Photochemistry and phototoxicity studies of flutamide, a phototoxic anti-cancer drug

The phototoxic anti-cancer drug flutamide is photolabile under UV-B light in either aerobic or anaerobic conditions. Irradiation of a methanol solution of this drug produces several photoproducts, one by photoreduction of the nitro group, one by rupture of the aromatic-NO2 bond of the parent compound, two as a result of the rupture of the CO-NH bond and one derived from the photoreduction product by scission of the aromatic-NH2 bond. Flutamide shows a photohemolytic effect on human erythrocytes and photoinduces lipid peroxidation. Studies on peripheral blood polymorphonuclear cells (neutrophils) demonstrated the phototoxicity of flutamide as well as inhibition of the cytotoxicity respiratory burst by the photoproduct derived from its photoreduction. The results suggest that the inhibition of the respiratory burst observed in phorbol myristate acetate (PMA)-activated cells is mediated by photosensitization and concomitant singlet oxygen production and/or formation of toxic photoproducts.     

Dinuclear Cobalt(III) Complexes Showing a Co2O2 Metallacycle

The heptadentate Schiff base H₃L reacts with cobalt(II) acetate in methanol to form the discrete dinuclear complex Co₂L(OAc)₂(OMe)(H₂O)₂ ( 1 ·2H₂O). The reaction of 1 ·2H₂O with NMe₄OH·5H₂O in methanol gives rise to displacement of the acetate by methanolate groups, yielding Co₂L(OMe)₃(H₂O) ( 2 ·1H₂O). Recrystallizations of the Schiff base, 1 ·2H₂O and 2 ·H₂O in different solvents, produce single crystals of H₃L, 1 ·2.5H₂O and 2 ·2MeOH, respectively. The crystal structures of 1 ·2.5H₂O and 2 ·2MeOH show the cobalt atoms double bridged by and endogenous phenol oxygen atom and an exogenous methanolate oxygen donor, giving rise to Co₂O₂ cores with Co···Co distances of ca. 2.87 Å.     

Room-temperature synthesis and conductivity of the pyrochlore type Dy2(Ti1−yZry)2O7 (0?y?1) solid solution

Different compositions in a solid solution of general formula Dy₂(Ti_1−yZr_y)₂O₇, showing high oxygen ion conductivity, have been successfully prepared at room temperature via mechanochemical synthesis. Stoichiometric mixtures of the constituent oxides were dry milled together in a planetary ball mill by using zirconia vials and balls. Chemical changes in the powder mixtures as a function of composition and milling time were followed by X-ray diffraction and revealed that, in all cases and after milling for 19 h, the powder mixtures consisted of a single phase. Electrical properties were measured on sintered pellets as a function of frequency, temperature and zirconium content, revealing an increase in conductivity of more than one order of magnitude for y?0.4, which, as observed in the similar Y₂(Ti_1−yZr_y)₂O₇, has been related with the onset of disordering of the anion sublattice. Despite increasing structural disorder with increasing Zr content, conductivity remains almost constant for y>0.6, reaching a maximum value of ∼5×10⁻³ for Dy₂Zr₂O₇ at 900 °C.     

The effect of octyl glucoside on the lamellar phase of diluted C12E4 and alcohol systems

A systematic study on phase behavior of the mixture of nonionic surfactants with alcohols at 30.0+/-0.1 degrees C was carried out. The total surfactant concentration was kept to 0.1 M varying the mole ratio of n-octyl beta-d-glucopyranoside (OG) and tetraethylene glycol monododecyl ether. Two uniphasic regions were found, the lamellar phase at low OG mole fraction and micelles at high OG mole fraction. The presence of OG favors the lamellae-micelle transition. Alkanols and benzyl alcohol were used as cosurfactants. The more hydrophobic alcohols (octanol and decanol) increase the OG content in the mixed bilayers. On the contrary, benzyl alcohol is not as favorable to the OG incorporation in the lamellar phase as in the mixed micelles. The L(3) phase has only been found as a uniphasic region with hexanol.     

Rhodium-catalyzed hydroformylation of C6 alkenes and alkene mixtures - a comparative study in homogeneous and aqueous-biphasic media using PPh3, TPPTS and TPPMS ligands

The complexes RhH(CO)L₃, where L = PPh₃, P(m-C₆H₄SO₃Na)₃ (TPPTS), and (C₆H₅)₂P(m-C₆H₄SO₃Na) (TPPMS) were used as catalyst precursors for a comparative study of the catalytic hydroformylation of several C6 alkenes and alkene mixtures under moderate reaction conditions in homogeneous (PPh₃) and aqueous-biphasic (TPPTS, TPPMS) media. The biphasic systems are efficient for the hydroformylation of hex-1-ene, 2,3-dimethyl-1-butene, styrene, cyclohexene, and mixtures thereof, in water/n-heptane at 80 °C. The main problem associated with these catalysts is their tendency to promote alkene isomerization if the effective syngas concentration in the liquid phases is low, but this side-reaction can be suppressed by using higher CO/H₂ pressures (54 atm). The selectivity of both water-soluble catalysts for linear products of hex-1-ene and for branched products of styrene is modest in comparison with the homogeneous system, which may limit their utility for classical oxo uses, but this is not a disadvantage for other interesting applications related to the hydroformylation of alkene mixtures and particularly to naphtha upgrading where linear and branched products are equally useful. The catalysts can be recycled without significant loss of activity and are resistant to the presence of benzothiophene in the mixture.     

Insights into the absorption of carbon dioxide by zinc substrates: isolation and reactivity of di- and tetranuclear zinc complexes

The heptadentate Schiff base H(3)L can react with zinc acetate to form the discrete dinuclear complex Zn(2)L(OAc)(H(2)O), 1.H(2)O. The reaction of 1.H(2)O with NMe(4)OH.5H(2)O both in air and under an argon stream has been investigated. On one hand, this reaction in air yields the tetranuclear complex (Zn(2)L)(2)(CO(3))(H(2)O)(6), 2.5H(2)O, by spontaneous absorption of adventitious carbon dioxide. This process can be reverted in an acetic acid medium, whereas the treatment of 2.5H(2)O with methanoic acid yields crystals of [Zn(2)L(HCOO)].0.5MeCN.1.25MeOH.2H(2)O, 3.0.5MeCN.1.25MeOH.2H(2)O. On the other hand, the interaction under an argon atmosphere of 1.H(2)O with NMe(4)OH.5H(2)O in methanol allows the isolation of the dinuclear complex Zn(2)L(OMe)(H(2)O)(4), 4.4H(2)O. Recrystallisations of 1.H(2)O, 2.5H(2)O and 4.4H(2)O, in different solvents, yielded single crystals of 1.MeCN.2.5H(2)O, 2.4MeOH and 4.3MeOH.H(2)O, respectively. The crystal structure of 2.4MeOH can be understood as resulting from an unusual asymmetric tetranuclear self-assembly from two dinuclear units, and shows three different geometries around the four zinc atoms.     

Influence of aromatic substituents on metal(II)salen catalysed, asymmetric synthesis of α-methyl α-amino acids

The influence of substituents on both the aromatic rings of the catalyst, and the benzylidene unit of the substrate are investigated in the (salen)copper(II) catalysed asymmetric benzylation of alanine derivatives. Catalysts with electron-donating, and electron-withdrawing substituents of various sizes and at various locations on the aromatic rings of the salen ligand were prepared, but all exhibited inferior enantioselectivity to the parent (salen)copper(II) complex. In contrast, the introduction of halogenated substituents onto the aromatic ring of the N-benzylidene alanine methyl ester substrate was found to enhance the enantioselectivity of the alkylation with a para-chloro substituent giving optimal results. A new procedure for the preparation of the catalysts which avoids the need for chromatography on sephadex LH20 is reported, and the optimal catalyst obtained in this way was found to be a cobalt(salen) complex.     

Mass spectra of some 2-methyl-3-(o- and p;-R-phenyl)-3,3a,4,5,6,7-hexahydro-2H-indazoles

The mass spectra of twelve 2-methyl-3-(o- and p-R-phenyl)-3,3a,4,5,6,7-hexahydro-2H-indazoles which have potentially useful pharmacological properties are presented.     

Structure of a de novo designed protein model of radical enzymes

The use of side chains as catalytic cofactors for protein mediated redox chemistry raises significant mechanistic issues as to how these amino acids are activated toward radical chemistry in a controlled manner. De novo protein design has been used to examine the structural basis for the creation and maintenance of a tryptophanyl radical in a three-helix bundle protein maquette. Here we report the detailed structural analysis of the protein by multidimensional NMR methods. An interesting feature of the structure is an apparent pi-cation interaction involving the sole tryptophan and a lysine side chain. Hybrid density functional calculations support the notion that this interaction raises the reduction potential of the W degrees /WH redox pair and helps explain the redox characteristics of the protein. This model protein system therefore provides a powerful model for exploring the structural basis for controlled radical chemistry in protein.     

Stereoselective syntheses of 1,4-dideoxy-1,4-imino-octitols and novel tetrahydroxyindolizidines

A new route for the preparation of four new indolizidines, (1R,2S,6S,7S,8aS)- and (1R,2S,6R,7R,8aS)-1,2,6,7-tetrahydroxyindolizidine (30 and 32) and (1S,2R,7S,8S,8aR)- and (1S,2R,7R,8R,8aR)-1,2,7,8-tetrahydroxyindolizidine (44 and 46), is reported. The synthesis is based on Knoevenagel homologation of the readily available enantiomerically pure pyrrolidin-carbaldehydes 13 and 37followed by asymmetric dihydroxylation of the subsequent alkenyl pyrrolidines and cyclization of the corresponding imino-octitols. The new indolizidines and their precursors (imino-octitols 20, 25, 26) and indolizidinones 28a and 28b have been tested for inhibitory activities toward 26 glycosidases. The enzymatic inhibition of trans-7-hydroxy-d-(-)-swainsonine (44) toward alpha-mannosidases is similar to that described for trans-7-hydroxy-l-(+)-swainsonine (11b) toward naringinase (alpha-l-rhamnosidase from Penicillium decumbens).