Chen-Hsiung Hung

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.

New Dual Donor–Acceptor (2D‐π‐2A) Porphyrin Sensitizers for Stable and Cost‐Effective Dye‐Sensitized Solar Cells

A series of porphyrin sensitizers that featured two electron-donating groups and dual anchoring groups that were connected through a porphine π-bridging unit have been synthesized and successfully applied in dye-sensitized solar cells (DSSCs). The presence of electron-donating groups had a significant influence on their spectroscopic, electrochemical, and photovoltaic properties. Overall, the dual anchoring groups gave tunable electronic properties and stronger attachment to TiO2 . These new dyes were readily synthesized in a minimum number of steps in gram-scale quantities. Optical and electrochemical data confirmed the advantages of these dyes for use as sensitizers in DSSCs. Porphyrins with electron-donating amino moieties provided improved charge separation and better charge-injection efficiencies for the studied dual-push-pull dyes. Attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) and X-ray photoelectron spectroscopy of the porphyrin dyes on TiO2 suggest that both p-carboxyphenyl groups are attached onto TiO2, thereby resulting in strong attachment. Among these dyes, cis-Zn2BC2A, with two electron-donating 3,6-ditertbutyl-phenyl-carbazole groups and dual-anchoring p-carboxyphenyl groups, showed the highest efficiency of 4.07 %, with J(SC)=9.81 mA cm(-2), V(OC)=0.63 V, and FF=66 %. Our results also indicated a better photostability of the studied dual-anchored sensitizers compared to their mono-anchored analogues under identical conditions. These results provide insight into the developments of a new generation of high-efficiency and thermally stable porphyrin sensitizers.

Monomeric, Dimeric, and Trimeric Calcium Compounds Containing Substituted Pyrrolyl and Ketiminate Ligands: Synthesis and Structural Characterization

A series of monomeric, dimeric, and trimeric calcium compounds containing substituted pyrrolyl or ketiminate ligands were synthesized, and characterized by NMR spectroscopy and single crystal X-ray diffractometry. The reaction of Ca[N(SiMe(3))(2)](2)(THF)(2) with 1 equiv of [C(4)H(3)NH(2-CH(2)NEt(2))] in toluene generates the dimeric complex, [Ca{N(SiMe(3))}[mu-eta(1):eta(5)-{C(4)H(3)N(2-CH(2)NEt(2))}]](2) (1) in which two substituted pyrrolyl ligands bind two Ca centers in a eta(1) and eta(5) fashion. The reaction between Ca[N(SiMe(3))(2)](2)(THF)(2) and 2 equiv of [C(4)H(3)NH(2-CH(2)NEt(2))] in THF yields a monomeric calcium compound Ca[C(4)H(3)N(2-CH(2)NEt(2))](2)(THF)(2) (2) that exhibits a facial octahedral geometry on the central Ca atom. Similarly, the reactions of Ca[N(SiMe(3))(2)](2)(THF)(2) with 1 and 2 equiv of OCMeCHCMeNHAr (Ar = 2,6-diisopropylphenyl) generate [Ca(OCMeCHCMeNAr){N(SiMe(3))(2)}](2) (3) and [Ca(mu-OCMeCHCMeNAr)(OCMeCHCMeNAr)](2) (4), respectively. In 3, the Ca atom possesses a distorted tetrahedral geometry where as in 4, a square plane is developed by the two calcium atoms with the bridging participation of two oxygen atoms from two ketiminate ligands. The in situ reaction of OCMeCHCMeNHAr, Ca[N(SiMe(3))(2)](2)(THF)(2), and isopropyl alcohol results in a trimeric calcium alkoxide compound Ca(3)(mu-OCMeCHCMeNAr)(2)(OCMeCHCMeNAr)(mu(3)-O-(i)Pr)(2)(mu(2)-O-(i)Pr) (5). Compounds 1, 2, and 5 showed good catalytic activity in the ring-opening polymerization of epsilon-caprolactone and l-lactide.

Nitric Oxide Physiological Responses and Delivery Mechanisms Probed by Water-Soluble Roussin’s Red Ester and {Fe(NO)2}10 DNIC

Dinitrosyl-iron complexes (DNICs) are stable carriers for nitric oxide (NO), an important biological signaling molecule and regulator. However, the insolubility of synthetic DNICs, such as Roussins red ester (RRE), in water has impaired efforts to unravel their biological functions. Here, we report a water-soluble and structurally well-characterized RRE [Fe(mu-SC2H4COOH)(NO)2]2 (DNIC-1) and a {Fe(NO)2}(10) DNIC [(PPh2(Ph-3-SO3Na))2Fe(NO)2] (DNIC-2), their NO-induced protein regulation, and their cellular uptake mechanism using immortalized vascular endothelial cells as a model. Compared with the most common NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), the in vitro NO release assay showed that both DNICs acted as much slower yet higher stoichiometric NO-release agents with low cytotoxicity (IC50 > 1 mM). Furthermore, L-cysteine facilitated NO release from SNAP and DNIC-1, but not DNIC-2, in a dose- and time-dependent manner. EPR spectroscopic analysis showed, for the first time, that intact DNIC-1 can either diffuse or be transported into cells independently and can transform to either paramagnetic protein bound DNIC in the presence of serum or [DNIC-(Cys)2] with excess L-cysteine under serum-free conditions. Both DNICs subsequently induced NO-dependent upregulation of cellular heat shock protein 70 and in vivo protein S-nitrosylation. We conclude that both novel water-soluble DNICs have potential to release physiologically relevant quantities of NO and can be a good model for deciphering how iron-sulfur-nitrosyl compounds permeate into the cell membrane and for elucidating their physiological significance.

A N-(2-aminophenyl)-5-(dimethylamino)-1-naphthalenesulfonic amide (Ds-DAB) based fluorescent chemosensor for peroxynitrite.

A dansyl derivative (Ds-DAB) was prepared and used as a fluorescent probe for peroxynitrite (ONOO(-)) detection. The results showed that the addition of peroxynitrite to the aqueous solution of Ds-DAB would result in obvious fluorescence enhancement. This probe is highly specific for peroxynitrite in aqueous solution, avoiding interference from other reactive oxygen species (ROS) and nitrogen species (RNS). The advantages of high selectivity, fast reaction rate, and peroxynitrite bioimaging render Ds-DAB suitable for peroxynitrite detection.

Dimeric iron n-confused porphyrin complexesElectonic supplementary information (ESI) available: general information; preparation and crystal data for 6 and 7; Fig. S1: absorption spectra for 6 and 7; Figs. S2 and S3: magnetic susceptibility data for 6 and 7. See http://www.rsc.org/suppdata/cc/b2/b202679a/

A dimeric iron N-confused porphyrin, [Fe(NCTPP)]2 was obtained from the anaerobic reaction of Fe(NCTPP)Br with NaSePh while under aerobic conditions a hydroxo bridged iron dimer with Na bridging the outer-N atoms was obtained and oxygenation occurred on the inner core pyrrolic carbon to form a novel ONCTPP porphyrinic ring.

Novel expanded porphyrin sensitized solar cells using boryl oxasmaragdyrin as the sensitizer

Oxasmaragdyrin boron complexes were prepared and applied in DSSCs. The HOMO-LUMO energy gap analyses and theoretical calculations revealed that these expanded porphyrins are ideal sensitizers for DSSCs. A device containing oxasmaragdyrin-BF2 as the sensitizer achieves an energy conversion efficiency of 5.7%.

Nitrite-Mediated S-Nitrosylation of Caspase-3 Prevents Hypoxia-Induced Endothelial Barrier Dysfunction

Rationale: Hypoxia is a significant perturbation that exacerbates endothelial barrier dysfunction, contributing to the disruption of vascular homeostasis and the development of various diseases such as atherosclerosis and metastasis of tumors. To date, it is not known what strategy might be used to counter the effect of hypoxia on endothelial permeability. Objective: This study investigated the role of nitrite in regulating vascular integrity under hypoxic conditions. Methods and Results: We found denitrosylation and the resulting activation of caspase-3 to be critical for hypoxia-induced endothelial permeability. Nitrite treatment led to S-nitrosylation and the inactivation of caspase-3, suppressing the barrier dysfunction of endothelia caused by hypoxia. This process required the conversion of nitrite to bioactive nitric oxide in a nitrite reductase-dependent manner. Using primary human umbilical vein endothelial cells as a model, we showed that in the presence of nitrite, the S-nitrosylated and inactivated form of caspase-3 was unable to cleave &bgr;-catenin, a key component in the VE-cadherin complex. Therefore, nitrite treatment led to the maintenance of VE-cadherin–mediated adherens junctions under hypoxic conditions. In in vivo experiments using a zebrafish model, nitrite was found to protect blood vessels from hypoxia-induced vascular leakage. Conclusions: These results are the first to demonstrate that nitrite plays a critical role in the protection of endothelial barrier function against hypoxic insult. Our findings show that nitrite holds great potential for the treatment of diseases associated with hypoxia-induced disorder of vascular homeostasis.

Facile Nitrite Reduction and Conversion Cycle of {Fe(NO)}6/7 Species: Chemistry of Iron N-Confused Porphyrin Complexes via Protonation/ Deprotonation

Facile nitrite reduction was achieved using [Fe(II)(HCTPPH)NO] as the starting compound to react with NaNO(2). Stoichiometric studies allow the isolation of both {Fe(NO)}(6) and {Fe(NO)}(7) nitrosyl complexes and provide insight into the proton and electron transfer processes during the nitrite reduction. Treating [Fe(CTPP)NO] with acid or oxidizing [Fe(HCTPP)NO] with AgClO(4) yields intermediate [Fe(HCTPP)NO](+). The conversion cycles starting from {Fe(NO)}(6) [Fe(CTPP)NO] to {Fe(NO)}(6) [Fe(HCTPP)NO][ClO(4)] then to {Fe(NO)}(7) [Fe(HCTPP)NO] and vice versa were constructed.

Cu-Mediated Syntheses of N-Fused and Ring-Modified Trithiahexaphyrins

The reaction of the antiaromatic [28]trithiahexaphyrin (TTHP) with Cu(I) in DMF gives a novel fused-ring trithiahexaphyrin with the elimination of a chloride on a dichlorophenyl ring and bond formation to the outward oriented pyrrolic nitrogen to form a 5,5,6-tricyclic internal ring system. The NMR spectra, which display characteristics of an antiaromatic compound, agree with the proposed structure. Meanwhile, reactions of TTHP with amines in the presence of Cu(I) give amino-group-inserted hexaphyrins with the amino nitrogen joined to a beta-thiophenic carbon and the alpha-carbon of the alkylamine cyclized to the inward pyrrolic nitrogen to form a 5,7,5-tricyclic rings. The crystal structure of the fused-ring product indicates a rectangular geometry with a tilted tricyclic ring system, while the ring-modified TTHP-DMA complex gives a triangular trithiahexaphyrin core. This report demonstrates methods to incorporate functionalized heterocyclic rings into expanded porphyrins.