Fluorescent Probes with Multiple Binding Sites for the Discrimination of Cys, Hcy, and GSH.

Biothiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play crucial roles in maintaining redox homeostasis in biological systems. This Minireview summarizes the most significant current challenges in the field of thiol-reactive probes for biomedical research and diagnostics, emphasizing the needs and opportunities that have been under-investigated by chemists in the selective probe and sensor field. Progress on multiple binding site probes to distinguish Cys, Hcy, and GSH is highlighted as a creative new direction in the field that can enable simultaneous, accurate ratiometric monitoring. New probe design strategies and researcher priorities can better help address current challenges, including the monitoring of disease states such as autism and chronic diseases involving oxidative stress that are characterized by divergent levels of GSH, Cys, and Hcy.

9,10-Dioxo-9,10-di-hydro-anthracene-1,4-diyl di-acetate.

In the title compound, C18H12O6, the anthra-quinone ring system is nearly planar [maximum deviation = 0.161 (3) Å] and both acetate groups are located on the same side of the ring plane. A supra-molecular architecture arises in the crystal owing to π-π stacking between parallel benzene rings of adjacent mol-ecules [centroid-centroid distance = 3.883 (4) Å] and weak inter-molecular C-H⋯O hydrogen bonding.

Ultraviolet-visible light (UV-Vis)-reversible but fluorescence-irreversible chemosensor for copper in water and its application in living cells.

An ultraviolet-visible light (UV-Vis)-reversible but fluorescence-irreversible chemosensor was developed for the detection of copper. Coordination between the probe, 2-pyridylaldehyde fluorescein hydrazone (FHP), and Cu(2+) gave a reversible UV-Vis response, Storage of the probe-Cu complex resulted in hydrolytic cleavage of the N═C bond, which released the fluorophore (ring-opened fluorescein hydrazine) and gave irreversible fluorescence. Thus, FHP becomes a multifunctional chemosensor, and its reversibility can be controlled by the reaction time. Cu(2+) in living cells could be detected using FHP and general fluorescence methods.

Indicator approach to develop a chemosensor for the colorimetric sensing of thiol-containing water and its application for the thiol detection in plasma.

A strategy for the determination of the presence of thiol-containing amino acids was successfully established by simply assembling copper chloride and xylenol orange (3,3'-bis[N,N-bis(carboxymethyl)aminomethyl]-o-cresolsulfonephthalein trisodium salt; XO) in a 1 : 1 molar ratio in quasi-physiological water solution (pH 6.0). The copper(II)-XO ensemble was highly selective for thiol species such as cysteine, homocysteine, and glutathione without interference from other amino acids and could quantitatively detect thiol in the range from 10 to 200 µM with a linear relationship having an average molar absorbance constant of 6530 L mol(-1) cm(-1) in pure water. The whole recognition process for thiol gave rise to a rapid visual color change from purple-red to yellow which can be observed simultaneously with the naked-eye.

Naked-eye determination of oxalate anion in aqueous solution with copper ion and pyrocatechol violet.

A novel strategy for the determination of oxalate anions was successfully established using a copper ion and pyrocatechol violet (PV) ensemble. The sensor ensemble can discriminate oxalate over other common anions including F(-), Cl(-), I(-), Br(-), HPO(4)(2-), PO(4)(3-), AcO(-), CO(3)(2-), SO(4)(2-), ClO(4)(-), P(2)O(7)(4-), S(2-) (deposited by Ag(+)), CN(-) (shielded by Fe(3+)) and can detect oxalate at low microgram levels in quasi-physiological aqueous solutions. The detection of the oxalate anion gives rise to a rapid observable visual color change from blue to yellow.

[Preliminary study on laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy on cervical cancer.].

OBJECTIVE: To evaluate the feasibility of laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy in treatment of cervical cancer. METHODS: From Dec. 2008 to Aug. 2009, 5 cervical cancer patients at stage Ib1 to IIa underwent laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy. The following clinical parameters were recorded and compared, including operative time, blood loss, intraoperative and postoperative complications, the changes of hemoglobin before and after surgery, postoperative temperature, the time of postoperative anus exhaust and urination, hospitalization, pathologic exam, and the number of lymph nodes. RESULTS: Laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy were performed successfully on those 5 patients without the conversion to laparotomy. No intraoperative and postoperative complications were observed. The operative time were 305, 365, 275, 240 and 245 minutes, respectively, with a mean value of 286 minutes. Estimated blood loss was 200, 400, 650, 300 and 400 ml, respectively. The mean blood loss was 390 ml. Temperatures of all patients were not higher than 37.5 degrees C and anus exhaust was recovered at 36 hours after surgery. Those five patients were hospitalized for 11, 13, 9, 12 and 12 days respectively. Squamous carcinoma of cervix were diagnosed by the pathologic examination. The resected margin of vagina and parametrium was clear. The numbers of pelvic lymph nodes were 14, 22, 16, 21 and 18, respectively. No evidence of lymph nodes metastasis was found. CONCLUSION: Laparoscopically robotic assisted radical hysterectomy and pelvic lymphadenectomy is feasible as a novel approach in the treatment of cervical cancer.

Synthesis, characterization and studies on DNA-binding of a new Cu(II) complex with N1,N8-bis(l-methyl-4-nitropyrrole-2-carbonyl)triethylenetetramine.

A new Cu(II) complex of CuLCl(2) (here, L=N(1),N(8)-bis(1-methyl-4-nitropyrrole-2- carbonyl)triethylenetetramine) had been synthesized and characterized. The structure of the complex was investigated with density functional theory (DFT) calculations. DNA-binding of the Cu(II) complex and its effects on tumor cell viability were firstly studied. The interactions between the complex and calf thymus DNA had been investigated using UV spectra, fluorescent spectra, viscosity and CV (cyclic voltammetry). The cleavage reaction on plasmid DNA has been monitored by agarose gel electrophoresis. The experimental results show that the mode of binding of the complex to DNA is classical intercalation and the complex can cleave pBR322 DNA. The effects of the CuL on cell viability were tested using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) dye assay and the results indicate that the CuL had certain effect on cancer cells.

A single pH fluorescent probe for biosensing and imaging of extreme acidity and extreme alkalinity.

A simple tailor-made pH fluorescent probe 2-benzothiazole (N-ethylcarbazole-3-yl) hydrazone (Probe) is facilely synthesized by the condensation reaction of 2-hydrazinobenzothiazole with N-ethylcarbazole-3-formaldehyde, which is a useful fluorescent probe for monitoring extremely acidic and alkaline pH, quantitatively. The pH titrations indicate that Probe displays a remarkable emission enhancement with a pKa of 2.73 and responds linearly to minor pH fluctuations within the extremely acidic range of 2.21-3.30. Interestingly, Probe also exhibits strong pH-dependent characteristics with pKa 11.28 and linear response to extreme-alkalinity range of 10.41-12.43. In addition, Probe shows a large Stokes shift of 84 nm under extremely acidic and alkaline conditions, high selectivity, excellent sensitivity, good water-solubility and fine stability, all of which are favorable for intracellular pH imaging. The probe is further successfully applied to image extremely acidic and alkaline pH values fluctuations in E. coli cells.

Berberine inhibits tumor necrosis factor-α-induced expression of inflammatory molecules and activation of nuclear factor-κB via the activation of AMPK in vascular endothelial cells.

Berberine, which is a well­known drug used in traditional medicine, has been demonstrated to exert diverse pharmacological effects, including anti­inflammatory effects. However, whether berberine can affect the production of inflammatory molecules in vascular endothelial cells remains to be elucidated. Therefore, the present study aimed to determine the effects of berberine, and the underlying molecular mechanisms of these effects. The effect of berberine on tumor necrosis factor (TNF)­α­induced inflammatory molecule expression was examined in cultured human aortic endothelial cells (HAECs). The HAECs were stimulated with TNF­α and incubated with or without berberine. The activation of nuclear factor (NF)­κB and adenosine monophosphate­activated protein kinase (AMPK) were analyzed using western blotting, and the protein secretion of intercellular adhesion molecule (ICAM)­1 and monocyte chemoattractant protein (MCP)­1 was measured using ELISA kits. The mRNA expression levels of ICAM­1 and MCP­1 were analyzed using reverse transcription­quantitative polymerase chain reaction. The results of the present study demonstrated that berberine significantly inhibited the TNF­α­induced expression of ICAM­1 and MCP­1, as well as the activation of NF­κB in the HAECs. These effects were attenuated following co­treatment with AMPK inhibitor compound C, or specific small interfering RNAs. In conclusion, the results of the present study indicated that berberine inhibits the TNF­α­induced expression of ICAM­1 and MCP­1, and the activation of NF­κB in HAECs in vitro, possibly through the AMPK­dependent pathway.

Berberine suppresses in vitro migration of human aortic smooth muscle cells through the inhibitions of MMP-2/9, u-PA, AP-1, and NF-κB.

Berberine, a type of isoquinoline alkaloid isolated from Chinese medicinal herbs, has been reported to have various pharmacological activities. Studies have demonstrated that berberine has beneficial effects on vascular remodeling and alleviates restenosis after vascular injury. However, its mechanism of action on vascular smooth muscle cell migration is not fully understood. We therefore investigated the effect of berberine on human aortic smooth muscle cell (HASMC) migration. Boyden chamber assay was performed to show that berberine inhibited HASMC migration dosedependently. Real-time PCR and Western blotting analyses showed that levels of matrix metalloproteinase (MMP)-2, MMP-9, and urokinase-type plasminogen activator (u-PA) were reduced by berberine at both the mRNA and protein levels. Western blotting assay further confirmed that activities of c-Fos, c-Jun, and NF-κB were significantly attenuated. These results suggest that berberine effectively inhibited HASMC migration, possibly by down-regulating MMP-2, MMP-9, and u-PA; and interrupting AP-1 and NF-κB mediated signaling pathways.

Chromene "lock", thiol "key", and mercury(II) ion "hand": a single molecular machine recognition system.

A regenerative, molecular machine-like "ON-OFF-ON" chemosensor based on a chromene molecule with the pyran ring "OFF-ON-OFF" cycle is reported for the first time. It behaves as a molecular lock that requires a thiol "key" to open the lock and a mercury(II) ion "hand" that unlatches the key for unsheathing the key to close the lock.

Colorimetric detection of thiols using a chromene molecule.

A new thiol-containing colorimetric probe has been developed by using a chromene derivative, 7-nitro-2,3-dihydro-1H-cyclopenta[b]chromen-1-one (1). The molecule exhibited high selectivity and sensitivity for detecting thiol species as cysteine, homocysteine, and glutathione in aqueous solution through a rapid visual color change from colorless to yellow.

The crystal structure, self-assembly, DNA-binding and cleavage studies of the [2]pseudorotaxane composed of cucurbit[6]uril.

The [2]pseudorotaxanes of cucurbit[6]uril with guest molecule 1,6-bis(imidazol-1-yl)hexane (BIMH) were synthesized and characterized by ESI-MS spectrometry, (1)H NMR spectra, and X-ray diffraction crystallography. The influence of different anions on self-assembly in solid-state was discussed by X-ray diffraction crystallography. However, more interestingly, and to our amazement, we discovered the CB[6]/BIMH [2]pseudorotaxane exhibiting efficient cleavage of pBR322 DNA in physiological environment. The cleavage mechanism were studied by fluorescence spectra and the hydrolysis of bis(2,4-dinitrophenyl)-phosphate (BDNPP). From DNA-binding mode being electrostatic force and the first-order kinetics equation, we prove indirectly that the mechanism may be hydrolytic cleavage.

Synthesis of Zn(II)-cloxacillin sodium complex and study of its interaction with calf thymus DNA.

In this paper, a solid complex of cloxacillin sodium (CS) with Zn(II) was prepared by coprecipitation and characterized by UV, fluorescence, IR, and thermal spectra. Furthermore, the nature of the complex has been studied by 1H-NMR and 13C-NMR spectroscopy. The influence of Zn(II) on the combination of CS and calf thymus DNA (CT DNA) was studied using fluorescence spectrophotometry, and the formation of binary CS-Zn(II) and CS-CT DNA complexes and ternary CS-Zn(II)-CT DNA complex was studied. The results show that the fluorescence intensity of CS can be quenched in the presence of Zn(II) or DNA. In the presence of Zn(II), the fluorescence quenching action of DNA on CS was strongly enhanced. Based on the fluorescence intensity, the formation constants of CS-Zn(II) and CS-CT DNA complexes were calculated, and the mechanism of interaction between CS, Zn(II), and DNA is discussed.

An oxonium hydrogen sulfate of 3a,6a-diphenylglycoluril.

In the title compound, (5-oxo-3a,6a-diphenylperhydroimidazo[4,5-d]imidazol-2-ylidene)oxonium hydrogen sulfate, C16H15N4O2+ x HSO4-, the asymmetric unit contains a hydrogen sulfate anion and a 3a,6a-diphenylglycoluril oxonium cation. The hydrogen sulfate anion is joined to the oxonium cation via a strong O-H...O hydrogen bond (H...O = 1.69 A). The crystal packing is mainly dominated by interactions involving the hydrogen sulfate anion. The diphenylglycoluril oxonium cations also self-assemble through N-H...O hydrogen bonds, forming molecular chains along the [001] vector. Four intramolecular C-H...N hydrogen bonds are observed, having an S(5) motif.

3,3a-Dihydrocyclopenta[b]chromen-1(2H)-ones from the reaction of salicylaldehyde and 2-cyclopenten-1-one.

The two title chromene compounds, 3,3a-dihydrocyclopenta[b]chromen-1(2H)-one, C16H12O2, (I), and 2-(2-hydroxybenzylidene)-3,3a-dihydrocyclopenta[b]chromen-1(2H)-one, C19H14O3, (II), have been determined in the monoclinic space group P2(1)/n. Compound (I) is mainly stabilized by C-H...pi interactions. Compound (II) is linked into infinite one-dimensional chains with a C(3) motif via intermolecular O-H...O hydrogen bonds. The intermolecular C-H...pi and pi-pi interactions also play key roles in stabilizing the crystal packing. Two intramolecular C-H...O hydrogen bonds with S(5) motifs were detected in (II).