Cyclocurcumin as Promising Bioactive Natural Compound: An Overview.

Although identical in molecular formula and weight, curcumin and cyclocurcumin show remarkable differences in their reactivity. Both are natural compounds isolated from the rhizome of turmeric, the former is involved in the diketo/keto-enol tautomerism through the bis-α,ß-unsaturated diketone unit according to the polarity of the solvent, while the latter could react by trans-cis isomerization due to the presence of the α,ß-unsaturated dihydropyranone moiety. Even if curcumin is generally considered responsible of the therapeutical properties of Curcuma longa L. due to its high content, cyclocurcumin has attracted great interest over the last several decades for its individual behavior and specific features as a bioactive compound. Cyclocurcumin has a hydrophobic nature characterized by fluorescence emission, solvatochromism, and the tendency to form spherical fluorescent aggregates in aqueous solution. Molecular docking analysis reveals the potentiality of cyclocurcumin as antioxidant, enzyme inhibitor, and antiviral agent. Promising biological activities are observed especially in the treatment of degenerative and cardiovascular diseases. Despite the versatility emerging from the data reported herein, the use of cyclocurcumin seems to remain limited in clinical applications mainly because of its low solubility and bioavailability.

Structure and Properties of Electrochemically Synthesized Silver Nanoparticles in Aqueous Solution by High-Resolution Techniques.

The aim of this work was to deeply investigate the structure and properties of electrochemically synthesized silver nanoparticles (AgNPs) through high-resolution techniques such as transmission electron microscopy (TEM), scanning electron microscopy (SEM), Zeta Potential measurements, and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Strong brightness, tendency to generate nanoclusters containing an odd number of atoms, and absence of the free silver ions in solution were observed. The research also highlighted that the chemical and physical properties of the AgNPs seemed to be related to their peculiar oxidative state as suggested by X-ray photoelectron spectroscopy (XPS) and X-ray powder diffraction (XRPD) analyses. Finally, the MTT assay tested the low cytotoxicity of the investigated AgNPs.

Dual targeting of cancer-related human matrix metalloproteinases and carbonic anhydrases by chiral N-(biarylsulfonyl)-phosphonic acids.

A series of nanomolar phosphonate matrix metalloproteinase (MPP) inhibitors was tested for inhibitory activity against a panel of selected human carbonic anhydrase (CA, EC 4.2.1.1) isozymes, covering the cancer-associated CA IX and XII. None of the reported sulfonyl and sulfonylamino-derivatives sensitively affected the catalytic activity of the cytosolic isoforms CA I and II, which are considered off-target isoforms in view of their physiological role. The most active inhibitors were in the series of chiral N-(sulfonyl)phosphovaline derivatives, which showed good to excellent inhibitory activity over target CAs, with compound 15 presenting the best isoform-selectivity toward CA IX. We suggest here that the phosphonates have the potential as dual inhibitors of MMPs and CAs, both involved in tumor formation, invasion and metastasis.

Kinetics and Energetics of Thermal Cis-Trans Isomerization of a Resonance-Activated Azobenzene in BMIM-Based Ionic Liquids for PF6-/Tf2N- Comparison.

BMIM PF6 (1-butyl-3-methylimidazolium hexafluorophosphate) and BMIM Tf2N (1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) are two conventional room-temperature ionic liquids widely employed and investigated as reaction media. Despite the presence of the same imidazolium ring in their structure they are different in many chemical and physical properties due to the nature of the anions. The thermal cis-trans isomerization of an electronically activated azobenzene have been used as reaction model to compare the behavior of PF6- and Tf2N-. Rotation is the mechanism by which the investigated azobenzene is converted into the trans isomer spontaneously in the dark both in BMIM PF6 and in BMIM Tf2N. The kinetic rate constants of the process have been determined at different temperatures and the activation energies of the reaction have been calculated according to the Arrhenius and Eyring equations. The results presented herein highlight different solute-solvent interactions involving the PF6- and Tf2N- anions during the cis-trans isomerization.

The Compounds Responsible for the Sensory Profile in Monovarietal Virgin Olive Oils.

Monovarietal virgin olive oils (VOOs) are very effective to study relationships among sensory attributes, the compounds responsible for flavour, and factors affecting them. The stimulation of the human sensory receptors by volatile and non-volatile compounds present in monovarietal virgin olive oils gives rise to the sensory attributes that describe their peculiar delicate and fragrant flavours. The formation of these compounds is briefly illustrated and the influence of the agronomic and technological factors that affect their concentrations in the oil is examined. The relationships between compounds responsible for the olive oil flavour and sensory attributes are discussed. Several approaches for the varietal differentiation of monovarietal virgin olive oils are also overviewed.

Single-Walled Carbon Nanotubes in Highly Viscous Media: A Comparison between the Dispersive Agents [BMIM][BF4 ], L121, and Triton X-100.

Dispersions of single-walled carbon nanotubes (SWNTs) have been prepared by using the room-temperature ionic liquid [BMIM][BF4 ] (1-butyl-3-methylimidazolium tetrafluoroborate), the triblock copolymer Pluronic L121 [poly(ethylene oxide)5 -poly(propylene oxide)68 -poly(ethylene oxide)5 ] and the non-ionic surfactant Triton X-100 (TX100) in the pure state. The size of the SWNTs aggregates and the dispersion degree in the three viscous systems depend on the sonication time, as highlighted by UV/Vis/NIR spectroscopy and optical microscopy analysis. A nonlinear increase in conductivity can be observed as a function of the SWNTs loading, as suggested by electrochemical impedance spectroscopy. The generation of a three-dimensional network of SWNTs showing a viscoelastic gel-like behavior above a critical percolation concentration has been found at 25 °C in all the investigated systems by oscillatory rheology measurements.

Preparation and Antiproliferative Activity of Liposomes Containing a Combination of Cisplatin and Procainamide Hydrochloride.

We have previously reported the enhancement of the antiproliferative and apoptotic activities of cis-diamminedichloroplatinum(II) (DDP) when it is coadministered with a class I antiarrhythmic drug procainamide hydrochloride (PA). Here, we determined the antiproliferative activity of DDP, either in solution or loaded in liposomes, in the presence of PA, in the bulk solution, or directly embedded in liposomes together with DDP. Our results show that PA potentiates the activity of DDP-liposomes and that this effect is maintained at least in some of the investigated cell types when both drugs were mixed and loaded together into liposomes.

Role of Solvent and Effect of Substituent on Azobenzene Isomerization by Using Room-Temperature Ionic Liquids as Reaction Media.

The effects of a para substituent, as the electron-donating -OCH3 and -OtBu groups and the electron-withdrawing -Br and -F atoms, on azobenzene isomerization have been investigated in a series of imidazolium ionic liquids (BMIM PF6, BMIM BF4, BMIM Tf2N, EMIM Tf2N, BM2IM Tf2N, and HMIM Tf2N). The thermal cis-trans conversion tends to be improved in the presence of the substituent, as pointed out by the first-order rate constants measured at 25 °C. Both the rotation and the inversion mechanisms occur in BMIM Tf2N, EMIM Tf2N, and HMIM Tf2N, as highlighted by typical V-shape Hammett plots, but only rotation takes place in BMIM PF6, BMIM BF4, and BM2IM Tf2N. The possible interactions between the cation and the anion of the solvent and both the isomers of the azobenzene derivatives have been studied by small-wide-angle X-ray scattering (SWAXS). The calculated cis population in the photostationary state and the hardness parameter η of the trans isomer show that azobenzene and F-azobenzene are the less reactive molecules for the trans-cis conversion in all the investigated ionic liquids.

Neutral liposomes containing crown ether-lipids as potential DNA vectors.

Three crown ether derivatives, 1,2-O-dioleoyl-3-O-{2-[(12-crown-4)methoxy]ethyl}-sn-glycerol (12C4L), 1,2-O-dioleoyl-3-O-{2-[(15-crown-5)methoxy]ethyl}-sn-glycerol (15C5L) and 2,3-naphtho-15-crown-5 (NAP5), have been incorporated into 1-palmitoyl-2-oleoyl-phosphatydilcholine (POPC) liposomes. The size of the crown ether and the lipophilic moiety of 12C4L, 15C5L and NAP5 influence the stability and the properties of the extruded POPC liposomes determined at 25°C in buffered aqueous solution at pH7.4. The investigated liposomes are zwitterionic for POPC headgroups but can be turned into cationic aggregates in the presence of divalent cations. The capability of these systems to complex DNA has been demonstrated by SAXS experiments.

Kinetics of demetallation of a zinc-salophen complex into liposomes.

A Zn-salophen complex has been incorporated into POPC large unilamellar liposomes (LUV) obtained in phosphate buffer at pH 7.4. Fluorescence optical microscopy and anisotropy measurements show that the complex is located at the liposomal surface, close to the polar headgroups. The interaction of the POPC phosphate group with Zn(2+) slowly leads to demetallation of the complex. The process follows first order kinetics and rate constants have been measured fluorimetrically in pure water and in buffered aqueous solution. The coordination of the phosphate group of monomeric POPC with salophen zinc also occurs in chloroform as detected by ESI-MS measurements. The effect of the Zn-salophen complex on the stability of POPC LUV has been evaluated at 25°C by measuring the rate of release of entrapped 5(6)-carboxyfluorescein (CF) in the presence and in the absence of Triton X-100 as the perturbing agent. It turns out that the inclusion of the complex significantly increases the stability of POPC LUV.

Effect of ring size on the tautomerization and ionization reaction of cyclic 2-nitroalkanones: an experimental and theoretical study.

The keto-enol tautomerism of some cyclic 2-nitroalkanones was studied in cyclohexane. Keto-enol equilibrium constants, K(T), at 25 °C were obtained from (1)H NMR spectra. The relative enol content for the investigated ketones as a function of ring size decreases in the order 6 > 7 > 11 > 12 > 15. This trend apparently is different from that observed in water. Density functional theory (DFT) calculations have been performed to rationalize the effects of ring size and of the solvent on tautomerism. The acidity constants, K(a)(KH), for the different keto tautomers were measured spectrophotometrically at 25 °C in buffered aqueous solutions. No simple correlations between K(a)(KH) and ring size was observed, and this is in agreement with a DFT analysis performed on the same compounds.

Basicity of pyridine and some substituted pyridines in ionic liquids.

The equilibrium constants for ion pair formation of some pyridines have been evaluated by spectrophotometric titration with trifluoroacetic acid in different ionic liquids. The basicity order is the same in ionic liquids and in water. The substituent effect on the equilibrium constant has been discussed in terms of the Hammett equation. Pyridine basicity appears to be less sensitive to the substituent effect in ionic liquids than in water.

Fine-tuning of POPC liposomal leakage by the use of beta-cyclodextrin and several hydrophobic guests.

The effect of entrapped beta-cyclodextrin (beta-CD) on the stability of multilamellar vesicles (MLVs) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), prepared by the dehydration-rehydration method, was studied by monitoring the release of 5(6)-carboxyfluorescein encapsulated into the liposomes. Different hydrophobic guests, such as Fullerene C(60), have been incorporated into the POPC bilayer in order to modify the membrane composition. The kinetic results as well as ESI-MS measurements evidenced that the destabilizing activity of beta-CD is due to the formation of beta-CD inclusion complexes and the consequent removal of selected bilayer constituents from the liposomal membrane. Hence, when beta-CD was added to the liposomes in the form of a strong, water-soluble 2:1 beta-CD/C(60) inclusion complex, such a destabilizing effect was not observed. However, the same beta-CD/C(60) inclusion complex does not form as a result of C(60) extraction from the bilayer. This may be attributed either to the overwhelming concentration of POPC with respect to C(60) and/or to the fact that C(60) is largely aggregated in the bilayer. Turbidimetric and fluorimetric determinations of lamellarity and entrapped volume of the studied MLVs provided further evidence of the alteration of the liposomal bilayer as a consequence of the addition of beta-CD and/or the presence of the studied guests.

Microwave-assisted simple synthesis of 2-anilinopyrimidines by the reaction of 2-chloro-4,6-dimethylpyrimidine with aniline derivatives.

A series of 2-anilinopyrimidines including novel derivatives has been obtained from 2-chloro-4,6-dimethylpyrimidine by aromatic nucleophilic substitution with differently substituted anilines under microwave conditions. The substituents had a significant impact on the course and efficiency of the reaction. The results reported herein demonstrate the efficacy of microwaves in the synthesis of the title heterocyclic compounds as compared to the results obtained with conventional heating. The 2-anilinopyrimidines described are of potential bioactivity.

Microwave-assisted functionalization of carbon nanostructures in ionic liquids.

The effect of microwave (MW) irradiation and ionic liquids (IL) on the cycloaddition of azomethine ylides to [60]fullerene has been investigated by screening the reaction protocol with regard to the IL medium composition, the applied MW power, and the simultaneous cooling of the system. [60]Fullerene conversion up to 98 % is achieved in 2-10 min, by using a 1:3 mixture of the IL 1-methyl-3-n-octyl imidazolium tetrafluoroborate ([omim]BF(4)) and o-dichlorobenzene, and an applied power as low as 12 W. The mono- versus poly-addition selectivity to [60]fullerene can be tuned as a function of fullerene concentration. The reaction scope includes aliphatic, aromatic, and fluorous-tagged (FT) derivatives. MW irradiation of IL-structured bucky gels is instrumental for the functionalization of single-walled carbon nanotubes (SWNTs), yielding group coverages of up to one functional group per 60 carbon atoms of the SWNT network. An improved performance is obtained in low viscosity bucky gels, in the order [bmim]BF(4)> [omim]BF(4)> [hvim]TF(2)N (bmim=1-methyl-3-n-butyl imidazolium; hvim=1-vinyl-3-n-hexadecyl imidazolium). With this protocol, the introduction of fluorous-tagged pyrrolidine moieties onto the SWNT surface (1/108 functional coverage) yields novel FT-CNS (carbon nanostructures) with high affinity for fluorinated phases.

The base-catalyzed keto-enol interconversion of 2-nitrocyclohexanone in ionic liquids.

While the solvent effect on the rate of tautomerization of 2-nitrocyclohexanone in several organic solvents appears to depend essentially on the permittivity of the solvent, a different behavior is observed in some ionic liquids. In particular the rate of the reaction in ionic liquids (ILs) is much faster than expected solely on the basis of the permittivity of the studied ILs. However, if more solvent parameters are taken into consideration (namely the polarizability, H-bond acidity, and cohesive pressure of the solvent) one comprehensive linear solvation energy relationship (LSER) for both organic and IL media can be obtained and no special "ionic liquid effect" can be highlighted. The kinetic results have also been discussed in terms of the Brønsted equation. It turns out that on passing from molecular solvents to ILs the transition state structure of the enolization reaction becomes markedly enolate-like (Brønsted beta value close to 1).

Solvent effects on the rate of the keto-enol interconversion of 2-nitrocyclohexanone.

The rates of tautomerization of 2-nitrocyclohexanone (2-NCH) have been measured spectrophotometrically at 25.0 +/- 0.1 degrees C in several organic aprotic solvents and their binary mixtures. In cyclohexane the reaction is effectively catalyzed by bases and inhibited by acids while the so-called "spontaneous reaction" appears essentially due to autocatalysis. Apparent second order rate constants (k(app)(B)) for the reaction catalyzed by triethylamine (TEA) and pyridine (Pyr) have been obtained. From the experimental k(app)(B) values rate constants for the enolization (k(1)(B)) and ketonization (k(-1)(B)) reactions have been calculated. A Kamlet-Taft type linear solvation energy relationship (LSER) adequately accounts for the observed solvent effects. Activation parameters for both reactions show that solvent effects are mainly entropic in origin and that there is a shift of the transition state from a ketone-like to an enol-like structure on passing from less to more polar solvents.

Learning organic chemistry day by day: The best choice of the best pharmacy students.

BACKGROUND AND PURPOSE: During over ten years of experience in teaching organic chemistry at the Department of Pharmacy we have tried to answer the following question: why do most students tend to take the exam one, two, or more years after the end of the course they have attended? Several reasons could justify this delay, but three seem to be the most common drawbacks for our students: a) time needed for the comprehension of the arguments; b) the number of mandatory exams to pass before organic chemistry; c) lack of a self-evaluation method. EDUCATIONAL ACTIVITY AND SETTING: To increase the number of students in the exam sessions of the semester just after the course we have proposed two strategies: 1) a systematic, but stressless, approach by which homework and everyday life examples concerning organic chemistry are used to increase the sense of responsibility in studying; 2) the modification of the number of mandatory exams required for organic chemistry. FINDINGS: The rate of successful students in the exam sessions at the end of the course increased from 38.3 up to 61.3%. Interestingly, the highest scores tend to be obtained by students in the first session available just after the conclusion of the course. DISCUSSION AND SUMMARY: The combined effect of Strategy 1 and Strategy 2 seems to be effective in promoting the learning of organic chemistry and points out that the best performances tend to be associated with students which follow organized studying.

Liposomes entrapping ß-cyclodextrin/ibuprofen inclusion complex: Role of the host and the guest on the bilayer integrity and microviscosity.

Multilamellar vesicles (MLVs) from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were prepared by using the dehydration-rehydration method. The ß-cyclodextrin/Ibuprofen inclusion complex (ß-CD/Ibu) was formed and solubilised into the aqueous compartments of the investigated vesicles. The resulting POPC MLVs entrapping ß-CD/Ibu complex were essentially homogeneous in shape as demonstrated by Transmission Electron Microscopy (TEM). The liposomal stability was determined at 37.0±0.1°C by following the outflux rate of 5(6)-carboxyfluorescein (CF) at pH 7.40, while the membrane microviscosity was estimated by the ratio of the fluorescence intensities of pyrene in excimer and monomer state. The results presented herein confirm that interactions between POPC and ß-CD occur and suggest that associations between POPC and Ibuprofen are also involved in the properties of the investigated liposomes.

Polymeric Aggregates in Ionic Liquids: The Green Future of the Delivery Systems.

The self-assembly of a series of triblock co polymers Pluronics (P85, P105 and L121) has been investigated in some ionic liquids (BMIMBF4, BMIMPF6 and BMIMTf2N) by using Near-Infrared spectroscopy. The formation of supramolecular s tructures has been confirmed by optical microscopy. The solvation degree and the aggregation behaviour of P85, P105 and L121 depend on the interactions between the imidazolium ring of the ionic liquid and the hydrophilic moiety of the copolymer. Fluorescent vesicles can be observed after the incorporation of Nile Red into the polymeric bilayer of L121 or by linking fluorescein isothiocyanate to the copolymer structure.