Cytotoxic trans-oriented platinum complexes only form adducts with single-stranded oligodeoxynucleotides

The reactions of the anticancer complex trans-[PtCl(2)[(E)-HN==C(OMe)Me](2)] (trans-EE) with both single-stranded and double-stranded deoxyribonucleotides have been studied by HPLC and 2D [(1)H,(15)N] HMQC NMR spectroscopy and compared with those of cis-[PtCl(2)(NH(3))(2)] (cis-DDP). Reactions of trans-EE with the single-stranded oligonucleotides d(CCTCGCTCTC) and d(CCTGGTCC) proceed rapidly through solvolysis of the starting substrate and subsequent formation of G-N7/monochloro trans-EE adducts. The rate of reaction is comparable to that of formation of an adduct from trans-EE and the dinuclotide d(ApG). Quite unexpectedly, the double-helical duplexes, d(TATGGTACCATA)(2) and d(TATGGCCATA)(2), with no terminal G residues, are practically inert towards trans-EE, and only minor species (< 5 % as estimated from HPLC traces) appear during 24 h reaction time. However, the duplexes d[(CCTCGCTCTC). (GAGAGCGAGG)] and d(GATAGGCCTATC)(2), which contain both terminal and central G residues, undergo platination only at the terminal, solvent-exposed, G residues, thereby confirming that the interior of the duplex is not accessible to trans-EE due to steric hindrance. In contrast, cis-DDP was found to bind exclusively to the central GG pair in d(GATAGGCCTATC)(2).     

Photoinduced Double Addition of Acetylene to 3-Oxocyclopent-1-ene-1-carbonitrile or 3-oxocyclopent-1-enyl acetate leading to 2,3-dihydro-1H-inden-1-one and other rearranged products

UV Irradiation of 3-oxocyclopent-1-enyl acetate ( 17 ) and acetylene in MeCN at 0° gives, besides the product of normal enone-alkyne [2 + 2] cycloaddition (cis-4-oxobicyclo[3.2.0] hept-6-en-1-yl acetate, 18 ) and its product of oxa-di-π-methane rearrangement (5-oxotricyclo[4.1.0.0^2,7]hept-2-yl acetate, 19 ), unexpected products of further addition of a molar equivalent of acetylene. These are indanone ( = 2,3-dihydro-1H-inden-1-one, 16 ), in 21% yield, cis-1-cisoid-1,2-cis-2- ( 20 ) and cis-1-transoid-1,2-cis-2-7-oxotricyclo[4.3.0.0^2,5]non-3-en-1-yl acetate ( 21 ), 4-oxo-7-‘exo’-vinyltricyclo[3.2.0.0^2,6]hept-2-yl acetate ( 22 ), cis-4-oxo-6-‘endo’- ( 23 ) and cis-4-oxo-6-‘exo’-vinylbicyclo[3.2.0]hept-1-yl acetate ( 24 ), and cis-4-oxo-7-‘exo’-vinylbicyclo[3.2.0]hept-1-yl acetate ( 25 ). At least in part, indanone must be formed via intermediates 20 and 21 . In fact, on heating a 9:1 mixture 20/21 , indanone is obtained quantitatively. With 3-oxocyclopent-1-ene-1-carbonitrile ( 15 ) in place of 17 , indanone is formed in lower (8%) yield besides much tars.     

Oxidative Breaking of Long-Chain Acetylenic Enol Ethers of Glycerol of the Marine Sponges Raspailia pumila and of Model Compounds with Aerial Oxygen

The raspailynes (novel long-chain enol ethers of glycerol having the enol ethers double bond conjugated in sequence, to an acetylenic and an olefinic bond, isolated from the North-East-Atlantic sponges Raspailia pumila and R. ramosa) are stable under normal hydrolytic conditions for enol ethers. In contrast, when their solutions are evaporated, these lipids such as raspailyne Bl (=(?))-3-[(1Z,5Z)-(tetradeca-1,5-dien-3-ynyl)oxy]-1,2-propanediol;(?- 2 ) rapidly react with aerial O₂ under normal laboratory-daylight conditions, with rupture of the C=C enol ether bond to give 1-O-formylglycerol ( 3 ) and an aldehyde (such as tridec-4-en-2ynal( 4 ) from (?)- 2 ). This reaction must be caused by triplet O₂, since thermally generated singlet O₂ has no effect on (?)- 2 in solution. That the mere presence of an enol-ether moiety conjugated to an acetylenic group is responsible for such a behaviour is demonstrated with the model compounds 1-methoxypentadec-1-en-3-yn-5-ol ( 6a ) and its 5-O-acetyl or 5-O-tetra-hydropyranyl derivatives 6b and 6c , respectively. Resistance to both hydroytic conditions and singlet O₂ of these compounds is thought to arise from electron depletion at the enol-ether C(beta;) atom by the acetylenic group. Plausible reaction pathways for enol-ether bond rupture in these compounds by aerial O₂ are outlined.     

Stereospecific palladium(0)-catalyzed reduction of 2-cyclobutylidenepropyl esters. A versatile preparation of diastereomeric monoterpenoids: (±)-fragranol and (±)-grandisol

Mixtures of (E and Z)-2-cyclobutylidenepropyl sulfonates, readily available from α,α-disubstituted cyclobutanones arising from suitable cyclopropane derivatives ring expansion, underwent regioselective and stereospecific reduction by formate anion to offer, through π-1,1-trimethyleneallylpalladium complexes formed upon treatment with palladium(0), a new and convenient entry to the diastereomeric four-membered ring monoterpenoids (±)-fragranol and (±)-grandisol.     

Critical comparison of alternating current and differential pulse voltammetry in the determination of some heavy metals in sea-water

A critical comparison of phase-selective fundamental harmonic a.c. anodic stripping voltammetry and differential pulse anodic stripping voltammetry for the determination of Pb, Cd, Cu and Zn in sea-water is reported. Differential pulse anodic stripping voltammetry was found to be slightly more sensitive than the a.c. technique, but the effect of the charging current could be more effectively eliminated by the latter, especially in the determination of zinc(II) and copper(II). The detection limits for both techniques were found to be about 10^–10-10^–8 M for all four elements. The precision, expressed as relative standard deviation, was of the order of 2–5% for the fundamental harmonic a.c. method and 5–8% for differential pulse voltammetry. The accuracy (expressed as recovery) was 95–105% for the former and 90–110% for the latter.     

Leucascandrolide A,a New Type of Macrolide: The first powerfully bioactive metabolite of calcareous sponges (Leucascandra caveolata,a new genus from the coral sea)

Leucascandrolide A ((+)- 1 ), a doubly O-bridged 18-membered macrolide of a new type, i.e., showing little C₁-branching vs. extensive 1,3-dioxygenation and a peculiar side chain, was isolated from a calcareous sponge of a new genus, Leucascandra caveolata BOROJEVIC and KLAUTAU from the Coral Sea. Transesterification of (+)- 1 gave the methyl ester 3 , derived from the side chain, and the 5-hydroxy derivative (+)- 2 , derived from the macrolide portion and with the natural configuration at C(5) (axial). Mosher's MTPA esters 4 and 5 obtained from (+)- 2 showed scattered Δδ = (δ(S) ? δ(R)) data. However, inversion of the configuration at C(5) led, via ketone (+)- 6 , to the less encumbered 5-equatorial hydroxy derivative (+)- 7 , whose MTPA esters 8 and 9 gave consistent Δδ data, allowing the assignment of the absolute configuration of (+)- 7 , and hence of (+)- 1 . The structural novelty of (+)- 1 and its powerful antifungal and cytotoxic activities are likely to renew interest in calcareous sponges, previously limited to scarcely biologically active 2-aminoimidazoles.     

Luminescence of mixed-ligand Ru(II) chelates is there any bona fide case of dual emission?

The luminescence behavior of Ru(bpy)₂(pq)²⁺, Ru(bpy)₂(biq)²⁺, Ru(bpy)₂(NO₂-bpy)²⁺, Ru(phen)₂(pq)²⁺, Ru(phen)₂ (biq)²⁺, Ru(phen)₂ (DMCH)²⁺, Ru(bpy)₂(i-biq)²⁺ and Ru(bpy)(i-biq)₂²⁺ has been carefully studied. In no case has bona fide dual emission been observed. The reason for the previously reported dual emissions of Ru(bpy)₂(NO₂-bpy)²⁺ and Ru(phen)₂(pq)²⁺ are discussed.     

Spin adducts of group IVB organometallic radicals with Thioketones. an esr study

The radical adducts resulting from the reaction between group IVB organometallic radicals MR₃ (M = Si, Ge, Sn; R = alkyl or aryl) and a number of thioketones of the chromone and flavone series have been investigated by ESR spectroscopy. The spectral parameters obtained for these species have been compared with those of similar adducts of the corresponding ketones. Both classes of radicals adopt an orthogonal conformation, and the differences between the former and the latter paramagnetic species can be accounted for by the different electronegativity of oxygen and sulphur. the effects of substitution of the heterocyclic oxygen with a sulphur or selenium atom on the spin density distribution are likewise explained. INDO calculations have been carried out on the model systems CH₂XSiH₃ (X = O, S).     

Synthesis,catalytic properties and biological activity of new water soluble ruthenium cyclopentadienyl PTA complexes [(C5R5)RuCl(PTA)2] (R = H,Me; PTA = 1,3,5-triaza-7-phosphaadamantane)

The new water soluble ruthenium complexes [(C5R5)RuCl(PTA)2] (R = H, Me; PTA = 1,3,5-triaza-7-phosphaadamantane) were synthesised and characterised. Their evaluation as regioselective catalysts for hydrogenation of unsaturated ketones in aqueous biphasic conditions and as cytotoxic agents towards the TS/A adenocarcinoma cell line is briefly presented.     

A novel glyceryl ester (glyceryl dendryphiellate A), a trinor-eremophilane (dendryphiellin A1), and eremophilanes (dendryphiellin E1 and E2) from the marine deuteromycete Dendryphiella salina (SUTHERLAND) PUGH et NICOT

Continuing studies of the global extracts from cultures of the marine deuteromycete Dendryphiella salina have led to the isolation of novel compounds that add to the scarce list of marine fungal metabolites. Besides (22E)-ergosta-4.6,8(14),22-tetraen-3-one which, though known from basidiomycetes, was unknown in the sea, they are an unusual glyceryl ester, i.e. glycer-1-yl dendryphiellale A (= (+)-(2R)-2,3-dihydroxyprop-l-yl (6S,2E,4E)6-methylocta-2,4-dienoate; (+)- 1 ), a trinor-eremophilane, i.e. dendryphiellin A1 ( = (+)-(3R*,4E,6E)-7-{[(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2yl]oxycarbonyl}-3-methylhepta-4,6-dienoic acid; (+)- 11 ), and two eremophilanes, i.e. dendryphiellin El ( = (+)-(1R*, 2S*, 7S*,8aR*)-1,2,6,7,8,8a-hexahydro-1,8a-dimethyl-7-(1-methylethenyl)-6-oxonaphthalen-2-yl(6S,2E,4E)-6-methyl-octa-2,4-dienoate; (+)- 13 ) and dendryphiellin E2 ( = (+)-(1R*, 2S*, 8aR*)-1,2,6,7,8,8a-hexahydro-7-isopropyl-idene-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S,2E,4E)-6-Methylocta-2,4-dienoate; (+)- 14 ). Absolute configurations have been established for (+)- 1 via total synthesis and for the acid portion of (+)- 13 and (+)- 14 via transesterification in NaOMe/MeOH which gave in both cases melhyl dendryphiellate A ((+)- 16 ) of known configuration and the free alcoholic moiety of (+)- 14 , i.e. (+)- 17 .