Ferrocene clicked polypyrrole derivatives: effect of spacer group on electrochemical properties and post-polymerization functionalization

In this study, novel ferrocene-functionalized N-alkyl substituted pyrrole derivatives, namely 4-ferrocenyl-1-[3-(pyrrol-1-yl)propyl]-1H-1,2,3-triazole (Py3Fc), 4-ferrocenyl-1-[4-(pyrrol-1-yl)butyl]-1H-1,2,3-triazole (Py4Fc), and 4-ferrocenyl-1-[6-(pyrrol-1-yl)hexyl]-1H-1,2,3-triazole (Py6Fc), were synthesized via click reaction and the monomers were characterized by ¹H NMR, ¹³C NMR, FTIR, and HRMS techniques. Redox properties of the monomers were investigated by cyclic voltammetry (CV) studies. Contrary to general literature, both Py4Fc and Py6Fc were electrochemically polymerized without loss in redox activity of ferrocene group. Moreover, click chemistry was utilized in post-polymerization functionalization. For this purpose, three azide-containing polypyrroles, P(Py3N₃), P(Py4N₃), and P(Py6N₃) were electrochemically synthesized and subjected to click reaction in the presence of ethynylferrocene. CV studies of the post-polymerization functionalized polymers revealed quasi-reversible waves, while only P(Py6-post-Fc) showed the characteristic redox behavior of both polypyrrole and ferrocene. Thus, in this study preparation of a conducting homopolymers of pyrrole having covalently bonded ferrocene units was demonstrated and effect of spacer group is investigated.     

Synthesis,characterization, and in vitro drug‐release properties of 2‐hydroxyethyl methacrylate copolymers

2‐Hydroxyethyl methacrylate was copolymerized with acrylamide, N‐vinyl‐2‐pyrrolidone, and n‐butyl methacrylate by free‐radical solution polymerization with α,α′‐azobisisobutyronitrile as an initiator at 70 ± 1°C. The average molecular weights and molar compositions of the resultant copolymers were determined with gel permeation chromatography and ¹H‐NMR spectroscopy data, respectively. Diclofenac or 2‐[(2,6‐dichlorophenyl)amino]benzene acetic acid, a nonsteroidal anti‐inflammatory drug, was chemically attached to the copolymers by transesterification reaction in the presence of N,N′‐dicyclohexylcarbodiimide to give macromolecular prodrugs. All the synthesized polymers were characterized with Fourier transform infrared, ¹H‐, and ¹³C‐NMR spectroscopy techniques. The polymer–drug conjugates were hydrolyzed in cellophane member dialysis bags containing aqueous buffered solutions (pH 8) at 37°C, and the hydrolysis solutions were detected by UV spectrophotometer at selected intervals. The results showed that the drug could be released by selective hydrolysis of the ester bond from the side chain of the drug moiety. The release profiles of the drug indicated that the hydrolytic behavior of polymeric prodrugs strongly depends on the hydrophilicity of the polymer. The results suggest that the synthesized copolymers could be useful carriers for the release of diclofenac in controlled‐release systems. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2403–2409, 2007     

Synthesis and corrosion inhibition mechanism of ammonium-based ionic liquids on API 5L X60 steel in sulfuric acid solution

A novel class of four new-free-halide-ionic liquids (ILs) derived from ammonium was synthesized and characterized via spectroscopic methods such as ¹H NMR and ¹³C NMR. The synthesized compounds were evaluated as corrosion inhibitors (CIs) of API 5L X60 steel in 1 M sulfuric acid by means of the potentiodynamic polarization and weight loss techniques. The results confirmed that the inhibition efficiency displayed by the four ILs is a function of their concentration and molecular structure. The obtained inhibition efficiency (η) ranged from 51 to 89%, confirming that the new class of ILs is good for corrosion inhibition purposes. The analysis of the potentiodynamic results showed that these compounds inhibit the corrosion of steel, classifying them as mixed-type CIs. The adsorption process of these new CIs on the API 5L X60 steel surface, which obeyed the Langmuir isotherm, was found to be physical and chemical. The SEM and EDX analyses confirmed the protection of steel in the corrosive medium.     

Synthesis and electrochemical properties of redox active polyurethanes with ferrocene units in polyether soft segments

Electrochemical active segmented polyurethane with ferrocene units in polyether soft segments (PU‐S‐Fc) has been originally synthesized and identified by ¹H‐NMR spectra. Electrochemical behaviors of PU‐S‐Fc blending with lithium perchlorates were investigated by cyclic voltammetry. In N,N′‐dimethyl formide solution, PU‐S‐Fc exhibited normal cathodic and anodic peaks of the ferrocene/ferricinium (Fc/Fc⁺) couple. Compared with that of ferrocene molecules blended in ordinary polyurethane (PU‐B‐Fc), redox peaks of ferrocene units in PU‐S‐Fc were found to be broader, which may be ascribed to the weak adsorption of the polyurethane on the electrode surface. The influence of lithium perchlorate concentration on peak potentials indicated that supporting electrolytes played an important role in electrochemical redox of PU‐S‐Fc. In the solid state, PU‐S‐Fc/Li⁺ showed discernible redox peaks at temperatures higher than 60°C, and an exponential increase curve of electrochemical response with an increase of temperature was found. Temperature variations of the solid‐state ionic conductivity for PU‐S‐Fc/Li⁺ can be interpreted by the Arrhenius equation. The similarity between the temperature dependence of ionic conductivity and electrochemical response revealed that transport mechanism of ionic and redox species in the polyurethane matrix was controlled by the mobility of polyether chains. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 2674–2680, 1999     

The Cytotoxic Activity of Macromolecular Ferrocene Conjugates Against the Colo 320 DM Human Colon Cancer Line

Water-soluble and biocompatible polymers containing bioreversibly attached ferrocene units as side chain terminals have in recent years attracted interest in drug research. In preliminary screens, polymers of this type have shown high antiproliferative activity against selected human carcinoma cell lines, paired with low in vivo toxicity. They may thus lend themselves as efficacious prodrugs in cancer chemotherapy. Cancers of the intestinal system are known to resist chemotherapeutic treatment. This general lack of sensitivity of the colorectal malignancies prompted us to investigate the in vitro behavior of selected carrier-bound ferrocene prodrugs against the Colo 320 DM cell line, a representative human adenocarcinoma of the colon. The findings of this investigation are reported in the present communication. The carriers 1 to 10 used for conjugation with the metallocene are water-soluble aliphatic polyamides featuring primary or secondary amine functionality as side chain terminals or main chain constituents. By previously developed methodology these amino groups are coupled with the ferrocenylation agent, 4-ferrocenylbutanoic acid, generating the target conjugates 1-Fc to 10-Fc, in which the metallocene is bound through amide or hydrazone links. Cell culture tests are performed by established protocol against the Colo line and, for comparison, also against the HeLa cells. Significantly, while outstanding performance is observed for most of the conjugates against both cell lines, the results indicate activities in the Colo screens to be higher on average than determined in the sensitive HeLa tests.     

Electronic Communication in the Mixed-valence States of Cyclobutadienecobalt Complexes having Two Ferrocenes and Two Anthraquinones

Two geometric isomers, Z and E forms of (η⁴-cyclobutadiene)(η⁵-cyclopentadienyl) cobalt simultaneously containing two ferrocene moieties and two anthraquinone moieties, 1 and 2, respectively, were synthesized, and their crystal structures were determined. These molecules formed double mixed-valence states caused by ferrocene–ferrocenium and anthraquinone–anthrasemiquinone electronic communications. In both 1 and 2, the thermodynamic stability of the mixed-valence state for the ferrocene moieties was higher than that of the anthraquinone moieties because of the orbital coupling of the CB–Co bridging unit. The comproportionation constant, K _c, for the ferrocene moieties was similar between 1 and 2, whereas the mixing coefficient, α, and the off-diagonal matrix-coupling element in the Marcus-Hush two-state model, H _AB, evaluated from analysis of the intervalence charge transfer (IVCT) band were larger for 1 than for 2. These results suggest the existence of higher electrostatic repulsion between two ferrocenium cations in 1 than in 2 and the occurrence of through-bond electronic communication. K _c for the anthraquinone moieties in the E form is smaller than that of the Z form, probably due to the through-space electronic interaction.     

Synthesis,antibacterial and antifungal evaluation of thio- or piperazinyl-substituted 1,4-naphthoquinone derivatives

A series of S-, S,S-, S,O-, N- and N,S-derivatives from 2,3-dichloro-1,4-naphthoquinone compound 1 were synthesized in different reaction media and evaluated for their antibacterial and antifungal activities. The structures of the novel products were characterized by spectroscopic methods, such as microanalysis, ¹H NMR, ¹³C NMR and MS. Among the tested compounds 9, 12 and 18 are the most effective compounds against Candida tenuis as potent antifungal compounds. Compound 9 is also the most effective compound against Staphylococcus aureus as a potent antifungal compound.     

Synthesis,characterization, biological evaluation,and drug release study of polyamidoamine-containing neridronate

Polyamidoamines were synthesized by Michael-type polyaddition reaction and conjugates characterized by ¹H NMR, ³¹ Mosmann, T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. J. Immunol. Meth. 1983, 65, 55–63.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]P NMR, FTIR, SEM, and EDX. The biological evaluation of the new materials revealed 12–30% inhibition of the human breast cancer cells (MCF7) and 25% of the Plasmodium falciparum malaria parasites by the conjugates. The hemolysis assay revealed that these materials did not have any effect on the host red blood cell membrane. The release mechanism of neridronate followed Korsmeyer–Peppas model at pH 1.2 with a diffusion coefficient of 0.45 indicating a Fickian diffusion mechanism; Higuchi model at pH 6.0 thus indicating a diffusion mechanism.     

Synthesis of Conjugated Polymers Containing Phosphole with the 5-Member Fused Carbocycle

Summary Novel conjugated polymers 9a–c possessing the phosphole ring with the 5-member fused carbocycle were synthesized by palladium catalyzed coupling reaction of 1-phenyl-2,5-bis(p-bromophenyl)phosphole 7 with diethynylarenes 8a–c. The obtained polymers 9a–c had the regio-regulated 2,5-substituted phosphole ring in the polymer main chain, and were characterized by ¹H, ¹³C, ³¹P NMR, and FTIR. The ³¹P NMR spectra revealed that the extension of π-conjugation changed the phosphole ring angles. The optical properties of polymers 9a–c were independent of the size of the fused carbocycle.     

Electrochemical studies and self diffusion coefficients in cyclic ammonium based ionic liquids with allyl substituents

Several cyclic ammonium-based ionic liquids (ILs) with allyl substituent are synthesized, these allyl substituent ILs have high ionic conductivity (up to 4.72 mS cm⁻¹ at 30 °C) and wide electrochemical window of 5 V. The electrochemical behaviors of two organometallic redox couples Fc/Fc⁺ (ferrocene/ferrocenium) and Cc/Cc⁺ (cobaltocene/cobaltocenium) have been studied in these ILs, the calculated Stokes–Einstein product (Dη T⁻¹) of ferrocene in ILs is larger than that of cobaltocenium in ILs. The self-diffusion coefficients of cation and anion in these ILs are studied using pulsed gradient spin-echo NMR technique. There are very few reports where electrochemically derived diffusion coefficients and self diffusion coefficients are available for comparison, so a new key concept in electrochemistry could be developed in this paper.     

Liquid phase synthesis of aromatic poly(azomethine)s,their physicochemical properties,and measurement of ex situ electrical conductivity of pelletized powdered samples

Aromatic bis-aldehydes have been used as building blocks in the synthesis of polyazomethines (a class of conjugated Schiff bases) and their physicochemical properties have been studied. Six dialdehydes have been synthesized, 3a-3f, via etherification reaction between aromatic diols (2a-2f) and 4-fluorobenzaldehyde (1) (see Scheme 1), and then polymerized with 1,4-phenylenediamine (4a) and 4,4′-oxydianiline (4b) (see Scheme 2). The chemical structures of the bis-aldehydes were elucidated by FTIR, ¹H NMR and ¹³C NMR spectroscopic studies, elemental analysis and single crystal whereas the polymers were studied by FTIR and NMR spectroscopy. Their physicochemical properties were examined by their inherent viscosity, organosolubility, differential scanning calorimetry, X-ray powder diffraction, thermogravimetric analysis, solvatochromism, and photoluminescence. We report the electrical conductivity of each polymer measured by the four probe method. The results indicate that the electrical conductivity of polymers lies in range 0.019–0.051 mScm^?1 which is reasonably higher than any reported value.     

Preparation,characterization, and antimicrobial activity of ferrocene-containing polymeric materials

Ferrocenyl(benzyl) imidazole (FcIm) and two related methyl-imidazolium salts (FcMIm⁺I^– and FcMIm⁺PF₆^–) were synthesized for their incorporation into plasticized PVC by solvent casting technique. The obtained materials were investigated for their thermal stability and, compared to pure polymer, films containing ionic ferrocene derivatives in 0.5% w/w loading were found slightly more stable. The pure ferrocene compounds showed antibacterial activity against Staphylococcus epidermis, but not against Escherichia coli, with a maximum for FcMIm⁺PF₆^– salt. After incorporation into PVC polymer, antibacterial activity against S. epidermis was observed (by disk diffusion test) only for PVC/FcMIm⁺PF₆^– (5% w/w) film, from which a release of 14.6% of the ferrocenilimidazolium cation in aqueous medium was measured after 24 hr.     

Effect of ferrocene substituents and ferricinium additive on the properties of polyaniline derivatives and catalytic activities of palladium‐doped poly(m‐ferrocenylaniline)‐catalyzed Suzuki–Miyaura cross‐coupling reactions

Poly(aniline‐co‐m‐ferrocenylaniline) and ferricinium‐doped poly(aniline‐co‐m‐ferrocenylaniline) were synthesized by a conventional chemical oxidative polymerization, then characterized by spectroscopic techniques and quantitative analyzes. Increasing of the percentages of m‐ferrocenylaniline in the copolymers resulted to a blue shift of UV–Vis absorption spectra. Broader EPR spectra indicated the loss of conjugation and crystallinity of copolymers. ¹H NMR spectra confirmed the presence of ferrocene moieties and ferricinium in the polymers. The CV measurements showed that the electron withdrawing power of ferrocene moieties could lead to the decreasing of electron delocalization on the polymer main chain. The VSM results showed that as‐prepared copolymers were soft magnetic materials with very low magnetization. Pd‐doped poly(m‐ferrocenylaniline) as catalysts were utilized in the Suzuki–Miyaura cross‐coupling reactions to improve the catalytic activities. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1489–1497, 2013     

Thermally Stable and Optically Active Poly(amide-imide)s Derived from 4,4’–(Hexafluoroisopropylidene)-N,N’-bis-(phthaloyl-L-methionine) Diacid Chloride and Various Aromatic Diamines: Synthesis and Characterization

Summary Thermally stable and optically active poly(amide-imide)s (PAIs) have been synthesized and their properties such as optical activity, solubility, thermal stability were studied. Polymers were synthesized by solution polymerization of 4,4’–(hexafluoroisopropylidene)-N,N’-bis-(phthaloyl-L-methionine) diacid chloride and various aromatic diamines by three different methods. The compounds obtained were characterized by elemental C, H and N analysis, solubility, FTIR, ¹H NMR and ¹⁹F NMR spectroscopy. Thermogravimetric curves were also recorded. All data agree with the proposed structures.     

Dual chemosensing properties of new ferrocene-based receptors towards fluoride and copper(II) ions

The new ferrocene based receptors N-[4-ferrocenyl-2-methyl-4-oxobut-1-enyl]-N′-phenylthiourea (1), N-[4-ferrocenyl-2-methyl-4-oxobut-1-enyl]-N′-[4-nitrophenyl]thiourea (2) were synthesized and characterized. Fluorescence titrations of receptors 1 and 2 with various transition metal ions showed selective response to Cu²⁺ ions and the emission intensities quenched significantly. Electrochemical titrations with anions revealed that receptors 1 and 2 sensed the F⁻ anion in high selectivity with a cathodic shift of 100 mV.     

Study on synthesis and electrochemical properties of novel ferrocene-based compounds and their applications in anion recognition

Two novel ferrocene-based compounds glycidyl ester of ferrocene carboxylate (GEFC) and 1,3-diferrocenecarboxylic acid diacylglycerol (DFCDG) were synthesized and characterized by ¹H NMR and mass spectrum. The influence of some factors, namely, solvent type, potential scan rate, electrolyte concentration and [Fe] unit concentration, on the electrochemical behaviors of two novel ferrocene-based compounds was investigated, and the mechanism of the electrode processes was studied. Finally, two compounds were applied to sense the H₂PO₄⁻ by cyclic voltammetry (CV) method and it was found that the DFCDG with a symmetric structure which was synthesized through ring opening reaction of ferrocene carboxylate and GEFC showed stronger interaction with the H₂PO₄⁻ than GEFC.     

Synthesis of Ferrocene-Based Hyperbranched Polyether and Its Catalytic Performance for Thermal Decomposition of Ammonium Perchlorate

A series of ferrocene-based hyperbranched polyethers (HBPE-Fc) with different ferrocene content were synthesized by esterification of ferrocenecarbonyl chloride and hyperbranched polyether (HBPE). ¹H NMR and FT-IR were used to confirm the structure of HBPE and HBPE-Fc. GPC was used to calculate the molecular weights. The catalytic performance of the synthesized HBPE-Fc for thermal decomposition of ammonium perchlorate (AP) was investigated by TG and DTG techniques. The results showed that HBPE-Fc exhibited good catalytic activity on the thermal decomposition of AP. The influence factors on catalytic performances, such as substitution degree of ferrocene and mass ratio of AP/HBPE-Fc were discussed as well.     

Synthesis, Structure, and Properties of Aromatic Ring-Layered Polymers Containing Ferrocene as a Terminal Unit

[2.2]Paracyclophane-layered polymers 4a and 4b end-capped by ferrocene and [2.2]paracyclophane, respectively, were synthesized by using a xanthene skeleton as a scaffold. Two model compounds, 4,5-bis(ferrocenylethynyl)-9,9-dimethylxanthene 7 and pseudo-p-bis(4-ferrocenylethynyl-9,9-dimethylxanthen-5-yl)[2.2]paracyclophane 8, comprising ferrocenes arranged in a face-to-face manner were also prepared. According to the X-ray molecular structure of compound 8, [2.2]paracyclophane between the ferrocenes had sufficient space for twisting and there was no interaction between two ferrocenes via [2.2]paracyclophane in the ground state. These polymers exhibited blue-light emission originating from the layered cyclophanes; however, the photoluminescence intensity of polymer 4a was lower than that of polymer 4b. The fluorescence emission of polymer 4a was effectively quenched by the end-capping ferrocene group. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

1,3,5‐Triazino Peptide Derivatives: Synthesis,Characterization, and Preliminary Antileishmanial Activity

A library of short di‐, tri‐, and tetra‐peptides with an s‐triazine moiety at the N terminus and either an amide or ethyl ester C terminus was prepared in solution and on the solid phase. The two remaining positions of the s‐triazine moiety were substituted with methoxy, morpholino, or piperidino groups. All the synthesized peptide derivatives were analyzed by HPLC and fully characterized by IR spectroscopy, ¹H and ¹³C NMR spectroscopy, elemental analysis, and mass spectrometry (MALDI TOF/TOF). A preliminary study of the antileishmanial activity of the 1,3,5‐triazinyl peptide derivatives revealed that four dipeptide amide derivatives showed higher antipromastigote or antiamastigote activity than the reference standard drug miltefosine with no significance acute toxicity.     

Water‐soluble poly(ethylene glycol) prodrug of pemetrexed: Synthesis,characterization, and preliminary cytotoxicity

Pemetrexed is a novel antifolate of antimetabolite with multiple enzyme targets involved in both pyrimidine and purine synthesis. It has entered the clinical usage due to favorable profiles especially in the cancer treatment of mesothelioma and non–small‐cell lung carcinoma. But it presents numerous challenges associated with poor water solubility and unstability in its original form of glutamic acid. The aim of this study is to solubilize pemetrexed by designing and synthesizing its aqueous‐soluble prodrug using high aqueous‐soluble polymeric carrier poly(ethylene glycol) (PEG). A new type of soluble pemetrexed prodrug was synthesized with dihydroxyl PEG and a single amino acid linkage, and was extensively characterized using ¹H‐NMR, ¹³C‐NMR, Fourier‐transform infrared, and matrix‐assisted laser desorption time of flight mass spectrometry. In addition, the prodrugs were evaluated for the drug loading capability, the aqueous solubility, and the preliminary in vitro cytotoxicity. The results indicate that the new PEGylated pemetrexed conjugates possess enhanced water solubility and stability, and provide another feasible choice of the pharmaceutical form of pemetrexed in the clinical application. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009