Photochemical reactivity of α,β-unsaturated δ-lactams: Synthesis of seco-steroids. Photochemical reactions. XIII [1]

The UV. irradiation of 17 β-hydroxy-2-aza-4-androsten-3-one (1) , N-methyl-17 β-hydroxy-2-aza-4-androsten-3-one (3) , 17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (2) and N-methyl-17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (4) , gives rise to 1,10-seco (from 1 and 3 ) and 5, 10-seco (from 2 and 4 ) steroids.     

Two Highly Populated Conformations at Room Temperature of Monterine and Granjine, Antitumor Bisbenzylisoquinoline Alkaloids: Origin and Tridimensional Structures

Monterine 1 as well as granjine 3, 1R,1'S configured biphenylic bisbenzylisoquinoline alkaloids, generate two highly populated conformers. The interconversion of two forms was detected by saturation tranfer in (1)H NMR NOEs experiments. Tridimensional structure of the conformers was determined on the basis of (1)H NMR analysis of anisotropic shielding protons, by NOEs measurements and vicinal proton coupling constants of CH1-CH(2)alpha and CH1'-CH(2)alpha'. The structures established from NMR data were further refined to observe the mobility of 3D conformations by molecular dynamics simulation in vacuo. The highly populated conformers, monterine 1a and 1b, as well as granjine 3a and 3b, are interconvertible by rotation about the C1'-Calpha', Calpha'-C9', and C11'-C11 bonds and inversion of the benzyl D ring by reference to CH(2)alpha'. The slow exchange system was investigated by dynamic NMR spectroscopy: DeltaG()(c) 77.9 KJ/mol and k(c) 200 s(-)(1) for monterine 1; DeltaG()(c) 77.7 KJ/mol and k(c) 211 s(-)(1) for granjine 3. Natural and synthetic biphenylic bisbenzylisoquinolines displayed, in vitro, cytotoxic activities against human prostate and breast cancer cell lines.     

Mononuclear and dinuclear copper(I) complexes with a particularly bulky phosphine ligand. Unusual synthesis and crystal structure characterizations

Summary The addition of NPm (diphenylaminodiphenylphosphinomethane) to CuI or the addition of KI to (NPm)₂CuNO₃ leads to the same P-bonded Cu^I complex, (NPm)₂CuI, presenting a trigonal geometry around the Cu atom. The reaction of this new complex (or of its chloro analogue) with a Cu^II salt yields dinuclear species of general formula [(NPm)Cu(-X)₂Cu(NPm)] (X = Cl or I). X-ray analysis of these complexes show that they are isostructural and retain the trigonal geometry around the metal atom. The Cu···Cu distances are 2.775(1)Å for X = Cl and 2.642(1) Å for X = I. The Cu-(-X)-Cu angle is more acute for the iodide [61.48(3)°] than for the chloride [74.17(8)°] complex. These values are discussed in terms of Cu···Cu interactions induced by the electron donor ability of X and the bulk of the phosphine L.     

The peripheral benzodiazepine receptor in photodynamic therapy with the phthalocyanine photosensitizer Pc 4

The peripheral benzodiazepine receptor (PBR) is an 18 kDa protein of the outer mitochondrial membrane that interacts with the voltage-dependent anion channel and may participate in formation of the permeability transition pore. The physiological role of PBR is reflected in the high-affinity binding of endogenous ligands that are metabolites of both cholesterol and heme. Certain porphyrin precursors of heme can be photosensitizers for photodynamic therapy (PDT), which depends on visible light activation of porphyrin-related macrocycles. Because the apparent binding affinity of a series of porphyrin analogs for PBR paralleled their ability to photoinactivate cells, PBR has been proposed as the molecular target for porphyrin-derived photocytotoxicity. The phthalocyanine (Pc) photosensitizer Pc 4 accumulates in mitochondria and structurally resembles porphyrins. Therefore, we tested the relevance of PBR binding on Pc 4-PDT. Binding affinity was measured by competition with 3H-PK11195, a high-affinity ligand of PBR, for binding to rat kidney mitochondria (RKM) or intact Chinese hamster ovary (CHO) cells. To assess the binding of the Pc directly, we synthesized 14C-labeled Pc 4 and found that whereas Pc 4 was a competitive inhibitor of 3H-PK11195 binding to the PBR, PK11195 did not inhibit the binding of 14C-Pc 4 to RKM. Further, 14C-Pc 4 binding to RKM showed no evidence of saturation up to 10 microM. Finally, when Pc 4-loaded CHO cells were exposed to activating red light, apoptosis was induced; Pc 4-PDT was less effective in causing apoptosis in a companion cell line overexpressing the antiapoptotic protein Bcl-2. For both cell lines, PK11195 inhibited PDT-induced apoptosis; however, the inhibition was transient and did not extend to overall cell death, as determined by clonogenic assay. The results demonstrate (1) the presence of low-affinity binding sites for Pc 4 on PBR; (2) the presence of multiple binding sites for Pc 4 in RKM and CHO cells other than those that influence PK11195 binding; and (3) the ability of high supersaturating levels of PK11195 to transiently inhibit apoptosis initiated by Pc 4-PDT, with less influence on overall cell killing. We conclude that the binding of Pc 4 to PBR is less relevant to the photocytotoxicity of Pc 4-PDT than are other mitochondrial events, such as photodamage to Bcl-2 and that the observed inhibition of Pc 4-PDT-induced apoptosis by PK11195 likely occurs through a mechanism independent of PBR.     

Solvent extraction of protactinium(v) with bis(2-ethylhexyl)phosphoric acid in toluene

The extraction of Pa(V) from 1M perchloric acid medium with HDEHP in toluene was carried out. The different factors affecting the metal distribution coefficient such as HDEHP concentration in the organic phase, pH of the aqueous phase and the equilibrium temperature were followed. From the data obtained the equilibrium constants of the extraction reaction were calculated. From the temperature variation, the corresponding thermodynamic parameters (G, H and S) were also derived. In the same way, the effect of addition of some N-and 0-containing solvents such as pyridine, 2,2-dipyridyl, n-amyl alcohol, n-decyl alcohol and n-butyl acetate, to the HDEHP organic phase was demonstrated. From the data obtained the suggested mechanisms for the synergistic extraction reactions were discussed together with the corresponding values of the thermodynamic parameters.     

Conformation of DNA modified by monofunctional Ru(II) arene complexes: recognition by DNA binding proteins and repair. Relationship to cytotoxicity

We analyzed DNA duplexes modified at central guanine residues by monofunctional Ru(II) arene complexes [(eta(6)-arene)Ru(II)(en)(Cl)](+) (arene = tetrahydroanthracene or p-cymene, Ru-THA or Ru-CYM, respectively). These two complexes were chosen as representatives of two different classes of Ru(II) arene compounds for which initial studies revealed different binding modes: one that may involve DNA intercalation (tricyclic-ring Ru-THA) and the other (mono-ring Ru-CYM) that may not. Ru-THA is approximately 20 times more toxic to cancer cells than Ru-CYM. The adducts of Ru-THA and Ru-CYM have contrasting effects on the conformation, thermodynamic stability, and polymerization of DNA in vitro. In addition, the adducts of Ru-CYM are removed from DNA more efficiently than those of Ru-THA. Interestingly, the mammalian nucleotide excision repair system has low efficiency for excision of ruthenium adducts compared to cisplatin intrastrand crosslinks.     

Synergistic mechanisms of β-diketone derivatives and zinc-calcium soaps in PVC stabilisation

It has been possible to explain the mechanisms of stabilisation and of the synergistic effects of the β-diketone derivatives claimed in a patent as new stabilisers for improving the efficiency of those recipes based upon zinc and calcium soaps in the prevention of the initial discoloration of poly(vinyl chloride).Using chlorohexene as a model compound for allylic chloride structures and benzoylacetone as a model compound for enolised β-diketone derivatives, it has been shown that the benzoylacetone can substitute allylic chlorine atoms through a C-alkylation reaction which takes place only in the presence of ZnCl₂ as catalyst. This reaction drastically changes the percentage of the enol and causes the appearance of two bands at 1720 cm^?1 and 1680 cm^?1 in the infra-red spectrum due to the ketonic structures During the processing of the PVC on a rolling mill at 180°C in the presence of zinc and calcium stearates and benzoylacetone there is grafting of the ketone derivative through a C-alkylation reaction. There is a closed parallelism between the influence of the benzoylacetone on the dehydrochlorination of the chlorohexene and on the accumulation of chloride ions in the polymer matrix in the presence of zinc and calcium stearate. The synergistic effect of the benzoylacetone in the prevention of the initial discoloration is related to the substitution reaction through a C-alkylation which takes place only in the presence of zinc stearate which generates ZnCl₂ which, in turn, acts as a catalyst for both the C-alkylation and dehydrochlorination.     

Cars study of vibrationally excited H2 produced in formaldehyde dissociation

Coherent anti-Stokes Raman scattering (CARS) has been used to observe H₂ from H₂CO + hv H₂ + CO. Photolysis of K = 1 (ortho) lines of the 2¹4¹ S₁ ← S₀ transition produced no para-H₂ (<4% statistical); and demonstrated nuclear spin conservation. H₂ states v = 1, 2 and 3 were comparably populated.