Hsing-Yin Chen

Nitric Oxide Turn-on Fluorescent Probe Based on Deamination of Aromatic Primary Monoamines

The stable, water-soluble, and nonfluorescent FA-OMe can sense nitric oxide (NO) and form the intensely fluorescent product dA-FA-OMe via reductive deamination of the aromatic primary amine. The reaction is accompanied by a notable increase of the fluorescent quantum yield from 1.5 to 88.8%. The deamination mechanism of FA-OMe with NO was proposed in this study. The turn-on fluorescence signals were performed by suppression of photoinduced electron transfer (PeT), which was demonstrated by density functional theory (DFT) calculations of the components forming FA-OMe and dA-FA-OMe. Furthermore, FA-OMe showed water solubility and good stability at physiological pHs. Moreover, the selectivity study indicated that FA-OMe had high specificity for NO over other reactive oxygen/nitrogen species. In an endogenously generated NO detection study, increasing the incubation time of FA-OMe with lipopolysaccharide (LPS) pretreated Raw 264.7 murine macrophages could cause an enhanced fluorescence intensity image. In addition, a diffusion/localization cell imaging study showed that FA-OMe could be trapped in Raw 264.7 cells. These cell imaging results demonstrated that FA-OMe could be used as a turn-on fluorescent sensor for the detection of endogenously generated NO.

Proton Transfer in Guanine-Cytosine Radical Anion Embedded in B-Form DNA

The electron-attachment-induced proton transfer in the guanine-cytosine (G:C) base pair is thought to be relevant to the issues of charge transport and radiation damage in DNA. However, our understanding on the reaction mainly comes from the data of isolated bases and base pairs, and the behavior of the reaction in the DNA duplex is not clear. In the present study, the proton-transfer reaction in reduced G:C stacks is investigated by quantum mechanical calculations with the aim to clarify how each environmental factor affects the proton transfer in G:C(*-). The calculations show that while the proton transfer in isolated G:C(*-) is exothermic with a small energetic barrier, it becomes endothermic with a considerably enhanced energetic barrier in G:C stacks. The substantial effect of G:C stacking is proved to originate from the electrostatic interactions between the dipole moments of outer G:C base pairs and the middle G:C(*-) base-pair radical anion; the extent of charge delocalization is very small and plays little role in affecting the proton transfer in G:C(*-). On the basis of the electrostatic model, the sequence dependence of the proton transfer in the ionized G:C base pair is predicted. In addition, the water molecules in the first hydration shell around G:C(*-) display a pronounced effect that facilitates the proton-transfer reaction; further consideration of bulk hydration only slightly lowers the energetic barrier and reaction energy. We also notice that the water arrangement around an embedded G:C(*-) is different from that around an isolated G:C(*-), which could result in a very different solvent effect on the energetics of the proton transfer. In contrast to the important influences of base stacking and hydration, the effects of sugar-phosphate backbone and counterions are found to be minor. Our calculations also reveal that a G:C base pair embedded in DNA is capable of accommodating two excess electrons only in bulk hydration; the resultant G(N1-H)(-):C(N3+H)(-) dianion is stable and exists long enough to lead to DNA damage. The combination of the present results with the previous findings in literature suggests that the behaviors of charge transport and low-energy electron-induced damage in DNA are highly susceptible to the hydration level.

Crystal Engineering for π−π Stacking via Interaction between Electron-Rich and Electron-Deficient Heteroaromatics

New dipolar compounds containing alternating electron-rich thieno[3,2-b]thiophene units and electron deficient units have been synthesized. Compounds with 5-pyrimidinyl (compound 2) or benzothiazole (compound 5) as the electron-deficient unit were structurally characterized by the single-crystal X-ray diffraction method. The arrangement of the molecules is found to be one-dimensional slipped-pi-stack for 2. That of 5 is of slipped-pi-stack, albeit with a tilt angle between neighboring pi-stacks. The pi-pi interfacial distances of the molecules in the crystal lattice are 3.47 and 3.59 A for 2 and 5, respectively. On the basis of the crystal structure, compound 2, with negligible pi-pi slip along the short axis of the molecules, has a calculated electronic coupling value (0.153 eV) twice as large as that of the largest coupling of pentacene. Accordingly, the theoretically estimated hole mobility (mu(+)) for 2 (2.32 cm(2) s(-1) V(-1)) compares favorably with that of pentacene (1.93-5.43 cm(2) s(-1) V(-1)), despite of the larger reorganization energy for hole transport in 2. The symmetric intrastack S...C contacts found between the thieno[3,2-b]thiophene and pyrimidinyl units explain the unique features of the crystal structure of 2 and the resulting large electronic coupling.

Succinated chitosan as a gene carrier for improved chitosan solubility and gene transfection.

UNLABELLED Chitosan (CHI), a linear polysaccharide, has been intensively studied as a nonviral gene delivery vector. The low physiological solubility of CHI has limited its gene transfection efficiency. Here we report the synthesis of different substitution degrees of succinated chitosans (CHI-succ) to increase water solubility. According to the proton nuclear magnetic resonance spectra, the degree of deacetylation of hydrolyzed CHI was roughly 88% and the degrees of succinylation in three CHI-succ polymers were approximately 5, 10, and 20%. Various weight ratios of CHI/DNA and CHI-succ/DNA polyplexes were prepared for gel electrophoresis retardation, particle size, zeta potential, and morphology studies. The results suggest that the plasmid DNA is readily entrapped at a CHI-succ/DNA weight ratio of 20; the sizes and zeta potentials were between 110 and 140 nm and ±1-5 mV, and the polyplexes exhibited low cytotoxicity against HEK 293T cells. CHI-succ with 5 and 10% degrees of substitution showed improved transfection efficiency as compared with nascent CHI. FROM THE CLINICAL EDITOR Chitosan, a cationic polysacchride with gene therapy potential, has inherently poor water solubility, which is improved by partial succinylation according to this report. The new DNA/Chitosan polyplexes exhibit improved safety against HEK 293T cells.

Iodine effect on the relaxation pathway of photoexcited I-(H2O)n clusters

Abstract The iodine effect on the photoexcited I − (H 2 O) n relaxation pathway is studied using ab initio calculations. Critical behavior of the vertical binding energy (VBE) of the excited I − (H 2 O) n is seen at short distances between the iodine and the remaining (H 2 O) n , which is correlated to the rapid experimental VBE increase within 1 ps (L. Lehr, M.T. Zanni, C. Frischkorn, R. Weinkauf, D.M. Neumark, Science 284 (1999) 635). Further comparisons of computed results with experimental data reveal that iodine detachment is a crucial step in the cluster relaxation dynamics, intrinsically different from the electron-detachment pathway of photoexcited aqueous iodide.

Characterization of A New Copper(I)-Nitrito Complex That Evolves Nitric Oxide

The complexes [Cu(kappa(2)-Ph(2)PC(6)H(4)(o-OMe))(2)(CH(3)CN)](BF(4)) (1) and [CuCl(Ph(2)PC(6)H(4)(o-OMe))(2)] (2) have been prepared by treating [Cu(CH(3)CN)(4)](BF(4)) or CuCl with two equivalents o-(diphenylphosphino)anisole (Ph(2)PC(6)H(4)(o-OMe)) at room temperature, respectively. The reaction of 1 and (PPN)(NO(2)) in acetonitrile solution affords a neutral compound [Cu(Ph(2)PC(6)H(4)(o-OMe))(2)(ONO)] (3). In contrast to the synthesis of 3, mixing NaNO(2) and 1 in MeOH yielded a unique dicopper(I) cationic species, [((Ph(2)PC(6)H(4)(o-OMe))(2)Cu)(2)(mu-NO(2))](+) (4) after ether/CH(2)Cl(2) crystallization. The molecular structures of 1-4 have been determined by an X-ray diffraction study. The copper(I)-nitrito adduct 3 containing phosphine-ether ligands forms nitric oxide gas from the reaction with acetic acid, suggesting the first example and model compound in the asymmetric O-bound copper(I) nitrite intermediate microenvironment of copper nitrite reductases (Cu-NIRs).

Hybrid polyethylenimine and polyacrylic acid-bound iron oxide as a magnetoplex for gene delivery.

Low transfection efficiency is always an issue when cationic polymers are used as a nonviral gene vector in the physiological condition, especially in the presence of proteins. A cationic magnetic nanoparticle (MNP) may be an alternative to solve this problem because a magnetic field can help to attract the MNP and internalize it into cells. The aim of this study was to determine the potency of polyethylenimine (PEI)-decorated MNPs for efficiently complexing and delivering plasmid DNA in vitro with the help of a magnetic field. PEI is associated with poly(acrylic acid)-bound superparamagnetic iron oxide (PAAIO) through electrostatic interactions (PEI-PAAIO). PEI-PAAIO formed stable polyplexes with pDNA in the presence and absence of 10% fetal bovine serum (FBS) and could be used for magnetofection. The effect of a static magnetic field on the cytotoxicity, cellular uptake, and transfection efficiency of PEI-PAAIO/pDNA was evaluated with and without 10% FBS. Magnetofection efficacy in HEK 293T cells and U87 cells containing 10% FBS was significantly improved in the presence of an external magnetic field. The amount of internalized iron was quantitatively measured using an inductively coupled plasma-optical emission spectrometer and directly visualized using Prussian blue staining. The internalized pDNA was visualized using a confocal laser scanning microscope.

Improvement in Titanium Complexes Bearing Schiff Base Ligands in the Ring-Opening Polymerization of L-Lactide: A Dinuclear System with Hydrazine-Bridging Schiff Base Ligands

A series of titanium (Ti) complexes bearing hydrazine-bridging Schiff base ligands were synthesized and investigated as catalysts for the ring-opening polymerization (ROP) of L-lactide (LA). Complexes with electron withdrawing or steric bulky groups reduced the catalytic activity. In addition, the steric bulky substituent on the imine groups reduced the space around the Ti atom and then reduced LA coordination with Ti atom, thereby reducing catalytic activity. All the dinuclear Ti complexes exhibited higher catalytic activity (approximately 10-60-fold) than mononuclear L(Cl-H)-TiOPr2 did. The strategy of bridging dinuclear Ti complexes with isopropoxide groups in the ROP of LA was successful, and adjusting the crowded heptacoordinated transition state by the bridging isopropoxide groups may be the key to our successful strategy.

Comparative Study of Aluminum Complexes Bearing N,O- and N,S-Schiff Base in Ring-Opening Polymerization of ε-Caprolactone and l-Lactide

A series of Al complexes bearing Schiff base and thio-Schiff base ligands were synthesized, and their application for the ring-opening polymerization of ε-caprolactone (CL) and l-lactide (LA) was studied. It was found that steric effects of the ligands caused higher polymerization rate and most importantly the Al complexes with N,S-Schiff base showed significantly higher polymerization rate than Al complexes with N,O-Schiff base (5-12-fold for CL polymerization and 2-7-fold for LA polymerization). The reaction mechanism of CL polymerization was investigated by density functional theory (DFT). The calculations predicted a lower activation energy for a process involved with an Al complex bearing an N,S-Schiff base ligand (17.6 kcal/mol) than for that of an Al complex bearing an N,O-Schiff base ligand (19.0 kcal/mol), and this magnitude of activation energy reduction is comparable to the magnitude of rate enhancement observed in the experiment. The reduction of activation energy was attributed to the catalyst-substrate destabilization effect. Using a sulfur-containing ligand to decrease the activation energy in the ring-opening polymerization process may be a new strategy to design a new Al complex with high catalytic activity.

A New Approach to 1,4-Oxazines and 1,4-Oxazepines via Base-Promoted Exo Mode Cyclization of Alkynyl Alcohols: Mechanism and DFT Studies

A new approach was developed to synthesize 1,4-oxazine and 1,4-oxazepine derivatives without solvent and metal. Regioselective cyclization occurred to afford exclusively the exo-dig product, and stereochemistry was studied by circular dichroism and specific optical rotation techniques. The Grignard reaction is a key synthetic step to produce high diastereomeric compounds via Crams rule and was well supported by DFT calculations. A hydroalkoxylation mechanism was proposed and supported by DFT calculations.