Β-diketone Groups Research Articles

Effect of mono- and diketone group in curcumin analogues on amyloid fibrillation of hen egg white lysozyme

Curcumin has attracted more attention because of its inhibition efficacy on protein amyloid fibrillation. However, the inhibition mechanism was still ambiguous and the clinical application of curcumin was greatly limited because of its poor stability at physiological conditions for the presence of β-diketone moiety. In this paper, a new mono-ketone-containing curcumin analogue (MDHC) was designed and synthesized to realize the possible inhibition mechanism and unveil the important role of β-diketone moiety of curcumin in the inhibition process of amyloid fibrillation using hen egg white lysozyme (HEWL) as model protein. Although all experiment results (ThT, CR, ANS and TEM) showed that the inhibitory capacity of curcumin was better than MDHC, MDHC still could show obvious inhibition effect. Molecular docking showed that both curcumin and MDHC could bind with HEWL by hydrogen bond of phenloic hydroxyl and the binding energy of MDHC was higher than that of curcumin. All the findings inferred that β-diketone group was one of great important groups in the inhibition process of HEWL amyloid fibrillation, which provided more room to construct novel inhibition reagents.

Chloro- and BF2bdk-substituted dithienylethene: Synthesis, photophysical properties, and optical switching behavior

A novel chloro- and BF2bdk-substituted dithienylethene derivative, in which a chlorine atom and a difluoroboron β-diketonate (BF2bdk) group are appended at the termini of the dithienylethene core, is developed. The structure was confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry (electrospray ionization). It displayed solvent-dependent photophysical properties, and blue/red light-triggered optical switching behavior in nonpolar or less polar solvents.

Fluorescence of curcumin in alkaline dimethyl sulfoxide and the effects of alkali metal cations on it

Earlier, we reported our finding of the fluorescence emission derived from the triple-deprotonated form of curcumin (Cur3–) in dimethyl sulfoxide (DMSO) in the presence of NaOH. Herein, we disclose the results of the studies on the luminescent properties of Cur3– in the presence of LiOH, NaOH and KOH, which are indicative of the cation-dependent behavior of the Cur3– fluorescence excitation and the emission spectra. The fluorescence quantum yield in the presence of LiOH and NaOH significantly increases compared to that of neutral curcumin. Studying the fluorescence polarization properties revealed that the observed increase in the quantum yield is accounted for by the decreased rate of the nonradiative excited-state deactivation. We assume that the origin of the cation-dependent fluorescence properties refers to the formation of coordination bonds between the alkali metal cations and the oxygen atoms of the β-diketone (keto-enol) group of curcumin, which is substantiated by the experimental results and supported by the semiempirical modeling.

Theoretical exploration on free radical scavenging mechanism of curcumin analogues in water solvent

One way to improve curcumin’s possibility in preventing lipid peroxidation is through modification of carbon linker, β-diketone group and aromatic rings. However, there remains a need to explore the role of carbon linker on the free radical scavenging mechanisms of curcumin. This study uses density functional theory to explore two descriptors of free radical scavenging mechanisms, which are bond dissociation enthalpy (BDE) and adiabatic ionization potential (AIP) of curcumin and its analogues. Five analogues with different amount of carbon atoms in the linker in the presence / absence of β-diketone group are chosen. Our result shows that decreasing the amount of carbon atom from 7 to 5 atoms in the linker decreases the BDE at β-diketone group of the curcumin analogue. Moreover, increasing the amount of carbon atoms in the linker decreases the AIP of the analogues.

Synthesis and Molecular Docking Study of 1-(3-Chloropropyl)-3,5-Bis((E)-4-Methoxybenzylidene)Piperidin-4-One as Dengue Virus Type 2 (DEN2) NS2B/NS3 Protease Inhibitor Candidate

Curcumin is a secondary metabolite compound that has diverse biological activities. However, it is easily hydrolyzed at physiological pH due to the presence of the β-diketone group. Therefore, the replacement of the β-diketone group with mono ketone is expected to overcome this issue. We hereby report the synthesis of mono ketone curcumin derivatives from piperidone by two-steps reactions. The synthesis of curcumin derivate 3 was carried out by Claisen-Schmidt condensation between 4-piperidone and 4-methoxybenzaldehyde using alkaline catalyst. The synthesized curcumin derivate 3 was then reacted with the 1-bromo-3-chloropropane to produce curcumin derivate 5, 1-(3-chloropropyl)-3.5-bis((E)-4-methoxybenzylidene)piperidin-4-one, with 72% yield. The calculated docking scores, the curcumin derivate 5 possessed a better affinity for receptors than the standard panduratin A. The curcumin derivate 5 has a lower docking score of -6.40 kcal/mol compared to panduratin A with value of -5.18 kcal/mol and also had strong binding interactions to DEN2 NS2B/NS3 protease. Thus, this compound is promising candidate as a new anti-dengue agent.

THERMOGRAVIMETRIC STUDIES OF POLYSTYRENE OF MODIFIED COBALT 5-METHYL-5-HEXEN-2,4-DIONATE

Thermogravimetry was used to study polystyrene samples modified with cobalt 5-methyl-5-hexene-2,4-dionate (MHD-Co) in two ways. The first method consists in copolymerizing styrene with the metal monomer MHD-Co, which simultaneously acts as an initiator and an inhibitor in this process, namely it exhibits a multifunctional effect in radical copolymerization with vinyl monomers. The polystyrene obtained in this way contains ≤ 0,5% cobalt in the form of β-diketonate groups covalently linked to the macromolecule, which are located both at the ends and in the middle of the polymer chain. Such polymers can be macroinitiators and graft side chains already at the stage of their synthesis; therefore, they have a branched structure of macrochains. The second modification method consists in the preliminary preparation of a styrene copolymer with unsaturated β-diketone followed by the complexation reaction of the obtained macroligand with a metal salt. In this case, when using the Co (III) salt, polymer chelates are formed as a result of the interaction of several polymer chains, and in the case of the Co (II) salt, two β-diketone groups inside the same macromolecule form a chelate structure. Moreover, for coordination saturation, metal complexes include solvent molecules. Thus, depending on the production method, polystyrene samples containing cobalt β-diketonate have a different structure, which affects the destruction mechanism, which will be different in each method. However, regardless of the modification method, all the studied samples have increased resistance to thermal oxidative degradation compared to the sample obtained using the traditional initiator benzoyl peroxide. The paper discusses the reasons for increasing the thermal stability of polystyrene containing an organometallic modifier.

Fused Fluorinated Bis-β-diketones and Luminescent-Spectral Properties of Their Complexes with Europium

Claisen condensation of diacetylated fused aromatic and heteroaromatic compounds (fluorene, dibenzofuran, dibenzothiophene, or carbazole) with polyfluorocarboxylic acids esters in the presence of bases has afforded the ligands containing two β-diketonate groups. Their complexation with Eu3+ ions has been studied by the luminescence spectral method.

In Situ Growth and Size Regulation of Single Gold Nanoparticles in Composite Microgels.

Herein, a novel method for the in situ growth of single gold nanoparticles (AuNPs) in microgel (MG) networks is presented. The key feature in this approach is the localization of β-diketone groups capable of both complexation and reduction of aurate ions in the MGs' core, which allows localization of the nucleation and growth of single AuNPs. The MG synthesis is carried out via precipitation polymerization in water with N-vinylcaprolactam as the main monomer and with the two comonomers acetoacetoxyethyl methacrylate (AAEM) and acrylic acid (AAc), where AAEM is mainly located in the MGs' core and AAc in their shell. For the synthesis of AuNPs, a certain amount of chloroauric acid (HAuCl4 ) is added to the dispersion, followed by fast reduction with sodium borohydride (NaBH4 ). In situ synthesized AuNPs in MGs possess a spherical shape, with a diameter of 8.1 ± 0.8 nm, being localized in the center of every MG. In addition, these AuNPs embedded into MG networks can be used as seeds that grow in their size after the addition of HAuCl4 up to 46.0 ± 9.5 nm under mild reaction conditions (room temperature, aqueous dispersion) and without the use of any additional reducing and stabilizing agents.

A comparative study on the antioxidant properties of curcuminoids and its rubrocurcumin analogues

The yellow colored pigment, curcumin present in turmeric is responsible for its various biological activities like antioxidant, anti-inflammatory and anticarcinogenic activity. Different functional group present in curcumin includes a β-diketone group, carbon-carbon double bond and two phenyl rings with hydroxy and methoxy substituents. A controversy exists in literature on the site and mechanism for the antioxidant activity (AOA), the keto-enol/phenolic moiety present in curcumin. In the present work AOA of curcuminoids and its boron complex with oxalic acid-rubrocurcumin analogues were conducted which differ in the substituent in the benzene ring. Since in rubrocurcumin analogue β-diketone group is blocked through bonding with boron its influence will be absent in its antioxidant activity.

A comparative study of the spectral, fluorometric properties and photostability of natural curcumin, iron- and boron- complexed curcumin

Curcumin is a yellow phenolic compound with a wide range of reported biological effects. However, two main obstacles hinder the use of curcumin therapeutically, namely its poor bioavailability and photostability. We have synthesized two curcumin complexes, the first a boron curcumin complex (B-Cur2) and the second an iron (Fe-Cur3) complex of curcumin. Both derivatives showed high fluorescence efficiency (quantum yield) and greater photostability in solution. The improved photostability could be attributed to the coordination structures and the removal of β-diketone group from curcumin.The fluorescence and ultra violet/visible absorption spectra of curcumin, B-Cur2 and Fe-Cur3 all have a similar spectral pattern when dissolved in the same organic solvent. However, a shift towards a lower wavelength was observed when moving from polar to non-polar solvents, possibly due to differences in solvent polarity. A plot of Stokes' shift vs the orientation polarity parameter (Δf) or vs the solvent polarity parameter (ET 30) showed an improved correlation between the solvent polarity parameter than with the orientation polarity parameter and indicating that the red shift observed could be due to hydrogen-bonding between the solvent molecules. A similar association was obtained when Stokes' shift was replaced by maximum synchronous fluorescence. Both B-Cur2 and Fe-Cur3 had larger quantum yields than curcumin, suggesting they may be good candidates for medical imaging and in vitro studies.

Localization and dynamics of the anticarcinogenic curcumin with GM1 and other miceller assemblies.

Structural transitions involving shape changes play an important role in cellular physiology and enhance the bioavailability of the natural food like curcumin in surfactant aggregates. In this work, we have studied the localization, dynamics and stability of curcumin in various miceller assemblies using a combination of absorbance and fluorescence spectroscopic approaches. The measurements of absorption and fluorescence spectra of curcumin revealed that the nature of interactions of ionic and nonionic surfactants and the glycosphingolipid, GM1 with curcumin is significantly different with surfactant concentrations. At low concentrations of SDS and the GM1 the head group of SDS and GM1 binds to the central β-diketone group of curcumin to form SDS-curcumin or GM1-curcumin complexes. At high concentrations, both formed micelles with curcumin completely solubilized inside. Cucurmin is solubilized in the stern layer of SDS micelles. Compared to spherical micelles, rod shaped micelles allow more curcumin to bind through hydrophobic interactions indicated by higher absorption and fluorescence, enhanced partition coefficient and stability. Whereas curcumin associates with GM1 micelles with lower partition coefficient, solubility and remain closer to aqueous phase decreasing its bioavailability and stability. While cucurmin is solubilized in the palisade layer of deoxycholate and octyl glucopyranoside micelles through the alkyl chains providing more hydrophobic microenvironment to curcumin with enhanced stability and bioavailability. Graphical abstract Schematic diagram of the two different types of detergent micelles and larger GM1 micelles.

Ironclad fluoroemulsion boosts MRI sensitivity

Magnetic resonance imaging has become a critical technology in medical diagnostics, and chemists continue to devise new types of MRI contrast agents. In one of the latest examples, a team led by Eric T. Ahrens, Roger Y. Tsien, and Alexander A. Kislukhin of the University of California, San Diego, has created a paramagnetic fluorinated nanoemulsion with embedded metal ions that provides up to a fivefold boost in sensitivity over previously reported 19F MRI cellular detection systems (Nat. Mater. 2016, DOI: 10.1038/nmat4585). The researchers first crafted a metal-binding fluorinated compound by introducing β-diketone groups to the ends of a perfluoropolyether precursor. They then emulsified this fluorinated oil (yellow) in an aqueous solution containing a commercial surfactant. The researchers next added various transition and lanthanide metals, which were bound by the diketonate groups. In a surprise finding, the team observed that iron(III) provided the best MRI sensitivity, surpassing that of gadolinium(III), which

Fabrication of Superhydrophobic Surface with Controlled Wetting Property by Hierarchical Particles.

Hierarchical particles were prepared by synthetically joining appropriately functionalized polystyrene spheres of poly[styrene-co-(3-(4-vinylphenyl)pentane-2,4-dione)] (PS-co-PVPD) nanoparticles and poly(styrene-co-chloromethylstyrene) (PS-co-PCMS) microparticles. The coupling reaction of nucleophilic substitution of pendent β-diketone groups with benzyl chloride was used to form the hierarchical particles. Since the polymeric nanoparticles and microparticles were synthesized by dispersion polymerization and emulsion polymerization, respectively, both the core microparticles and the surface nanoparticles can be different size and chemical composition. By means of changing the size of the PS-co-PVPD surface nanoparticles, a series of hierarchical particles with different scale ratio of the micro/nano surface structure were successfully prepared. Moreover, by employing the PS-co-PVPD microparticles and PS-co-PCMS nanoparticles as building blocks, hierarchical particles with surface nanoaprticles of different composition were made. These as-prepared hierarchical particles were subsequently assembled on glass substrates to form particulate films. Contact angle measurement shows that superhydrophobic surfaces can be obtained and the contact angle of water on the hierarchically structured surface can be adjusted by the scale ratio of the micro/nano surface structure and surface chemical component of hierarchical particles.

Regioselective addition of amines to the trifluoromethyl-β-diketonate moiety of a chlorophyll derivative

The terminal trifluoroacetyl moiety in a β-diketonate group at the 3 position of a synthetic chlorophyll derivative was reacted with butylamine in dichloromethane to give the hemiaminal-type adduct. Electronic absorption spectra showed the keto carbonyl group at the 3 position of the adduct was converted into the enol type under the basic conditions.

A new method for pH triggered curcumin release by applying poly(l-lysine) mediated nanoparticle-congregation

We introduce a novel method for encapsulation of curcumin by synthesizing microcapsule containing self-assembled nanoparticles using poly (l-lysine), trisodium citrate and silica sol. Such microcapsules can only be prepared in neutral and alkaline environment and unencapsulated curcumin can be effectively removed by simple centrifugation with encapsulation efficiency 57.34%. The particle sizes are in the range 0.7–3μm with an effective diameter 1.05μm. The structure of the microcapsules is dependent upon the solubility of curcumin in the solvent environment, the microcapsule are spherical when prepared in 10% acetone and bowl-shaped/conical when prepared in water suspension, however, the size of these curcumin encapsulated microcapsules remain similar. Fluorescence microscope images confirm that curcumin is predominantly concentrated within the shell wall of the capsules. Photophysical behavior of Micro-curcumin with respect to curcumin alone is evaluated. Release of curcumin is found to be triggered by pH where acidic environment trigger maximum release compared to basic and neutral conditions. Micro-curcumin is as stable as curcumin. Drug release efficiency is found to be 61.44% and the drug release profile of Micro-curcumin follow Higuchi model. It is also revealed that β-diketone group of curcumin responsible for scavenging activity is retained in the Micro-curcumin, thus suggesting applicability of such system as a poorly water soluble drug delivery vehicle. In contrast to other curcumin delivery systems, the presented method is easy, fast and does not need flow rate monitoring device. In addition poly (l-lysine) as a non-toxic and highly stable material that prevents metabolic degradation is used in the present preparation method.

Interaction of Cationic CTAB Surfactant with Curcumin, an Anticarcinogenic Drug: Spectroscopic Investigation

Abstract Curcumin, the most active polyphenolic constituent of turmeric cucuminoids obtained from rhizome Curcuma longa, holds a high place in ayurvedic medicine but its role in conventional disease management is also established. Unfortunately, the compound has poor aqueous solubility, which results in poor bioavailability following high doses by oral administration. In order to enhance its effectiveness and improve bioavailability, surfactant assemblies as the colloidal drug carriers with desired properties have been largely utilized. The interaction of curcumin with cetyltrimethylammonium bromide (CTAB) surfactant has been investigated by absorption spectroscopy as a function of surfactant concentration in pre-micellar and micellar range at acidic pH of 6.4. The pre-micellar and micellar region of pure CTAB surfactant at acidic pH of 6.4 is examined through tensiometry and conductometry techniques. Spectral data shows that in presence of curcumin at lower CCTAB, the change in absorbance and peak form initially was assigned to attraction of positive head group of CTAB towards the β-diketone group of drug. In micellar region including CMC, the type of interaction corresponds to the attachment of C16 chains of CTAB to nonpolar aryl groups of drug and simultaneously displacement of polar head group from β-diketone group of the drug. Finally at post micellar CCTAB, the encapsulation of the curcumin into micelles, predominantly in intact monomeric form is observed with the sharp peak at λmax = 423 nm.

Hierarchical assembly of discrete copper(ii) metallo-structures from pre-assembled dinuclear (bis-β-diketonato)metallocycles and flexible difunctional co-ligands

The sequential interaction of preformed [Cu2(L1)2(THF)2] (where H2L1 is 1,1-(1,3-phenylene)-bis(4,4-dimethylpentane-1,3-dione incorporating a 1,3-phenylene linker between its two β-diketone domains) and [Cu2(L4)2]·2H2O (where H2L4 is 1,1-(4,4′-oxybiphenylene)-bis(4,4-dimethylpentane-1,3-dione) incorporating a flexible oxybiphenylene linkage between the two β-diketone groups) with the potentially difunctional aliphatic non-planar co-ligands, N-methylpiperazine (mpip), N,N′-dimethylpiperazine (dmpip) and 1,4-thiomorpholine (thiomorph) is reported. A series of extended molecular assemblies exhibiting a range of di- and tetranuclear assemblies were obtained and their X-ray structures determined. Dinuclear [Cu2(L1)2(mpip)2]·2mpip incorporates two 5-coordinate, square pyramidal metal centres as does tetranuclear [{Cu2(L1)2}2(dmpip)2]·2dmpip. In contrast, dinuclear [Cu2(L1)2(dmpip)4]·dmpip and [{Cu2(L1)2}2(thiomorph)4]·3thiomorph each contain two 5-coordinate and two 6-coordinate centres. Each of [Cu2(L4)2(THF)2]·2THF and Cu2(L4)2(mpip)2]·H2O incorporate only 5-coordinate metal centres, with the latter complex forming a one-dimensional hydrogen bonded ribbon-like structure directed along the crystallographic a-axis. In keeping with the documented tendency for the smallest, least strained assembly to form in supramolecular self-assembly processes, the incorporation of the flexible “oxy” linkage between the 4,4′-linked phenylene rings of H2L3 results in generation of a dinuclear [Cu2L2] species rather than a trinuclear (triangular) [Cu3L3] species of the type formed by the more rigid bis-β-diketonato ligand analogue in which the biphenylene rings separating the β-diketone domains are directly coupled in their 4,4′ positions.

A new copper(II) complex with 2-thenoyltrifluoroacetone and 2,2-bipyridine: Crystal structure, spectral properties and cytotoxic activity

This work reports the synthesis and characterization of a new copper(II) complex with 2-thenoyltrifluoroacetone (HTTA) and 2,2-bipyridine (bipy). The complex was characterized by elemental analysis, UV–Vis, IR and EPR. The crystal structure was determined by single-crystal X-ray diffraction. The copper ion has a distorted square-pyramidal geometry and is coordinated to two bidentate ligands (HTTA and bipy) and a perchlorate ion weakly bonded in the apical position. The crystal packing is stabilized by non-classical hydrogen bonds and weak interactions π–π stacking. In the copper complex, the metal ion binds to HTTA via the oxygen atoms of the β-diketone group and to bipy via its two heterocyclic nitrogens. The title compound inhibits the growth of K562 cells with an IC50 value equal to 28.2μmolL−1.

Dinuclear Cu(II) Complexes of Isomeric Bis-(3-acetylacetonate)benzene Ligands: Synthesis, Structure, and Magnetic Properties

Highly versatile coordinating ligands are designed and synthesized with two β-diketonate groups linked at the carbon 3 through a phenyl ring. The rigid aromatic spacer is introduced in the molecules to orient the two acetylacetone units along different angles and coordination vectors. The resulting para, meta, and ortho bis-(3-acetylacetonate)benzene ligands show efficient chelating properties toward Cu(II) ions. In the presence of 2,2'-bipyridine, they promptly react and yield three dimers, 1, 2, and 3, with the bis-acetylacetonate unit in bridging position between two metal centers. X-ray single crystal diffraction shows that the compounds form supramolecular chains in the solid state because of intermolecular interactions. Each of the dinuclear complexes shows a magnetic behavior which is determined by the combination of structural parameters and spin polarization effects. Notably, the para derivative (1) displays a moderate antiferromagnetic coupling (J = -3.3 cm(-1)) along a remarkably long Cu···Cu distance (12.30 Å).

Microgel/SiO2 hybrid colloids prepared using a water soluble silica precursor

In the present work we demonstrate that functional polymer microgels may act as smart self-catalyzing system inducing controlled formation of silica nanoparticles inside the polymer network and formation of hybrid colloids. We synthesized a water soluble silica precursor PEG-PEOS via post-modification of hyperbranched poly(ethoxysiloxane) (PEOS) with poly(ethylene glycol) monomethyl ether. We used poly(N-vinylcaprolactam)-based microgel functionalized with imidazole and β-diketone groups as a matrix for biomimetic deposition of silica. Composite microgel particles containing silica nanoparticles (up to 20 wt.-%) have been prepared by simultaneous PEG-PEOS conversion and silica deposition in the microgels. TEM studies indicate the infiltration of silica nanoparticles (∼10 nm) inside the corona region of the microgels due to the strong acid–base interaction between the acidic silica and basic imidazole groups. The resulting composite particles were found to be colloidally stable and no aggregation was observed even after months of storage. The incorporation of silica nanoparticles increased the rigidity of the microgel particles and reduced their thermal sensitivity.