Pi-Tai Chou

Insulin‐Directed Synthesis of Fluorescent Gold Nanoclusters: Preservation of Insulin Bioactivity and Versatility in Cell Imaging

Fluorescent nanomaterials have received great attention and have been intensively studied, because of their unique optical and photophysical properties, as replacements for conventional organic dyes in optical cell imaging. Although semiconductor quantum dots show promising signals in biomedical imaging, their high inherent cytotoxicity and self-aggregation inside living cells fatally limit pragmatic biomedical applications. Fluorescent nanoclusters (NCs), in contrast, exhibit superior properties such as low toxicity and high biocompatibility. Among the various NCs, much effort has been dedicated to the study of fluorescent Au NCs. Au NCs carry quantum-mechanical properties when their sizes are comparable to or smaller than the Fermi wavelength (ca. 1 nm) of conductive electrons. The fluorescent Au NCs, with their ultrafine size, do not disturb the biological functions of the labeled bioentities; therefore, there is great potential to develop Au NCs as a new luminescent label. For example, Lin et al. successfully used water-soluble fluorescent Au NCs capped with dihydrolipoic acid (AuNC@DHLA) and modified with polyethylene glycol (PEG), bovine serum albumin (BSA), and streptavidin for cell bioimaging. Compared with organic-monolayer-protected Au NCs, the usage of proteins as a green-chemical reducing and stabilizing agent is advantageous because their complex 3D structures can withstand a wide range of pH conditions. Accordingly, Au NC synthesis with BSA and lysozyme has been reported and applied to several devices, such as nanosensors of Hg, CN , and H2O2. [12] Very recently, through the conjugation of BSA–Au NCs to folic acid, targetspecific detection of cancer-cell imaging has been demonstrated. Also, BSA–Au NCs have been applied in MDAMB-45 and HeLa tumor xenograft model imaging. Nevertheless, up to this stage, there has been a lack of reports on bioactive protein-directed fluorescent Au NCs that can still preserve their own biological role. Conversely, using Au nanoparticles encapsulated in certain enzymes, several reports claimed significant changes of enzymatic functionality. The goal of this project is thus to search for a bioactive protein to exploit as a template to direct the growth of fluorescent Au NCs. The resulting protein–Au NC nanocomposites are able to retain bioactivity, so that the associated biological role can be pursued by various imaging techniques. Among a number of proteins of vital importance, insulin is of prime interest. Insulin is a polypeptide hormone comprising only 51 amino acids. Its function primarily lies in the regulation of insulin-responsive tissues and it is also directly/indirectly related to many diseases, including diabetes, Alzheimer s disease, obesity, and aging. Its signaling pathway controls the growth of an organism, and hence exerts a profound influence on metabolism and reproduction. Herein, we report for the first time the synthesis of fluorescent Au NCs by using insulin as a template. The resulting insulin–Au NCs exhibit intense red fluorescence maximized at 670 nm and, more importantly, retain their bioactivity and biocompatibility. Several key experiments have been performed in vitro and/or in vivo to assess their viability and versatility. Detailed synthetic procedures are elaborated in the Supporting Information. In brief, by mixing insulin and HAuCl4 in Na3PO4 buffer by continuously stirring at 4 8C for 12 h, reddish luminescent insulin–Au NCs were readily prepared. The crude product was then purified by centrifugal filtration (4000g) for 30 min with a cutoff of 5 kDa to obtain the insulin–Au NCs for subsequent applications. The absorption and photoluminescence emission spectra of insulin–Au NCs are shown in Figure 1. The emission quantum yield Ff was determined to be 0.07, with observed lifetimes fitted to be 439 ns (4%) and 2041 ns (96%). The inset of Figure 1 displays a high-resolution transmission electron microscopy (HRTEM) image of insulin–Au NCs. From the respective histograms, the as-prepared insulin– Au NCs revealed a spherical shape and good size uniformity (for size distribution, see Figure S1 in the Supporting Information). The diameters of insulin–Au NCs, upon averaging over 100 particles, were calculated to be (0.92 0.03) nm (mainly for Au NCs). The hydrodynamic radii of [*] C.-L. Liu, Y.-H. Hsiao, Dr. C.-W. Lai, C.-W. Shih, Y.-K. Peng, Dr. K.-C. Tang, H.-W. Chang, Prof. P.-T. Chou Department of Chemistry, National Taiwan University 1, Section 4, Roosevelt Road, Taipei 10617 (Taiwan) Fax: (+886)2-369-5208 E-mail: chop@ntu.edu.tw

Systematic Investigation of the Metal-Structure–Photophysics Relationship of Emissive d10-Complexes of Group 11 Elements: The Prospect of Application in Organic Light Emitting Devices

A series of new emissive group 11 transition metal d(10)-complexes 1-8 bearing functionalized 2-pyridyl pyrrolide together with phosphine ancillary such as bis[2-(diphenylphosphino)phenyl] ether (POP) or PPh(3) are reported. The titled complexes are categorized into three classes, i.e. Cu(I) complexes (1-3), Ag(I) complexes (4 and 5), and Au(I) metal complexes (6-8). Via combination of experimental and theoretical approaches, the group 11 d(10)-metal ions versus their structural variation, stability, and corresponding photophysical properties have been investigated in a systematic and comprehensive manner. The results conclude that, along the same family, how much a metal d-orbital is involved in the electronic transition plays a more important role than how heavy the metal atom is, i.e. the atomic number, in enhancing the spin-orbit coupling. The metal ions with and without involvement of a d orbital in the lowest lying electronic transition are thus classified into internal and external heavy atoms, respectively. Cu(I) complexes 1-3 show an appreciable metal d contribution (i.e., MLCT) in the lowest lying transition, so that Cu(I) acts as an internal heavy atom. Despite its smallest atomic number among group 11 elements, Cu(I) complexes 1-3 exhibit a substantially larger rate of intersystem crossing (ISC) and phosphorescence radiative decay rate constant (k(r)(p)) than those of Ag(I) (4 and 5) and Au(I) (6-8) complexes possessing pure π → π* character in the lowest transition. Since Ag(I) and Au(I) act only as external heavy atoms in the titled complexes, the spin-orbit coupling is mainly governed by the atomic number, such that complexes associated with the heavier Au(I) (6-8) show faster ISC and larger k(r)(p) than the Ag(I) complexes (4 and 5). This trend of correlation should be universal and has been firmly supported by experimental data in combination with empirical derivation. Along this line, Cu(I) complex 1 exhibits intensive phosphorescence (Φ(p) = 0.35 in solid state) and has been successfully utilized for fabrication of OLEDs, attaining peak EL efficiencies of 6.6%, 20.0 cd/A, and 14.9 lm/W for the forward directions.

Contemporary progresses on neutral, highly emissive Os(II) and Ru(II) complexes

This tutorial review highlights recent and current advances in Os(II) and Ru(II) based luminescent complexes in view of their potential in providing models for photophysical properties and in serving as active materials in optoelectronic devices. It starts with a discussion of the fundamentals of pyridyl azolate chromophores and presents several prototypical designs that allow subtle variation of their basic properties. The third section of this article concerns the preparation of Os(II) and Ru(II) metal complexes and discusses the key factors that control their phosphorescence efficiencies and peak wavelengths. Attention is focused on the properties of their lowest lying excited states. In the last section, we present a series of related Os(II) complexes possessing pyridyl azolate, cyclometalated benzo[h]quinoline, beta-diketonates and quinolinates to demonstrate the power of fundamental basis to chemistry and theoretical approaches in rationalizing the corresponding photophysical behavior and hence to discuss the implications regarding their possible routes for future research.

Ruthenium(II) Sensitizers with Heteroleptic Tridentate Chelates for Dye‐Sensitized Solar Cells

Dye-sensitized solar cells (DSSCs) are a promising technology with the potential to harvest sunlight at low cost. Specifically, DSSCs based on either organometallic dyes or organic push-and-pull dyes adsorbed on nanocrystalline TiO2 photoanodes have attracted intensive research interest in the past two decades. The use of ruthenium(II)-based sensitizers is still the most attractive approach, because their photophysical and electrochemical properties can be systematically fine-tuned to achieve optimal material characteristics. Key examples of Ru sensitizers for DSSCs include the wellestablished N3 and N719 dyes and their functionalized derivatives. 6] These dyes are commonly assembled by incorporation of at least one 4,4’-dicarboxy-2,2’-bipyridine chelate (Scheme 1), on which the carboxy anchors allow efficient electron injection into the TiO2 nanoparticles. The accompanying thiocyanate ancillary ligands are pointed away from the TiO2 surface, thus providing intimate contact to the I /I3 redox couple in the electrolyte and subsequently triggering rapid regeneration of the oxidized sensitizer. The lower-lying absorption bands are attributed to metal-toligand charge transfer (MLCT) and display absorption thresholds close to 800 nm, unmatched by the majority of organic dyes known to date. For optimizing Ru sensitizers, it has been reported that, upon introduction of 4,4’,4’’-tricarboxy-2,2’:6,2’’-terpyridine (H3tctpy), the lowest energy transition could be extended toward the near-IR region, thus affording the panchromatic sensitizer known as N749, or black dye [nBu4N]3[Ru(Htctpy)(NCS)3]. [7] Although this design seems to show satisfactory sensitization up to 900 nm, it still possesses two major deficiencies. One is the inferior absorptivity in the visible region, attributed to the lack of effective auxochrome. The second is the presence of three thiocyanate ligands, which not only reduce the synthetic yield owing to coordination isomerism but also deteriorate the lifespan of the as-fabricated cell units, because the weak Ru NCS dative bonding causes notable dye decomposition during operation. In conjunction with current endeavors, we described one panchromatic dye PRT4, which possesses a styrene-substituted pyridyl pyrazolate (pypz) auxochrome. Its recorded solar-cell performance supersedes our best reference cells using N749, thus providing the first success for our research initiative. Herein we present a breakthrough design employing both the H3tctpy anchor and a newly designed tridentate ancillary ligand; the latter is also targeted for replacing the last remaining thiocyanate in our PRT4 dye as well as all three thiocyanates in N749 sensitizer. Thiophene derivatives or other auxochrome units were tethered to the central pyridyl group in an attempt to increase the light-harvesting capability. In this synthetic protocol (Scheme 2), the functionalized 2,6-bis(5-pyrazolyl)pyridine chelate was first prepared using a multistep process starting from chlorination of chelidamic acid, except for the synthesis of parent 2,6-bis(5-pyrazolyl)pyridine, which employed the commercially available 2,6diacetylpyridine. Bis-tridentate Ru complexes were then obtained from addition of the relevant 2,6-dipyrazolylpyridine derivative with source complex [Ru(tectpy)Cl3] in ethanol solution (tectpy = 4,4’,4’’-triethoxycarbonyl2,2’:6’,2’’-terpyridine). The crude ethoxycarbonyl Ru products were purified on a silica gel column and eluted with a mixture of hexane and ethyl acetate. To confirm their molecular structure, single-crystal X-ray analysis of one derivative (TF-2OEt; TF = thiocyanate-free) was carried Scheme 1. Ru sensitizers N3, N719, N749, and PRT4.

Iridium-complex-functionalized Fe3O4/SiO2 core/shell nanoparticles: a facile three-in-one system in magnetic resonance imaging, luminescence imaging, and photodynamic therapy.

Highly uniform Fe3O4/SiO2 core/shell nanoparticles functionalized by phosphorescent iridium complexes (Ir) have been strategically designed and synthesized. The Fe3O4/SiO2(Ir) nanocomposite demonstrates its versatility in various applications: the magnetic core provides the capability for magnetic resonance imaging and the great enhancement of the spin-orbit coupling in the iridium complex makes it well suited for phosphorescent labeling and simultaneous singlet oxygen generation to induce apoptosis.

Facile synthesis of highly emissive carbon dots from pyrolysis of glycerol; gram scale production of carbon dots/mSiO2 for cell imaging and drug release

We report on a facile method to synthesize carbon dots (CDs) using glycerol solvent as a single precursor via a pyrolysis process free from catalysts. This method is extremely simple and economical, and provides a feasible route for mass production of highly emissive CDs. For rationalization, a mechanism incorporating dehydration of glycerol, followed by acrylaldehyde formation is tentatively proposed for CD production. Further systematic improvement of particle homogeneity is made by harnessing the growth of CDs inside the mesoporous silica nanoparticles that act as a nano-reactor to regulate the size distribution. Simultaneously capping a polyethylene glycol (PEG)-derived reactant onto the CDs@SiO2 enhances their luminescence, stability and bio-compatibility. The as-prepared CDs@mSiO2–PEG nanocomposites are then loaded with the anti-cancer drug doxorubicin (DOX), so that the controlled release of DOX could be monitored by both time-dependent and spatially resolved ratiometric fluorescence intensity for CDs versus DOX in HeLa cells, successfully demonstrating that the CDs@mSiO2–PEG nanocomposites are suitable for cell imaging and drug release.

Organic light-emitting diodes based on charge-neutral Os(II) emitters: generation of saturated red emission with very high external quantum efficiency

The OLED device using 6% of Os(fptz)2(PPh2Me)2 as the dopant emitter in a CBP host and BPAPF as hole transporting material shows an external quantum efficiency of 15.3% and luminous efficiency of 21.3 cd A−1, power efficiency of 6.3 lm W−1 at 20 mA cm−2. An even higher external quantum efficiency of ∼20% was achieved at a low current density of ∼1 mA cm−2.

Potassium ion recognition by 15-crown-5 functionalized CdSe/ZnS quantum dots in H2O

Based on 15-crown-5 functionalized CdSe/ZnS quantum dots (QDs), we report a novel fluorogenic sensor to probe K+ ions in H2O; recognition of K+ can be achieved via the Förster type of energy transfer between two different color QDs, so that [K+] of the order of 10(-6) M can be promptly detected.

Carbon Nanoparticle-Enhanced Immunoelectrochemical Detection for Protein Tumor Marker with Cadmium Sulfide Biotracers

We have developed a sensitive electrochemical immunoassay system for the detection of a protein tumor marker, carcinoembryonic antigen (CEA), that is based on a carbon nanoparticle (CNP)/poly(ethylene imine) (PEI)-modified screen-printed graphite electrode (CNP-PEI/SPGE) covered with anti-CEA antibodies. The signal amplification strategy--using CdS nanocrystals as biotracers and CNPs to enhance electron transfer--improves the sensitivity and detection limit for CEA, suggesting that this system holds promise for development into a point-of-care or disposable home-care self-diagnostic tool. This biosensor is based on a sandwich complex immunoassay, which we assembled from sequential layers of the anti-CEA antibody (alphaCEA) on CNP-PEI/SPGE, the CEA sample, and the CdS nanocrystal quantum dots (QDs) sensitized with alphaCEA (alphaCEA-CdS QD). We used square wave anodic stripping voltammetry (SWASV) to amplify the signal current response obtained from the dissolved alphaCEA-CdS QDs. The calibration curve for CEA concentration was linear in the range of 0.032-10 ng/mL; the detection limit (estimated as the mean of the blank sample plus three times the standard deviation obtained on the blank sample) was 32 pg/mL (equivalent to 160 fg in a 5 microL sample). This method is suitably precise and sensitive to function as a means of determining urinary CEA, which is a better marker than serum CEA for the early detection of urothelial carcinoma.

Iridium(III) Complexes of a Dicyclometalated Phosphite Tripod Ligand: Strategy to Achieve Blue Phosphorescence Without Fluorine Substituents and Fabrication of OLEDs†

Organic light-emitting diodes (OLEDs) based on heavy transition-metal complexes are playing a pivotal role in next generation of, for example, flat panel displays and solid-state lighting. The readily available, Os-, Pt-, and in particular Ir-based phosphorescence complexes grant superior advantage over fluorescent materials. This is mainly due to heavyatom-induced spin–orbit coupling, giving effective harvesting of both singlet and triplet excitons. However, tuning of phosphorescence over the entire visible spectrum still remains a challenge. Particularly, designing new materials to show higher energy, such as deep-blue emission—with an ideal CIEx,y coordinate (CIE = Commission Internationale de L Eclairage) of (0.14, 0.09)—encounters more obstacle than the progress made for obtaining green and red colors. Representative blue phosphors are a class of Ir complexes possessing at least one cyclometalated 4,6-difluorophenyl pyridine {(dfppy)H} ligand, known as FIrpic, FIr6, FIrtaz, and others. The majority of blue phosphors showed inferior color chromaticity with a sum of CIEx+y values being much greater than 0.3 or with single CIEy coordinate higher than 0.25. Such inferior chromaticity, in part, has been improved upon adoption of carbene-, triazolyl-, and fluorine-substituted bipyridine (dfpypy) based chelates. The above urgency prompted us to search for better and new blue phosphors. We produced a class of 2-pyridylazolate chelates possessing very large ligand-centered p–p* energy gap, as evidenced by the blue-emitting Os complexes. Subsequently, room-temperature blue phosphorescence was also visualized for the respective heteroleptic Ir complexes, particularly for those dubbed “nonconjugated” ancillary chelate(s). The nonconjugated ligands so far comprise a benzyl substituted pyrazole, an N-heterocyclic carbene, phosphines, and other ingenious molecular designs. Herein, we report the preparation of a novel class of heteroleptic Ir complexes by incorporation of tripodal, facially coordinated phosphite (or phosphonite), denoted as the P^C2 chelate, for serving as the ancillary, together with the employment of 2-pyridyltriazolate acting as blue chromophore. The reaction intermediate, which possesses an acetate chelate, was isolated and characterized to establish the synthetic pathway. The tridentate P^C2 ancillary chelate offers several advantages: 1) Good stabilization of complex and necessary long-term stability in application of for example, emitting devices. 2) The strong bonding of phosphorous donors is expected to destabilize the ligand field d–d excited state, thus minimizing its interference to the radiative process from the lower lying excited state. 3) P^C2 inherits profound and versatile functionality (see below) capable of fine-tuning the electronic character. As a result, highly efficient blue phosphorescence is attained with good OLED performance. Treatment of a mixture of [IrCl3(tht)3] (tht = tetrahydrothiophene) with an equimolar amount of triphenylphosphine (PPh3), triphenylphosphite {P(OPh)3}, and an excess of sodium acetate resulted in a high yield conversion (> 80%) into [Ir(P^C2)(PPh3)(OAc)] (1a); P^C2 = tripodal dicyclometalated phosphite (Scheme 1). Subsequent replacement of acetate in 1a with chelating 3-tert-butyl-5-(2-pyridyl)triazo-