Preparation and characterization of bolaform surfactant vesicles

Vesicular formulations (liposomes and niosomes) play an increasingly important role since they can be used as drug delivery and targeting systems. We described the formation of two niosomal systems based on synthetic bolaform surfactants (4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecanedioc acid diamide (BD-16) and alpha,omega-(4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecane (BC-16). Systems containing BD-16 or BC-16 and different amount of cholesterol (CH) were prepared by aqueous dispersion of films, followed by examination of methylene blue (MB) entrapment, particle size and morphology. Indeed, we also studied the hydration in the distilled water and physiological solution, in order to investigate the complexing ability on vesicle formation. The results obtained in this study show a high encapsulation capacity and this ability and the size depends on cholesterol content.     

In situ spectroscopic characterization of rectifying molecular monolayers self-assembled on gold.

We report visible, Raman, and infrared spectra of self-assembled monolayers (SAMs) formed by the donor-(pi-bridge)-acceptor chromophore, Z-beta-[N-(omega-acetylthioalkyl)-4-quinolinium]-alpha-cyano-4-styryldicyanomethanide (CH3CO-S-CnH2n-Q3CNQ where n=8, 10), on gold-coated substrates. The data are compared with the spectra collected for the same compound in solution and in the solid state, and with those obtained for a Langmuir-Blodgett (LB) monolayer of C16H33-Q3CNQ deposited on gold. Spectral analysis confirms that in solution, in the solid state and in the LB film the chromophore has a zwitterionic (D+-pi-A-) ground state. At variance with this well-known result, our data show that in SAMs deposited on gold the chromophore has a more neutral, quinoid ground state. We relate this difference to the different packing of the molecules in the two different films: in SAMs in fact the chromophores stand almost vertical with respect to the substrate, whereas in LB films they make an angle of about 45 degrees. The Q3CNQ molecule is a well-known molecular rectifier, and for SAMs we were able to check the direction of electron flow at forward bias on the same samples that have been characterized spectroscopically, shedding light on the rectification mechanism.     

Study of ruthenium(II) complexes with anticancer drugs as ligands. Design of metal-based phototherapeutic agents

The reaction of trans-[RuCl(2)(PPh(3))(3)] (Ph = C(6)H(5)) with 2-thio-1,3-pyrimidine (HTPYM) and 6-thiopurines (TPs) produced mainly crystalline solids that consist of cis,cis,trans-[Ru(PPh(3))(2)(N,S-TPYM)(2)] (1) and cis,cis,trans-[Ru(PPh(3))(2)(N(7),S-TPs)(2)]X(2) (X = Cl(-), CF(3)SO(3)(-)). In the case of TPs, other coordination isomers have never been isolated and reported. Instead, the mother liquor obtained after filtration of 1 produced red single crystals of trans,cis,cis-[Ru(PPh(3))(2)(N,S-TPYM)(2)].2H(3)O(+).2Cl(-) (2.2H(3)O(+).2Cl(-)). Selected ruthenium(II)-thiobase complexes were studied for their structural, reactivity, spectroscopic, redox, and cytotoxic properties. Single crystals of 1 contain thiopyrimidinato anions chelated to the metal center via N and S. The Ru[bond]N bonds are significantly elongated for 1 [2.122(2) and 2.167(2) A] with respect to 2 [2.063(3) A] because of the trans influence from PPh(3). The coordination pseudo-octahedron for 2 is significantly elongated at the apical sites (PPh(3) ligands). Solutions of cis,cis,trans isomers in air are stable for weeks, whereas those of 2 turn green within 24 h, in agreement with the respective redox potentials. cis,cis,trans- and trans,cis,cis-[Ru(PH(3))(2)(N,S-TPYM)(2)], as optimized through the DFT methods at the Becke3LYP level are in good agreement with experimental geometrical parameters (1 and 2), with cis,cis,trans being more stable than trans,cis,cis by 3.88 kcal. The trend is confirmed by molecular modeling based on semiempirical (ZINDO/1) and molecular mechanics (MM) methods. Cytotoxic activity measurements for cis,cis,trans-[Ru(PPh(3))(N-THZ)(N(7),S -H(2)TP)(2)]Cl(2) (4) (THZ = thiazole, H(2)TP = 6-thiopurine) and cis,cis,trans-[Ru(PPh(3))(2)(N(7),S-HTPR)2]Cl(2) (5) (HTPR = 6-thiopurine riboside) against ovarian cancer cells A2780/S gave IC(50) values of 17 +/- 1 and 29 +/- 9 microM, respectively. Furthermore, the spectral analysis of HTPYM, TPs, and their Ru(II) complexes in solution shows that intense absorptions occur in the UVA/vis region of light, whereas standard nucleobases absorb in the UVB region.     

Separation and analysis of glycyrrhizin, 18beta-glycyrrhetic acid and 18alpha-glycyrrhetic acid in liquorice roots by means of capillary zone electrophoresis

Glycyrrhizin is the main active compound of Glycyrrhiza glabra root extracts; according to recent studies, glycyrrhizin and its aglycon, glycyrrhetic acid, have interesting therapeutic properties. A new capillary electrophoretic method has been developed for the separation and quantification of glycyrrhizin, beta-glycyrrhetic acid and its isomer a-glycyrrhetic acid. Separation of the analytes was achieved in less than 3 min on a fused silica capillary, by injecting the samples at the short end of the capillary (effective length: 8.5 cm). The background electrolyte was composed of pH 10.0 carbonate buffer, methanol and ethylene glycol (80/10/10) and contained 0.4% beta-cyclodextrin; indomethacin was used as the internal standard. Diode array detection was used, with quantitative assays carried out at 254 nm. Linearity was found over the 5-200 and 2.5-100 microg mL(-1) concentration ranges for glycyrrhizin and glycyrrhetic acid, respectively. This method has been applied to the determination of the analytes in different matrices (liquorice roots and commercial confectionery products), and to the purity control of beta-glycyrrhetic acid obtained from the hydrolysis of glycyrrhizin. When analysing beta-glycyrrhetic acid and its epimer in roots, the samples were purified by means of a suitable solid-phase extraction (SPE) procedure with Oasis HLB cartridges, which granted good selectivity, eliminating matrix interference.     

Synthesis and Chemical and Electrochemical Characterization of Fe-S Carbonyl Clusters. X-ray Crystal Structures of [N(PPh(3))(2)](2)[Fe(5)S(2)(CO)(14)] and [N(PPh(3))(2)](2)[Fe(6)S(6)(CO)(12)

A reinvestigation of the redox behavior of the [Fe(3)(&mgr;(3)-S)(CO)(9)](2)(-) dianion led to the isolation and characterization of the new [Fe(5)S(2)(CO)(14)](2)(-), as well as the known [Fe(6)S(6)(CO)(12)](2)(-) dianion. As a corollary, new syntheses of the [Fe(3)S(CO)(9)](2)(-) dianion are also reported. The [Fe(5)S(2)(CO)(14)](2)(-) dianion has been obtained by oxidative condensation of [Fe(3)S(CO)(9)](2)(-) induced by tropylium and Ag(I) salts or SCl(2), or more straightforwardly through the reaction of [Fe(4)(CO)(13)](2)(-) with SCl(2). The [Fe(6)S(6)(CO)(12)](2)(-) dianion has been isolated as a byproduct of the synthesis of [Fe(3)S(CO)(9)](2)(-) and [Fe(5)S(2)(CO)(14)](2)(-) or by reaction of [Fe(4)(CO)(13)](2)(-) with elemental sulfur. The structures of [N(PPh(3))(2)](2)[Fe(5)S(2)(CO)(14)] and [N(PPh(3))(2)](2)[Fe(6)S(6)(CO)(12)] were determined by single-crystal X-ray diffraction analyses. Crystal data: for [N(PPh(3))(2)](2)[Fe(5)S(2)(CO)(14)], monoclinic, space group P2(1)/c (No. 14), a = 24.060(5), b = 14.355(6), c = 23.898(13) ?, beta = 90.42(3) degrees, Z = 4; for [N(PPh(3))(2)](2)[Fe(6)S(6)(CO)(12)], monoclinic, space group C2/c (No. 15), a = 34.424(4), b = 14.081(2), c = 19.674(2) ?, beta = 115.72(1) degrees, Z = 4. The new [Fe(5)S(2)(CO)(14)](2)(-) dianion shows a "bow tie" arrangement of the five metal atoms. The two Fe(3) triangles sharing the central Fe atom are not coplanar and show a dihedral angle of 55.08(3) degrees. Each Fe(3) moiety is capped by a triply bridging sulfide ligand. The 14 carbonyl groups are all terminal; two are bonded to the unique central atom and three to each peripheral iron atom. Protonation of the [Fe(5)S(2)(CO)(14)](2)(-) dianion gives reversibly rise to the corresponding [HFe(5)S(2)(CO)(14)](-) monohydride derivative, which shows an (1)H-NMR signal at delta -21.7 ppm. Its further protonation results in decomposition to mixtures of Fe(2)S(2)(CO)(6) and Fe(3)S(2)(CO)(9), rather than formation of the expected H(2)Fe(5)S(2)(CO)(14) dihydride. Exhaustive reduction of [Fe(5)S(2)(CO)(14)](2)(-) with sodium diphenyl ketyl progressively leads to fragmentation into [Fe(3)S(CO)(9)](2)(-) and [Fe(CO)(4)](2)(-), whereas electrochemical, as well as chemical oxidation with silver or tropylium tetrafluoroborate, in dichloromethane, generates the corresponding [Fe(5)S(2)(CO)(14)](-) radical anion which exhibits an ESR signal at g = 2.067 at 200 K. The electrochemical studies also indicated the existence of a subsequent one-electron anodic oxidation which possesses features of chemical reversibility in dichloromethane but not in acetonitrile solution. A reexamination of the electrochemical behavior of the [Fe(3)S(CO)(9)](2)(-) dianion coupled with ESR monitoring enabled the spectroscopic characterization of the [Fe(3)S(CO)(9)](-) radical monoanion and demonstrated its direct involvement in the generation of the [Fe(5)S(2)(CO)(14)](n)()(-) (n = 0, 1, 2) system.     

Solvation dynamics in acetonitrile: a study incorporating solute electronic response and nuclear relaxation

The solvent reorganization process after electronic excitation of a polar solute in a polar solvent such as acetonitrile is related mainly to the time evolution of the solute-solvent electrostatic interaction. Modern laser-based techniques have sufficient time resolution to follow this decay in real time, providing information to be confirmed and interpreted by theories and models. We present here a study aimed at the investigation of the different steps involved in the process taking place after a vertical S(0) --> S(1) excitation of a large size chromophore, coumarin 153 (C153), in acetonitrile, from both the solute and the solvent points of view. To do this, we use accurate quantum mechanical calculations for the solute properties within the polarizable continuum model (PCM) and classical molecular dynamics (MD) simulations, both equilibrium and nonequilibrium, for C153 in the presence of the solvent. The geometry of the solute is allowed to change in order to study the role of internal motions in the time-dependent solvation process. The solvent response function has been obtained from the simulation data and compared to experiment, while the comparison between equilibrium and nonequilibrium MD results for the solvation response confirms the validity of the linear response approximation in the C153-acetonitrile system. The MD trajectories have also been used to monitor the structure of the solvation shell and to determine its change in response to the change in the solute partial charges.     

New organic nitrates. II. Synthesis of 2H-pyrido[2,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazin-4(3H)-ones, 2H-thieno[2,3-e]-1,3-oxazin-4(3H)-ones and 2H-thieno[3,4-e]-1,3-oxazin-2,4(3H)-diones

The preparation and the physico-chemical characterization of 2H-pyrido[2,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazin-4(3H)-ones, 2H-thieno[2,3-e]-1,3-oxazin-4(3H)-ones and 2H-thieno[3,4-e]-1,3-oxazine-2,4(3H)-diones are reported.     

Synthesis of a ditopic cyclophane based on the cyclobutane ring by chalcone photocycloaddition

The intramolecular photocycloaddition of chalcones to give cyclobutanes has proven to be a fast and simple method to shrink a cyclophane ring to a tricyclic system, in order to prepare potential ditopic receptors. In particular, the chalcone 1, having dioxyethylene chains as spacers, is converted in high yield to the cyclobutane 2. NOESY spectroscopy indicates that the formation of 2 occurs by a head-to-head syn ring closure.     

Modified micellar electrokinetic chromatography in the analysis of catechins and xanthines in chocolate

Modified micellar electrokinetic chromatography (MEKC) analysis of monomeric flavanols (catechin and epicatechin) and methylxanthines (caffeine and theobromine) in chocolate and cocoa was performed by using sodium dodecyl sulfate (SDS) as a principal component of the running buffer. Because of the reported poor stability of catechins in alkaline solutions, acidic conditions (pH 2.5) were chosen and consequently the electroosmotic flow (EOF) was significantly suppressed; this resulted in a fast anodic migration of the analytes partitioned into the SDS micelles. Under these conditions, variations of either pH value in acidic range or SDS concentration, showed to be not suitable to modulate the selectivity. To overcome this limit, use of additives to the SDS-based running buffer was successfully applied and three different systems were optimized for the separation of (+)-catechin, (-)-epicatechin, caffeine, and theobromine in chocolate and cocoa powder samples. In particular, two mixed micelle systems were applied; the first consisted of a mixture of SDS and 3-[(3-cholamidopropyl)dimethylammonio]-1-propansulfonate (CHAPS) with a composition of 90 mM and 10 mM, respectively; the second was SDS and taurodeoxycholic acid sodium salt (TDC) with a composition of 70 mM and 30 mM, respectively. A further MEKC approach was developed by addition of 10 mM hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to the SDS solution (90 mM); it provided a useful cyclodextrin(CD)-modified MEKC. By applying the optimized conditions, different separation profiles of the flavanols and methylxanthines were obtained showing interesting potential of these combined systems; their integrated application showed to be useful for the identification of the low level of (+)-catechin in certain real samples. The CD-MEKC approach was validated and applied to the determination of catechins and methylxanthines in aqueous extracts from four different commercial chocolate types (black and milk) and two cocoa powders.