Rational Design of Diphenyldiacetylene-Based Fluorescent Materials Enabling a 365-nm Light-Initiated Topochemical Polymerization.

Photopolymerization of diacetylenes usually requires stringent reaction conditions like high energy irradiation of 254-nm light or even γ-rays, which are generally harmful to the human body and thus mild conditions with lower energy irradiation are required. In this study, different diphenyldiacetylene (DPDA) derivatives were rationally designed followed by the investigation of their photopolymerization behavior. It was found that the para-substituted amino groups could render the absorption band of DPDA bathochromically shifted, ensuring a 365-nm light wavelength coverage. On this basis, an organogel system was constructed by chemically modifying cholesteryl and lipoic acid onto the DPDA moiety in aromatic solvents. Such uniform self-assemblies further facilitated to a rather high degree of polymerization by 365-nm irradiation. As a kind of fluorescent materials, the whole polymerization process of this system can be visualized by a photoluminescent signal.

Allostery-Mimicking Self-assembly of Helical Poly(phenylacetylene) Block Copolymers and the Chirality Transfer.

Allostery can regulate protein self-assembly which further affects biological activities, and achieving precise control over the chiral suprastructures during self-assembly remains challenging. Herein, to mimic the allosterical nature of proteins, the poly(phenylacetylene) block copolymers PPA-b-PsmNap with the dynamic helical backbone were synthesized to investigate their conformational-transition-induced self-assembly. As the helical conformation of the block PsmNap spontaneously transforms from cis-transiod to cis-cisoid, the decreasing solubility of PsmNap blocks in THF induced self-assembly of PPA-b-PsmNap. The self-assembly structures of copolymers can sequentially evolve from vesicles to nanobelts to helical strands during the process of conformation transformation. The screw sense of final helical strands was strictly correlated to the helicity of the block PsmNap. This is helpful to understand the mechanism of allostery-modulated self-assembly.

Synthesis and conformational analysis of poly(phenylacetylene)s with serinol-tethered carbohydrate appendages.

We synthesized phenylacetylenes containing ß-lactoside, ß-cellobioside, or ß-maltoside, and polymerized them to produce the corresponding poly (phenylacetylene)s. In these poly (phenylacetylene)s, the pendent carbohydrates were tethered to the mainchains by serinol spacers. Because similar glycosyl serinol units are found in the natural glycosphingolipids in cell membranes, the densely packed carbohydrate clusters along the poly (phenylacetylene) mainchains act as molecular mimics of cell surface glycoclusters. We analyzed the conformation of the glycosylated poly (phenylacetylene)s using circular dichroism spectroscopy, and found that the spatial carbohydrate packing within the glycoclusters changed on the addition of salts.

An atom efficient synthesis of tamoxifen.

The direct carbolithiation of diphenylacetylenes and their cross-coupling procedure taking advantage of the intermediate alkenyllithium reagents are presented. By employing our recently discovered highly active palladium nanoparticle based catalyst, we were able to couple an alkenyllithium reagent with a high (Z/E) selectivity (10 : 1) and good yield to give the breast cancer drug tamoxifen in just 2 steps from commercially available starting materials and with excellent atom economy and reaction mass efficiency.

Synthesis and Magnetic Properties of Stable Radical Derivatives Carrying a Phenylacetylene Unit.

A nitronyl nitroxide derivative, 2-phenylethynyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl-3-oxide (1), and two verdazyl derivatives carrying a phenylacetylene unit, 1,5-diphenyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (2) and 1,5-diisopropyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (3), were synthesized and their packing structures were studied by X-ray crystallographic analysis and magnetically characterized in the solid state. While 1 and 3 had an isolated doublet spin state, 2 formed an antiferromagnetically coupled pair (2J/kB = -118 K). Density functional theory (DFT) calculations reveal that the spin density polarized in the phenyl group decreases as the dihedral angle between the phenyl ring and radical plane increases.

Three-Component Reaction of Benzothiazole, Acetylenic Esters, Phenoles; Synthesis of Dialkyl 2-benzo[d]thiazol Derivatives Under Grinding.

AIM AND OBJECTIVE: Due to biological activity of a significant number of compounds containing benzothiazole ring system and in continuation of our interest in developing new environmentally benign methods for the synthesis of heterocyclic compounds by MCRs in this study we performed an efficient three-component from benzothiazole, acetylenic esters and hydroxyl aromatics compounds to synthesize of 2- benzothiazole derivatives in high yield. MATERIALS AND METHODS: IR spectra were recorded using an FTIR apparatus. Melting points measured on an Electrothermal 9100 apparatus. Spectra were obtained in solution of CDCl3 using TMS as internal standard. Elemental analyses were carried out using a Heracus CHN-O- Rapid analyzer. A mixture of benzothiazole, dimethyl acetylenedicarboxylate and phenol were placed in a mortar. The mixture was ground with a mortar and pestle at room temperature for 12 min. After completion of the reaction, as indicated by TLC (ethyl acetate: n-hexane, 1: 3), the solvent was distilled off under reduced pressure and the residue was crystallized from diethyl ether. RESULTS: Treatment of benzothiazole and dialkyl acetylenedicarboxylates in presence of resorcinol and ß-naphthol led to products 4 (dialkyl (E)-2-(2-(2-hydroxyphenyl)benzo[d]thiazol-3(2H)-yl-3- methylbut-2-enedioate), while we observed two isomer (Z) and (E) configurations (major and minor) in nearly 70:30 ratio when the reaction was repeated in presence of 8-hydroxy quinolone and DMAD. Also when we examined 2-nitro phenol, 4-nitrophenol, and 4-hydroxy quinoline, only one product 5 was obtained. This indicates that the reaction proceeds efficiently with electron-releasing substituted phenols. CONCLUSION: The reaction between benzothiazole and dialkyl acetylenedicarboxylates in the presence of some phenols without electron-withdraw substitution, presents a novel, one-pot, clean, convenient, simple and inexpensive approach into the synthesis of 2-benzothiazole derivatives of potential synthetic and pharmacologically interest. This procedure carries significant advantages because of the minimization of labor, time, and cost.

Temperature-Triggered Switchable Helix-Helix Inversion of Poly(phenylacetylene) Bearing l-Valine Ethyl Ester Pendants and Its Chiral Recognition Ability.

A phenylacetylene containing the l-valine ethyl ester pendant (PAA-Val) was synthesized and polymerized by an organorhodium catalyst (Rh(nbd)BPh4) to produce the corresponding one-handed helical cis-poly(phenylacetylene) (PPAA-Val). PPAA-Val showed a unique temperature-triggered switchable helix-sense in chloroform, while it was not observed in highly polar solvents, such as N,N'-dimethylformamide (DMF). By heating the solution of PPAA-Val in chloroform, the sign of the CD absorption became reversed, but recovered after cooling the solution to room temperature. Even after six cycles of the heating-cooling treatment, the helix sense of the PPAA-Val's backbone was still switchable without loss of the CD intensity. The PPAA-Val was then coated on silica gel particles to produce novel chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). These novel PPAA-Val based CSPs showed a high chiral recognition ability for racemic mandelonitrile (α = 2.18) and racemic trans-N,N'-diphenylcyclohexane-1,2-dicarboxamide (α = 2.60). Additionally, the one-handed helical cis-polyene backbone of PPAA-Val was irreversibly destroyed to afford PPAA-Val-H by heating in dimethyl sulfoxide (DMSO) accompanied by the complete disappearance of the Cotton effect. Although PPAA-Val-H had the same l-valine ethyl ester pendants as its cis-isomer PPAA-Val, it showed no chiral recognition. It was concluded that the one-handed helical cis-polyene backbone of PPAA-Val plays an important role in the chiral recognition ability.

Unprecedented Double aza-Michael Addition within a Sapphyrin Core.

A novel sapphyrin derivative was obtained from the reaction between a free-base sapphyrin and dimethyl acetylenedicarboxylate (DMAD). The formation of the new compound involved a double aza-Michael addition of two pyrrolic NH groups to a DMAD molecule, with the formation of a disubstituted ethano bridge. The NMR spectral data reveal a product with an unsymmetrical structure; DFT calculations provided support for a structure in which the ethano bridge links two adjacent pyrrole units. The present study provides a seemingly unprecedented example of an N,N'-dinucleophile reacting with DMAD to form a heterocyclic compound in which the two N-atoms are linked to the two sp(3) carbon atoms derived from a substituted acetylene.

Ultrasonic Synthesis, Molecular Structure and Mechanistic Study of 1,3-Dipolar Cycloaddition Reaction of 1-Alkynylpyridinium-3-olate and Acetylene Derivatives.

Regioselectively, ethyl propiolate reacted with 1-(propergyl)-pyridinium-3-olate to give two regioisomers; ethyl 4-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa-2,6-diene-6-carboxylate 4, ethyl 2-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa-3,6-diene-6-carboxylate 5 as well as ethyl 2,6-dihydro-6-(prop-2-ynyl)furo(2,3-c)pyridine-3-carboxylate 6. The obtained compounds were identified by their spectral (IR, mass and NMR) data. Moreover, DFT quantum chemical calculations were used to study the mechanism of the cycloaddition reaction. The regioselectivity was explained using transition state calculations, where the calculations agreed with the formation of products 4 and 5 in almost the same ratio. The reaction was also extended for diphenylaceylene as dipolarophile to give only two products instead of three.

Radiosynthesis and 'click' conjugation of ethynyl-4-[(18)F]fluorobenzene--an improved [(18)F]synthon for indirect radiolabeling.

Reproducible methods for [(18)F]radiolabeling of biological vectors are essential for the development of new [(18)F]radiopharmaceuticals. Molecules such as carbohydrates, peptides and proteins are challenging substrates that often require multi-step indirect radiolabeling methods. With the goal of developing more robust, time saving, and less expensive procedures for indirect [(18)F]radiolabeling of such molecules, our group has synthesized ethynyl-4-[(18)F]fluorobenzene ([(18)F]2, [(18)F]EYFB) in a single step (14 ± 2% non-decay corrected radiochemical yield (ndc RCY)) from a readily synthesized, shelf stable, inexpensive precursor. The alkyne-functionalized synthon [(18)F]2 was then conjugated to two azido-functionalized vector molecules via CuAAC reactions. The first 'proof of principle' conjugation of [(18)F]2 to 1-azido-1-deoxy-ß-D-glucopyranoside (3) gave the desired radiolabeled product [(18)F]4 in excellent radiochemical yield (76 ± 4% ndc RCY (11% overall)). As a second example, the conjugation of [(18)F]2 to matrix-metalloproteinase inhibitor (5), which has potential in tumor imaging, gave the radiolabeled product [(18)F]6 in very good radiochemical yield (56 ± 12% ndc RCY (8% overall)). Total preparation time for [(18)F]4 and [(18)F]6 including [(18)F]F(-) drying, two-step reaction (nucleophilic substitution and CuAAC conjugation), two HPLC purifications, and two solid phase extractions did not exceed 70 min. The radiochemical purity of synthon [(18)F]2 and the conjugated products, [(18)F]4 and [(18)F]6, were all greater than 98%. The specific activities of [(18)F]2 and [(18)F]6 were low, 5.97 and 0.17 MBq nmol(-1), respectively.

Dithiafulvenyl-substituted phenylacetylene derivatives: synthesis and structure-property-reactivity relationships.

A series of regioisomers for dithiafulvenyl-substituted phenylacetylene derivatives was synthesized and characterized to show structure-dependent electronic properties and different reactivities in their oxidized states.

Identification of dialkyl diacetylene diols with potent cancer chemopreventive activity.

An increasing importance of chemoprevention for controlling cancer risks prompted the discovery of new active cancer chemopreventive agents. In this study, we designed and synthesized substituted hexa-2,4-diyne-1,6-diols, more structurally simplified, tunable, and easily preparable than natural gymnasterkoreaynes, and evaluated their cancer chemopreventive activities by measuring concentration of doubling quinone reductase activity (CD), cell viability, and chemopreventive index (CI). Most of the diols exhibited good CD activity and low cytotoxicity. In particular, tetradeca-5,7-diyne-4,9-diol and 2-methyltetradeca-5,7-diyne-4,9-diol showed the best cancer chemopreventive activity, approximately equipotent to that of sulforaphane. And, by synthesizing optically active stereoisomers of selected active compounds, the effect of stereochemistry was also studied. Eventually, we produced a chemopreventive compound for in vivo study.

Real-time monitoring of the mitophagy process by a photostable fluorescent mitochondrion-specific bioprobe with AIE characteristics.

An isothiocyanate-functionalized tetraphenylethene is synthesized and used as a fluorescent bioprobe for mitochondrion imaging with high specificity and photostability. The covalent conjugation of the bioprobe to mitochondrial proteins endows it with high resistance to microenvironmental changes, enabling it for real-time monitoring of mitophagy.

Synthesis and photoelectric properties of new Dawson-type polyoxometalate-based dimeric and oligomeric Pt(II)-acetylide inorganic-organic hybrids.

A new synthesis route for preparing Dawson-type polyoxometalate (POM) based inorganic-organic hybrid materials is presented. Two new heteropolytungstate-based dimeric and oligomeric Pt(II) acetylide inorganic-organic hybrid compounds (2PtOD and PPtOD) were prepared by Hagihara's dehydrohalogenating coupling of a terminal diacetylene POM hybrid containing diphosphoryl functionality and an appropriate platinum(II) halide precursor. This method provides a rigid covalent linkage between the POM and the organometallic Pt(II) acetylide moiety. The redox potential of the polyanion can be tuned by grafting the organic and organometallic groups on it. The photoelectric properties of hybrid LB films derived from these inorganic-organic composites were studied.

Redox-dependent conformational switching of diphenylacetylenes.

Herein we describe the design and synthesis of a redox-dependent single-molecule switch. Appending a ferrocene unit to a diphenylacetylene scaffold gives a redox-sensitive handle, which undergoes reversible one-electron oxidation, as demonstrated by cyclic voltammetry analysis. (1)H-NMR spectroscopy of the partially oxidized switch and control compounds suggests that oxidation to the ferrocenium cation induces a change in hydrogen bonding interactions that results in a conformational switch.

Four new two-photon polymerization initiators with varying donor and conjugated bridge: synthesis and two-photon activity.

A specific series of dumbbell-shaped bis-carbazoles or bis-phenothiazines dyes (1, 2, 3 and 4) constructed with styrene or biphenylethyne as the π-bridge have been synthesized and characterized. Detailed spectral properties including linear absorption, one and two-photon fluorescence properties were investigated. The results show that extending conjugated chain and introducing donors have substantial effect on their photophysical properties. Among them, two-photon absorption cross sections (σ) of the four dyes in DMF determined by the Z-scan technique are successively increased from 1 to 4 with enhancing electron-donating ability and extending conjugated chain, but electron-donating ability has larger contribution to the σ values than extending conjugated chain based on the comparison of small molecules (D-π-D). Two-photon initiation polymerization (TPIP) microfabrication experiments have been carried out using compound 4 as an initiator under irradiation of 200 fs, 76 MHz femtosecond laser at 760 nm. The results confirm that the four dyes can be effectively used as organic two-photon photopolymerization initiators.

Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): discovery of 5-((3-fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide (ML254).

Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) represent a promising therapeutic strategy for the treatment of schizophrenia. Both allosteric agonism and high glutamate fold-shift have been implicated in the neurotoxic profile of some mGlu5 PAMs; however, these hypotheses remain to be adequately addressed. To develop tool compounds to probe these hypotheses, the structure-activity relationship of allosteric agonism was examined within an acetylenic series of mGlu5 PAMs exhibiting allosteric agonism in addition to positive allosteric modulation (ago-PAMs). PAM 38t, a low glutamate fold-shift allosteric ligand (maximum fold-shift ~ 3.0), was selected as a potent PAM with no agonism in the in vitro system used for compound characterization and in two native electrophysiological systems using rat hippocampal slices. PAM 38t (ML254) will be useful to probe the relative contribution of cooperativity and allosteric agonism to the adverse effect liability and neurotoxicity associated with this class of mGlu5 PAMs.

Exploring the potential of diarylacetylenediols as hydrogen bonding catalysts.

In the course of a search for new classes of hydrogen bonding catalysts, we have examined diarylacetylenediols as potential catalysts for the Diels-Alder reaction. General and efficient methods have been developed for the preparation of these diols. Their structures were systematically modified, and increased activity was observed for those possessing an electron-withdrawing group on the aryl groups. The electron-deficient diarylacetylenediol catalysts, while more active, undergo spontaneous cyclization to the corresponding benzo[b]furans. A mechanism is postulated to explain this facile transformation. Computational studies performed on 2-ethynylphenol help to explain the effect of the alkyne on the conformation and hydrogen bond donating ability of the adjacent OH group. Finally, the crystal structure of one of the diols is reported, and it displays an intricate network of intermolecular hydrogen bonds.

Novel planar and star-shaped molecules: synthesis, electrochemical and photophysical properties.

Three novel planar and star-shaped molecules containing thiophene-functionalized group and acetylenic spacers, 4-((5″-iodo-[2,2':5',2″-terthiophen]-5-yl)ethynyl)aniline (I3TEA), 4,4'-([2,2':5',2″-terthiophene]-5,5″-diylbis(ethyne-2,1-diyl))dianiline (3TDDA), 1,3,5-tris((5-((trimethylsilyl)ethynyl)thiophen-2-yl)ethynyl)benzene (TETEB) were synthesized through Sonogashira coupling reaction. Their photophysical and electrochemical properties were explored by UV-vis, photoluminescence (PL) emission and DFT calculation. Three compounds possess unusual phenomena of PL, with the concentration of gradually decreased, the intensity of PL firstly increased and then decreased, this may be due to the aggregate-enhanced emission (AEE) effect and aggregation-caused quenching (ACQ) effect. Their spectroscopic data demonstrate that D-π-A-π-D structured organic dye 3TDDA based on NH2 as donor units and 3T as acceptor units with acetylenic spacers π-conjugated chain between them exhibits good luminescent properties. Dye I3TEA with donor(D)-acceptor(A) structure shows good charge transfer because of amino functional group and iodine atom. Octupolar organic π-conjugated star-shaped molecule TETEB possesses excellent luminescent properties because of its unique structure applied in the optoelectronic field. The redox curves and results of DFT calculations suggest that three compounds have low ionization potential and low Eoxd. All the good properties demonstrate three compounds could be promising candidates for photovoltaic materials.

Topochemical polymerization of phenylacetylene macrocycles: a new strategy for the preparation of organic nanorods.

Soluble organic nanorods were prepared from phenylacetylene macrocycles using the topochemical polymerization of butadiyne moieties placed both inside and outside the macrocycles' skeletons. Macrocycles containing amide groups were self-assembled in a columnar fashion through the formation of an organogel in ethyl acetate. Upon irradiation with UV light, the Raman signals associated with butadiyne units completely vanished, indicating the creation of covalently linked nanorods.