EFFECTS OF RHODAMINE 123 IN THE DARK AND AFTER IRRADIATION ON MITOCHONDRIAL ENERGY METABOLISM

Isolated rat liver mitochondria have been used to study the mechanism of toxicity of Rhodamine 123 (Rho 123) in the dark and after irradiation with visible light. We report an inhibition of adenosine 5'-diphosphate phosphorylation which is increased after illumination. In the dark, the first steps of the phosphorylation process (i.e. the entry of substrates into the matrix, the electron transport to oxygen and the creation of the proton gradient) as well as ATPase activity are not significantly perturbed at Rho 123 concentration below 10 micrograms/mL. In contrast, the movements of the phosphate compounds are drastically impaired. Irradiation strengthens the detrimental effects in an oxygen dependent process. The nature of the noxious transient species is not clearly established, but it is suggested that singlet oxygen could be responsible for the observed damage.     

Synthesis and Structure of New Cobalt–Carbonyl Complexes Containing Tellurium Atoms

Co₂(CO)₈ and Te₂O react to form the well known Co₄(CO)₁₀Te₂, Co₄(CO)₁₁Te₂ complexes and the two new cluster complexes CCo₆(CO)₁₂Te₂(1), and CCo₆(CO)₁₀Te₂(Te₃) (2). The structures of 1 and 2 were determined by X-ray analysis, together with the triphenylphosphine derivative of 1, CCo₆(CO)₁₁(PPh₃)Te₂(3), which was analyzed to clarify the disordered structure of the parent compound. Complex 1 is formed by a prismatic cluster of cobalt atoms with a carbon embedded in the cage; two tellurium atoms cap the triangular faces of the prism and each cobalt atom links two terminal carbonyl groups. The complex 2 has a similar prismatic cage CCo₆; two ₄-Te atoms cap two rectangular faces of the prism, while other two Te atoms bridge two edges of the triangular faces and are linked each other through a third Te atom. Electron counting gives for complex 2 92 electrons: the presence of two long Co–Co distances suggests that the two excess electrons are located on Co–Co antibonding orbitals. Crystal data for 1, space group C2/c, a = 12.845(2) Å, b = 13.449(2) Å, c = 13.246(2) Å, = 91.95(2)°, Z = 4, R = 0.097 for 2555 reflections; for 2, space group Pnna, a = 17.219(5) Å, b= 14.969(6) Å, c = 9.178(4) Å, Z = 4,R = 0.037 for 3103 reflections; for 3, space group P2₁/c, a = 9.288(2) Å, b = 14.920(6) Å, c = 26.300(9) Å, = 99.99(2)°, Z = 4, R = 0.037 for 4300 reflections. The vibrational analysis of the complex 1 was performed and most of the (CO), (₆C–Co), (Co–Co) and (Co–Co) modes were assigned. The (Co–Te) modes were interpreted on the basis of the intermolecular coupling, due to the close contact between neighboring clusters in one distinct direction in the crystal.     

1,2,3-Triazolodiazepines. I. Preparation and benzodiazepine receptor binding of 1-benzyl- and 1-phenethyl-1,2,3-triazolo-[4,5-b][1,4]diazepines

Several new 1,2,3-triazolo[4,5-b][1,4]diazepines were prepared starting from 1-benzyl-1 and 1-phenethyl-4,5-diamino-1,2,3-triazole 2 (Scheme 1), by condensation reactions with β-diketones (Scheme 2), β-ketoesters (Scheme 3), and diethyl malonates (Scheme 4). In the first case we obtained compounds 3 and 4 with basic properties, while the ester function condensations gave cyclic amide derivatives 7, 8, 10, 12 and 13 with acid properties. Some N-methyl derivatives 11, 14 and 15 were obtained from the cyclic amide compounds. Most of compounds were tested for their ability to displace [³H]flunitrazepam from bovine brain membranes but no compound showed benzodiazepine receptor binding affinity.     

Triazolylbenzimidazolthiones and derivatives of the new 1,2,3‐triazolo[ 1,5‐a][ 1,3,5]benzotriazepine heterocycle

Four new triazolylbenzimidazolthione derivatives (2a‐d), analogous to triazolylbenzimidazolone derivatives previously tested as activators of the BK_Ca potassium channels, were prepared and assayed without success. Some derivatives of a new tricyclic nitrogen heterocycle, 1,2,3‐triazolo[1,5‐a][1,3,5]benzo‐triazepine, bearing a carboxamido group in the 3 position, other substituents in the 8 position and a carbonyl (5a‐d) or thione (6a‐c) or methylthio (7a‐c) function in the 5 position were synthesised. The nucleophilic displacement of the methylthio substituent with morpholine or cyclopentylamine provided the 5‐amino‐substituted tricyclic derivatives 8a‐d. Starting from the l‐(2‐nitrophenyl)‐4‐cyano‐5‐amino‐1,2,3‐triazole (9), the 3‐cyano‐triazolobenzotriazepin‐5‐one derivative 12 was also obtained. The majority of the new compounds were tested towards the BK_Ca potassium channels, the benzodiazepine and adenosine A₁ and A_2a receptors, but no remarkable activity was detected.     

Structural and infrared spectroscopic characterization of Co6C(CO)12S2: a high-nuclearity carbido carbonyl cluster spontaneously formed from dicobalt octacarbonyl and carbon disulphide

Co₆C(CO)₁₂S₂ (I) has been isolated in crystalline form from the mixture of more than a dozen of carbonyl products formed when Co₂(CO)₈ reacts at room temperature with CS₂. Crystals of I are monoclinic with space group Cc, and lattice constants a  16.250(5), b  9.413(4), c  16.036(5) Å, β  116.77(4)°. Structure refinement gave R  0.034 for 1974 reflections. The CCo₆S₂ core of the molecule possesses idealized D_3h geometry. It is composed of a Co₆ trigonal prism, enclosing a C atom in the centre, and the triangular faces are capped symmetrically by the two S atoms. The core contains two sorts od CoCo distances: short one (2.432 Å) along the triangular edges, and long ones (2.669 Å) along the lateral edges. The average CoC distance is 1.94 Å, and the average CoS distance 2.192 Å.¹³CO-enriched samples were prepared photochemically and their IR spectra used in the assignment of the CO stretching frequencies. The CO stretching force constant was calculated to be 1670(2) Nm^-1.By the use of ¹³CS₂, I has also been obtained in a selectively carbido-¹³C-labelled form. The vibrational frequencies of the carbide atom were observed, and that at 819 cm^-1 (¹³C: 790 cm^-1) assigned to the species

, and that at 548 cm^-1 (¹³C: 535.5 cm^-1) to species E′. For the Co-C(carbide) force constant a value of 155 Nm^-1 was calculated. The cobalt—sulphur stretching frequencies were found at 309 cm^-1 (

) and 239 cm^-1 (E′). The CoS stretching force constant, 78 Nm^-1, is considerably lower than that obtained for SCo₃-(CO)₉, viz. 112 Nm^-1.     

A new synthesis of 2,2′-dialkylchrom-3-enes and flav-3-enes

N-iodosuccinimide (NIS) induces cyclization of substituted 2-allyl-phenols to 3-iodochromanes which may be dehydrohalogenated to the corresponding chrom-3-enes.     

Synthesis of Polysubstituted Pyrrolizidines from Proline Derivatives and Conjugated Nitroolefins

The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and i-proline alkyl esters with several nitroolefins was investigated. Cyclic and acyclic nitroolefins add to the anti form of the ylide in a highly diastereoselective but poorly regioselective manner to give pyrrolizidine derivatives. In a few cases, the stereochemical results strongly support a stepwise mechanism.     

Preparation of new N6, 9‐disubstituted 2‐phenyl‐adenines and corresponding 8‐azaadenines.: A feasibility study for application to solid‐phase Synthesis. I

A suitably substituted pyrimidine 1 was converted to a number of title compounds. Nucleophilic substitu tion involving the chlorine atoms in 1 by treatment with phenylmethanethiol yielded 2 or 3 , depending on the reaction temperature. Treatment of 3 with an amine afforded 6‐phenylmethanesulfanyl‐N⁴‐substituted‐2‐phenyl‐pyrimidine‐4,5‐diamines 4–7 . These pyrimidines were converted into 2‐phenylpurines 8–11 and 2‐phenyl‐8‐azapurines 12–14 , by treatment with triethyl orthoformate in the presence of hydrochloric acid (or acetic anhydride), or with potassium nitrite and acetic acid respectively. The thioether function on C(6) was then converted into a sulfonyl group by oxidation with m‐chloroperoxybenzoic acid affording purines 15–18 and their 8‐azaanalogs 19–21 ; these compounds, as crude products, were treated with an amine to yield the corresponding adenines 22–25 or 8‐azaadenines 26–31. All reactions were performed under conditions com patible with the possible use of a thiomethyl resin in place of phenylmethanethiol to bind the pyrimidine ring of 1 to a solid phase.     

Convergent synthesis of mosloflavone, negletein and baicalein from crysin

An expeditious synthesis of three polyoxygenated flavones: mosloflavone, negletein and baicalein, starting from crysin, an easily available flavone, by a bromination/methoxylation procedure is reported. The convergent synthesis exploits a base induced Wesley-Moser type rearrangement.