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 ß-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.

Factors that regulate the conformation of m-benziporphodimethene complexes: agostic metal-arene interaction, hydrogen bonding, and η2,π coordination.

Group 12 and silver(I) tetramethyl-m-benziporphodimethene (TMBPDM) complexes with phenyl, methylbenzoate, or nitrophenyl groups as meso substituents were synthesized and fully characterized. The dimeric silver(I) complex displays an unusual η(2),π coordination from the ß-pyrrolic C=C bond to the silver ion. All of the complexes displayed a close contact between the metal ion and the inner C(22)-H(22) on the m-phenylene ring. The downfield chemical shifts of H(22) and large coupling constants between Cd(II) and H(22) strongly support the presence of an agostic interaction between the metal ion and inner C(22)-H(22). Crystal structures revealed that the syn form is the predominant conformation for TMBPDM complexes. This is distinctively different from the exclusive anti conformation observed in m-benziporphyrin and tetraphenyl-m-benziporphodimethene (TPBPDM) complexes. Evidently, intramolecular hydrogen-bonding interactions between axial chloride and methyl groups stabilize syn conformations. Unlike the merely syn conformation observed in the solid-state structures of TMBPDM complexes that contain an axial chloride, in solution these complexes display highly solvent- and temperature-dependent syn/anti ratio changes. The observation of dynamic (1)H NMR spectroscopic scrambling between syn and anti conformations from the titration of chloride ion into the solution of the TMBPDM complex suggests that axial ligand exchange is a likely pathway for the conversion between syn and anti forms. Theoretical calculations revealed that intermolecular hydrogen-bonding interactions between the axial chloride and CHCl(3) stabilizes the anti conformation, which explains the increased ratio for the anti form when dichloromethane or chloroform was used as the solvent.

m-Benziporphodimethene: a new porphyrin analogue fluorescence zinc(II) sensor.

m-Benziporphodimethene is presented here as a long-wavelength Zn2+ specific chemosensor; this sensor shows fluorescence switch-on upon Zn2+ binding with no apparent background fluorescence.

Effects of number and position of meta and para carboxyphenyl groups of zinc porphyrins in dye-sensitized solar cells: structure-performance relationship.

Porphyrin sensitizers containing meta- and para-carboxyphenyl groups in their meso positions have been synthesized and investigated for their performance in dye-sensitized solar cells (DSSCs). The superior performance of para-derivative compared to meta-derivative porphyrins was revealed by optical spectroscopy, electrochemical property measurements, density functional theory (DFT) calculations, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, incident photon-to-current conversion efficiency (IPCE), electrochemical impedance spectroscopy (EIS), and stability performance. Absorption spectra of para-carboxyphenyl-substituted porphyrins on TiO2 show a broader Soret band compared to meta-carboxyphenyl-substituted porphyrins. ATR-FTIR spectra of the studied porphyrins on TiO2 were applied to investigate the number and mode of carboxyl groups attached to TiO2. The VOC, JSC, and IPCE values of para-series porphyrins were distinctly superior to those of meta-series porphyrins. The Nyquist plots of the studied porphyrins show that charge injection in para-series porphyrins is superior to that in meta-series porphyrins. The orthogonally positioned para derivatives have more efficient charge injection and charge transfer over charge recombination, whereas the efficiencies of flat-oriented meta derivatives are retarded by rapid charge recombination. Photovoltaic measurements of the studied meta- and para-carboxyphenyl-functionalized porphyrins show that the number and position of carboxyphenyl groups play a crucial role in the performance of the DSSC. Our results indicate that para-carboxyphenyl derivatives outperform meta-carboxyphenyl derivatives to give better device performance. This study will serve as a guideline for the design and development of organic, porphyrin, and ruthenium dyes in DSSCs.

Three p-carboxyphenyl groups possessing zinc porphyrins: efficient, stable, and cost-effective sensitizers for dye-sensitized solar cells.

Zinc porphyrins possessing three p-carboxyphenyl anchoring groups with various substituents were prepared by a facile three-step route in good yields. Zn1NH3A with electron donating and anti-aggregation meso substituents has achieved the highest efficiency of 6.10%. These porphyrins with three p-carboxyphenyl groups are more stable toward photo-bleaching than their single anchoring group analogs.

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.

Tetramethyl-m-benziporphodimethene and isomeric alpha,beta-unsaturated gamma-lactam embedded N-confused tetramethyl-m-benziporphodimethenes.

The condensation reaction of alpha,alpha'-dihydroxy-1,3-diisopropylbenzene, pyrrole, and an aldehyde leads to the formation of tetramethyl-m-benziporphodimethene and outer alpha-pyrrolic carbon oxygenated N-confused tetramethyl-m-benziporphodimethenes containing a gamma-lactam ring in the macrocycle. Two isomers with the carbonyl group of the lactam ring either close to (O-Up) or away from (O-Down) the neighboring sp(3) meso carbon were synthesized and characterized. The single crystal X-ray diffraction analysis on the regular and gamma-lactam containing tetramethyl-m-benziporphodimethenes showed highly distorted macrocycles for all compounds. For O-Up and O-Down isomers, dimeric structures, assembling by intermolecular hydrogen-bonding interactions through lactam rings, were observed in the solid state. Fitting the concentration dependent chemical shifts of the outer NH proton using the non-linear regression method give a maximum association constant of 108.9 M(-1) for the meso 4-methylcarboxyphenyl substituted O-Down isomer. The DFT calculations concluded that the O-Up isomer is energetically more stable, and the keto form is more stable than the enol form.

Formation of a sulfur-atom-inserted N-confused porphyrin iron nitrosyl complex by denitrosation and C-S bond cleavage of an S-nitrosothiol.

The reaction of nitrosothiol, Ph3CSNO, with a divalent iron N-confused porphyrin complex, Fe(HCTPPH)Br, yields a {Fe(NO)}6 iron nitrosyl complex with a sulfur atom inserted in the Fe-C bond. The crystal structure reveals a bent Fe-N-O geometry and an eta2-(C,S) bonding mode between iron and the C-S bond. A reaction mechanism involving a transnitrosation and a nitrosothiol C-S bond cleavage is proposed.