Cinnamoyl Groups Research Articles

Developing and analyzing photo-crosslinkable cinnamoyl-modified pullulan hydrogels for drug delivery applications

A hydrogel created by modifying pullulan with cinnamoyl groups (Pul-CM) through an esterification process was developed as an effective vehicle for delivering the well-known drug model, caffeine. Initially, pullulan biopolymer was expanded, followed by the addition of cinnamoyl groups using cinnamoyl chloride. These modifications were confirmed through various spectroscopic and instrumental techniques, verifying their proposed chemical structures. The newly created Pul-CM hydrogel demonstrated the ability to crosslink without initiators when exposed to UV light for sufficient durations. This crosslinking is attributed to the creation of cyclobutane rings that link the pullulan chains via a [2π+2π] cyclization process facilitated by the cinnamoyl groups' –CH=CH– bonds. The progress of Pul-CM crosslinking was tracked by the reduction in the UV spectral peak associated with the cinnamate groups, followed by an examination of the gel's efficiency and its swelling behavior under UV light. Furthermore, these hydrogel derivatives show significant promise as drug delivery systems, offering adjustable drug release rates by altering the hydrogel's crosslinking level through either cinnamoyl modification or the duration of UV light exposure.

Cationic Alternating Copolymerization of Vinyl Esters and 3-Alkoxyphthalides: Side Chain-Crosslinkable Polymers for Acid-Degradable Single-Chain Nanoparticles.

Cationic copolymerization of vinyl acetate and 3-alkoxyphthalides (ROPTs) was demonstrated to proceed using GaCl3 as a Lewis acid catalyst. Both monomers did not undergo homopolymerization, while copolymerization smoothly occurred via the crossover reactions, resulting in alternating copolymers with molecular weights of over 104. The obtained copolymers could be degraded by acid due to the cleavage of the diacyloxymethine moieties, which were derived from the crossover reactions from vinyl acetate to ROPT, in the main chain. An advantage of not radical but cationic copolymerization of vinyl esters was exerted by copolymerizations of radically reactive group-containing vinyl esters with ROPTs. For example, vinyl cinnamate was successfully copolymerized with an ROPT by the cationic mechanism, while keeping the cinnamoyl groups intact. The obtained alternating copolymer was subjected to a photodimerization reaction of the cinnamoyl groups in the side chains, resulting in an acid-degradable single-chain nanoparticle via the intramolecular crosslinking reactions.

Microparticles comprising cinnamoyl cellulose and cinnamoyl gelatin prepared by emulsion method and their pH and electric field-responsive release property

pH- and electric field-responsive microparticles were prepared by photo cross-linking cinnamoyl gelatin (CinGel) and cinnamoyl cellulose nanocrystal (CinCNC) contained in the water droplet of W/O emulsion. Cinnamoyl chloride (CC) was covalently attached to Gel and CNC through a condensation reaction to obtain CinGel and CinCNC, confirmed by 1H NMR and FT-IR spectroscopy. Using a colorimetric method, the cinnamoyl group (CG) content of CinGel was determined to be 1.6 % and that of CinCNC to be 3–15.3 %, depending on the CC/CNC ratio in the reaction mixture. The maximum photo-dimerization degree of CG of CinGel obtained under UV irradiation was about 33 % and that of CinCNC was 4.4–7.5 %. Microparticles were prepared by cross-linking CinGel and CinCNC contained in the water droplet of the emulsion using UV irradiation. Sphere-like particles and irregularly shaped ones were found on the SEM photo of CinGel/CinCNC microparticles and the mean dimeters were determined to be 11.6–17.1 µm. CinGel/CinCNC ratio in the emulsion little affected the shape and size of the resulting microparticles. An energy dispersive spectroscopy revealed that the microparticle composition was reflecting CinGel/CinCNC ratio in the emulsion. The release of a payload (i.e. amaranth) markedly promoted as the medium pH value increased from 3 to 8, possibly due to the decomplexation of CinGel/CinCNC electrostatic complex and/or the electrostatic expulsion of the payload from CinGel. The release was expedited as the applied voltage increased up to 4.5 V, probably due to the shear stress-induced deformation of the microparticle matrix and/or the forced electrostatic expulsion of the payload.

Reading and erasing of histone crotonyllysine mimics by the AF9 YEATS domain and SIRT2 deacylase

Lysine acylations on histones and their recognition by chromatin-binding reader domains and removal by histone deacylases function as an important mechanism for eukaryotic gene regulation. Histone lysine crotonylation (Kcr) is an epigenetic mark associated with active transcription, and its installation and removal are dynamically regulated by cellular epigenetic enzymes. Here, we report binding studies and enzyme assays with histone H3K9 peptides bearing simplest Kcr analogs with varying hydrocarbon chain length, bulkiness, rigidity and polarity. We demonstrate that the AF9 YEATS domain displays selectivity for binding of different acylation modifications on histone H3K9 peptides and exhibits preference for bulkier cinnamoylated lysine over crotonylated lysine and its mimics. SIRT2 shows deacylase activity against most of acylated H3K9 peptides bearing different crotonyllysine mimics, however, it displays a poor ability for the removal of cinnamoyl and trifluorocrotonyl groups. These results demonstrate different substrate selectivities of epigenetic proteins acting on crotonyllysine and pave the way for rational design and development of AF9 YEATS and SIRT2 inhibitors for treatment of human diseases, including cancer.

Cell patterning on photocrosslinkable polymer films with micropatternable surfaces

AbstractThe regulation of cell behavior is crucial for understanding many fundamental biological processes and designing novel medical devices. Nano/micropatterning has been developed as a means of controlling cellular properties and behaviors. Using cinnamoyl groups that have undergone photodimerization, we have prepared facile photopatterning films with adjustable surface properties for cell patterning via simple steps. Our strategy for controlling surface properties uses the decrease in free volume induced by photocrosslinking. This paper describes the surface‐patterning properties of photocrosslinkable polymer films and the cell adhesion to their micropatterned surfaces. Upon culturing cells on micropatterned surfaces, preferential cell adhesion, alignment and proliferation are observed in the unexposed regions. Additionally, diverse surface patterns of photocrosslinkable polymer films have been fabricated using various photomasks, enabling effective control of cell adhesion and alignment. The ability to regulate cellular behavior via microfabricated surfaces of photocrosslinkable polymer films enables a new and facile approach for designing scaffolds for the development of novel advanced materials, tissue engineering, and regenerative medicine.

Genome-Directed Discovery of Bicyclic Cinnamoyl-Containing Nonribosomal Peptides with Anticoronaviral Activity from Streptomyces griseus.

Two novel cinnamoyl-containing nonribosomal peptides (CCNPs) grisgenomycin A and B were identified in Streptomyces griseus NBRC 13350 (CGMCC 4.5718) and ATCC 12475, through genome mining using conserved adjacent LuxR family regulators as probes and activators. Notably, grisgenomycins represent a new group of bicyclic decapeptides featuring an unprecedented C-C bond between the tryptophan carbocycle and the cinnamoyl group. A plausible biosynthetic pathway for grisgenomycins was deduced by a bioinformatics analysis. Grisgenomycins exhibited activity against human coronaviruses at the micromolar level.

Novel styryl-thiazole hybrids as potential anti-Alzheimer's agents.

In this study, combining the thiazole and cinnamoyl groups into the styryl-thiazole scaffold, a series of novel styryl-thiazole hybrids (6a-p) was rationally designed, synthesized, and evaluated by the multi-target-directed ligands strategy as potential candidates for the treatment of Alzheimer's disease (AD). Hybrids 6e and 6i are the most promising among the synthesized hybrids since they are able to significantly increase cell viabilities in Aβ1-42-exposed-human neuroblastoma cell line (6i at the concentration of 50 μg mL-1 and 6e at the concentration of 25 μg mL-1 resulted in ∼34% and ∼30% increase in cell viabilities, respectively). Compounds 6e and 6i exhibit highly AChE inhibitory properties in the experimental AD model at 375.6 ± 18.425 mU mL-1 and 397.6 ± 32.152 mU mL-1, respectively. Moreover, these data were also confirmed by docking studies and in vitro enzyme inhibition assays. Compared to hybrid 6e and according to the results, 6i also has the highest potential against Aβ1-42 aggregation with over 80% preventive activity. The in silico prediction of the physicochemical properties confirms that 6i possesses a better profile compared to 6e. Therefore, compound 6i presents a promising multi-targeted active molecular profile for treating AD considering the multifactorial nature of AD, and it is reasonable to deepen its mechanisms of action in an in vivo experimental model of AD.

Bioinspired Computational Design of Lankacidin Derivatives for Improvement in Antitumor Activity

Background: The 17-membered polyketide, lankacidin C, exhibits considerable antitumor activity as a microtubule stabilizer by binding to the paclitaxel binding site. Method: Esterification of theC-7/C-13 hydroxyl in lankacidin C was performedwith acetyl, cinnamoyland hydrocinnamoyl groupsand their antitumor activitywas assessedto improve the cytotoxicity of lankacidins through bioinspired computational design. Results: Compared with the cytotoxicity of parent lankacidin C against the HeLa cell line, 13-O-cinnamoyl-lankacidin C demonstrated sevenfold higher cytotoxicity. Furthermore, 7,13-di-O-cinnamoyl-lankacidin C exhibited considerable antitumor activity against three testedcell lines. Conclusion: C13-esterification by a cinnamoyl group dramatically improved antitumor activity, in agreement with computational predictions. This finding provides a potential substrate for next-generation lankacidin derivatives with significant antitumor activity.

Solution-processable and photocurable aromatic polyurea gate dielectrics for high-performance organic thin-film transistors

A solution-processable and photocurable polyurea (PU) with excellent electrical and dielectric properties is synthesized, characterized, and applied as a gate dielectric in high-performance organic thin-film transistors (OTFTs). The PU is synthesized from toluene-2,4-diisocyanate and 3,5-diaminobenzyl cinnamate via a condensation reaction. The PU containing cinnamoyl groups is photo-crosslinked without a photoinitiator and easily micropatterned by selective ultra-violet (UV) exposure. The photo-crosslinked PU (c-PU) film improves dielectric properties and thermal and chemical resistance compared with pristine PU films. We fabricated dinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophene (DNTT)-based OTFTs with a c-PU gate dielectric layer to investigate the performance of the c-PU thin film as a gate dielectric. The field-effect mobility and on/off ratio of DNTT-based OTFTs with surface-treated c-PU gate dielectric are 0.75 ± 0.03 cm2 V−1s−1 and 1.60 × 106, respectively. In addition, solution-processed diketopyrrolopyrrole-thienothiophene copolymer-based OTFTs with c-PU gate dielectric show field-effect mobility of 0.07 ± 0.01 cm2 V−1s−1 and on/off ratio of 2.88 × 105. Furthermore, the complementary inverter was successfully demonstrated by using c-PU with excellent insulating property as the gate dielectric.

Light‐driven self‐healing castor oil based polyurethane film with enhanced mechanical properties

AbstractTo meet the need of alleviating the pressure of petrochemical industry and environmental protection, polyurethane (PU) made from castor oil (CO) as polyols, replacing petrochemical based crude material has attracted a lot of recognition over the past decades. For the sake of prolonging the service life of materials, it is also necessary to endow vegetable oil‐based polymers with self‐healing properties, which is seldom involved in present study. Currently, optically responsive self‐healing system has attracted extensive attention because of its easy control and simple occurrence. However, the problem of low self‐healing efficiency also puzzles the current research of this self‐healing system. In this study, cinnamoyl group was introduced into bio‐based PU as end blocking agent. The photoresponse reversible cycloaddition reaction of cinnamyl groups and the acceptable chain fluidity of CO provided the possibility for the self‐healing properties of polymers. The dimerization degree of [2 + 2] cycloaddition reactions was as high as 58% under UV light for 36 h from UV–vis spectrum. Investigation of the optical healing property indicated that incision on the surface of certain PU sample was completely repaired and healing efficiency enhanced up to 93.1%, with the introduction of cinnamoyl group. What is more, the results from TGA, DMA and tensile tests suggested that the prepared PU samples showed excellent comprehensive performance.

Photoresponsive Gelation of Four-Armed Poly(ethylene glycol) with Photodimerizable Groups.

Standard hydrogels prepared by free radical polymerization (FRP) have heterogeneous structures with a wide mesh size distribution, which affect their mechanical and separation properties. Recent research has identified four-armed poly(ethylene glycol) (tetra-PEG) as a solution to this problem. tetra-PEG gels with a homogeneous network can be prepared and applied as high-strength gels and cell-culture substrates by reacting two types of tetra-PEG with different reactive groups at the ends. In this study, we report a photoresponsive tetra-PEG that undergoes a phase transition from a sol to a gel state in response to light. tetra-PEGs containing cinnamoyl and maleimide groups at the ends of the four-armed chains were found to gel when exposed to light. The effects of polymer concentration and light irradiation time on the gelation of tetra-PEG containing photodimerization groups were investigated. The results showed that the elastic modulus of the gel increased with the increase in the light irradiation time.

Thermally-stable photo-curing chemistry for additive manufacturing by direct melt electrowriting

In the present study, poly(ε-caprolactone) copolymers decorated with the random inclusion of thermally stable and photo-dimerizing cinnamoyl groups were synthesized for an electrically-assisted material extrusion additive manufacturing technique named melt electrowriting (MEW). The absence of thermally-induced reactions between cinnamoyl groups maintained the molten random copolymers processable at the elevated processing temperature while UV curing could improve thermo-mechanical properties of the films in the solid state. Random inclusion of non-crystallizable photo-reactive co-units was shown to enrich the thermodynamic state of the host polymer with the possibility of the formation of various microstructures, which correlated with the emergence of imperfections, such as spherulitic domains over the profile of fibers printed from molten random copolymers.

Photoresponsive Polymer Films with Directly Micropatternable Surfaces Based on the Change in Free Volume by Photo‐Crosslinking

AbstractPhotoresponsive polymers, whose structures or properties change when exposed to ultraviolet (UV) light, have been studied for the fabrication of micro‐ and nano‐devices for various applications. Herein, photoresponsive polymer films are investigated with directly micropatternable surfaces formed by only UV exposure without the development process using solvents. The photoresponsive polymer films are designed based on the decrease in free volume induced by the photodimerization of cinnamoyl groups. The photoresponsive polymers are synthesized by copolymerizing a monomer with photodimerizable groups and a poly(dimethylsiloxane) macromonomer. Micropatterns are easily formed on the film surfaces by only UV exposure using photomasks. The micropatterns are achieved due to the decrease in the film thickness with a decrease in the free volume induced by photo‐crosslinking. Using a decrease in free volume by photo‐crosslinking leads to wide practical applications with simple processes and low costs.

Experimental and theoretical study of three newly-synthesized iminochalcones: An example of dual emission induced by polarity changes

A series of iminochalcones derived from 3-(4-aminophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one, were synthesized using different p-substituted benzaldehydes (R = –N(CH3)2 (2a), –H (2b) and –NO2 (2c)). The melting points of these compounds depend on the substituent (2c > 2a > 2b) as a function of the intermolecular interactions. The absorption spectra of the iminochalcones present two bands and are very sensitive to solvent polarity due to the ICT character of the π → π* transition on the cinnamoyl group. The relative intensity between the two main absorption bands of 2c is induced by solvent polarity and depends on the character of the orbitals. Excitation and fluorescence experiments showed that iminochalcone 2a presents dual fluorescence. Together with DFT calculations, these results corroborate the polarity-induced change model in the energy order of the emissive states, indicating that both emission bands are derived from LE and ICT excited states.

Mechanistic Duality of Bacterial Efflux Substrates and Inhibitors: Example of Simple Substituted Cinnamoyl and Naphthyl Amides.

Antibiotic resistance poses an immediate and growing threat to human health. Multidrug efflux pumps are promising targets for overcoming antibiotic resistance with small-molecule therapeutics. Previously, we identified a diaminoquinoline acrylamide, NSC-33353, as a potent inhibitor of the AcrAB-TolC efflux pump in Escherichia coli. This inhibitor potentiates the antibacterial activities of novobiocin and erythromycin upon binding to the membrane fusion protein AcrA. It is also a substrate for efflux and lacks appreciable intrinsic antibacterial activity of its own in wild-type cells. Here, we have modified the substituents of the cinnamoyl group of NSC-33353, giving rise to analogs that retain the ability to inhibit efflux, lost the features of the efflux substrates, and gained antibacterial activity in wild-type cells. The replacement of the cinnamoyl group with naphthyl isosteres generated compounds that lack antibacterial activity but are both excellent efflux pump inhibitors and substrates. Surprisingly, these inhibitors potentiate the antibacterial activity of novobiocin but not erythromycin. Surface plasmon resonance experiments and molecular docking suggest that the replacement of the cinnamoyl group with naphthyl shifts the affinity of the compounds away from AcrA to the AcrB transporter, making them better efflux substrates and changing their mechanism of inhibition. These results provide new insights into the duality of efflux substrate/inhibitor features in chemical scaffolds that will facilitate the development of new efflux pump inhibitors.

Interfacial Photo-Cross-Linking: Simple but Powerful Approach for Fabricating Capsule Polymer Particles with Tunable pH-Responsive Controlled Release Capability.

Herein, we describe capsule polymer particles with precisely controlled pH-responsive release properties prepared directly via the interfacial photo-cross-linking of spherical poly(2-diethylaminoethyl methacrylate-co-2-cinnamoylethyl methacrylate) (P(DEAEMA-CEMA)) particles. In the interfacial photo-cross-linking, photoreactive cinnamoyl groups in the polymer particles were cross-linked via [2π + 2π] cycloaddition reactions at the polymer/water interface, showing that the shell-cross-linked hollow polymer particles can be directly prepared from spherical polymer particles. The approach has fascinating advantages such as using minimal components, simplicity, and not requiring sacrificial template particles and toxic solvents. The following important observations are made: (I) encapsulated materials were stably retained in the capsule particles under neutral pH conditions; (II) encapsulated materials were released from the capsule particles under acidic pH conditions; (III) the release kinetics of encapsulated materials were controlled by the pH conditions; i.e., immediate and sustained release was achieved by varying the acidity of the aqueous media; (IV) the photoirradiation time did not significantly affect the release kinetics under different pH conditions; and (V) the pH-responsive release properties were regulated by changing the polymer composition in P(DEAEMA-CEMA). Furthermore, by exploiting the pH-responsiveness, capsule particles are successfully obtained via an all-aqueous process from spherical polymer particles. The advantages of the all-aqueous encapsulation process allowed the water-soluble biomacromolecules such as DNA and saccharides to be successfully encapsulated in the P(DEAEMA-CEMA) hollow particles. With this simple interfacial photo-cross-linking strategy, we envision the ready synthesis of sophisticated particulate materials for broad application in advanced research fields.

Design and synthesis of 3, 5- hetero diesters of 4-deoxy quinic acid and their aphicidal activity against Acyrthosiphon pisum

Four analogs of 3,5-dicaffeoylquinic acid, including a new heterodiester of 4-deoxyquinic acid, were found toxic against the pea aphid. Several 4-deoxy quinic analogs featuring two different hydroxyl cinnamoyl moieties in position 3 and 5 were prepared for the first time and carefully analysed. Through an assay on pea aphid nymphs, interesting indications on the structure-aphicidal activity relationships and higher levels of toxicity were observed for four compounds related to the reference natural compound. • Analogs of chlorogenic acids featuring different and various hydroxyl cinnamoyl groups in 3 and 5 positions. • Four compounds were found to exhibit higher aphicidal activities than natural 3,5-di- O -caffeoylquinic acid. • Both acetylated 3- O -feruloyl-5- O -caffeoyl and 3- O -caffeoyl-5- O -coumaroyl compounds were active. • Observation of an interesting structure-activity difference for two regioisomers.

Photosynthesis of polymer networks with controlled properties by dimerization of cinnamoyl groups

AbstractPhotosensitive monomers/polymers/copolymers containing a variable amount of cinnamoyl (Ci) groups ranging from 3 up to 480 per molecule were synthesized. These precursors were photocrosslinked by irradiation with UV light of wavelength 320–380 nm via the photodimerization of the Ci units. The evolution of conversion, gel fraction, modulus and Tg during irradiation was followed. Two types of photosensitive systems were studied: (i) a blend of photosensitive precursors of different functionality fCi and (ii) copolymers with a different content of Ci units and Tg. The control of the precursors' structure and composition as well as photocuring time period make it possible to finely tune the properties of the formed polymer network films. The prepared photocrosslinked networks show a very broad range of thermomechanical properties with Tg from −25 °C up to 135 °C and moduli over a range of three orders of magnitude. © 2021 Society of Chemical Industry

Self-assembling behaviour of new functional photosensitive cinnamoyl-based reactive mesogens

ABSTRACT One of the most exciting classes of organic materials that is able to self-assemble at nanoscopic scale are those exhibiting the liquid crystalline (LC) behaviour which can be distantly tuned by an external stimulus. Under UV/Vis light irradiation, the reversible photoisomerisation process can take place if the compounds possess the photosensitive group, e.g. N=N or cinnamoyl group incorporated in their molecular structure. This can drastically affect the LC behaviour. However, the compounds possessing the cinnamoyl fragment with C=C double bond are capable of both photoisomerisation and photocycloaddition processes. Several cinnamoyl-based reactive mesogens with polymerisable vinyl group have been designed; their mesomorphic and structural behaviour have been studied. Depending on the molecular structure, the reactive mesogens exhibit nematic, orthogonal smectic A and tilted smectic C phases; the kinetics of the phase transition temperatures has been checked. The structure of the mesophases is confirmed by small-angle X-ray scattering. The main objective of the present work is to contribute to better understanding of molecular structure – mesomorphic property relationship for new functional cinnamoyl-based photosensitive reactive mesogens which can be further used for design of smart self-assembling macromolecular materials.

Synthesis of novel cellulose mixesters for transparent responsive films with switchable mechanical properties

Soft actuators have attracted much attention during the last decades due to their potentially broad applications ranging from sensors to artificial muscles. Up to now, most of such soft actuators are still based on synthetic polymers. Herein, we described a novel group of materials derived from sustainable cellulose as potential starting materials for the preparation of soft actuators. To be precisely, cellulose mixesters with acyl esters of distinct chain lengths and cinnamic ester were synthesized through a two-step synthesis and used for the preparation of responsive thin film actuators. These cellulose mixesters have degree of substitution ascribed to stearoyl groups (DSSt) of 1.51 or lauroyl groups (DSLa) of 1.48 and degree of substitution ascribed to cinnamoyl groups (DSCi) around 1.35. Furthermore, the influence of the chain lengths of the two different aliphatic esters as well as the switchable crosslinking of cinnamoyl moieties on the materials properties was further shown. Using these cellulose mixesters, transparent thin films with thickness of 4−15 μm were prepared via facile solvent casting. These films had light-responsive mechanical properties from rigid to elastic after illumination with UV light of distinct wavelengths (254 nm and 310−400 nm). Moreover, the thin films showed shape memory effect and the ability of self-healing.