Synthesis and studies of covalently linked meso-furyl boron-dipyrromethene-ferrocene conjugates

Four meso-furyl BODIPY-ferrocene conjugates 1–4 in which one or more ferrocene groups were connected directly to BODIPY core or meso-furyl group were synthesized by coupling of appropriate bromo meso-furyl BODIPYs with α-ethynylferrocene under mild Pd(0) coupling conditions. The compounds were characterized by HR-MS mass, NMR, absorption, electrochemistry and fluorescence techniques. The absorption studies of compounds 1–4 showed charge transfer band in addition to BODIPY absorption bands indicating that the BODIPY and ferrocene moieties interact within the conjugates. On the other hand, the charge transfer band is absent in meso-phenyl BODIPY-ferrocene conjugate due to the orthogonal arrangement of ferrocene appended meso-phenyl group with BODIPY core which prevents the interaction between the two moieties. The electrochemical studies showed strong oxidation due to ferrocene moiety and reduction due to meso-furyl BODIPY unit. The compounds 3 and 4 which contain two and three ferrocenyl groups respectively were oxidized at the same potential with two and three electrons involved in the redox process. The compounds 1–4 are weakly fluorescent due to electron transfer from ferrocene unit to BODIPY unit. However, the fluorescence can be restored by oxidizing the ferrocene to ferrocenium ion which prevents the electron transfer between the two moieties. The computational studies support the experimental results.     

Synthesis and properties of covalently linked thiaporphyrin-ferrocene conjugates

Four examples of ferrocene-thiaporphyrin conjugates in which the ferrocenyl group was covalently connected either directly at meso-position of thiaporphyrin or to meso-phenyl group of thiaporphyrin via ethyne bridge were prepared by coupling bromo- or iodo thiaporphyrin with α-ethynylferrocene under mild Pd(0) coupling conditions. NMR, absorption and electrochemical studies indicated that the thiaporphyrin and ferrocenyl units interact strongly in ethyne bridged porphyrin-ferrocene conjugates but the interaction is very weak in phenyl ethyne bridged porphyrin-ferrocene conjugates. The steady state fluorescence studies indicated that the fluorescence yields are reduced to 50% in phenyl ethyne conjugates but the fluorescence is completely quenched in ethyne bridged conjugates. The partial or complete quenching of porphyrin fluorescence in these conjugates is due to electron transfer from ferrocene unit to excited state of porphyrin sub-unit. Oxidation of ferrocene to ferrocenium ion with an oxidizing agent in ethyne bridged conjugates resulted in a recovery of porphyrin fluorescence.     

Synthesis and properties of triazole bridged BODIPY-conjugates

A series of triazole bridged BODIPY-conjugates were synthesized under click reaction conditions. The 3-azido BODIPY was generated in situ by treating 3-bromo BODIPY with NaN₃ in CH₃CN at room temperature for 60 min and reacted with appropriate ethynyl containing chromophore/redox active unit, such as ferrocene, BODIPY, Zn(II) porphyrin, 21,23-dithiaporphyrin, BF₂-smaragdyrin in the presence of CuI/DIPEA in THF/CH₃CN solvent. The conjugates were purified by column chromatography and obtained pure compounds in 45–50% yields. The conjugates were characterized by HR-MS, 1D, 2D, ¹⁹F and ¹¹B NMR and X-ray crystallography for BODIPY-ferrocene conjugate. Absorption and electrochemical studies showed features of both the moieties present in the conjugates and also support interaction between the two moieties in the conjugates. The fluorescence studies supported an efficient energy transfer from BODIPY unit to BF₂-smaragdyrin unit in BODIPY–BF₂-smaragdyrin conjugate but the energy transfer was not efficient in BODIPY–Zn(II) porphyrin and BODIPY–21,23-dithiaporphyrin conjugates.     

Ferrocene–β‐Cyclodextrin Conjugates: Synthesis,Supramolecular Behavior,and Use as Electrochemical Sensors

Ferrocene with a β‐cyclodextrin unit bound to one or both cyclopentadienyl rings through the secondary face were conveniently synthesized by regiospecific copper(I)‐catalyzed cycloaddition of 2‐O‐propargyl‐β‐cyclodextrin to azidomethyl or bis(azidomethyl)ferrocene. The supramolecular behavior of the synthesized conjugates in both the absence and presence of bile salts (sodium cholate, deoxycholate, and chenodeoxycholate) was studied by using electrochemical methods (cyclic and differential pulse voltammetry), isothermal titration calorimetry, and NMR spectroscopy (PGSE, CPMG, and 2D‐ROESY). These techniques allowed the determination of stability constants, mode of inclusion, and diffusion coefficients for complexes formed with the neutral and, in some cases, the oxidized states of the ferrocenyl conjugates. It was found that the ferrocenyl conjugate with one β‐cyclodextrin unit forms a redox‐controllable head‐to‐head homodimer in aqueous solution. The ferrocene–bis(β‐cyclodextrin) conjugate is present in two distinguishable forms in aqueous solution, each one having a different half‐wave oxidation potential for the oxidation of the ferrocene. By contrast, only one distinguishable form for the oxidized state of the ferrocene–β‐cyclodextrin conjugate is detectable. The redox‐sensing abilities of the synthesized conjugates towards the bile salts were evaluated based on the observed guest‐induced changes in both the half‐wave potential and the current peak intensity of the electroactive moiety.     

Redox monomer ionic liquid based on quaternary ammonium: From electrochemistry to polymer brushes

Bifunctional quaternary ammonium ionic liquid bearing redox and polymerisable units was synthesized. The electrochemical investigations of the ferrocene monomer ionic liquid were performed. Following that, surface-initiated atom transfer radical polymerization (SI-ATRP) was used to build polymer brushes onto the electrode surface. The presence of the Poly(ferrocenyl quaternary ammonium) was evidenced by surface and electrochemical analysis. The latter exhibits high electron transfer rate and the presence of ions within the polymer framework leads to record the attached ferrocenyl redox signal in solution without adding supporting electrolyte. Finally, the wettability of the surface was modulated by electrochemical switch and by anion exchange within the polymer.     

Redox-active ferrocene-modified pyrimidines and adenine as antitumor agents: structure,separation of enantiomers,and inhihibition of the DNA synthesis in tumor cells

The structures, electrochemical properties, enantiomeric separation of ferrocenyl-(alkyl)pyrimidines and ferrocenyl(ethyl)adenine and their effects on the DNA synthesis in tumor cells were studied. Enantiomeric mixtures were separated by HPLC on modified cellulose as the chiral selector. The electrochemical properties of compounds were studied by cyclic voltammetry. All compounds have reversible single-electron redox transition in the region of 0.52–0.60 V, which belongs to ferrocene—ferrocenium with a positive shift compared to ferrocene (0.52 V). The molecular structure of 1-N-(ferrocenylbenzyl)-5-iodocytosine was studied by X-ray diffraction. 1-N-(Ferrocenylethyl)adenine was studied for ability to inhibit the DNA synthesis in the human ovarian cancer cell culture by the ³H-thymidine test.     

Donor–acceptor perylenediimide–ferrocene conjugates: synthesis,photophysical, and electrochemical properties

Donor–acceptor, perylenediimide–ferrocene conjugates have been synthesized by Suzuki, and Sonogashira coupling reactions. The photophysical and electrochemical properties of these conjugates are discussed. It has been shown that fluorescence as well as the electron affinity of the perylenediimide can be tuned by attaching the appropriate ferrocenyl derivatives.     

Modified expanded corrole-ferrocene conjugates: syntheses, structure and properties

Syntheses, characterization and properties of expanded corrole-ferrocene conjugates are reported. Ferrocenyl group are covalently linked to the corrole macrocycle through three different spacers groups. The synthetic strategy involved prior insertion of ferrocene with spacers to the dipyrromethane unit followed by a "3+2" acid-catalyzed oxidative coupling methodology. The optical and emission data of the expanded corrole-ferrocene conjugates depend on the nature and length of the spacer groups and the maximum effects are seen where ferrocene is directly linked to the meso carbon of macrocycle. The single crystal X-ray structure of two expanded corrole-ferrocene conjugates; [22]pentaphyrin (1.1.0.1.0) with different meso substituents, clearly reveal shortening of the C-C bond length linking the meso carbon and the aryl substituent containing the ferrocene moiety relative to meso aryl substituents without ferrocene. The results suggest that an electronic interaction between the two pi systems. Electrochemical data reveal harder oxidation for the ferrocene unit in the conjugates relative to free ferrocene; this suggests the electron donating nature of the ferrocene. The first corrole ring oxidation shows easier oxidation relative to 1 and the magnitude of shifts in potential is inversely proportional to the length of spacer. The molecular first hyperpolarizabilities (beta) measured at 1064 nm by HRS method vary in the range 20-32x10(-30) esu and imply that the beta values can be increased by enhancing the number of mobile electrons in the conjugation. The conjugates form 1:1 metal complex with the Rh(I) where rhodium is coordinated to one amino and one imino nitrogen of the dipyrromethane unit.     

二茂铁基超支化聚氨酯的电化学性能

通过循环伏安法(CV)测定了二茂铁基超支化聚氨酯(HAPE-Fc)的电化学性能.结果表明:HPAE-Fc表现为单对氧化还原峰,在二茂铁接枝到超支化聚氨酯上以后,二茂铁基团依然保持着自身的氧化还原独立性,具有较强的电子转移速率,这是其具有电化学特性和催化作用的前提条件.通过分析扫描速率与HPAE-Fc电化学行为之间的关系,发现HPAE-Fc的电极过程既受扩散控制,同时也受电极反应的控制.     

A luminescence molecular switch via modulation of PET and ICT processes in DCM system

A novel versatile dicyanomethylene-4H-pyran (DCM) based derivative bearing ferrocenyl group (DCM-N-Fc) is designed as modulator to construct “off-on” logic operation. The optical properties of DCM-N-Fc are characterized by absorption and steady-state fluorescence technique, showing that the fluorescence from DCM chromophore via intramolecular charge transfer (ICT) is strongly quenched by photoinduced electron transfer (PET) process from ferrocene moiety. In contrast with the references (DCM-N and DCM-Fc), the fluorescence of DCM-N-Fc can be triggered by oxidizing ferrocenyl unit either chemically or electrochemically, exhibiting a characteristic emission modulation at around 610 nm with an electrofluorochromic behavior. Furthermore, the free energy and the fluorescence lifetime in the PET path verify the thermodynamic feasibility. Cyclic voltammetry, absorption spectroscopy, time-resolved fluorescence as well as DFT calculation have been used to elaborate the manipulation via both PET and ICT processes.     

Donor-acceptor-donor tetrazines containing a ferrocene unit: synthesis, electrochemical and spectroscopic properties

Donor-acceptor-donor tetrazines containing ferrocene moieties and phenyl unit as a pi-bridge have been synthesized and characterized. UV-vis spectroscopic and cyclic voltamperometric results indicate sizable intramolecular charge transfer interactions in the ground state when the ferrocene is directly bound to the tetrazine. On the other hand, the results show reduction of the electron-donor strength of ferrocene moieties when there is a phenyl linkage. Both tetrazines display a high reduction potential. The role of ferrocenyl groups appear to be detrimental to maximize the cubic hyperpolarizability gamma of tetrazines, as compared to purely organic groups such as thiophene. A possible explanation for this behavior may originate from metal-to-ligand charge transfer processes.     

Specific solvent effects on the intramolecular electron transfer reaction in a neutral ferrocene donor polychlorotriphenylmethyl acceptor radical with extended conjugation

The synthesis and the optical, magnetic and electrochemical properties of the ferrocenylbutynene substituted polychlorotriphenylmethyl radical 1 are reported. Radical 1 is prepared in a three step synthetic route starting with a Wittig reaction to yield (E,Z)-{4-[4-(bis(2,3,4,5,6-pentachlorophenyl)methyl)-2,3,5,6-tetra-chlorophenyl]but-3-en-1-ynyl}-ferrocene (1H) which is subsequently deprotonated to yield the corresponding anion K⁺(18-crown-6) [1]^? and finally oxidized to (E)-4-[4-(ferrocenyl)but-3-yn-1-enyl]-2,3,5,6-tetrachlorophenyl-bis(2,3,4,5,6-pentachlorophenyl) methyl radical (1). Radical 1 exhibits a charge-transfer band transition in the near infrared region which is associated with an intramolecular electron transfer from the ferrocene unit (donor) to the radical unit (acceptor) of this dyad molecule; its solvatochromism is studied in detail. The X-ray crystal structure of [K⁺(18-crown-6)](E)-[4-[4-(ferrocenyl)but-3-yn-1-enyl]-2,3,5,6-tetrachlorophenyl-bis(2,3,4,5,6-pentachlorophenyl) methide] [1]^? has been determined. This organic salt forms an interesting one-dimensional coordination polymer by the coordination of the K⁺ cation with chlorine atoms of the organic carbanion.     

2'-Ribose-ferrocene oligonucleotides for electronic detection of nucleic acids

We have synthesized two novel phosphoramidites with a ferrocenyl moiety at the 2'-ribose position linked through a butoxy linker. Using automated DNA/RNA synthesis techniques, oligonucleotides containing ferrocene at various positions were prepared and characterized by HPLC, MALDI-TOF mass spectrometry, and electrochemistry. Thermal stability studies of the ferrocene-modified DNA duplexes revealed that introduction of one or two ferrocenyl complexes does not result in an observed change of the T(m) values of the corresponding DNA duplexes when compared to the nonmodified hybrids. These data indicate that the introduction of a ferrocenyl group at the 2'-position of the ribose ring containing either a purine or pyrimidine base has no effect on the stability of the modified DNA. The electrochemical behavior of the ferrocene-containing DNA was examined by cyclic voltammetry. The modified 2'-ferrocene-oligonucleotides are electrochemically active and can be used as signaling probes for the electronic detection of nucleic acids on bioelectronic sensors.     

Monosubstituted thermotropic ferrocenomesogens containing heterocyclic pyrazole

The synthesis and mesomorphic properties of two series of ferrocenyl derivatives, 5-[4-(4-alkoxylbenzyloxy)phenyl]-3-(4-ferrocenylphenyl)-1H-pyrazoles 1a and 3-[4-(4-ferrocenylbenzyloxy)phenyl]-5-(4-alkoxylphenyl)-1H-pyrazoles 1b are reported. Compounds 1a exhibited either nematic (N) or smectic A (SmA) phases, whereas compounds 1b formed N/SmC or SmA/SmC phases depending on the terminal carbon length. The formation of SmC phases in compounds 1b was attributed to better molecular interaction between layers since the ferrocenyl unit was remotely located one phenyl ring away from pyrazole core. In contrast, their precursors, ferrocenyl β-diketonates, were in fact non-mesogenic. A less bent shape formed by ferrocenyl pyrazoles than ferrocenyl β-diketones was believed to be responsible for the formation of observed mesophases. The crystal and molecular structure of 3-[4-(4-ferrocenylbenzyloxy)phenyl]-5-(4-hexyloxyphenyl)-1H-pyrazole (1b; n=6) was determined by means of X-ray structural analysis. It crystallizes in the triclinic space group p-1, with a=11.0725(5) Å, b=12.5514(5) Å, c=14.2085(6) Å, and Z=2. The molecular arrangement was quite consistent with the layer structure observed by powder X-ray diffractometer. The cyclic voltammogram measured for 1 and 2 (n=16) indicated that incorporation of pyrazole group hardly influenced the electrochemical behavior of the ferrocenyl moiety.     

Synthesis and electro-spectroelectrochemistry of ferrocenyl naphthaquinones

A practical approach to ferrocenyl naphthaquinone derivatives involving thermal rearrangement of variously substituted 4-aryl-4-hydroxycyclobutenones was described. The reaction of 3-ferrocenyl-4-isopropoxy-3-cyclobutene-1,2-dione with different aryl lithiums gave the corresponding 4-aryl-4-hydroxycyclobutenones, which were heated in p-xylene at reflux open to the air to yield ferrocenyl naphthaquinones. The redox chemistry of the ferrocenyl naphthaquinones was studied by electrochemical and in situ spectroelectrochemical techniques in CH₂Cl₂ solution and in CH₃CN solution with water, weak and strong acidic additives. Ferrocenyl naphthaquinones displayed reversible two reduction processes involving semiquinone radical anion (Fc-snq⁻), dianion (Fc-nq²⁻) species and a one-electron oxidation process based on the ferrocenium/ferrocene (Fc⁺-nq/Fc-nq) couple in CH₂Cl₂. The redox reaction mechanism of the ferrocenyl naphthaquinones in the presence of the additives proceeded via hydrogen bonding or proton-coupled electron transfer. Effects of the substituents on the reduction potentials and intramolecular charge-transfer bands of ferrocenyl naphthaquinones were also discussed.     

1,2-disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential antimalarial agents

This work presents a new family of organometallic antimalarial compounds consisting of ferrocene bearing a chloroquine-derived moiety as well as a 1,2;3,5-diisopropylidene glucofuranose moiety at a cyclopentadienyl scaffold in a 1,2-substitution pattern. The synthetic route proceeds via a stereoselective functionalization of ferrocene carboxaldehyde to the 1,2-disubstituted conjugates. After complete characterization of these new, trifunctional conjugates, they were examined for their cytotoxicity in two cancerous cell lines (MDA-MB-435S and Caco2) and one non-cancerous cell line (MCF-10A), showing that increased cytotoxicity can be observed for the chloroquine ferrocenyl conjugates compared to their carbohydrate-substituted precursors. The antiplasmodial activity of the conjugates in a chloroquine-sensitive strain of Plasmodium falciparum (D10) and a chloroquine-resistant strain (Dd2) was determined. Monosubstituted conjugates 13, 14 and 15 exhibit decreasing activity with increasing alkyl chain length between the ferrocene and quinoline moiety, bifunctional conjugates 16, 17, 18 show constant activity, performing better than chloroquine in the Dd2 strain.     

Synthesis and characterization of novel ferrocenyl glycidyl ether polymer,ferrocenyl poly (epichlorohydrin) and ferrocenyl poly (glycidyl azide)

Poly (ferrocenyl glycidyl ether) was synthesized by polymerization of 2-[(4-ferrocenylbutoxy)methyl]oxirane (FcEpo) using toluene solution of methylaluminoxane as the catalyst. Copolymerization of 2-[(4-ferrocenylbutoxy)methyl]oxirane with epichlorohydrin was used for the synthesis of another ferrocenyl based poly (epichlorohydrin). Ferrocenyl based poly (glycidyl azide), GAP, was synthesized by treatment of sodium azide with this copolymer in DMF as solvent at room temperature. The synthesized ferrocenyl based polymers were characterized by FT-IR, ¹HNMR, UV–Vis, TGA, DSC and GPC analysis. The UV–Vis spectra of synthesized polymers show the absorption band of ferrocene moiety at about 450 nm. The TGA and DSC analysis show that poly (ferrocenyl glycidyl ether) has good thermal stability. The TGA analysis shows that the copolymerization of 2-[(4-ferrocenylbutoxy)methyl]oxirane with epichlorohydrin improved the thermal stability of the copolymer. The GPC analysis of poly (ferrocenyl glycidyl ether), ferrocenyl based poly (epichlorohydrin) and Ferrocenyl based poly (glycidyl azide) show the PDI between 1.14–1.17. The electrochemical behavior of synthesized polymers was investigated by cyclic voltammetry (CV) measurements. The CV curves of synthesized polymers show good electrochemical performance and there is one redox system with the single-electron reversible reaction that associated with ferrocene moiety in polymers structure. The anodic and cathodic peak currents increased with scan rate confirmed redox reactions in the system are kinetically fast diffusion-controlled reactions.     

Synthesis of covalently linked boron-dipyrromethene-chromophore conjugates using 3-bromo boron-dipyrromethene as a key precursor

3-Bromo boron dipyrromethene (3-bromo BODIPY) has been used as key synthon to prepare one ethynyl bridged and six ethynylphenyl bridged BODIPY-chromophore conjugates using mild Pd(0) coupling conditions. The chromophores possessing very distinct features, such as anthracene, BODIPY, terpyridine, porphyrin, Zn(II)porphyrin, 21,23-dithiaporphyrin and thiasapphyrin were connected at 3-position of boronboron-dipyrromethene dye by coupling of 3-bromo BODIPY with ethynyl or ethynylphenyl chromophore in toluene/triethylamine in the presence of catalytic amount of AsPh₃/Pd₂(dba)₃ at 40 °C followed by column chromatographic purification. The spectral studies indicated that the interaction is stronger in ethynyl bridged BODIPY-chromophore conjugate compared to ethynylphenyl bridged BODIPY-chromophore conjugates. The steady-state fluorescence indicated that in ethynyl bridged BODIPY-anthracene conjugate, the BODIPY unit act as energy acceptor and showed a possibility of energy transfer from donor anthracene unit to acceptor BODIPY unit on selective excitation of anthracene unit. However, in ethynylphenyl bridged BODIPY-porphyrin conjugates, the BODIPY unit act as energy donor and exhibited a possibility of singlet-singlet energy transfer from BODIPY unit to porphyrin unit.     

A new triferrocenyl-tris(hydroxymethyl)aminomethane derivative as a highly sensitive electrochemical marker of biomolecules: application to the labelling of PNA monomers and their electrochemical characterization

We have designed and synthesised a new organometallic molecule containing three ferrocene groups for use as a highly sensitive electrochemical marker in biological assays. This trisferrocene derivative was conjugated to different PNA monomers, and the electrochemical activities of the conjugates were extensively investigated in organic solvents, in view of their potential diagnostic applications. The results showed that the introduction of a trisferrocene unit on the PNA monomer triples the current signal in comparison with the monoferrocene-labelled one. Despite their greater molecular complexity, trisferrocene-conjugated PNA monomers are even more electrochemically active than the reference ferrocene. By using differential pulse voltammetry (DPV), the detection limit can reach 10(-8) M in acetonitrile solution. These results are a good premise for the use of the trisferrocene unit as an effective electrochemical probe for biomolecules.     

Synthesis of ferrocenyl conjugates of thio analogs of hydroxyl-containing biomolecules via the Mitsunobu reaction with N-(ethoxycarbonyl)ferrocenecarbothioamide as the pronucleophile

A new method for attachment of a ferrocenyl moiety to hydroxyl-containing biomolecules is reported, based on the Mitsunobu reaction with N-(ethoxycarbonyl)ferrocenecarbothioamide. The reaction results in the replacement of the OH group with a (ferrocenyl)thioimidoyl moiety. Using this method, ferrocenyl conjugates of cholesterol, stigmasterol, as well as protected and nonprotected adenosine and 2′-deoxy adenosine were obtained in high yield and with high chemo- and stereoselectivity.