Isolation,Structure Determination and Synthesis of New Acetylenic Steroids from the Sponge Calyx nicaaensis

Two acetylenic steroids, cholest-5-en-23-yn-3β-ol ( 5 ) and 26,27-dinorcholest-5-en-23-yn-3β-ol ( 3 ), and another unsaturated steroidalcohol, stigmasta-5,23-dien-3β-ol ( 7 ), were isolated from the sponge Calyx nicaaensis. The structures of these two acetylenic steroids were established by synthesis. Several attempts to synthesize the marine steroids alcohol calysterol ( 1 ), with a cyclopropene-containing side chain, starting from cholest-5-en-23-yn-3β-ol are also recorded. Addition of ethyl-diazo-acetate to the triple bond was performed, but the reduction to the methyl derivative yielded decomposition products.     

N-Haloamidines-V: Reaction of N-chloro-N'-aroyl-acetamidines and -benzamidines with enamines

The reaction between N-chloro-N'-aroyl-amidines and β,β-disubstituted enamines affords 1 - aroyl - 4 -amino - 4,5 - dihydro - imidazoles in low yields, the main reaction product being N - (2 - morpholino - 2,2 -disubstituted) - ethylidene - N' - aroyl - amidines. A similar reaction course was not observed with enamines bearing a hydrogen atom in the β-position. In this case only products derived from electrophilic chlorination on enamines were isolated.     

Effect of glycerol on micelle formation by ionic and nonionic surfactants at 25 degrees C

The effect of glycerol on the micellization of the cationic surfactant cetyltrimethylammonium bromide (CTAB) and of the ethoxylated nonionic surfactant Brij 58 has been investigated by various experimental techniques. For both surfactants the critical micellar concentration (cmc), determined by surface tension measurements, is almost unaffected by the presence of glycerol in the mixture; only at high glycerol concentrations (>/=20% w/w) does the cmc significantly increase. The area per surfactant molecule at the air-solution interface, A, increases with increasing glycerol weight percentage, w(g). Fluorescence quenching measurements indicate that the presence of glycerol induces a lowering of the aggregation number of both surfactants. The glycerol intradiffusion coefficient has been measured by the pulsed-gradient spin-echo NMR technique as a function of glycerol content at constant surfactant concentration. It is almost unaffected by the presence of the surfactants, indicating that no direct glycerol-surfactant interaction occurs in the mixture. The surfactant intradiffusion coefficient has been also measured. In the case of CTAB, it increases with increasing glycerol concentration, a reflection of the decreased aggregation number. For Brij 58, in spite of the lowering of the aggregation number, the surfactant intradiffusion coefficient decreases with increasing glycerol concentration, suggesting an increase of the intermicellar interaction. The experimental evidence shows that for both surfactants the micellization is affected by the presence of glycerol through an indirect, solvent-mediated mechanism. In the case of CTAB, the main effect of glycerol is a lowering of the medium dielectric constant, which enhances the electrostatic interactions in solution. In the case of Brij 58, the results can be interpreted in terms of a salting-out effect according to which glycerol competes with the surfactant for water molecules, causing a dehydration of the surfactant ethoxylic headgroup.     

The static dielectric constant of solutions of water inn-alcohols at 15, 25, 35, and 45°C

Dielectric constants (measured at 1 MHz) are reported for solutions of water (concentration range 0 to 0.2 mole fraction) in 1-propanol at 25°C, and in 1-butanol, 1-pentanol, and 1-hexanol at 15, 25, 35, and 45°C. These results, together with literature values for solutions of water in methanol, ethanol, 1-heptanol, and 1-octanol, show that water interacts with alcohols in at least two ways: (1) it can participate in the formation of dynamic hydrogen-bonded chains, thereby raising the polarizability; (2) it can form relatively stable structures such as H₂O(ROH)₄ which have zero net dipole moment and consequently diminish volume polarizability. For C _n H _2n+1 OH alcohols,n≥4, most of the initially added water forms complexes: consequently, addition of water to these alcohols lowers the dielectric constant.     

New taxane derivatives: synthesis of baccatin[14,1-d]furan-2-one nucleus and its condensation with the norstatine side chain

New taxanes 15 and 18, containing the unsaturated and saturated baccatin[14,1-d]furan-2-one nucleus, respectively, were prepared starting from the readily available 13-oxo-7-Tes-baccatin III (3). Sequential formation of the enolate of 3 and reaction with ethyl glyoxylate gave the 13-oxo-7-Tes-baccatin[14,1-d]-3,4-dehydrofuran-2-one 4. The reduction of 4 can result in the formation of a mixture of compounds corresponding to 13-hydroxy alcohol 5 and 13-enol derivative 6. Both 5 and 6 were transformed into 13-oxo-7-Tes-baccatin[14,1-d]furan-2-one 8 by treatment with a base. Further reduction of 8 gave 13-hydroxy compound 9. Esterification of 6 and 9 with N,O-protected norstatine 12, followed by deprotection, gave the new promising anticancer taxanes 15 and 18, respectively.     

Separable geodesic action slicing in stationary spacetimes

A simple observation about the action for geodesics in a stationary spacetime with separable geodesic equations leads to a natural class of slicings of that spacetime whose orthogonal geodesic trajectories represent the world lines of freely falling fiducial observers. The time coordinate function can then be taken to be the observer proper time, leading to a unit lapse function, although the time coordinate lines still follow Killing trajectories to retain the explicitly stationary nature of the coordinate grid. This explains some of the properties of the original Painlevé-Gullstrand coordinates on the Schwarzschild spacetime and their generalization to the Kerr-Newman family of spacetimes, reproducible also locally for the Gödel spacetime. For the static spherically symmetric case the slicing can be chosen to be intrinsically flat with spherically symmetric geodesic observers, leaving all the gravitational field information in the shift vector field.     

Spin–Orbit Charge-Transfer Intersystem Crossing (ISC) in Compact Electron Donor–Acceptor Dyads: ISC Mechanism and Application as Novel and Potent Photodynamic Therapy Reagents

Spin–orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers (PSs). Herein, a series of perylene-Bodipy compact electron donor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studied with steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield Φ_T=60 %) was observed, with a triplet state lifetime (τ_T=436 μs) much longer than that accessed with the conventional heavy atom effect (τ_T=62 μs). The SOCT-ISC mechanism was unambiguously confirmed by direct excitation of the charge transfer (CT) absorption band by using nanosecond transient absorption spectroscopy and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The factors affecting the SOCT-ISC efficiency include the geometry, the potential energy surface of the torsion, the spin density for the atoms of the linker, solvent polarity, and the energy matching of the ¹CT/³LE states. Remarkably, these heavy atom-free triplet PSs were demonstrated as a new type of efficient photodynamic therapy (PDT) reagents (phototoxicity, EC₅₀=75 nm ), with a negligible dark toxicity (EC₅₀=78.1 μm ) compared with the conventional heavy atom PSs (dark toxicity, EC₅₀=6.0 μm, light toxicity, EC₅₀=4.0 nm ). This study provides in-depth understanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, and underlines their application as a new generation of potent PDT reagents.