S₁ excitation, the electronic delocalization in the three-branched triarylamine end-capped triazine is resolved to be 680 ± 130 fs, followed by a slow (28 ± 3 ps) electronic localization into one branch and consequently a rotational depolarization of 2.0 ± 0.1 ns. Similar delocalization dynamics was resolved for the two-branched triarylamine end-capped triazine (electronic delocalization, 500 ± 90 fs; twisting localization, 21 ± 5 ps; rotational depolarization, 700 ± 30 ps). The comparable electron delocalization and solvent relaxation time scale may set up a new paradigm to investigate their specific correlation in the early time domain