Tandem Reactions of Electrophilic Indoles toward Indolizines and Their Subsequent Transformations through Pd(II)-Mediated C-H Functionalization to Access Polyring-Fused N-Heterocycles.

A simple and efficient synthetic approach for generating a library of structurally novel indolizines has been developed via sequential 1,3-dipolar cycloaddition-ring opening processes. Using this methodology, a series of indolizines bearing different substituents were made in moderate to good yields. The presence of two functionalizable C-H bonds in these indolizine motifs makes them attractive for accessing fused indolizine scaffolds. In this line, we have introduced palladium-mediated site-selective C-H functionalizations, where the N-center and the two C-H centers of the indolizine moiety can be readily functionalized to generate fused N-heterocycles. Utilizing a Pd-mediated dual C-H activation of 5-benzoyl-substituted indolizine afforded 6H-indeno-indolizine, and a tetracene, viz., indolizino[2,1-b]indoles, was produced in the same substrate by the Pd-catalyzed selective C-H amination in the presence of oxygen.

Discovery of Oxygen Induced Chemoselectivity in Pd-Catalyzed C-H Functionalization: Cross-Dehydrogenative Coupling vs C-H Amination.

We have come across a substrate namely, 5-benzoyl-pyrrolo[2,1-a]isoquinoline in which three different functionalizable C-H bonds were identified that could be judiciously transformed site selectively for the generation of complex polyring fused N-heterocycles. A Pd-catalyzed cross-dehydrogenative coupling of 5-benzoyl-pyrrolo[2,1-a]isoquinoline afforded 8H-indeno-pyrrolo[2,1-a]isoquinolinone and an oxygen induced palladium catalyzed selective C-H amination in the same substrate provided a pentacene viz., 9H-indolo-pyrrolo[2,1-a]isoquinoline. We also observed the formation of a multiring fused benzazepine scaffold by the site selective C-H amination in 5-(4-nitro benzoyl)-pyrrolo[2,1-a]isoquinoline.

Synthesis and Liquid Crystalline Properties of Low Molecular Weight Bis- Chalcone Compounds.

AIMS: In this paper, we report on the synthesis and liquid crystalline properties of some low molecular weight bis-chalcone compounds derived from acetone, cyclopentanone and cyclohexanone mesogenic cores. BACKGROUND: Structurally bis-chalcones belong to a broader family of chalcone compounds. Chalcone is a compound that consists of two aromatic rings linked by an unsaturated α, ß-ketone. OBJECTIVE: Liquid crystalline chalcones are prepared by aliphatic chain substituents on two aromatic rings. Chalcones are well studied for their mesomorphic properties. Compared to a large number of chalcone based LCs reported, only a few articles have been published on the mesomorphic properties of bis-chalcone compounds. The target compounds of the present study varied not only in their central core but also in number and position of terminal aliphatic chain substitution-a key structural unit in deciding the liquid crystalline properties of a compound. METHODS: All target compounds were synthesized in good yield by base catalyzed Claisen-Schmidt condensation reaction. Molecular structures were confirmed by FT-IR, 1H NMR, 13C NMR, and mass spectroscopic methods. Liquid crystalline property of these compounds was evaluated using polarizing optical microscopy and differential scanning calorimetry. RESULTS: Although none of the acetone based compounds exhibited mesomorphism, cyclopentanone and cyclohexanone based compounds with octyloxy chain at para position on either side of the dibenzylidine ring stabilized liquid crystalline smectic (SmA and SmC) and nematic (N) phases. The observed structure-liquid crystalline property relationship was explained by structural analysis of molecules using DFT calculations. Considering the inherent photoluminescence nature of the chalcone moiety, a preliminary study was carried out on a selected compound to reveal its fluorescence property. CONCLUSION: Our study brings about an important structure-liquid crystalline property relationship in a relatively unexplored class of bis-chalcone liquid crystals.

Generation and EPR Spectroscopy of the First Silenyl Radicals, R2 C=Si. -R: Experiment and Theory.

The first two persistent silenyl radicals (R2 C=Si. -R), with a half-life (t1/2 ) of about 30 min, were generated and characterized by electron paramagnetic resonance (EPR) spectroscopy. The large hyperfine coupling constants (hfccs) (a(29 Siα )=137.5-148.0 G) indicate that the unpaired electron has substantial s character. DFT calculations, which are in good agreement with the experimentally observed hfccs, predict a strongly bent structure (∡C=Si-R=134.7-140.7°). In contrast, the analogous vinyl radical, R2 C=C. -R (t1/2 ≈3 h), exhibits a small hfcc (a(13 Cα )=26.6 G) and has a nearly linear geometry (∡C=C-R=168.7°).

Isolation and Characterization, Including by X-ray Crystallography, of Contact and Solvent-Separated Ion Pairs of Silenyl Lithium Species.

Reaction of bromoacylsilane 1 (pink solution) with tBu2 MeSiLi (3.5 equiv) in a 4:1 hexane:THF solvent mixture at -78 °C to room temperature yields the solvent separated ion pair (SSIP) of silenyl lithium E-[(tBuMe2 Si)(tBu2 MeSi)C=Si(SiMetBu2 )](-) [Li⋅4THF](+) 2 a (green-blue solution). Removal of the solvent and addition of benzene converts 2 a into the corresponding contact ion pair (CIP) 2 b (violet-red solution) with two THF molecules bonded to the lithium atom. The 2 a⇌2 b interconversion is reversible upon THF⇌ benzene solvent change. Both 2 a and 2 b were characterized by X-ray crystallography, NMR and UV/Vis spectroscopy, and theoretical calculations. The degree of dissociation of the Si-Li bond has a large effect on the visible spectrum (and thus color) and on the silenylic (29) Si NMR chemical shift, but a small effect on the molecular structure. This is the first report of the X-ray molecular structure of both the SSIP and the CIP of any R2 E=E'RM species (E=C, Si; E'=C, Si; M=metal).

A Three-Photon Active Organic Fluorophore for Deep Tissue Ratiometric Imaging of Intracellular Divalent Zinc.

Deep tissue bioimaging with three-photon (3P) excitation using near-infrared (NIR) light in the second IR window (1.0-1.4 µm) could provide high resolution images with an improved signal-to-noise ratio. Herein, we report a photostable and nontoxic 3P excitable donor-π-acceptor system (GMP) having 3P cross-section (σ3 ) of 1.78×10(-80)  cm(6) s(2) photon(-2) and action cross-section (σ3 η3 ) of 2.31×10(-81)  cm(6) s(2) photon(-2) , which provides ratiometric fluorescence response with divalent zinc ions in aqueous conditions. The probe signals the Zn(2+) binding at 530 and 600 nm, respectively, upon 1150 nm excitation with enhanced σ3 of 1.85×10(-80)  cm(6) s(2) photon(-2) and σ3 η3 of 3.33×10(-81)  cm(6) s(2) photon(-2) . The application of this probe is demonstrated for ratiometric 3P imaging of Zn(2+) in vitro using HuH-7 cell lines. Furthermore, the Zn(2+) concentration in rat hippocampal slices was imaged at 1150 nm excitation after incubation with GMP, illustrating its potential as a 3P ratiometric probe for deep tissue Zn(2+) ion imaging.

Highly photostable zinc selective molecular marker bearing flexible pivotal unit: opto-fluorescence enhancement effect and imaging applications in living systems.

Novel molecular probes for imaging zinc in biological systems are gaining interest as they help in understanding the role of zinc in regulating various bio-events. In this regard, a new C2-symmetric molecular system has been developed and successfully applied as light-up material for signaling divalent zinc with green emission. The fluorescence enhancement was highly zinc specific and this newly developed probe bears a submicromolar detection capability. While probe and the ensemble -Zn(2+) exhibited remarkably high photostability, light-triggered fluorescence enhancement was observed in the case of -Zn(2+). The nature of the -Zn(2+) complex and the associated spectral shift are further supported by theoretical calculations. As the present probe absorbs in the visible region and emits in the green, it was preferred as a potential material for imaging zinc in biological systems including animal and plant cells such as pollen grains and fish egg cells. Such fluorescence imaging of zinc revealed the efficacy of the probe in detection and localization of zinc in various biological systems.

Formation of three new bonds and two stereocenters in acyclic systems by zinc-mediated enantioselective alkynylation of acylsilanes, Brook rearrangement, and ene-allene carbocyclization reactions.

Diastereoisomerically pure (dr > 99:1) and enantiomerically enriched (er up to 98:2) substituted propargyl diols possessing a tertiary hydroxyl group were synthesized in a single-pot operation from simple acylsilanes through a combined catalytic enantioselective alkynylation of acylsilanes, followed by an allenyl-Zn-Brook rearrangement and Zn-ene-allene (or Zn-yne-allene) cyclization reaction. Two remarkable features of these reactions are the near complete transfer of chirality in the allenyl-Zn-Brook rearrangement and the highly organized six-membered transition state of the Zn-ene-allene carbocyclization found by DFT calculations. In this process, three new bonds and two new stereogenic centers are created in a single-pot operation in excellent diastereo- and enantiomeric ratios. DFT calculations show that the allenyl-Zn-Brook rearrangement occurs in preference to the classic [1,2]-Zn-Brook rearrangement owing to its significantly lower activation barrier.

Triazole-based Zn²âº-specific molecular marker for fluorescence bioimaging.

Fluorescence bioimaging potential, both in vitro and in vivo, of a yellow emissive triazole-based molecular marker has been investigated and demonstrated. Three different kinds of cells, viz Bacillus thuringiensis, Candida albicans, and Techoma stans pollen grains were used to investigate the intracellular zinc imaging potential of 1 (in vitro studies). Fluorescence imaging of translocation of zinc through the stem of small herb, Peperomia pellucida, having transparent stem proved in vivo bioimaging capability of 1. This approach will enable in screening cell permeability and biostability of a newly developed probe. Similarly, the current method for detection and localization of zinc in Gram seed sprouts could be an easy and potential alternative of the existing analytical methods to investigate the efficiency of various strategies applied for increasing zinc-content in cereal crops. The probe-zinc ensemble has efficiently been applied for detecting phosphate-based biomolecules.

Cysteamine-based cell-permeable Zn(2+)-specific molecular bioimaging materials: from animal to plant cells.

Structure-interaction/fluorescence relationship studies led to the development of a small chemical library of Zn(2+)-specific cysteamine-based molecular probes. The probe L5 with higher excitation/emission wavelengths, which absorbs in the visible region and emits in the green, was chosen as a model imaging material for biological studies. After successful imaging of intracellular zinc in four different kinds of cells including living organisms, plant, and animal cells, in vivo imaging potential of L5 was evaluated using plant systems. In vivo imaging of translocation of zinc through the stem of a small herb with a transparent stem, Peperomia pellucida, confirmed the stability of L5 inside biological systems and the suitability of L5 for real-time analysis. Similarly, fluorescence imaging of zinc in gram sprouts revealed the efficacy of the probe in the detection and localization of zinc in cereal crops. This imaging technique will help in knowing the efficiency of various techniques used for zinc enrichment of cereal crops. Computational analyses were carried out to better understand the structure, the formation of probe-Zn(2+) complexes, and the emission properties of these complexes.

One-pot zinc-promoted asymmetric alkynylation/brook-type rearrangement/ene-allene cyclization: highly selective formation of three new bonds and two stereocenters in acyclic systems.

It's as easy as 1, 2, 3: In a one-pot sequence, two stereocenters and three new bonds were created with high selectivity through an asymmetric alkynylation of acyl silanes, a tandem Brook-type rearrangement and Zn-ene-allene cyclization, the addition of an electrophile, and finally oxidation. The straightforward nature of the synthetic procedure contrasts strongly with the complexity of the densely functionalized products obtained.

Heteroaromatic donors in donor-acceptor-donor based fluorophores facilitate zinc ion sensing and cell imaging.

The excited state intra molecular charge transfer (ICT) property of fluorophores has been extensively used for the design of fluorescent chemosensors. Herein, we report the synthesis and properties of three donor­π-acceptor­π-donor (D­π-A­π-D) based molecular probes BP, BT and BA. Two heteroaromatic rings, pyrrole (BP), and thiophene (BT) and a non-heteroaromatic ring N-alkoxy aniline (BA) were selected as donor moieties which were linked to a bipyridine binding site through a vinylic linkage. The heteroaromatic systems BP and BT perform selective and ratiometric emission signalling for zinc ions whereas the non-heteroaromatic probe BA does not. The advantages of the D­π-A­π-D design strategy in the design of ICT based probes for the selective fluorescent ratiometric signalling of zinc ions in biological media is discussed. Further, the use of BP, BT and BA for imaging Zn(2+) ions from MCF-7 cell lines is demonstrated.

Use of molecular electrostatic potential at the carbene carbon as a simple and efficient electronic parameter of N-heterocyclic carbenes.

Topographical analysis of the molecular electrostatic potential (MESP) has been carried out for a variety of N-heterocyclic carbenes at the B3LYP, BP86, and M05 levels of density functional theory (DFT) using a 6-311++G** basis set. The electron rich character of the carbene carbon is assessed in terms of the absolute minimum of the MESP at the carbene lone pair region (V(min)), as well as the MESP at the carbene nucleus (V(C)). A linear relationship is established between the V(C) and Tolman electronic parameter (TEP) which suggested the use of the former as a simple and efficient descriptor for the electron donating power of N-heterocyclic carbene ligands toward metal coordination. The V(min) of the carbene also showed good correlation with TEP. However, the deviation from linearity was higher than V(C)-TEP correlation, and the reason for this was attributed to the steric effect of N-substituents at the lone pair region. The greater coordinating power of N-heterocyclic carbenes over phosphines is explained on the basis of deeper V(min) values obtained for the former, and in fact even the V(min) of the least electron rich N-heterocyclic carbene is comparable to the highly electron rich phosphine ligands. Thus the MESP topographical approach presented herein offers quantification of the inherent electron donating power of a free N-heterocyclic carbene ligand.

Quantitative assessment of the stereoelectronic profile of phosphine ligands.

The stereoelectronic profile of a variety of phosphine ligands (PR3) have been estimated using a combined approach of quantum mechanics (QM) and molecular mechanics (MM). The quantum mechanically derived molecular electrostatic potential minimum (Vmin) of a PR3 ligand at the phosphorus lone pair region provides a direct measure of the total electronic (Eeff) and steric effects (Seff) of the ligand. The difference between the Vmin of unsubstituted PH3 (Vmin(PH3)) and the Vmin of PR3 is considered as Eeff + Seff. It is found that a two-layer QM-MM ONIOM method comprising PH3 in the inner QM layer and the R groups in the outer MM layer is useful to locate the structure of a PR3 ligand in an electronic effect free environment of the substituents. The Vmin of the ONIOM-optimized PR3 at the phosphorus lone-pair region thus provides the quantification of the steric effect as Seff = Vmin(PH3)-Vmin(ONIOM_PR3). Because Vmin(PR3) contains both Eeff and Seff, the Eeff can be easily defined as Eeff = Vmin(ONIOM_PR3)-Vmin(PR3). A modified form of the symmetric deformation coordinate (S4) is calculated for all of the fully optimized and ONIOM-optimized free phosphines to obtain their S4-based steric effect values. Good linear correlation between S4 of ONIOM-optimized phosphines and the MESP-based Seff values was obtained. Further, the determination of the stereoelectronic profile of PR3 ligands has been achieved, leading to a general classification of the ligands into four categories, namely, ligands with (i) (+Eeff, +Seff), (ii) (+Eeff, -Seff), (iii) (-Eeff, +Seff), and (iv) (-Eeff, -Seff), where plus and minus signs indicate electron donation and electron withdrawal properties, respectively.