Synthesis of soluble bis-terpyridine ligands bearing ethynylene-phenylene spacers

Soluble and rigid terpyridine-based ditopic ligands bearing one to five phenylene/ethynylene modules have been synthesized by way of a stepwise procedure. Each module is attached to the terpyridine unit via an ethynylene fragment and functionalized at the 4-position with an additional ethynylene connector and in the 2,5-positions with two flexible dodecyloxy chains. The synthetic protocol is based on sequential Pd(0)-catalyzed cross-coupling reactions between a terpyridine subunit grafted with the necessary diethynyl/phenyl or ethynylphenyl/bromide appendage. For ditopic ligands displaying an even number of phenyl/ethynylene modules, the final step involves a single cross-coupling reaction between 4'-ethynylene-2,2':6',6' '-terpyridine and the appropriate bromo derivative. In the case of the ligands having an odd number of phenylene/ethynylene fragments, a double cross-coupling reaction between an extended dibromopolyphenylene intermediate and 4'-ethynylene-2,2':6',6' '-terpyridine or 1-(4'-ethynylene-2,2':6',2' '-terpyridine)-4-ethynylene-2,5-didodecyloxy-benzene is required. For ligands I-V, optimal preparative conditions were found with [Pd(0)(PPh(3))(4)] (6 mol %) in n-propylamine at 70 degrees C. Oxidative dimerization of the 1-(4'-ethynylene-2,2':6',2' '-terpyridine)-4-ethynylene-2,5-didodecyloxybenzene derivative in the presence of cupric salts and oxygen gives the corresponding homoditopic ligand II(2)() bearing a central diphenyldiacetylene spacer. Spectroscopic data for the new oligomers are discussed in terms of the extent of pi-electron conjugation. Upon increasing the number of phenylene/ethynylene modules, there is a progressive lowering in energy of absorption and fluorescence transitions.     

Mononuclear and binuclear wirelike ruthenium(II) complexes with oligo-diethynyl-thiophene bridged back-to-back terpyridine ligands: synthesis and electrochemical and photophysical properties

The syntheses, structural features, electrochemical behavior, absorption spectra, and photophysical properties of five mononuclear complexes [(terpy)Ru(terpy-DEDBT(n)-terpy)](2+), RuT(n), and five binuclear complexes [(terpy)Ru(terpy-DEDBT(n)-terpy)Ru(terpy)](4+), RuT(n)Ru, are reported, where n varies from 1 to 5 so that the metal-metal distance is estimated to be 42 A for the largest binuclear complex, RuT(5)Ru (terpy is 2,2':6',2"-terpyridine and DEDBT is 2,5-diethynyl-3,4-dibutylthiophene). The metal-centered oxidation potentials for the mononuclear and binuclear species are slightly more positive than for the reference [Ru(terpy)(2)](2+) complex, owing to the withdrawing nature of the back-to-back terpyridine ligands incorporating the repeat diethynyl-thiophene units. Comparison of the reduction potentials for the mononuclear and binuclear complexes reveals that the reduction steps are localized either at the terpy fragments of the T(n) ligands or at the terpy peripheral ligands. The spectroscopic results (absorption spectra at room temperature, luminescence spectra and lifetimes at room temperature and at 77 K) in acetonitrile solvent are consistent with the establishment of electronic delocalization within the oligomeric diethynyl-thiophene fragments (DEDBT(n)) of the T(n) ligands; however, the results also indicate that the terpy units of these ligands and the DEDBT(n)fragments are not strongly coupled. Both at room temperature and at 77 K, the (3)metal-to-ligand charge-transfer luminescence of RuT(n) and RuT(n)Ru complexes is strongly depressed in the larger species with respect to what happens for n < or = 2 (where the luminescence quantum yield is phi approximately 10(-4)); this is discussed in terms of the possible intervention of triplet levels localized at the oligothiophene DEDBT(n)(fragments.     

A convenient protocol for the synthesis of ligands from a 4-methyl-3,5-diacylaminophenyl platform

The synthesis of stable and highly organized phenanthroline, terpyridine, and pyridino-oxazoline ligands bearing one or two 4-methyl-3,5-diacylaminophenyl modules equipped with two lateral dialkoxyphenyl groups has been performed using EDC.HCl and DMAP reagents in the final coupling reaction. Evidently, in the final ligands and in the solid state intermolecular hydrogen bonding maintains the coherence of the tridimensional structure as clearly evidenced by FT-IR and X-ray diffraction spectroscopy in the cases of the methoxy ligands. The supramolecular packing is also maintained by additional pi-pi stacking interactions.     

Synthesis of bipyridine and terpyridine based ruthenium metallosynthons for grafting of multiple pyrene auxiliaries

The synthesis of novel ruthenium(II) bipyridine or terpyridine complexes bearing an increasing number of pyrene or toluyl moieties is described. The ruthenium complexes are constructed in a first step with ligands bearing the required bromine functions, followed in a second step by stepwise grafting of 1-ethynylpyrene or 4-ethynyltoluene promoted by Pd(0). A complex bearing a protected triethylsilylacetylene function was also prepared. In situ deprotection of this function with K₂CO₃ and cross-coupling with 1-bromopyrene afforded a soluble complex in which two pyrene moieties are linearly linked via ethynyl spacers to one of the bipyridine ligands. These highly coloured complexes exhibit well defined absorption and emission properties in solution at both rt and 77 K.     

The Structural Basis for Optimal Performance of Oligothiophene‐Based Fluorescent Amyloid Ligands: Conformational Flexibility is Essential for Spectral Assignment of a Diversity of Protein Aggregates

Protein misfolding diseases are characterized by deposition of protein aggregates, and optical ligands for molecular characterization of these disease‐associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease‐associated protein aggregates than conventional ligands, such as thioflavin T and Congo red. Herein, the molecular requirements for achieving LCOs able to detect nonthioflavinophilic Aβ aggregates or non‐congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by: 1) replacing thiophene units with selenophene or phenylene moieties, or 2) alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene‐based optical ligands for sensitive detection and spectral assignment of disease‐associated protein aggregates.     

Photophysical properties of ruthenium(II) tris(2,2'-bipyridine) complexes bearing conjugated thiophene appendages

A small series of ruthenium(II) tris(2,2'-bipyridine) complexes has been synthesized in which ethynylated thiophene residues are attached to one of the 2,2'-bipyridine ligands. The photophysical properties depend on the conjugation length of the thiophene-based ligand, and in each case, dual emission is observed. The two emitting states reside in thermal equilibrium at ambient temperature and can be resolved by emission spectral curve-fitting routines. This allows the properties of the two states to be evaluated in both fluid butyronitrile solution and a transparent KBr disk. It is concluded that both emitting states are of metal-to-ligand charge-transfer (MLCT) character, and despite the presence of conjugated thiophene residues, there is no indication for a low-lying pi,pi*-triplet state that promotes nonradiative decay of the excited-state manifold. A key feature of these systems is that the conjugation length imposed by the thiophene-based ligand helps to control the rate constants for both radiative and nonradiative decay from the two MLCT triplet states.     

A convenient method of producing thiophene linked bipyridine oligomers

A series of soluble polybipyridine ligands comprising one to five bipyridine modules sandwiched between rigid carbon-carbon triple bonds substituted by 3,4-dibutylthiophene repeating units was synthesized. Two different protocols have been explored with the idea to use a divergent/convergent approach starting from bisymmetrically and symmetrically substituted bipyridine modules. At each stage of the iteration two bipy/thiophene modules are connected. The use of triethylsilylacetylene and 2-methylbut-3-yn-2-ol insures an easy entry to pivotal building blocks, which could be selectively deprotected from the TES or 2-hydroxyprop-2-yl sites. All cross-coupling reactions are promoted with palladium(0) tetrakistriphenylphosphine under mild conditions.     

Hexacoordinated MIV (M=Ti,Zr, Hf) Tetrachlorido Complexes with Chelating Dithienylethane Based 1,2 Diketone Ligand – π-Conjugation as Decisive Factor for Axial Chirality Mode

1,2-bis(2,5-dimethylthiophen-3-yl)ethane-1,2-dione ( 1 , DTEthane) reacts with MCl₄ metal precursors of group four (M=Ti, Zr, Hf) via coordination of the carbonyl groups. The molecular structure of complex 2–4 were determined in scXRD studies in the solid state and characterized by means of multi-nuclear and multi-dimensional NMR spectroscopy in solution. While the resulting titanium complex [TiCl₄(DTEthane)] 2 shows a monomeric structure, where 1 binds in a bidentate fashion, complexes with a Zr ( 3 ) and Hf ( 4 ) center have dimeric scaffolds in which the ligands adopt a bridging mode. Quantum chemical calculations using density functional theory (G16, B97D3/def2-TZVP) were used to evaluate the general trend of dimer formation (Ti<Zr<Hf). The molecular structures derived from both scXRD and the DFT optimized structures reveal the carbonyl groups in conjugation with the adjacent thiophene substituent. As a result, they are coplanar and rotation about the two C−C axes (C1−C7; C8−C9) is restricted allowing for only one chiral axis along C7−C8. This gains special importance with respect to previously described complexes carrying the closely related 1,2-endiolato ligand (1,2-bis(2,5-dimethylthiophen-3-yl)ethene-1,2-diolate), in which no coplanarity of the thiophene rings to their neighboring metallacycle was observed allowing for two chiral axes. Noteworthy, further DFT calculations addressing the pathway of racemization found transition states, which are characterized by contrary rotations of both thiophene rings and a loss of conjugation rather than a direct rotation around the axis C7−C8.     

Synthesis of quasi-linear and segmented bis- to penta-2, 2'-bipyridine polytopic ligands built via a convergent approach

Reliable and practical routes for the preparation of segmented oligomeric 2,2'-bipyridine-based ligands possessing rigid and conjugated spacers are presented. The first series of ligands bears a single alkyne function as a bridge and has been built by Pd(0)-catalyzed cross-coupling reactions between ethynylated and bromo-substituted derivatives of 2,2'-bipyridine (bipy). These new ligands provide access to numerous hexameric, octameric, and decameric pyridine-based materials. Optimum conditions were found with [Pd(PPh(3))(4)] (6 mol %) in benzene containing diisopropylamine at 80 degrees C. The second series of soluble ligands was synthesized around a 1,4-diethynyl-2, 5-didodecyloxybenzene bridging unit. The synthesis required a protection/deprotection methodology, as well as a chemioselective palladium-catalyzed Sonogashira-Hagihara cross-coupling protocol to obtain the target multitopic ligands. Within this strategy, the pivotal 15b, 17, and 19b intermediates bearing one or two bipy and phenyl units are required and such entities have been isolated in excellent yield. The products are highly soluble and photostable. In each case, the final step involves a double cross-coupling reaction between the appropriate constituents, with the best preparative conditions involving [Pd(PPh(3))(4)] (6 mol %) in n-propylamine at 70 degrees C. The main advantage of this methodology lies in its synthetic versatility and adaptability for creating multitopic metal-binding scaffolds with a potentially large variety of bridging units and phenyl substituents. Spectroscopic data for the new oligomers show a steady decrease in optical energy with an increasing degree of oligomerization. The different results obtained with these ligands highlight the importance of the rigid 1, 4-diethynylphenyl linker in directing the outcome of the nanosized molecules.     

Synthesis,electrochemistry, and electrochromic properties of branched thiophene polymers with different conjugation lengths

Here the authors designed and synthesized three branched thiophene polymers with different effective conjugation lengths of thiophene groups, pTPBT, pTPTT, and pTPQT, mainly based on bithiophene, trithiophene, and quadruple thiophene. The electrochemical curves and theoretical calculation results reflect that the oxidation potential of polymers decreased gradually as the conjugation lengths of thiophene groups increased, which is favorable for the appearance of electrochromism. Electrochromic properties demonstrate that pTBTT displays no electrochromism, pTPTT exhibits an unstable one, while pTPQT shows an obvious stable electrochromism between yellow‐orange and blue‐violet colors. These results indicate that thiophene polymers with effective electrochromism should be the smallest conjugation length of quadruple thiophene at least. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2340–2348     

Design, synthesis, and biological evaluation of novel fluorinated ethanolamines

The preparation of novel fluorinated allylamines and their use as key fragments for the stereoselective synthesis of hydroxyethyl secondary amine (HEA)-type peptidomimetics is described. Our strategy employs chiral sulfinyl imines as synthesis intermediates, by treatment of hemiaminal precursors with two equivalents of vinylmagnesium bromide. The subsequent oxidation of the allylic amines to the corresponding epoxides was achieved by treatment with methyl(trifluoromethyl)dioxirane. Finally, epoxide ring opening with a range of nitrogen nucleophiles provided a library of HEA-derived peptidomimetics with a phenyldifluoromethylene moiety. The biological evaluation of these derivatives revealed compounds with remarkable BACE1 inhibitory activity. Docking studies revealed the influence of the fluorine atoms in the binding mode of the synthesized ligands. Furthermore, the biological evaluation of our final products and synthesis intermediates led to the discovery of compounds with antimicrobial activity against Mycobacterium and Nocardia species.     

Synthesis,Properties, and π‐Dimer Formation of Oligothiophenes Partially Bearing Orthogonally Fused Fluorene Units

A series of oligothiophenes that incorporate cyclopenta[c]thiophene‐based units bearing spiro‐substituted dialkylfluorene was synthesized. Photophysical measurements indicated that there was no interruption in the conjugation along the oligothiophene backbones, irrespective of the number or position of this unit. Electrochemical measurements showed that the thiophene 7‐mers and 11‐mer exhibit reversible multi‐oxidation waves. The formation of cationic species was clearly observed from UV/Vis/NIR measurements. Furthermore, the UV/Vis/NIR spectra at 223 K under one‐electron oxidation conditions revealed that the unsubstituted thiophene or bithiophene units remained in the absence of intermolecular π–π interactions, whereas the formation of π‐dimeric species was observed for the thiophene 7‐mer containing an unsubstituted terthiophene ( U₃ ) unit. Theoretical calculations indicated that the combination of the U₃ unit and the all‐trans conformation decreased the intermolecular steric repulsion between the fused cyclopentene ring and its facing thiophene, which may contribute to the formation of the dimeric structure.     

Dipole moments of phenyl,benzo, and benzo[b]thiopheno derivatives of thiophene; 1, 4-dithiin,and thianthrene and their sulfones

The dipole moments of a series of phenyl, benzo-, and benzo[b]thiopheno-derivatives of thiophene, 1,4-dithiin, and thianthrene have been determined. An increase in the dipole moments of the phenyl derivatives of thiophene with an increase in the number of phenyl groups is connected with the existence of conjugation between the thiophene and benzene rings, a quantitative evaluation of the nature of which is given. It is suggested that the structure of the 1, 4-dithiin ring is close to coplanar.     

X-shaped oligothiophenes as a new class of electron donors for bulk-heterojunction solar cells

Four X-shaped oligothiophenes with different conjugation length were investigated as novel electron donors in single-layer bulk-heterojunction solar cells. The UV-vis absorption spectra of blends of compounds 1-4 with 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C(61) show a remarkably red shift and broadening with increasing thiophene number at each of the four branches. The performance of the photovoltaic cells varied significantly with molecular structures of the four oligothiophenes. Conversion efficiencies increased from 0.008% to 0.8% with changing the electron donors from 1 to 4. The maximum incident photon-to-current conversion efficiency of the device based on 4 reaches 31.6%, much higher than those of three other compounds 1-3. Remarkable improvement of the device performance was achieved with increasing the substituted thiophene number. The results show that the photovoltaic effect is dependent on the structural characteristics and the film forming abilities of the X-shaped thiophenes.     

Oligomeric ligands incorporating multiple 5,5'-diethynyl-2,2'-bipyridine moieties bridged and end-capped by 3,4-dibutylthiophene units

In this work, we detail the synthesis and photophysical properties of a series of soluble polybipyridine ligands comprising one to five bipyridine units sandwiched between rigid carbon-carbon triple bonds substituted by 3,4-dibutylthiophene repeating units. The dual Sonogashira coupling reaction of 5,5'-dibromo-2,2'-bipyridine with TMS- and (CH3)2C(OH)-protected acetylene allows the synthesis of a dissymmetrically functionalized building block which was selectively deprotected at either the TMS or 2-hydroxyprop-2-yl site. Various combinations allow the interconnection of the terminal alkyne to 3,4-dibutyl-2,5-diiodothiophene or 3,4-dibutyl-2-iodothiophene leading to bipyridine frameworks bearing two acetylene-protected groups or one acetylenethiophene/one acetylene-protected function. It is possible therefore to construct dimeric to pentameric bipyridine ligands where the chelating subunit is bridged by a 3,4-dibutyl-2,5-diethynylthiophene spacer and end-capped by a 3,4-dibutyl-2-ethynylthiophene stopper. All cross-coupling reactions are promoted with palladium(0) tetrakistriphenylphosphine under mild conditions. Spectroscopic data for the new oligomers are discussed in terms of the extent of pi-electron conjugation. Upon increasing the number of pi-electrons from 24 to 104, there is a progressive lowering in the energy of absorption and fluorescence transitions, while the emission quantum yields remain essentially constant. The LUMO levels of these large molecules, estimated by cyclic voltammetry, lie in the range -3.06 to -3.18 eV.     

Versatile site-specific conjugation of small molecules to siRNA using click chemistry

We have previously demonstrated that conjugation of small molecule ligands to small interfering RNAs (siRNAs) and anti-microRNAs results in functional siRNAs and antagomirs in vivo. Here we report on the development of an efficient chemical strategy to make oligoribonucleotide-ligand conjugates using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) or click reaction. Three click reaction approaches were evaluated for their feasibility and suitability for high-throughput synthesis: the CuAAC reaction at the monomer level prior to oligonucleotide synthesis, the solution-phase postsynthetic "click conjugation", and the "click conjugation" on an immobilized and completely protected alkyne-oligonucleotide scaffold. Nucleosides bearing 5'-alkyne moieties were used for conjugation to the 5'-end of the oligonucleotide. Previously described 2'- and 3'-O-propargylated nucleosides were prepared to introduce the alkyne moiety to the 3' and 5' termini and to the internal positions of the scaffold. Azido-functionalized ligands bearing lipophilic long chain alkyls, cholesterol, oligoamine, and carbohydrate were utilized to study the effect of physicochemical characteristics of the incoming azide on click conjugation to the alkyne-oligonucleotide scaffold in solution and on immobilized solid support. We found that microwave-assisted click conjugation of azido-functionalized ligands to a fully protected solid-support bound alkyne-oligonucleotide prior to deprotection was the most efficient "click conjugation" strategy for site-specific, high-throughput oligonucleotide conjugate synthesis tested. The siRNA conjugates synthesized using this approach effectively silenced expression of a luciferase gene in a stably transformed HeLa cell line.     

Derivatives of 4,9-dihydro-s-indaceno[1,2-b:5,6-b']dithiophene-4,9-dione: synthesis and properties

A new family of organic semiconducting materials (1-4) integrating the structural components of thiophene and fluorene into a single molecular entity was synthesized and characterized. Optical and electrochemical properties of these previously unknown 4,9-dihydro-s-indaceno[1,2-b:5,6-b']dithiophene-4,9-dione derivatives were studied in detail. These materials possess unique optical properties with the longest wavelength absorption maxima around 500-800 nm, which gradually reached a saturation limit with the total number of thiophene units approaching eight. They also display dramatic change in the redox properties with increasing conjugation chain lengths. A thin film of oligomer 3 prepared by a solution-casting method showed a well-ordered solid-state structure according to X-ray diffraction analysis.     

Encapsulated oligothiophenes having electron-affinity characteristics

Oligothiophenes composed of dioxocyclopenta[c]thiophene bearing bulky bis(di-t-butylphenyl) groups were designed and synthesized to develop molecular wires having electron-transporting characteristics. Their effective conjugation, electron affinity, and encapsulation effects were investigated by photophysical and electrochemical measurements.     

Thiophene-based bent-shaped luminescent liquid crystals: synthesis and characterisation

Five new bent-shaped compounds based on the 2,5-disubstituted thiophene central core were successfully synthesised. The lengths of the rigid centres as well as the degree of conjugation were varied by coupling benzene, naphthalene and biphenyl systems to the thiophene through Sonogashira cross-coupling. The thermal, mesomorphic and optical properties of these variants were determined. Compounds 5a,b and 8a displayed liquid-crystalline smectic and nematic mesophases. Strong blue fluorescence was observed for the final compounds.