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This work shows that S-atom substitution in phosphate, controls the directionality of hole transfer processes between base and sugar-phosphate backbone in DNA systems. The investigation combines synthesis, electron spin resonance (ESR) studies in supercooled homogeneous solution, pulse radiolysis in aqueous solution at ambient temperature and density functional theory (DFT) calculations of in-house synthesized model compound dimethylphosphorothioate (DMTP(O(−))=S) and nucleotide (5’-O-methoxyphosphorothioyl-2’-deoxyguanosine (G-P(O(−))=S)). ESR investigations show that DMTP(O(−))=S reacts with Cl(2)(•−) to form the σ(2)σ*(1) adduct radical -P-S∸Cl which subsequently reacts with DMTP(O(−))=S to produce [-P-S∸S-P-](−). -P-S∸Cl in G-P(O(−))=S undergoes hole transfer to Gua forming the cation radical (G(•+)) via thermally activated hopping. However, pulse radiolysis measurements show that DMTP(O(−))=S forms the thiyl radical (-P-S•) by one-electron oxidation which did not produce [-P-S∸S-P-](−). Gua in G-P(O(−))=S is oxidized unimolecularly by -P-S• intermediate in sub-picosecond range. DFT thermochemical calculations explain the differences in ESR and pulse radiolysis results obtained at different temperatures.

We wish to draw attention to an important issue concerning scientific practice with regard to enhancing the quality of publications in Molecules (as well as for other journals) [...]

This review includes recent developments in the synthesis of benzo[4,5]imidazo[2,1-a]isoquinolines with particular attention given to categorizing protocols based on the structural features of the ring architecture and crystallographically characterized reaction products.

On behalf of my Section Editor-in-Chief co-author colleagues I am pleased to announce a Special Issue to commemorate the recent publication of Molecules’ 20,000th paper [...]

A 5-endo-dig halocyclization of 2-fluoroalk-3-yn-1-ones with the use of N-iodo- and N-bromosuccinimide, in the presence of gold chloride/zinc bromide (5:20 mol-%, dichloromethane), under ambient conditions, provides a facile method for the synthesis of 2,5-disubstituted 3-bromo-4-fluoro- and 3-fluoro-4-iodofurans. The sequential procedure starts at monofluorination of the alk-1-en-3-yn-1-yl silyl ethers with Selectfluor and proceeds with good overall yields (62-78%).

The 5-endo-dig chlorocyclization of 1,4-disubstituted alk-3-yn-1-ones (propargylic ketones) with the use of trichloro-s-triazinetrione (trichloroisocyanuric acid, TCCA; 0.4 equiv.) in toluene, at room temperature, in the absence of base, provides 2,5-disubstituted 3-chlorofurans in high yields (79–96 %). The reaction can be accomplished by using commercially available swimming pool sanitizer. Selected 3-chlorofuran was validated as a substrate for Suzuki–Miyaura coupling. In a similar manner, chlorocyclization of 5-alkynyl-2′-deoxyuridines produces 5-chlorofuropyrimidine nucleosides (76–83 %), which are analogues of potent anitviral agents. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Reactions of 5-alkynyl-2'-deoxyuridines with dicobalt octacarbonyl Co2(CO)8 in THF at room temperature gave hexacarbonyl dicobalt nucleoside complexes (77-93%). The metallo-nucleosides were characterized, including an X-ray structure of a 1-cyclohexanol derivative. In crystalline form, the Co-Co bond is perpendicular to the plane of the uracil base, which is found in the anti position. The level of growth inhibition of MCF-7 and MDA-MB-231 human breast cancer cell lines was examined and compared to results obtained with the alkynyl nucleoside precursors. The cobalt compounds displayed good antiproliferative activities with IC50 values in the range of 5-50 microM. Interestingly, the coordination of the dicobalt carbonyl moiety to 5-alkynyl-2'-deoxyuridines led to a significant increase in the cytotoxic potency for alkyl/aryl substituents at the non-nucleoside side of the alkyne, but in the case of hydrogen (terminal alkyne) or a silyl group, a decrease of the cytotoxic effect was observed. As demonstrated using examples for an active and a low active target compound, the cytotoxicity was significantly influenced by the uptake into the tumor cells and the biodistribution into the nuclei.

[structure: see text]. 5-Endo-dig cycloisomerization of 1,4-di- and 1,2,4-trisubstituted but-3-yn-1-ones in the presence of a catalytic amount of zinc chloride (10 mol %) in dichloromethane at room temperature (22 degrees C) provides 2,5-di- and 2,3,5-trisubstituted furans in high yields (85-97%).

[reaction: see text] Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, N,N'-acylhydrazines, and acyl-protected uridines with the use of a fluorous analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3-thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation of the final products in high yields is achieved in most cases by a simple filtration (fluorous solid-phase extraction).

The diyne (η5-C5Me5)Re(NO)(PPh3)(CCCCSiMe3) is elaborated to (η5-C5Me5)Re(NO)(PPh3)(CCCCCCSiR3) (R=Me, 3a; Et, 3b) by sequences involving n-Bu4N+F− in aqueous THF to give (η5-C5Me5)Re(NO)(PPh3)(CCCCH) (91%), n-BuLi/CuI or t-BuOCu to give (η5-C5Me5)Re(NO)(PPh3)(CCCCCu) (4), and coupling with ICCSiMe3 (48%) or BrCCSiEt3 (84–65%). Complex 3b is similarly converted to (η5-C5Me5)Re(NO)(PPh3)(CCCCCCH) (88%) and (η5-C5Me5)Re(NO)(PPh3)(CCCCCCCu) (6). Reactions of 4 and 6 with BrCC-p-C6H4Me give the title compounds (η5-C5Me5)Re(NO)(PPh3)((CC)n-p-C6H4Me) (n=3, 7; 4, 8; 77–66%). Optimized one flask conversions of 1a and 3b to 7 (81%) and 8 (71%) are described. The crystal structures of 7 (monoclinic, P21/c, a/b/c=17.951(8)/8.377(5)/22.160(9) A, β=103.63(5)°, Z=4), and 8 (monoclinic, P21/n, a/b/c=8.426(3)/16.400(6)/25.400(9) A, β=97.51(3)°, Z=4) show markedly curved sp carbon chains—much more than hexatriynes or octatetraynes reported to date. The bond angles associated with the Re(CC)nC moieties (min/max/avg) are 169.1(10)°/178.8(13)°/174.7° (7) and 170.0(9)°/178.8(10)°/175.7° (8). Other structural features are normal, and bending is provisionally ascribed to packing forces. Reaction of 7 and HBF4·OEt2 gives the cationic vinylidene complex [(η5-C5Me5)Re(NO)(PPh3)(CC(H)CCCC-p-C6H4Me)]+BF4−, the structure of which is established by extensive NMR analyses.

Synthesis of highly substituted 3-fluorofurans is reported. The sequence began with preparation of tert-butyldimethylsilyl alk-1-en-3-yn-1-yl ethers from 1,4-disubstituted alk-3-yn-1-ones. Subsequent fluorination of alkenynyl silyl ethers with Selectfluor gave 2-fluoroalk-3-yn-1-ones in almost quantitative yield. Subsequent 5-endo-dig cyclizations using chlorotriphenylphosphine gold(I)/silver trifluoromethanesulfonate (5/5 mol%), N-bromo- or N-iodosuccinimide and gold(I) chloride/zinc bromide (5/20 mol%), all at room temperature, provided a facile method for the generation of substituted 3-fluoro-, 3-bromo-4-fluoro-, and 3-fluoro-4-iodofurans in good yields. Also, 2,2-difluoroalk-3-yn-1-ones were prepared by fluorination of alk-3-yn-1-ones under organocatalytic conditions. The structures of (Z)-tert-butyldimethylsilyl but-1-en-3-yn-1-yl ether, 3-bromo-4-fluorofuran, and 3-fluoro-4-(phenylethynyl)furan were confirmed by X-ray crystallography.

[formula: see text] The reaction of secondary and primary alcohols with highly fluorinated 3,4,5-tris(5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-heptadecafluorododecan- 1-yloxy)benzoic acid in the presence of Ph3P and DIAD in THF at room temperature (fluorous Mitsunobu) resulted in a simple, chromatography-free isolation protocol with excellent yields (83-96%).

Reactions of (η5-C5Me5)Re(NO)(PPh3)(C⋮CC⋮CR) (R = Me, H) and (t-BuO)3W⋮W(O-t-Bu)3 give (t-BuO)3W⋮CR and the title complex (79−76%), which crystallizes from toluene as a solvated tert-butoxy-bridged dimer. The NMR, IR, and crystallographic properties establish dominant Re−C⋮C−C⋮W as opposed to +ReCCCW- character.

[reaction: see text] 5-Endo-dig electrophilic cyclization of 1,4-diaryl but-3-yn-1-ones with N-bromosuccinimide or N-iodosuccinimide/acetone and iodine monochloride/CH(2)Cl(2), at room temperature, in the absence of base, provides 3-halo-2,5-diarylfurans with excellent regiocontrol and high yields (81-94%).

Recent progress in synthetic approaches to the Mitsunobu reaction are reviewed. Efforts that have focused on the phase-switching modifications of phosphane, azodicarboxylate, and nucleophilic components are emphasized. An approach to product separation with fluorous compounds is reviewed in detail. Alternative reagents and recently introduced products are cited. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

5-Exo-dig cyclocondensation of alk-3-yn-1-ones with hydrazines, in the presence of montmorillonite K-10, provides an effective method with a high atom economy for the synthesis of diversely 1,3,5-trisubstituted pyrazoles. The microwave-accelerated reaction proceeds in the absence of solvent and leads to 5-benzyl substituted pyrazoles with good yields (72-91%). The regiochemistry of the process was confirmed by the X-ray crystallographic structure determination of 1-(2-fluorophenyl)-5-(4-methylbenzyl)-3-phenyl-1H-pyrazole.