Ethynyl Spacer Research Articles

2-Substituted (N)-Methanocarba A3 Adenosine Receptor Agonists: In Silico, In Vitro, and In Vivo Characterization.

2-Arylethynyl (N)-methanocarba adenosine 5'-methylamides are selective A3 adenosine receptor (AR) agonists containing a preestablished receptor-preferred pseudoribose conformation. Here, we compare analogues having bulky 2-substitution, either containing or lacking an ethynyl spacer between adenine and a cyclic group. 2-Aryl compounds 9-11, 13, 14, 19, 22, 23, 27, 29, 31, and 34, lacking a spacer, had human (h) A3AR K i values of 2-30 nM, and others displayed lower affinity. Mouse (m) A3AR affinity varied, with 2-arylethynyl having a higher affinity than 2-aryl analogues (7, 8 > 3c, 3d > 3b). However, 2-aryl-4'-truncated derivatives had greatly reduced hA3AR affinity, even containing affinity-enhancing N 6-dopamine-derived substituents. Molecular modeling, including molecular dynamics simulation, predicted stable poses in the canonical A3AR agonist binding site, but 2-aryl (ECL2 interactions) and 2-arylethynyl (TM2 interactions) substituents have different conformations and environments. In a hA3AR miniGαi recruitment assay, 31 (MRS8062) was (slightly) more potent compared to a β-arrestin2 recruitment assay, both in engineered HEK293T cells, and its maximal efficacy (E max) was much higher (165%) than reference agonist NECA's. Thus, in the 2-aryl series, A3AR affinity and selectivity were variable and generally reduced compared to the 2-arylethynyl series, with a greater dependence on the specific aryl group present. Selected compounds were studied in vivo in an ischemic model of peripheral artery disease (PAD). Rigidified 2-arylethynyl analogues 3a-3c were protective in this model of skeletal muscle ischemia-reperfusion injury/claudication, as previously shown only for moderately A3AR-selective ribosides or (N)-methanocarba derivatives. Thus, we have expanded the A3AR agonist SAR for (N)-methanocarba adenosines.

Effects of Connectivity Isomerization on Electron Transport Through Thiophene Heterocyclic Molecular Junction.

Connectivity isomerization of the same aromatic molecular core with different substitution positions profoundly affects electron transport pathways and single-molecule conductance. Herein, we designed and synthesized all connectivity isomers of a thiophene (TP) aromatic ring substituted by two dihydrobenzo[b]thiophene (BT) groups with ethynyl spacers (m,n-TP-BT, (m,n = 2,3; 2,4; 2,5; 3,4)), to systematically probe how connectivity contributes to single-molecule conductance. Single-molecule conductance measurements using a scanning tunneling microscopy break junction (STM-BJ) technique show ∼12-fold change in conductance values, which follow an order of 10-4.83 G0 (2,4-TP-BT) < 10-4.78 G0 (3,4-TP-BT) < 10-4.06 G0 (2,3-TP-BT) < 10-3.75 G0 (2,5-TP-BT). Electronic structure analysis and theoretical simulations show that the connectivity isomerization significantly changes electron delocalization and HOMO-LUMO energy gaps. Moreover, the connectivity-dependent molecular structures lead to different quantum interference (QI) effects in electron transport, e.g., a strong destructive QI near E = EF leads the smallest conductance value for 2,4-TP-BT. This work proves a clear relationship between the connectivity isomerization and single-molecule conductance of thiophene heterocyclic molecular junctions for the future design of molecular devices.

Direction Switching and Self-Recovering Mechanochromic Luminescence of Anthracene-Modified o-Carboranes.

Luminochromic behaviors regarding mechanochromic luminescence (MCL) of o-carborane-modified anthracene derivatives are reported. We have previously synthesized bis-o-carborane-substituted anthracene and found that its crystal polymorphs show dual-emission properties composed of excimer and charge transfer (CT) emission bands in the solid state. Initially, we observed the bathochromic MCL behavior from 1 a originating from emission mechanism alteration from dual emission to CT emission. By inserting the ethynylene spacers between anthracene and o-carboranes, compound 2 was obtained. Interestingly, 2 showed hypsochromic MCL originating from the emission mechanism alteration from CT to excimer emission. Furthermore, luminescent color of ground 1 a can be recovered to the initial state by allowing to stand at room temperature, meaning that self-recovery proceeds. Detailed analyses are described in this study.

Cell Uptake of Steroid-BODIPY Conjugates and Their Internalization Mechanisms: Cancer Theranostic Dyes.

Estradiol-BODIPY linked via an 8-carbon spacer chain and 19-nortestosterone- and testosterone-BODIPY linked via an ethynyl spacer group were evaluated for cell uptake in the breast cancer cell lines MCF-7 and MDA-MB-231 and prostate cancer cell lines PC-3 and LNCaP, as well as in normal dermal fibroblasts, using fluorescence microscopy. The highest level of internalization was observed with 11β-OMe-estradiol-BODIPY 2 and 7α-Me-19-nortestosterone-BODIPY 4 towards cells expressing their specific receptors. Blocking experiments showed changes in non-specific cell uptake in the cancer and normal cells, which likely reflect differences in the lipophilicity of the conjugates. The internalization of the conjugates was shown to be an energy-dependent process that is likely mediated by clathrin- and caveolae-endocytosis. Studies using 2D co-cultures of cancer cells and normal fibroblasts showed that the conjugates are more selective towards cancer cells. Cell viability assays showed that the conjugates are non-toxic for cancer and/or normal cells. Visible light irradiation of cells incubated with estradiol-BODIPYs 1 and 2 and 7α-Me-19-nortestosterone-BODIPY 4 induced cell death, suggesting their potential for use as PDT agents.

Controlling AIE and ACQ properties of conjugated carbazole-tetraphenylethene copolymers by ethynylene spacer

Aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) are controlled by ethynylene spacers between the carbazole and tetraphenylethene. AIE polymers are applied to polymer dots with good emission and water dispersion stability.

Synthesis, photophysical properties, anti-Kasha photochemical reactivity and biological activity of vinyl- and alkynyl-BODIPY derivatives

New photoactivable BODIPY fluorescent dyes, which are quinone methide (QM) precursors, were synthesized. The series of BODIPY dyes has a photoreactive group linked to the BODIPY core by vinyl or ethynyl spacers. Molecules have bathochromic shifted absorption and emission maxima and higher fluorescence quantum yields compared to the previously reported BODIPY QM precursors. They show anti-Kasha photochemical reactivity and undergo photomethanolysis reaction upon photoexcitation at λ < 350 nm. Although UV light is needed for the photochemical generation of QMs and attachment to potential bio-targets, bathochromic shifted absorption and emission has advances in sensing and fluorescence labeling. Antiproliferative investigation was conducted for the vinyl derivative against three human cancer lines with the cells kept in dark or irradiated. Upon excitation with visible light antiproliferative activity was enhanced with IC50 values in low micromolar concentration.

Impact of ethynylene linkers on the optical and electrochemical properties of benzothiadiazole based alternate conjugated polymers

The effect of ethynylene spacers on the bandgap of alternating polymers, comprising 4,7-linked benzothiadiazole units and 2,7-linked fluorene, 2,7-linked carbazole or 2,6-linked anthracene repeat units has been investigated. The three novel polymers PFDEBT , PCDEBT and PPADEBT were prepared via the Sonogashira coupling reaction. The optical, electrochemical and thermal properties of the resulting polymers were compared and analysed. All polymers displayed low solubility in common organic solvents and have moderate molecular weights. Optical studies revealed that all the new ethynylene based-polymers displayed large bandgaps in excess of 2.1 eV. Results highlighted that incorporation of acetylene units between the benzothiadiazole electron accepting units and the other electron donor units over polymer chains leads to wide bandgaps as a result of the electron accepting properties of the acetylene units. The HOMO levels of the resulting polymers are unaffected by the different donor moieties used. However, varying the electron donor units can perturb the electron accepting ability of the main chain of polymers in this series and their LUMO levels. Anthracene-based polymer ( PPADEBT ) displayed the lowest LUMO level, while the fluorene-based polymer ( PFDEBT ) displayed the highest LUMO level. All polymers showed good stability to thermal degradation. The amorphous nature of these polymers was confirmed with powder X-ray diffraction studies.

Contrasting Photochromic and Acidochromic Behaviors of Pyridyl- and Pyrimidylethynylated Mono- and Bis-Benzopyrans.

Investigation of photochromic and acidochromic behaviors of a set of pyridyl- and pyrimidylethynylated mono- and bis-benzopyrans reveals an intriguing influence of the N-heteroaryl ring on spectrokinetic properties of the photogenerated o-quinonoid colored reactive intermediates. While the absorption maxima of the pyridylethynylated bis-benzopyran and its photogenerated o-quinonoid colored species undergo bathochromic shifts by ca. 40 and 22 nm, respectively, in the presence of an acid (e.g., trifluoroacetic acid (TFA)), the same remain unaffected for the analogous pyrimidylethynylated bis-benzopyran and its photogenerated o-quinonoid colored species under similar conditions. Modification of the photochromic behavior of these benzopyrans and, hence, spectrokinetic properties of their photogenerated o-quinonoid species in the presence of H+ is a consequence of relative proton affinities of N-heteroaryl rings, i.e., pyridyl/pyrimidyl, and the resonance effects relayed through the ethynyl spacers in a push–pull π-delocalized-type skeleton; the mesomeric effects operate in a contrasting manner depending on the N-heteroaryl ring in the absence and in the presence of an acid. These molecular systems offer a unique opportunity to modulate both photochromic and acidochromic properties of benzopyrans and their photogenerated colored o-quinonoid intermediates by leveraging N-heteroaromatic rings.

Silicon‐Bridged Bi‐ and Tridentate Lewis Acidic Host Systems

AbstractConnecting multiple organic spacer functions via silicon core units leads to various organosilanes that are excellently suited as backbones for poly‐Lewis acids (PLAs). Using ethynyl spacer groups, rigid bis‐ and tris‐dioxabenzoborole (BCat)‐substituted PLAs were prepared. The fixed orientation of the Lewis acidic functions of the PLAs is reflected in their solid‐state structures. Further flexible PLAs were obtained by hydroboration of vinylsilanes using 9‐borabicyclo[3.3.1]nonane (9‐BBN), which shows the flexibility of the backbone motif. Host‐guest experiments of the bidentate representatives with pyridine demonstrate the ability of both PLA‐types (BCat or 9‐BBN) for complexing neutral guest molecules. The rigid host system shows additionally a 1 : 1 adduct formation using a bridged diamine as guest compound.

A novel BODIPY-based fluorescent probe for sensitive and selective detection of nerve agent simulants through base-assisted photo-induced electron transfer process

• A novel BODIPY-based molecular fluorescent probe was designed and synthesized. • The probe exhibited excellent selectivity and sensitivity toward nerve agent simulants. • Detection mechanism of base-assisted tunable PET process was clearly discussed. • In situ monitoring of DCNP in liquid and gas phase was realized by strips immobilized with probe. A fluorescent BODIPY probe (SO-BOD) conjugated with a 2-salicylaldoxime group via an ethynyl spacer was designed and synthesized for highly sensitive and selective detection of DCNP (a simulant of Tabun). The probe exhibited significant fluorescent quenching in the presence of Et 3 N, and 30-fold fluorescence enhancement was achieved in the presence of DCNP. Integration of experimental and computational methods well illustrated that these fluorescence variations were attributed to the intramolecular photo-induced electron transfer (PET) process. Except for the low limit of detection (34 nM) to DCNP, SO-BOD also showed a rapid response (t 1/2 = 175 s) and high selectivity. Furthermore, naked-eye detection of DCNP was carried out in both the liquid and vapor phases by test strips immobilized with the probe.

Tuning of spin-polarized current in high spin organic molecules

Organic magnetic molecules are potential candidates to act as spin filters owing to the spin degeneracy caused by unpaired electron. Based on density functional theory in combination with non-equilibrium Green’s function (NEGF-DFT) method, we study the spin-filtering capability employing the much cultivated and stable organic radicals nitronyl nitroxide (NN) and oxo-verdazyl (OVER). The spin-resolved electronic transportations across the organic radicals connected to the framework of pentacene is investigated by bridging the radical–pentacene moiety between gold electrodes. Unexpectedly, both the stable radicals do not act as efficient spin filters due to the orthogonal arrangement of radical moiety w.r.t pentacene core. On the other hand, the planar arrangement of the radical attached to the pentacene via ethynyl spacer enhances the spin polarization due to much larger delocalization of spin density on pentacene core. Further, the introduction of methyl radical provides an alternative way to use such stable radicals for efficient spin filtering.

Synthesis of dipolar molecular rotors as linkers for metal-organic frameworks.

We report the synthesis of five dicarboxylic acid-substituted dipolar molecular rotors for the use as linker molecules in metal-organic frameworks (MOFs). The rotor molecules exhibit very low rotational barriers and decent to very high permanent, charge free dipole moments, as shown by density functional theory calculations on the isolated molecules. Four rotors are fluorescent in the visible region. The linker designs are based on push–pull-substituted phenylene cores with ethynyl spacers as rotational axes, functionalized with carboxylic acid groups for implementation in MOFs. The substituents at the phenylene core are chosen to be small to leave rotational freedom in solids with confined free volumes. The dipole moments are generated by electron-donating substituents (benzo-1,3-dioxole, benzo-1,4-dioxane, or benzo-2,1,3-thiadiazole annelation) and withdrawing substituents (difluoro, or dicyano substitution) at the opposite positions of the central phenylene core. A combination of 1,4-dioxane annelation and dicyano substitution generates a theoretically predicted, very high dipole moment of 10.1 Debye. Moreover, the molecules are sufficiently small to fit into cavities of 10 Å3. Hence, the dipolar rotors should be ideally suited as linkers in MOFs with potential applications as ferroelectric materials and for optical signal processing.

Improvement of Solid‐State Excimer Emission of the Aryl–Ethynyl‐o‐Carborane Skeleton by Acridine Introduction

We report highly‐efficient and solid‐state excimer emission based on the acridine–o‐carborane dyad possessing the ethynyl spacer. The previous pyrene‐modified o‐carborane showed excimer emission only at 77 K in the crystalline state, meanwhile, the current acridine‐modified molecule presented excimer emission with high efficiency (ΦPL = 0.23) in the crystalline state at room temperature. From single‐crystal X‐ray crystallography, it was indicated that two acridine moieties were stacked and the third acridine molecule was out of alignment. Such a packing mode could restrict exciton splitting over the columnar packing structure. Moreover, molecular interactions through the nitrogen atom in the acridine moiety and the hydrogen atom in the o‐carborane unit contribute to suppression of molecular motions. As a consequence, an improved emission efficiency was obtained. This study demonstrates that the ethynyl–o‐carborane skeleton should work as the excimer‐inducible component in the solid state.

Synthesis of Aroylbenzoate‐Based Push‐Pull Molecules for OFET Applications

AbstractSolution‐processable organic semiconductors have attracted great attention in recent years, because of their performance and reliability in potential applications. Here, we report the solution processable donor‐acceptor (D−A) conjugated molecules comprised of aroylbenzoate as acceptor, triarylamine or methoxyphenyl groups as donor and ethynyl spacer. Molecules with triarylamine donor exhibited strong absorption at 350–380 nm. HOMO levels around 5.5 eV ensures low barrier for hole injection. Optimized geometry and charge distribution over the molecules are visualized by density functional theory (DFT). Organic field effect transistors of these molecules are fabricated with bottom gate‐top contact configuration. The devices exhibited charge carrier mobility up to 2.16 × 10−3 cm2 V–1 s–1 and ON/OFF of 104 with low threshold voltage of −3.2 V.

New meso-tetrafluorenylethynyl porphyrin platform

To improve conjugation between a central porphyrin core and its peripheral fluorenyl antennae, we have introduced in the meso-tetrafluorenyl porphyrin (TFP-Bu) unit an ethynyl spacer at the meso positions. By this means, we have synthesized and characterized a new meso-alkynyl fluorenyl porphyrin (TAFlP). We discuss the effect of this extra extension of the [Formula: see text] manifold on the optical properties. This enlarged porphyrin core, TAFlP, is foreseen as a key building block for the design of new dendrimers for theranostic applications. The constant improvement of porphyrin-based dendrimers featuring conjugated fluorenyl dendrons is recalled herein and demonstrates the important role of the central core structure in determining linear and nonlinear optical properties. Further improvement of these properties seems possible with TAFlP-like structures based on observations made for dendrimers recently obtained. This makes the exploration of such new molecular architectures appealing for photodynamic therapy (PDT) and related applications.

Design of liquid crystals with ‘de Vries-like’ properties: the effect of an ethynyl spacer in the core structure

ABSTRACTWe investigate the origins of ‘de Vries-like’ liquid crystalline behaviour by introducing an ethynyl spacer in the core of the tricarbosilane-terminated 5-phenylpyrimidine mesogens QL16-6 and QL17-6. The rationale for this structural change is based on the assumption that an ethynyl spacer would create more free volume in the core sub-layer and therefore decrease the orientational order parameter S2 in the SmA phase. The tricarbosilane-terminated mesogens WL41-5 and WL42-6 with a 5-(phenylethynyl)pyrimidine core in either a normal or inverted orientation were synthesised, and their mesomorphic and ‘de Vries-like’ properties characterised using polarised optical microscopy, differential scanning calorimetry, birefringence measurements, small–angle (SAXS) and 2D X-ray scattering. Reduction factors R derived from SAXS and optical tilt angle measurements suggest that neither WL41-5 (R = 0.49) nor WL42-6 (R = 0.80) exhibit ‘de Vries-like’ properties. The S2(T) profiles show an increase in orientational order with decreasing temperature and a sharp discontinuity at the SmA-SmC transition, which is consistent with ‘de Vries-like’ behaviour. However, the Leff(T) profiles suggest an increase in interdigitation that reduces the positive effect of increasing S2 in compensating for the molecular tilt.

A Smart Sensing Method for Object Identification Using Circularly Polarized Luminescence from Coordination-Driven Self-Assembly.

The potential use of circularly polarized luminescence for object identification in a sensor application is demonstrated. New luminescence probes using pyrene derivatives as sensor luminophores were developed. (R,R)-Im2 Py and (S,S)-Im2 Py contain two chiral imidazole moieties at 1,6-positions through ethynyl spacers (angle between spacers ca. 180°). The probe molecules spontaneously self-assemble into chiral stacks (P or M helicity) upon coordination to metal ions with tetrahedral coordination (Zn2+ ). The chiral probes display neither circular dichroism (CD) nor circularly polarized luminescence (CPL) without metal ions. However, (R,R)-Im2 Py and (S,S)-Im2 Py exhibit intense chiroptical activity (CD and CPL) upon self-assembly with Zn2+ ions. (R,R)-Im2 Py and (S,S)-Im2 Py with chemical stimuli-responsibility allow sensing using the CPL signal as detection output, enabling us to discriminate between a signal from the target analyte and that from non-target species.

A combined experimental and computational investigation on pyrene based D-π-A dyes.

The geometry (twist vs. planar) of a dye is one of the most pivotal factors for determining intramolecular charge transfer (ICT), light harvesting and photovoltaic properties of dye-sensitized solar cells. In order to comprehend the role of dye geometry on the above properties, we have devised the pyrene based D-π-A dyes namely 2-cyano-3-(5-pyren-1-yl-furan-2-yl)-acrylic acid (PFCC) and 2-cyano-3-(5-pyren-1-ylethynyl-furan-2-yl)-acrylic acid (PEFCC). The synthesized pyrene dyes were well characterized by NMR and EI-MS spectrometry. In both the dyes, the donor (pyrene) and acceptor (cyanoacrylic acid) segments remained the same. The varied π-spacers were furan and ethynyl furan. The influences of the ethynyl spacer on the energy levels, light absorption, dynamics of excited states and photovoltaic properties of the DSCs were systematically investigated via theoretical calculations and spectroscopic measurements. UV-visible absorption spectral measurements indicated that the introduction of the ethynyl spacer enhances the molar absorptivity of a dye (PEFCC) in the order of 2, but does not shift the absorption range, which is consistent with the results obtained from density functional theory (DFT) calculations. The theoretical analysis indicated that the charge transfer transition is mainly constituted of the HOMO to the LUMO that were found to be located on donor and acceptor segments, respectively, which is supportive for efficient charge separation and electron injection processes. TDDFT calculations highlighted that the LUMO of the PEFCC dye is more stabilized by the incorporation of the ethynyl group between the pyrene and furan moieties that aid to inject electrons efficiently into TiO2 thereby resulting in an enhanced power conversion efficiency of 2.47% when compared to the PFCC dye. Notably, the overall conversion efficiency of the PEFCC dye reached 60% with respect to that of an N719-based device (4.12%) fabricated under similar conditions. Transient absorption kinetic studies demonstrated that a slower charge recombination rate is an essential factor behind enhanced efficiencies in PEFCC based cells.

Front Cover: Solid‐State Thermochromic Luminescence through Twisted Intramolecular Charge Transfer and Excimer Formation of a Carborane−Pyrene Dyad with an Ethynyl Spacer (Asian J. Org. Chem. 12/2017)

Front Cover: Solid‐State Thermochromic Luminescence through Twisted Intramolecular Charge Transfer and Excimer Formation of a Carborane−Pyrene Dyad with an Ethynyl Spacer (Asian J. Org. Chem. 12/2017)

Solid‐State Thermochromic Luminescence through Twisted Intramolecular Charge Transfer and Excimer Formation of a Carborane−Pyrene Dyad with an Ethynyl Spacer

AbstractThe pyrene‐tethered carborane CBEP, which exhibited rapid and dramatic luminochromism, was synthesized. Based on optical measurements, we found that CBEP exhibited orange emission at room temperature, which was caused by intramolecular charge transfer in the solid state, and green excimer emission at 77 K. We proposed that excimer formation could be encouraged by introducing a small amount of steric hindrance with an ethynyl spacer group. We found that o‐carborane could suppress aggregation‐caused quenching without the inhibition of excimer formation because of this steric hindrance.