Synthesis and Photophysical Study of Tetraphenyl Substituted BODIPY Based Phenyl-Monoselenide Probe for Selective Detection of Superoxide.

Selenium containing tetraphenyl substituted BODIPY probe was successfully synthesized from respective selenium aldehyde and tetraphenyl pyrrole using Knoevenagel-type condensation. The product was characterized using various spectroscopic techniques (1 H, 13 C, 77Se, 11B, and 19 F) and mass spectrometry. The probe was found to be selective and sensitive towards detection of superoxide over other ROS with a "turn-off" (quenched) fluorescence response. The detection limit of the probe was found to be 4.87 µM. The probe reacted with superoxide in less than a sec with a stoke shift of 35 nm.

Synthesis and single crystal X-ray study of phenylselenyl embedded coumarin-based sensors for selective detection of superoxide.

Selenium-coumarin based probe 4 was synthesized from the reaction of a bromo derivative of coumarin with in situ prepared sodium phenyl selenide. Esterification of probe 4 resulted in the formation of probe 5. In the single crystal X-ray structure of probe 4, the phenylselenide group was placed parallel to the coumarin moiety whereas in probe 5, the phenylselenide group was perpendicular to the coumarin group. Hydrogen bonding interactions have been observed in the crystal packing of both the probes. Both the probes selectively detect superoxide over other reactive oxygen species (ROS). A kinetic study of the probes was performed, which suggested that probe 4 achieved maximum fluorescence intensity in less than 1 s while probe 5 required 30 min to attain maximum fluorescence intensity. Both probes 4 and 5 showed 37 fold and 48 fold increase in fluorescence intensity after the reaction with superoxide, respectively. The detection limits of probes 4 and 5 were found to be 46.4 nM and 48.9 nM, respectively. Both the probes showed reversibility with biothiols such as glutathione (GSH) and N-acetyl-L-cysteine (NAC). Probe 5 underwent more redox cycles with GSH compared to probe 4.

A BOPHY based fluorescent probe for Hg2+via NTe2 chelation.

A BOPHY-based organotellurium-containing probe was synthesized and characterized via single crystal XRD for the selective and sensitive detection of Hg2+ over other metal ions. The probe detects Hg2+ in less than 1 s with a 2.5-fold enhancement in fluorescent intensity. Due to the chalcogenophilicity of mercury, Hg2+ was facilely trapped in the NTe2 chelating cavity of the probe. The probe can detect Hg2+ in the nanomolar range (62 nM) and it showed reversibility with S2- ions. The sensitivity of the probe for the detection of Hg2+ was confirmed in living HeLa cells.

An efficient chemodosimeter for the detection of Hg(II) via diselenide oxidation.

Mercury ions are toxic and exhibit hazardous effects on the environment and biological systems, and thus demand for the selective and sensitive detection of mercury has become considerably an important issue. Here, we have developed a diselenide containing coumarin-based probe 3 for the selective detection of Hg(II) with a "turn-on" response (a 48 fold increase in fluorescence intensity) at 438 nm. The probe could quantitatively detect Hg(II) with a detection limit of 1.32 µM in PBS solution. Moreover, the probe has operable efficiency over the physiological range with an increase in the quantum yield from 1.2% to 57.3%. The reaction of the probe with Hg(II) yielded a novel monoselenide based coumarin 4via diselenide oxidation, which was confirmed by single crystal XRD. Furthermore, the biological use of the probe for the detection of Hg(II) was confirmed in the MCF-7 cell line. To the best of our knowledge, this is the first reaction-based probe for Hg(II) via diselenide oxidation.

Organoselenium-based BOPHY as a sensor for detection of hypochlorous acid in mammalian cells.

Phenylselenide substituted BOPHY probes (BOPHY-SePh and PhSe-BOPHY-SePh) were synthesized and characterized by NMR spectroscopy and single-crystal XRD. Both the probes selectively detect HOCl in water with high sensitivity over other reactive oxygen species. A fluorescence "turn-on" event was attained due to cease of the PET process through transformation of selenide to selenoxide. Both the probes react with HOCl in less than 1 s. PhSe-BOPHY-SePh probe depicted low background fluorescence due to presence of two phenylselenide groups at BOPHY. PhSe-BOPHY-SePh probe has a low detection limit (0.63 µM) than BOPHY-SePh probe (1.08 µM). The bioimaging studies of both the probes were carried out in MCF 7 cells. Both the probes exhibited a good fluorescence response for HOCl in vitro and in mammalian cells. In addition, the probes showed reversibility with all bio-thiols, which was validated in MCF 7 cells using GSH.

Cyclic Organoselenide BODIPY-Based Probe: Targeting Superoxide in MCF-7 Cancer Cells.

All aerobic cells contain reactive oxygen species (ROSs) in balance with biochemical antioxidants. Oxidative stress is developed when this balance gets disturbed because of excessive production of ROSs or depletion of antioxidants. Here, in this work, we have developed the first cyclic diselenide BODIPY-based (organoselenium-containing) probe for the selective detection of superoxide. The probe demonstrates excellent selective response for superoxide over other ROSs with nine-fold increase in fluorescence intensity. The detection limit was found to be 0.924 µM. The plausible "turn-on" mechanism has been proposed based on the spectroscopic and quantum chemical data. Usefulness of the probe for selective detection of superoxide was confirmed in mammalian breast cancer cell lines.

Novel intramolecular π-π-interaction in a BODIPY system by oxidation of a single selenium center: geometrical stamping and spectroscopic and spectrometric distinctions.

A new BODIPY system displaying an intramolecular π-π-interaction was synthesized and studied. When the selenium center was oxidized, the substituted phenyl group undergoes π-π stacking with one side of the BODIPY core. The oxidized form showed, not only a down-field shift in the NMR peak, but also splitting due to geometrical changes that arise when going from Cs to C1. The compound was characterized by X-ray diffraction; DFT methods helped elucidate the influence of the unexpected π-π stack and its connection to the photophysical properties imparted by the Se oxidation.

Transition metal mediated formation of dicationic diselenides stabilised by N-heterocyclic carbenes: designed synthesis.

Reactions of the N-heterocyclic carbene derivatives of selenium(ii) dihalides, LSeX2 (X = Cl, Br; L = 1,3-dibutylbenzimidazol-2-ylidene, C15H22N2) (4b, 4b'), L'SeX2 (X = Cl, Br; L' = 1,3-di(n)propylbenzimidazol-2-ylidene, C13H18N2) (4c, 4c') and L''SeX2 (X = Cl, Br; L'' = 1,3-di(i)propylbenzimidazol-2-ylidene, C13H18N2) (4d, 4d') with iron led to the formation of dicationic diselenides, [L2Se2(2+)]2[{FeCl4}(-)]3Cl(-) (7), [L2Se2(2+)][FeBr4](-)Br(-) (8), [L'2Se2(2+)][FeCl4](-)Cl(-) (9), [L'2Se2(2+)][FeBr4](-)Br(-) (10), [L''2Se2(2+)][FeCl4](-)Cl(-) (11) and [L''2Se2(2+)][FeBr4](-)Br(-) (12). The reactions of LSeX2 with copper gave selone (LSe) complexes of cuprous halides, [(LSe)2CuBr] (13) and [(LSe)2(CuI)2] (14) respectively. However, LSeX2 (X = Cl, Br, I) (4b-4b'') on treatment with zinc gave both the dicationic diselenides, [L2Se2(2+)]Y [Y = {ZnCl3(H2O)2}(2-) (15), {ZnBr4}(2-) (17)] and complexes, [(LSe)2ZnX2] (16, 18, 20). The plausible mechanism for the formation of dicationic diselenides, [L2Se2(2+)], has been proposed and is supported by performing various test reactions. To validate these mechanisms, DFT calculations have been carried out. Interestingly, the reactions of the mixture of LSeX2/L'SeX2/L''SeX2 and L'Se(0)/L'Se(0)/L''Se(0) with metal halides (FeCl3, ZnX2; X = Cl, Br, I; CdI2, HgI2, PdCl2, and PtCl2) produced dicationic diselenides, 7-12, 15, 17 and [L2Se2(2+)]Y [Y = {ZnI4}(2-) (19), {CdI4}(2-) (22), {HgI4}(2-) (25), {PdCl4}(2-) (26), {PtCl4}(2-) (27)]. The methodology is more general than the previous method and gives better yields of [L2Se2(2+)]Y. The controlled oxidation of complexes, [(LSe)2MX2] (M = Zn, Cd, Hg; X = Cl, Br, I) (16, 18, 20, 28-32) with halogenating agents (SOCl2/Br2/I2) also gave dicationic diselenides, 15, 17, 19, 22, 25 and [L2Se2(2+)]Y [Y = {CdCl4}(2-) (21), {Hg2Cl6}(2-) (23), {HgBr4}(2-) (24)], proving to be the most general method for the synthesis of [L2Se2(2+)]. Attempted syntheses of unsymmetrical dicationic diselenides, [LSe-SeL'](2+)[FeCl4](-)Cl(-) and dicationic ditelluride, [L2Te2(2+)]2[{FeCl4}(-)]3Cl(-) by the reaction of LSeX2/LTeX2 (X = Cl, Br, I) with Fe metal were unsuccessful. This observation has been corroborated with DFT calculations.

Bis(chalcogenones) as pincer ligands: isolation and Heck activity of the selone-ligated unsymmetrical C,C,Se-Pd pincer complex.

The reaction of meta-phenylene-bis(1-methyl-1H-imidazole-2(3H)-selone) with [Pd2(µ-Cl)2(2-C6H4CH2NMe2)2] in dry benzene and glacial acetic acid resulted in the formation of an unsymmetrical 5,6-membered C,C,Se-Pd(II) pincer complex through C-H bond activation and extrusion of one selenium. This is the first example of a C,C,Se-Pd(II) complex wherein the central Pd(II) is simultaneously coordinated to a selone and an N-heterocyclic carbene. The chelated complex of the type [PdL2](2+)2[PF6](-) (L = bis(selone)) was isolated from the reaction of the bis(selone) with [PdCl2(PhCN)2] and NH4PF6. The unsymmetrical pincer complex was studied for Heck activity revealing its application as an acceptable catalyst in coupling of iodobenzene with acrylates and styrene.

H(+)-Assisted fluorescent differentiation of Cu(+) and Cu(2+): effect of Al(3+)-induced acidity on chemical sensing and generation of two novel and independent logic gating pathways.

A novel Schiff base probe exhibited strong 'turn-ON' fluorescence for Cu(2+) at 345 nm, Al(3+) at 445 nm, and Cu(+) at 360 nm in the presence of Al(3+) in organic solvent (acetonitrile), which allowed for construction of molecular logic gates 'INH' and '1:2 DEMULTIPLEXING.' H(+) generated from Al(3+) contributed greatly to Cu(+) chemosensing based on a redox non-innocence mechanism.

Crystal structure of (N (1)-benzyl-N (1),N (2),N (2)-tri-methyl-ethane-1,2-di-amine-κ(2) N,N')di-chloridomercury(II).

In the structure of the title compound, [HgCl2(C12H20N2)], the Hg(II) atom has a distorted tetra-hedral coordination sphere defined by two tertiary amine N-atom donors, as well as two Cl(-) anions [the dihedral angle between the N-Hg-N and Cl-Hg-Cl planes is 82.80 (9)°]. The five-membered chelate ring adopts an envelope conformation, with puckering parameters of Q(2) = 0.446 (6) Šand ϕ(2) = 88.8 (6)°, with the two amine CH3 substituents on opposite sides of the ring. In the crystal, the mol-ecules are linked by C-H⋯Cl inter-actions into a zigzag chain parallel to [101].

Selenium- and tellurium-containing fluorescent molecular probes for the detection of biologically important analytes.

As scientists in recent decades have discovered, selenium is an important trace element in life. The element is now known to play an important role in biology as an enzymatic antioxidant. In this case, it sits at the active site and converts biological hydrogen peroxides to water. Mimicking this reaction, chemists have synthesized several organoselenium compounds that undergo redox transformations. As such, these types of compounds are important in the future of both medicinal and materials chemistry. One main challenge for organochalcogen chemists has been to synthesize molecular probes that are soluble in water where a selenium or tellurium center can best modify electronics of the molecule based on a chemical oxidation or reduction event. In this Account, we discuss chemists' recent efforts to create chalcogen-based chemosensors through synthetic means and current photophysical understanding. Our work has focused on small chromophoric or fluorophoric molecules, in which we incorporate discrete organochalcogen atoms (e.g., R-Se-R, R-Te-R) in predesigned sites. These synthetic molecules, involving rational synthetic pathways, allow us to chemoselectively oxidize compounds and to study the level of analyte selectivity by way of their optical responses. All the reports we discussed here deal with well-defined and small synthetic molecular systems. With a large number of reports published over the last few years, many have notably originated from the laboratory of K. Han (P. R. China). This growing body of research has given chemists new ideas for the previously untenable reversible reactive oxygen species detection. While reversibility of the probe is technically important from the stand-point of the chalcogen center, facile regenerability of the probe using a secondary analyte to recover the initial probe is a very promising avenue. This is because (bio)chalcogen chemistry is extremely rich and bioinspired and continues to yield important developments across many scientific fields. Organochalcogen (R-E-R) chemistry in such chemical recognition and supramolecular pursuits is a fundamental tool to allow chemists to explore stable organic-based probe modalities of interest to develop better spectroscopic tools for (neuro)biological applications. Chalcogen donor sites also provide sites where metals can coordinate, and facile oxidation may extend to the sulfone analogues (R-EO2-R) or beyond. Consequently, chemists can then make use of reliable reversible chemical probing platforms based on the chemical redox properties valence state switching principally from 2 to 4 (and back to 2) of selenium and tellurium atoms. The main organic molecular skeletons have involved chemical frames including boron-dipyrromethene (BODIPY) systems, extended cyanine groups, naphthalimide, rhodamine, and fluorescein cores, and isoselenazolone, pyrene, coumarin, benzoselenadiazole, and selenoguanine systems. Our group has tested many such molecular probe systems in cellular milieu and under a series of conditions and competitive environments. We have found that the most important analytes have been reactive oxygen species (ROS) such as superoxide and hypochlorite. Reactive nitrogen species (RNS) such as peroxynitrite are also potential targets. In addition, we have also considered Fenton chemistry systems. Our research and that of others shows that the action of ROS is often reversible with H2S or biothiols such as glutathione (GSH). We have also found that a second class of analytes are the thiols (RSH), in particular, biothiols. Here, the target group might involve an R-Se-Se-R group. The study of analytes also extends to metal ions, for example, Hg(2+), and anions such as fluoride (F(-)), and we have developed NIR-based systems as well. These work through various photomechanisms, including photoinduced electron transfer (PET), twisted internal charge transfer (TICT), and internal charge transfer (ICT). The growing understanding of this class of probe suggests that there is much room for creative thinking regarding modular designs or unexpected organic chemical synthesis designs, interplay between analytes, new analyte selectivity, biological targeting, and chemical switching, which can also serve to further the neurological probing and molecular logic gating frontiers.

Selective and sensitive superoxide detection with a new diselenide-based molecular probe in living breast cancer cells.

A diselenide-based BODIPY probe was prepared; it was found to be sensitive and selective for superoxide in giving [-Se(O)Se(O)-] oxidation. Probing was reversible through the use of biothiols; (77)Se NMR and other types of spectroscopy were employed. Practical medicinal utility was demonstrated in MCF-7/ADR cancer cells.

Facile meso-BODIPY annulation and selective sensing of hypochlorite in water.

Annulated BODIPY chalcogenide (Se, Te) systems were synthesized from their respective bis(o-formylphenyl)dichalcogenide intermediates. The annulated BODIPY selenide product was confirmed by X-ray diffraction. The red-shifted telluride version was found to be sensitive and selective for hypochlorite detection, reversible upon treatment with biothiols.

Fluorescence probing of the ferric Fenton reaction via novel chelation.

A new probe-chelator PET dyad was synthesised, which can be used to detect Fe(3+)via fluorescence enhancement to discriminate between Fe(2+) and Fe(3+)via Fenton chemistry involving hydrogen peroxide. This is the first BODIPY which works as a 2 : 1 multiplexer for Fe(3+), Fe(2+) and H2O2.

Novel reversible Zn2+-assisted biological phosphate "turn-on" probing through stable aryl-hydrazone salicylaldimine conjugation that attenuates ligand hydrolysis.

A novel reversible zinc(II) chemosensing ensemble (2·Zn(2+)) allows for selective "turn-on" fluorescence sensing of ATP and PPi in aqueous media (detection limits: 2.4 and 1.0 µM, respectively) giving selective binding patterns: ATP ∼ PPi > ADP ≫ AMP > monophosphates ≈ remaining ions tested. The conjugated hydrazone [C═N-NH-R] resists hydrolysis considerably, compared to the imine [C═N-CH2-R, pyridin-2-ylmethanamine] functionality, and generalizes to other chemosensing efforts. Prerequisite Zn(2+)·[O(phenol)N(imine)N(pyr)] binding is selective, as determined by UV-vis and NMR spectroscopy; ATP or PPi extracts Zn(2+) to regenerate the ligand-fluorophore conjugate (PPi: turn-on, 512 nm; detection limit, 1.0 µM). Crystallography, 2-D NMR spectroscopy, and DFT determinations (B3LYP/631g*) support the nature of compound 2. 2-Hydrazinyl-pyridine-salicylaldehyde conjugation is unknown, as such; a paucity of chemosensing-Zn(2+) binding reports underscores the novelty of this modifiable dual cation/anion detection platform. A combined theoretical and experimental approach reported here allows us to determine both the potential uniqueness as well as drawbacks of this novel conjugation.

N-(2-Bromo-benz-yl)-N'-(2-pyrid-yl)benzene-1,2-diamine.

In the title compound, C(18)H(16)BrN(3), mol-ecules are linked into dimers by co-operative inter-molecular N-H⋯N hydrogen bonding. Only one N-H group is involved in hydrogen bonding. The planes of the pyridine and bromo-phenyl rings are twisted by 61.49 (3) and 79.11 (8)°, respectively, from the plane of the central phenyl ring.

N-[2-(2-Bromo-benzyl-amino)phen-yl]-N-butylformamide.

The title compound, C(18)H(21)BrN(2)O, crystallizes with two mol-ecules (A and B) in the asymmetric unit (Z' = 2). The major differences between the two mol-ecules are related to the conformations adopted by their n-butyl side chains. The phenyl rings in both mol-ecules are almost perpendicular, making dihedral angles of 79.2 (3) and 80.8 (3)°. The amide units are planar (r.m.s. deviations of 0.0018 and 0.021 Å) and almost perpendicular to the phenyl rings to which they are attached [dihedral angles of 68.9 (4) and 71.1 (4)°]. In the crystal, molecules A and B each form only an intermolecular N-H⋯O hydrogen bond with an adjacent molecule of the same kind. There are no significant intermolecular interactions between molecules A and B.

1-(2-Bromo-benz-yl)-3-isopropyl-benz-imid-azolin-2-one.

In the structure of the title compound, C(17)H(17)BrN(2)O, the central phenyl and imidazol-2-one rings are coplanar (dihedral angle between planes of 0.73 (11)°). The angles subtended by the substituents on the N atoms of the imidazol-2-one ring range from 109.71 (14)° to 128.53 (15) due to steric hindrance of these substituents with the phenyl H atoms. The carbonyl O and Br both make two weak C-H⋯O and C-H⋯Br inter-actions with two adjacent mol-ecules, thus forming an three-dimensional array.