Furan Moiety Research Articles

Nonlinear optical activity of imino-dyes with furan, thiophene or thiazole moieties as π-conjugated bridge: a computational investigation

ABSTRACT The electronic, linear and nonlinear optical properties of some heterocycle-containing imino-dyes, namely, the synthesised dyes 1–3 and the designed dye 4, were evaluated using suitable long-range corrected DFT functionals. HOMO–LUMO gaps, dipole moments, polarisabilities, and first hyperpolarisabilities were calculated using CAM-B3LYP, ωB97XD and LC-ωPBE methods combined with the 6-311++G(d,p) basis set using CAM-B3LYP/6-31G(d,p) optimised geometries. The calculated molecular hyperpolarisabilities, µβ, increase in the order 1 < 2 < 3 as expected experimentally. The enhancement of µβ when passing from dye 1 to dye 2 is due to the replacement of furan by thiophene and the increase of µβ when passing from dye 2 to dye 3 is due to the change of the thiophene position from the acceptor side to the donor side. Interestingly, the replacement of thiophene (dye 2) by thiazole (dye 4) leads to a notable increase of the NLO response. The electronic transitions data of dyes 1–4 were calculated at the CIS/6-31G(d,p) level of theory and the predicted order 1 < 2<3 < 4 of µβ values is conveniently explained using the two-level model based on the calculation of the dipole moment absolute change, |ΔµEG |, from the ground to the excited state. Consequently, dye 4 could be a promising candidate for organic NLO devices.

Valuable furan fatty acids in soybeans and soy products

Furan fatty acids (FuFAs) are valuable minor compounds in our food with excellent antioxidant properties. Naturally occurring FuFAs are characterised by a central furan moiety with one or two methyl groups in β-/β’-position of the heterocycle (monomethyl- or M-FuFAs and dimethyl- or D-FuFAs). Comparably high concentrations of D-/M-FuFAs were reported in soybeans, but soy is often consumed as a processed product, such as full-fat soy flour and flakes, soy drink, tofu and texturised soy protein (TSP). Due to the chemical lability of D-/M-FuFAs, e.g. in the presence of light or oxygen, a degradation during the processing is possible. For this purpose, freshly harvested soybeans (n = 4) and differently processed soybean products (n = 22) were analysed on FuFAs. Three FuFAs, i.e. 11-(3,4-dimethyl-5-pentylfuran-2-yl)-undecanoic acid (11D5), 9-(3,4-dimethyl-5-pentylfuran-2-yl)-nonanoic acid (9D5), and 9-(3-methyl-5-pentylfuran-2-yl)-nonanoic acid (9M5), were identified and quantified in all fresh soybeans and most of the processed soy products (n = 20). A trend towards lower D-/M-FuFA contents in higher processed products was observable. Lower FuFA concentrations were usually accompanied with a decrease of the share of the less stable D-FuFAs (9D5, 11D5) in favour of the M-FuFA 9M5. Furthermore, one or two 3,4-nonmethylated furan fatty acids (N-FuFAs), i.e. 8-(5-hexylfuran-2-yl)-octanoic acid (8F6) and partly 7-(5-heptylfuran-2-yl)-heptanoic acid (7F7), were detected in all processed products, but not in the freshly harvested soybeans. Our results indicate that D-/M-/N-FuFAs may serve as suitable markers for both, careful manufacturing processes and adequate storage conditions of soy products.

A theoretical study of X‐H∙∙∙π and X∙∙∙π interactions in the complexes of furan, thiophene, pyrrole and hydrogen halides

AbstractBy using ab initio geometry optimization calculations we obtained thirteen stable complexes containing H∙∙∙π and X∙∙∙π interactions between Furan, Thiophene, Pyrrole and HX (X = F, Cl, Br) at the MP2/6‐311++G(3df,2pd) high level of theory. The interaction energies corrected for only ZPE and both ZPE and BSSE range from ‐7.92 to ‐28.47 kJ.mol‐1 and ‐3.28 to ‐22.33 kJ.mol‐1, respectively. The results show that for the same HX, the stability of complexes decreases in going from Pyrrole to Thiophene and finally to Furan moiety, and increases in the order of HF &lt; HCl &lt; HBr monomer with the same π‐system. The obtained results from AIM and MEP analyses indicate that the H∙∙∙π interaction is more stable than X∙∙∙π one in all the investigated complexes. It is found that the electrostatic, dispersion and induction energy terms significantly contribute to strength of the studied complexes, in which two formers are for H∙∙∙π hydrogen bonded complexes and two latters are for X∙∙∙π halogen bonded complexes.

Synthesis of 1,6‐didecylnaphtho[1,2‐b:5,6‐b']difuran‐based copolymers by direct heteroarylation polymerization

AbstractThe use of direct CH arylation cross‐coupling polymerization was evaluated for the synthesis of donor–acceptor conjugated co‐polymers using the novel donor 1,6‐didecylnaphtho[1,2‐b:5,6‐b']difuran and either thieno[3,4‐c]pyrrole‐4,6‐dione (TPD) or 1,4‐diketopyrrolo[3,4‐c]pyrrole (DPP) as the acceptor. Thiophene and furan moieties were used to flank the DPP group and the impact of these heterocycles on the polymers' properties was evaluated. The alkyl chains on the diketopyrrolopyrrole monomers were varied to engineer the solubility and morphology of the materials. All of the polymers have similar optoelectronic properties with narrow optical band gaps around 1.3 eV, which is ideal for solar energy harvesting. Unfortunately, these polymers also had high‐lying highest occupied molecular orbital levels of −4.8 to −5.1, and as a result bulk‐heterojunction photovoltaic cells fabricated using the soluble fullerene derivative PC71BM as the electron‐acceptor and these polymers as donor materials exhibited poor performance due to limited Voc values. An examination of the films from these blends indicates that film‐thickness and morphology were also a major hindrance to performance and a potential point of improvement for future materials.

Dibenzofuranylethylamines as 5-HT2A/2C Receptor Agonists.

The human 5-HT2 receptor subtypes have high sequence identity in their orthosteric ligand-binding domain, and many agonists are poorly selective between the 5-HT2A and 5-HT2C subtypes. Nevertheless, their activation is associated with different pharmacological outcomes. We synthesized five phenethylamine analogs in which the benzene ring is replaced by a bulky dibenzo[b,d]furan moiety and found a couple with >70-fold 5-HT2C selectivity. Molecular docking studies of the most potent compound (5) at both receptor subtypes revealed the likely structural basis of its selectivity. Although in both cases, some crucial interactions are conserved, the change of the Ala2225.46 residue in the 5-HT2C receptor to the larger Ser2425.46 in the 5-HT2A subtype, which is the only structural difference between the orthosteric binding pockets of both receptors, weakens a π–π stacking interaction between the dibenzofuran moiety and the important Phe6.52 residue and breaks a hydrogen bond between the dibenzofuran oxygen and Ser5.43, explaining the selectivity of compound 5 for the 5-HT2C receptor. We believe that this effect of the residue at position 5.46 merits further exploration in the search for selective 5-HT2C receptor agonists that are of considerable interest in the treatment of schizophrenia and substance abuse.

Exploiting Double Exchange Diels-Alder Cycloadditions for Immobilization of Peptide Nucleic Acids on Gold Nanoparticles.

The generation of PNA-decorated gold nanoparticles (AuNPs) has revealed to be more difficult as compared to the generation of DNA-functionalized ones. The less polar nature of this artificial nucleic acid system and the associated tendency of the neutral poly-amidic backbone to aspecifically adsorb onto the gold surface rather than forming a covalent bond through gold-thiol interaction, combined with the low solubility of PNAs itself, form the main limiting factors in the functionalization of AuNP. Here, we provide a convenient methodology that allows to easily conjugate PNAs to AuNP. Positively charged PNAs containing a masked furan moiety were immobilized via a double exchange Diels-Alder cycloaddition onto masked maleimide-functionalized AuNPs in a one-pot fashion. Conjugated PNA strands retain their ability to selectively hybridize with target DNA strands. Moreover, the duplexes resulting from hybridization can be detached through a retro-Diels-Alder reaction, thus allowing straightforward catch-and-release of specific nucleic acid targets.

Highly Transparent and Colorless Self‐Healing Polyacrylate Coatings Based on Diels–Alder Chemistry

AbstractThe efficient integration of reversible polymer networks into acrylate‐based polymeric materials is of peculiar interest for the development of coatings that combine high transparency with self‐healing ability. In this work, reversible networks are obtained by reacting a series of linear copolymers of furfuryl methacrylate with aliphatic bismaleimides through Diels–Alder (DA) reaction between furan and maleimide moieties. Owing to dynamic crosslinking, the obtained coatings exhibit thermal reversibility, as determined by differential scanning calorimetry and dissolution experiments. Furthermore, upon heating over the retro‐DA temperature, an excellent recovery of mechanically induced surface damages proves successful thermal remendability. Compared to previous reports on DA‐based acrylate networks, the presented thermally responsive coatings exhibit outstanding transparency and absence of color, as a result of an accurate choice of suitable monomeric precursors. In addition, a pronounced hydrophobic behavior and excellent adhesive properties make the proposed material particularly suitable for optical applications.

Transposition of Aromaticity from a Furan to a Cyclohexane Ring in Furoisoindoles During the Interaction of 3-(Furyl)allylamines with Bromomaleic Anhydride

An unexpected four-step reaction sequence was discovered in the course of investigation of the interaction between 3-(furan-2-yl)allylamines and bromomaleic anhydride. This conversion begins with the initial N-acylation of the allylamines by the anhydride, followed by intramolecular Diels–Alder reaction, which is accompanied by a dehydrohalogenation, and ends with the formation of partially unsaturated furo[2,3-f]isoindoles followed by transposition of aromaticity from the furan moiety to the neighboring cyclohexane ring. The reaction between 3-(furan-3-yl)allylamines and bromomaleic anhydride does not stop at a furo[2,3-f]isoindole formation step, but proceeds further with the cleavage of the furan ring in a 100% atom-efficient fashion to provide polysubstituted isoindoline-4-carboxylic acids.

Design Strategy for Robust Organic Semiconductor Laser Dyes

A new molecular design for organic semiconductor laser dyes showing excellent optical properties and high robustness is disclosed in this work. The suitability of a furan moiety for increasing the ...

Development of an Innovative and Eco-Friendly UV Radiation Absorber, Based on Furan Moieties

The increasing concern about the environmental impact of ingredients largely used as sunscreens today is pushing research towards new frontiers for the synthesis and degradation potential of innovative sun protection structures. This study deals with the design, synthesis, efficacy evaluation, and environmental impact of new photo-stable molecules at extended electronic conjugation and which have the ‘charge-transfer’ type of optical transition (push and pull). They efficiently perform absorption of electro-magnetic radiation in the UVB and UVA regions. A preliminary screening, dealing with a whole series of aromatic donors, led to the selection of a key substrate derived from waste material, provided with low environmental impact and largely available on the market. As far as the acceptor was concerned, an ester with cyan-acrylic structure and functionalized with aliphatic chains emerged as the most suitable. This allowed a shift of the λ of absorption in the range of the ultraviolet wavelengths. The synthesis procedures include an acid-catalyst-fitted esterification, condensation, and cold crystallization. It was continuously monitored with suitable characterization instruments (GC-MS, 1H NMR, 13C NMR), in order to avoid by-products and parasitic reactions. The resulting structures (patent pending) are composed by a furan core condensed with cyano-acrylic esters, derivatized with branched chains of hydrocarbons of medium length. The obtained structures are capable of good absorption in the range of wavelengths between 300 and 400 nm. Because of their structures, the new molecules are largely soluble in many common oils and cosmetic ingredients. The new molecules have been successively evaluated in terms of photo-stability, biodegradability, compatibility, and UVB-UVA protection capability, both in-vivo and in-vitro, in comparison with existing sunscreens.

Doubly vinylogous and doubly rearomative functionalization of 2-alkyl-3-furfurals.

The manuscript describes a straightforward functionalization of 2-alkyl-3-furfurals via simple aminocatalytic conjugate addition. The reaction proceeds through the formation of dearomatized dienamine-like intermediate that undergoes 1,6-addition to 4-alkylidene-2,6-dialkylcyclohexa-2,5-dienones. This process can be described as doubly rearomative as it proceeds with the re-formation of both furan and phenyl aromatic moieties. Target products have been obtained in a highly stereoselective manner, providing an interesting example of 2-alkyl-3-furfural functionalization via doubly vinylogous Michael addition. The mechanism of the reaction has been studied by means of computational methods.

The crucial role of metabolic regulation in differential hepatotoxicity induced by furanoids in Dioscorea bulbifera.

Diterpenoid lactones (DLs), a group of furan-containing compounds found in Dioscorea bulbifera L. (DB), have been reported to be associated with hepatotoxicity. Different hepatotoxicities of these DLs have been observed in vitro, but reasonable explanations for the differential hepatotoxicity have not been provided. Herein, the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs (diosbulbins A, B, C, F). In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3A4 at the atomic level were simulated by molecular docking. Results showed that DLs exhibited varied cytotoxicities, and that CYP3A4 played a modulatory role in this process. Moreover, structural variation may cause different affinities between DLs and CYP3A4, which was positively correlated with the observation of cytotoxicity. In addition, analysis of the glutathione (GSH) conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs, whereas, GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity. Collectively, our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.

Visible-light triggered templated ligation on surface using furan-modified PNAs.

Oligonucleotide-templated reactions are frequently exploited for target detection in biosensors and for the construction of DNA-based materials and probes in nanotechnology. However, the translation of the specifically used template chemistry from solution to surfaces, with the final aim of achieving highly selective high-throughput systems, has been difficult to reach and therefore, poorly explored. Here, we show the first example of a visible light-triggered templated ligation on a surface, employing furan-modified peptide nucleic acids (PNAs). Tailored photo-oxidation of the pro-reactive furan moiety is ensured by the simultaneous introduction of a weak photosensitizer as well as a nucleophilic moiety in the reacting PNA strand. This allows one to ensure a localized production of singlet oxygen for furan activation, which is not affected by probe dilution or reducing conditions. Simple white light irradiation in combination with target-induced proximity between reactive functionalities upon recognition of a short 22mer DNA or RNA sequence that functions as a template, allows sensitive detection of nucleic acid targets in a 96 well plate format.

In situ forming hydrogel for sustained intraocular drug delivery

AbstractPurposeDelivery of therapeutic proteins to the posterior segment of the eye faces significant challenges because of frequent intraocular injections, related adverse effects and high treatment costs. This research project aims to design in situ forming hydrogels, which can be easily injected in the vitreous cavity using a small needle. After injection, the polymeric solution undergoes a phase transition to form a cross‐linked hydrogel at the site of administration, entrapping bioactives, which will be released over a prolonged period. In this study, Hyaluronic acid‐modified with furan moieties (HAFU) was successfully crosslinked with four arm‐PEG10K‐maleimide (4APM) yielding stable hydrogels. The potential use of this system for ocular applications was shown by testing the injectability, sustained release of a therapeutic protein and cytocompatibility to retinal cells.Methods &amp; ResultsHAFU‐4APM hydrogels were prepared by mixing an aqueous solution of HAFU and 4APM at physiological conditions to obtain transparent hydrogels. Rheological analysis showed rapid hydrogel network formation at 37°C. The gelation time and final hydrogel stiffness are strongly dependent on polymer concentration. Hydrogel solutions could be injected to the vitreous body of a porcine eye through a 29G needle. Swelling and degradation analysis showed that the hydrogel system is degradable at physiological conditions. The hydrogels showed no toxicity to retinal cells at the used concentrations. HAFU‐4APM hydrogels could sustain the delivery of bevacizumab for 71 days.ConclusionInjectable in situ forming hydrogels have been prepared for the sustained retinal delivery of bevacizumab. The formulation has potential for the treatment of age‐related macular degeneration and diabetic retinopathy.AcknowledgementsThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 722717.

A novel model to simulate the formation and healing of cracks in self-healing cross-ply composites under flexural loading

The formation and healing of cracks in fiber-reinforced composites made of a thermally remendable polymeric matrix were studied. A new thermally remendable polymer, using furan and maleimide moieties based on the Diels–Alder reaction was synthesized and employed for the fabrication of fiber-reinforced composites. To find the healing efficiency of composites, three-point bending specimens with the stacking sequence of [903/0/903] were prepared. The specimens were initially subjected to tensile loading until reaching the characteristic damage state. Then, the flexural modulus and strength after the healing up to different conversion degrees were obtained and compared with the virgin specimens. The results revealed over 95% recovery of the flexural strength and modulus after the complete healing. In addition, the effect of multiple healing on the healing efficiency was investigated and it was observed that the percentage of recovery would remain constant in the absence of fiber breakage. Using the shear-lag analysis and the classical lamination theory, a novel model was developed to simulate the residual flexural modulus of the damaged specimens as a function of the crack density. Moreover, the proposed model was extended to predict the recovered flexural stiffness after the healing of the specimens. A comparison of the results of the model and experiments validated the capability of the proposed model.

Synthesis and Biological Evaluation of Some Succinimide Hybrid Molecules

In this study, a new series of succinimide hybrid molecules containing isothiocyanate, coumarin, isatin, and furan moieties was synthesized and screened for α-glucosidase and antioxidant activities. Preliminary results revealed that all molecules showed good α-glucosidase inhibition effectiveness. Antioxidant activities of the hybrid molecules were determined using cupric reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP) assays. Also, the radical scavenging activities of the synthesized compounds were assayed by using $${\text{ABT}}{{{\text{S}}}^{{\centerdot {\text{ + }}}}}$$ and $${\text{DPP}}{{{\text{H}}}^{\centerdot }}$$ methods. The results showed that all compounds exhibited moderated to high scavenging activity.

The effect of triethylene glycol additive on the self-healing properties of epoxy binder

A triethyleneglycol-modified epoxy composition based on diglycidylfurfurylamine (FuEp) and 1,1’- (methylene-di-4,1-phenylene)bismaleimide (BMI) was cured with methyl hexahydrophthalic anhydride (MHPPA). The components of the composition can reversely binds through Diels-Alder reaction between furan and maleimide moieties. We studied the effect of TEG additive on the rheological and thermophysical properties of the binder, as well as the ability through thermal treatment. All compounds were characterized with NMR and IR spectroscopy. It was shown that TEG significantly reduces the curing time and the glass transition temperature of the cured samples, which allows to speed up the process of self-healing.

Thermally reversible nanocellulose hydrogels synthesized via the furan/maleimide Diels-Alder click reaction in water

The study deals with the synthesis of thermally reversible hydrogels from modified cellulose nanofibers via the Diels-Alder “click” reaction in an aqueous medium. “Never-dried” cellulose fibres derived from hardwood were submitted to shearing and surface TEMPO-oxidation before being modified with furfurylamine. The ensuing pendant furan moieties were reacted with a water-soluble bismaleimide via Diels-Alder coupling at 65 °C to produce a hydrogel, whose deconstruction was induced by the corresponding retro-Diels-Alder reaction carried out at 95 °C. Differential scanning calorimetry and rheological measurement were used to characterize the hydrogels. These aqueous cellulosic materials should provide original applications in such areas as strong paper-based artefacts and biocompatible gels.

Valuable furan fatty acids in soybeans and soy products

Furan fatty acids (FuFAs) are valuable minor compounds in our food with excellent antioxidant properties. Naturally occurring FuFAs are characterised by a central furan moiety with one or two methyl groups in β-/β’-position of the heterocycle (monomethyl- or M-FuFAs and dimethyl- or D-FuFAs). Comparably high concentrations of D-/M-FuFAs were reported in soybeans, but soy is often consumed as a processed product, such as full-fat soy flour and flakes, soy drink, tofu and texturised soy protein (TSP). Due to the chemical lability of D-/M-FuFAs, e.g. in the presence of light or oxygen, a degradation during the processing is possible. For this purpose, freshly harvested soybeans (n = 4) and differently processed soybean products (n = 22) were analysed on FuFAs. Three FuFAs, i.e. 11-(3,4-dimethyl-5-pentylfuran-2-yl)-undecanoic acid (11D5), 9-(3,4-dimethyl-5-pentylfuran-2-yl)-nonanoic acid (9D5), and 9-(3-methyl-5-pentylfuran-2-yl)-nonanoic acid (9M5), were identified and quantified in all fresh soybeans and most of the processed soy products (n = 20). A trend towards lower D-/M-FuFA contents in higher processed products was observable. Lower FuFA concentrations were usually accompanied with a decrease of the share of the less stable D-FuFAs (9D5, 11D5) in favour of the M-FuFA 9M5. Furthermore, one or two 3,4-nonmethylated furan fatty acids (N-FuFAs), i.e. 8-(5-hexylfuran-2-yl)-octanoic acid (8F6) and partly 7-(5-heptylfuran-2-yl)-heptanoic acid (7F7), were detected in all processed products, but not in the freshly harvested soybeans. Our results indicate that D-/M-/N-FuFAs may serve as suitable markers for both, careful manufacturing processes and adequate storage conditions of soy products.

Cytotoxic Spliceostatin Analogs from Pseudomonas sp.

Two new spliceostatin analogs, designed as spliceostatins J and K (1 and 2), were isolated and identified from the culture of Pseudomonas sp., along with two known ones, FR901464 (3) and spliceostatin E (4). Their structures were elucidated by detailed interpretation of their spectroscopic data, especially 2D-NMR and HR-ESI-MS. Spliceostatin J (1) represented the first example of spliceostatins bearing an unusual hexahydrofuro[3,4-b]furan moiety. Biological assay showed all the isolated compounds except 1 displayed potent cytotoxic activities against two cancer cell lines (MDA-MB-231 and A-549). Structure-activity-relationship studies revealed that the tetrahydropyran ring in spliceostatin analogs was necessary for their bioactive retention.