Efficient turn-on fluorescent probe cooperated by cascade response for disclosing the fluctuation of cysteine in cells.

BACKGROUND: The research on cysteine (Cys) determination is deemed as a hot topic, since it has been reported to be connected with various physiological processes and disease prediction. However, existing Cys-responding probes may expose some defects such as long reaction time, disappointing photostability, and suboptimal sensitivity. Under such a circumstance, our team has proposed an efficient fluorescent probe with novel sensing mechanism to perfectly cope with the above-mentioned drawbacks. RESULTS: A novel cascade reaction-based probe 9-(2,2-dicyanovinyl)-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-8-yl acrylate (DPQA) has been synthesized for the first time. Undergoing addition-cleavage and cyclization-rearrangement processes, DPQA reacts with Cys to generate an iminocoumarin product with relucent green fluorescence, namely 11-imino-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinoline-10-carbonitrile (IMC-J), and the relative fluorescence quantum yield (Φf) soars from 0.007 to 0.793. Utilizing such a mechanism, DPQA shows a superb turn-on signal (172-fold), low detection limit (4.1 nM), and wide detection range (5-6000 nM) toward Cys detection. Encouraged by the admirable sensing performance of DPQA, bioimaging of endogenous Cys has been attempted in HeLa cells with satisfactory results. Moreover, cell model of H2O2-induced oxidative stress has been established and the Cys fluctuation during this process has been inspected, elucidating how living cells confront with the eruption of reactive oxygen species (ROS) storm. SIGNIFICANCE: The probe DPQA with such an intriguing cascade responding process for Cys detection has been endowed with many merits, such as fast reaction and superior sensitivity, conducive to improving responsiveness and rendering it more suitable for further applications. Thereby, we expect that the DPQA would be an efficient tool for detecting Cys fluctuation in living cells of different physiological processes.

Designing of a high-performance fluorescent small molecule enables dual-mode and ultra-sensitive fluorescence visualizing of HSO3- and HClO in dried fruit, beverage, and water samples.

Herein, a novel hemicyanine derivative (E)-3-(1,1-dimethyl-2-(4-(methylthio)styryl)-1H-benzo[e]indol-3-ium-3-yl)propane-1-sulfonate (BIS) has been reasonably designed. Compound BIS is long-wavelength emissive and water-soluble with a large Stokes shift. Intriguingly, probe BIS provides a dual-mode fluorescence response pattern for the sensing of bisulfite (HSO3-) and hypochlorous acid (HClO) with great limit of detections (3.6 and 57.4 nM). First, the 1,4-Michael addition of HSO3- on the conjugated double bond triggers a ratiometric response (I465/I575). Second, the rapid oxidation of HClO on the thioether moiety provides a turn-on response (I575). Evaluation of HSO3- and HClO levels in dried fruit, beverage, and water samples has been carried out with satisfactory results. Moreover, motivated by an impressive chromatic variation (red to blue), smartphone-assisted signal readout system and thin-film sensing platform are facilely constructed for real-time and on-site measurement of HSO3- levels. Furthermore, probe BIS is used for the in vivo imaging of HSO3- in edible fish models.

Dual-emission ratiometric nanoprobe for visual detection of Cu(II) and intracellular fluorescence imaging.

Copper is an essential mineral nutrient for the human body. However, excessive levels of copper accumulated in the body can cause some diseases. Therefore, it is great significant to establish a sensitive bioprobe to recognize copper ions (Cu2+) in vivo. In our work, nitrogen-doped carbon dots (N-CDs) and gold nanoclusters (Au NCs) are selected as luminescent nanomaterials and the Au NCs/N- CDs nanohybrids is successfully synthesized by coupling method. The Au NCs/N-CDs exhibited characteristic dual-emission peaks at 450 and 620 nm when excited by a single-wavelength of 380 nm. When different amounts of Cu2+ are introduced, the fluorescence intensity of the Au NCs is gradually weakened and fluorescence intensity of the N-CDs is almost unchanged, which can facilitate the visual detection of Cu2+. The Au NCs/N-CDs nanohybrid possesses good selectivity to Cu2+ with a limit of detection (LOD) is 3.5 µM and linear detection range of 10-150 µM. Visualization detection of Cu2+ is implemented by using nanoprobe in water samples. Furthermore, the ratiometric nanoprobe is utilized to the toxicity test of liver cancer cells, indicating excellent biocompatibility and low toxicity. This nanoprobe has been used to the intracellular fluorescence imaging. Moreover, this method is expected to be used to monitor the changes of Cu2+ concentration in hepatocytes.

Enhanced photoelectrochemical sensing based on novel synthesized Bi2S3@Bi2O3 nanosheet heterostructure for ultrasensitive determination of L-cysteine.

The design of a low-cost and highly efficient photoactive heterojunction material for sensing is still a challenging issue. On the basis of the formation of sheet-like Bi2O3 via coating Bi2S3, a novel Bi2O3@Bi2S3 heterostructure is controllably synthesized via a facile water bath approach. The prepared Bi2O3@Bi2S3 nanosheets show a superior photoelectrochemical (PEC) performance for the detection of L-cysteine (L-Cys), and the photocurrent signal is three and four times higher than those of Bi2S3 and Bi2O3 under visible irradiation, respectively. Also, the heterostructure presents an outstanding linear range for the detection of L-Cys: 0.1-10,000 µM. In addition, the mechanism of improved PEC response of Bi2O3@Bi2S3 nanosheets is investigated according to the estimated energy band positions. Thus, the integration of the novel heterostructure and the photoelectrochemical technique demonstrates a rapid photocurrent response, showing a great effect on the performance of the sensing system and a new PEC method for highly selective and sensitive chemical detection. Graphical abstract.

A chronocoulometric aptasensor based on gold nanoparticles as a signal amplification strategy for detection of thrombin.

A sensitive chronocoulometric aptasensor for the detection of thrombin has been developed based on gold nanoparticle amplification. The functional gold nanoparticles, loaded with link DNA (LDNA) and report DNA (RDNA), were immobilized on an electrode by thrombin aptamers performing as a recognition element and capture probe. LDNA was complementary to the thrombin aptamers and RDNA was noncomplementary, but could combine with [Ru(NH3)6]³âº (RuHex) cations. Electrochemical signals obtained by RuHex that bound quantitatively to the negatively charged phosphate backbone of DNA via electrostatic interactions were measured by chronocoulometry. In the presence of thrombin, the combination of thrombin and thrombin aptamers and the release of the functional gold nanoparticles could induce a significant decrease in chronocoulometric signal. The incorporation of gold nanoparticles in the chronocoulometric aptasensor significantly enhanced the sensitivity. The performance of the aptasensor was further increased by the optimization of the surface density of aptamers. Under optimum conditions, the chronocoulometric aptasensor exhibited a wide linear response range of 0.1-18.5 nM with a detection limit of 30 pM. The results demonstrated that this nanoparticle-based amplification strategy offers a simple and effective approach to detect thrombin.

Probe-label-free electrochemical aptasensor based on methylene blue-anchored graphene oxide amplification.

Two novel probe-label-free electrochemical aptasensors based on methylene blue (MB)-anchored graphene oxide (GO) amplification were developed for thrombin (TB) and ATP detection, taking advantage of the specific binding affinity of the aptamer towards the target and the different affinities of GO for MB, ssDNA, dsDNA, and G-quadruplex.

A new Co(III)-hypocrellin B complex with enhanced photonuclease activity.

Hypocrellin B (HB), a naturally occurring photosensitizer, has been extensively and intensively studied as a promising photodynamic therapy (PDT) agent. In this work, a new Co(III) complex [Co(2)(HB)(tmp)(4)](4+) (tmp=3,4,7,8-tetramethyl-1,10-phenanthroline) was designed and synthesized with HB as bridging ligand and tmp as terminal ligand. [Co(2)HB(tmp)(4)](4+) exhibits improved water solubility, enhanced absorptivity in the phototherapeutic window, increased binding affinity and DNA photocleavage capability toward dsDNA with respect to HB. The photodynamic activity of [Co(2)(HB)(tmp)(4)](4+) stems from its (1)O(2) photosensitization ability, in sharp contrast to [Cu(2)(HB)(tmp)(2)](2+) which relies on superoxide anion radical (O(2)(-)) and hydroxyl radical (·OH) to photocleave DNA, though the both complexes possess similar electrochemical properties. The remarkable difference between the photodynamic mechanisms of [Co(2)(HB)(tmp)(4)](4+) and [Cu(2)(HB)(tmp)(2)](2+) was discussed in detail.

Dinuclear Cu(II) hypocrellin B complexes with enhanced photonuclease activity.

Five new dinuclear Cu(II) complexes were designed and synthesized, using hypocrellin B, a naturally occurring photosensitizer that has received extensive studies as promising photodynamic therapy (PDT) agent, as bridging ligand, and five kinds of diimine ligands, including 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-1,10-phenanthroline (tmp), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), and dipyrido[3,2-a:2',3'-c]phenazene (dppz), as terminal ligands, respectively. The Cu(2+)-HB complexes exhibit improved water solubility, enhanced absorptivity in the phototherapeutic window of 600-900 nm, and increased binding affinity toward dsDNA than their parent HB. The biologically accessible redox potential of Cu(II)/Cu(I) couple renders the five Cu(2+)-HB complexes chemical nuclease activities in the presence of reducing agent such as ascorbic acid. Moreover, the readily available redox potential of Cu(II)/Cu(I) couple switches the photodynamic activity from type II mechanism (singlet oxygen mechanism) for HB to type I mechanism (radical mechanism) for the Cu(2+)-HB complexes. Of the five Cu(2+)-HB complexes, complex 3-5 with terminal diimine ligands of tmp, dpq, and dppz, respectively, can photocleave supercoiled pBR322 DNA more efficiently than HB. These findings open a new avenue for the development of the HB derivatives with higher photodynamic activity and better clinical applicability.

[Ru(bpy)(3-n)(dpb)(n)](2+): unusual photophysical property and efficient DNA photocleavage activity.

The sequential replacement of a bpy ligand (bpy = 2,2'-bipyridine) by a dpb ligand (dpb = 2,3-bis(2-pyridyl) benzoquinoxaline) in the series [Ru(bpy)(3-n)(dpb)(n)](2+) (n = 1-3) leads to a remarkable increase of the excited state lifetime, the (1)O(2) quantum yield, and the binding affinity toward dsDNA, rendering both [Ru(bpy)(dpb)(2)](2+) and [Ru(dpb)(3)](2+) efficient DNA photocleavage activities upon red light irradiation (>or=600 nm).

A new heteroleptic ruthenium(II) polypyridyl complex with long-wavelength absorption and high singlet-oxygen quantum yield.

Ruthenium(II) polypyridyl complexes with long-wavelength absorption and high singlet-oxygen quantum yield exhibit attractive potential in photodynamic therapy. A new heteroleptic Ru(II) polypyridyl complex, [Ru(bpy)(dpb)(dppn)](2+) (bpy=2,2'-bipyridine, dpb=2,3-bis(2-pyridyl)benzoquinoxaline, dppn=4,5,9,16-tetraaza-dibenzo[a,c]naphthacene), is reported, which exhibits a (1)MLCT (MLCT: metal-to-ligand charge transfer) maximum as long as 548 nm and a singlet-oxygen quantum yield as high as 0.43. Steady/transient absorption/emission spectra indicate that the lowest-energy MLCT state localizes on the dpb ligand, whereas the high singlet-oxygen quantum yield results from the relatively long (3)MLCT(Ru-->dpb) lifetime, which in turn is the result of the equilibrium between nearly isoenergetic excited states of (3)MLCT(Ru-->dpb) and (3)pipi*(dppn). The dppn ligand also ensures a high binding affinity of the complex towards DNA. Thus, the combination of dpb and dppn gives the complex promising photodynamic activity, fully demonstrating the modularity and versatility of heteroleptic Ru(II) complexes. In contrast, [Ru(bpy)(2)(dpb)](2+) shows a long-wavelength (1)MLCT maximum (551 nm) but a very low singlet-oxygen quantum yield (0.22), and [Ru(bpy)(2)(dppn)](2+) shows a high singlet-oxygen quantum yield (0.79) but a very short wavelength (1)MLCT maximum (442 nm).

DNA photocleavage activity of cobalt(III) polypyridyl complexes containing dpq ligand.

Four cobalt(III) polypyridyl complexes, [Co(phen)(3-)(n)(dpq)(n)](3+) (phen=1,10-phenanthroline, dpq=dipyrido[3,2-f:2',3'-h]-quinoxaline) (n=0, 1, 2, and 3) were synthesized and the influences of the dpq ligand on the photophysical properties, electrochemical properties, DNA binding affinities, as well as photonuclease activities of the complexes, were examined in detail. The presence of dpq ligand increases the DNA binding affinities of the corresponding complexes remarkably with respect to [Co(phen)(3)](3+). With the sequential substitution of phen ligand by dpq ligand, the (1)O(2) quantum yields of the corresponding complexes are enhanced greatly. As a result, the photonuclease activities follow the order of [Co(dpq)(3)](3+)>[Co(phen)(dpq)(2)](3+)>[Co(phen)(2)(dpq)](3+)>>[Co(phen)(3)](3+). It was found all the examined complexes can generate ()OH upon UV irradiation, and ()OH is also involved in DNA photocleavage as reactive oxygen species.

Ruthenium(II) terpyridyl complexes exhibiting DNA photocleavage: the role of the substituent on monodentate ligand.

Five ruthenium(II) complexes, [Ru(II)(tpy)(dppz)(py-R)](2+) (tpy = 2,2':6',2''-terpyridine; dppz = dipyrido[3,2-a:2',3'-c]phenazine; py-R = 4-substituted pyridine; R = N(CH(3))(2), NH(2), OCH(3), H, NO(2)), were synthesized; and the substituent effects on the photophysical property, electrochemical property, DNA binding, and DNA photocleavage of the complexes were examined carefully. Increasing the electron-donating ability of the substituent R from NO(2) to N(CH(3))(2) leads to a cathodic shift of Ru-based oxidation potential, a red shift of the (1)MLCT absorption at room temperature and the (3)MLCT emission at 77 K, and enhancement of the DNA photocleavage ability. DNA photocleavage control experiments and the EPR spin-trapping technique confirm that the photocleavage abilities of the complexes originate from (1)O(2) production. Time-resolved absorption spectra suggest that the (3)MLCT lifetime plays an important role in the photosensitized (1)O(2) generation of these complexes, which in turn depends strongly on the electron-donating ability of the substituent R. By changing the substituent of pyridine from the electron-withdrawing to the electron-donating group, the photocleavage abilities of the complexes varied from inactive to active, providing a new strategy for the development of DNA photocleavers of tpy-based Ru(II) complexes.

Cephalosol: an antimicrobial metabolite with an unprecedented skeleton from endophytic Cephalosporium acremonium IFB-E007.

Cephalosol (1), a potent antimicrobial secondary metabolite with a new carbon skeleton, was characterized from the culture of Cephalosporium acremonium IFB-E007 that used to reside as an endophyte in Trachelospermum jasminoides (Apocynaceae). Its structure and absolute configuration were unambiguously determined by spectroscopic and computational approaches.

{µ-6,6'-Dimeth-oxy-2,2'-[ethane-1,2-diylbis(nitrilo-methyl-idyne)]diphenolato}-µ-nitrato-dinitratoterbium(III)zinc(II).

In the title heteronuclear Zn(II)-Tb(III) complex (systematic name: {6,6'-dimeth-oxy-2,2'-[ethane-1,2-diylbis(nitrilo-methyl-id-yne)]diphenolato-1κ(4)O(6),O(1),O(1'),O(6')}:2κ(4)O(1),N,N',O(1')-µ-nitrato-1:2κ(2)O:O'-dinitrato-1κ(4)O,O'-terbium(III)zinc(II)), [TbZn(C(18)H(18)N(2)O(4))(NO(3))(3)], with the hexa-dentate Schiff base compartmental ligand N,N'-bis-(3-methoxy-salicyl-idene)ethyl-enediamine (H(2)L), the Tb and Zn atoms are triply bridged by two phenolate O atoms of the Schiff base ligand and one nitrate ion. The five-coordinate Zn atom is in a square-pyramidal geometry with the donor centers of two imine N atoms, two phenolate O atoms and one of the bridging nitrate O atoms. The Tb(III) center has a ninefold coordination environment of O atoms, involving the phenolate O atoms, two meth-oxy O atoms, two O atoms from two nitrate ions and one from the bridging nitrate ion. Weak inter-molecular C-H⋯O inter-actions generate a two-dimensional layer structure.

A tyrosine-modified hypocrellin B with affinity for and photodamaging ability towards calf thymus DNA.

An enhanced photodamaging ability towards CT-DNA was achieved in a tyrosine-modified hypocrellin B by improving the affinity of the sensitizer to DNA.

The photodynamic property improvement of hypocrellin A by chelation with lanthanum ions.

A 1:1 complex of lanthanum ion with hypocrellin A (La3+-HA) possessing high singlet oxygen generation efficiency, large absorbance in the phototherapeutic window, and great water solubility exhibits promising photodynamic properties.