Concise syntheses of trifluoromethylated cyclic and acyclic analogues of cADPR

A novel trifluoromethylated analogue of cADPR, 8-CF3-cIDPDE (5) was designed and synthesized via construction of N1,N9-disubstituted hypoxanthine, trifluoromethylation and intramolecular condensation. A series of acyclic analogues of cADPR were also designed and synthesized. These compounds could be useful molecules for studying the structure-activity relationship of cADPR analogues and exploring the cADPR/RyR Ca2+ signalling system.     

A novel membrane-permeant cADPR antagonist modified in the pyrophosphate bridge

A concise method for the formation of cyclopyrophosphate of cIDPRE as well as sulfur and selenium-substituted pyrophosphate cIDPRE analogues (P(1)(S)-cIDPRE, P(1)(Se)-cIDPRE, P(2)(S)-cIDPRE and P(2)(Se)-cIDPRE) was reported and one of the P(S)-diastereoisomers, P(1)(S)-cIDPRE-1, is a novel membrane-permeant cADPR antagonist.     

A novel method for the synthesis of sulfur substituted-cyclopyrophosphate of cADPR analogs

A facile and efficient protocol for the synthesis of sulfur substituted-cyclopyrophosphate of cIDPRE(P_S~1-cIDPRE) was developed.The key step was the cyclization process which was completed by the sulfur substituted cyclization precursor 1b via the one-pot phosphoramidite strategy.     

Synthesis of cyclic adenosine 5'-diphosphate ribose analogues: a C2'endo/syn "southern" ribose conformation underlies activity at the sea urchin cADPR receptor

Novel 8-substituted base and sugar-modified analogues of the Ca(2+) mobilizing second messenger cyclic adenosine 5'-diphosphate ribose (cADPR) were synthesized using a chemoenzymatic approach and evaluated for activity in sea urchin egg homogenate (SUH) and in Jurkat T-lymphocytes; conformational analysis investigated by (1)H NMR spectroscopy revealed that a C2'endo/syn conformation of the "southern" ribose is crucial for agonist or antagonist activity at the SUH-, but not at the T cell-cADPR receptor.     

cADPR analogues: effect of an adenosine 2'- or 3'-methoxy group on conformation

[structure: see text] The 2'-OMe-A (2) and 3'-OMe-A (3) analogues of the calcium release agent cADPR (1) were prepared and their solution structures studied by NMR spectroscopy. Compared to 1, 2 shows a shift in its A ring conformation and changes in its R ring N:S and gammat:gamma+ ratios, while 3 displays a significant change in the conformation of its A ring gamma-bond.     

Synthesis and calcium mobilization activity of cADPR analogues which integrate nucleobase, northern and southern ribose modifications

Novel cADPR mimics, which integrate nucleobase, northern and southern ribose modifications were synthesized. The key steps of the synthesis were a Cu(I)-catalyzed Hüisgen [3+2] cycloaddition and a microwave-assisted intramolecular pyrophosphorylation. Preliminary biological investigations showed that these cADPR mimics are membrane-permeating agonists of the calcium signaling pathway. The introduction of chlorine or fluorine at the 2'-position of the southern riboses led to a decrease of activity. The existence of a hydrophobic group on the 3'-OH of the southern riboses does not obviously alter the agonistic activity.     

Formation of a hybrid compound composed of a saddle-distorted Tin(IV)-porphyrin and a Keggin-type heteropolyoxometalate to undergo intramolecular photoinduced electron transfer

Nonplanar Sn(IV)-porphyrin complexes, [Sn(TMPP(Ph)(8))-Cl(2)] (1) and [Sn(TMPP(Ph)(8))(OMe)(2)] (2) (TMPP(Ph)(8): 5,10,15,20-tetrakis(4-methoxyphenyl)-2,3,7,8,12,13,17,18-octaphenylporphyrinato), were prepared and characterized by spectroscopic and electrochemical methods together with X-ray crystallography. Variable-temperature (1)H NMR study revealed that the coordination of the methoxo ligand of 2 is weak enough in solution to enhance the axial ligand exchange with a Keggin-type phosphotungstate (α-[PW(12)O(40)](3-)) due to the steric stress between the axial methoxo ligand and the peripheral phenyl groups of the porphyrin ligand. The formation of a novel 1:1 donor-acceptor complex, [Sn(TMPP(Ph)(8))(OMe)(α-[PW(12)O(40)])](2-) (4) was confirmed by (1)H NMR and UV-vis spectral titrations, and also by MALDI-TOF-MS measurements. Electrochemical measurements for the donor-acceptor complex in PhCN revealed that the Sn(IV)-TMPP(Ph)(8) moiety acts as an electron donor and the α-[PW(12)O(40)](3-) moiety acts as an electron acceptor and that the energy level of the electron-transfer (ET) state of the 1:1 complex (1.17 eV) is lower than that of the triplet excited states of the SnTMPP(Ph)(8) complex (1.31 eV). Femtosecond and nanosecond laser flash photolysis measurements indicate that intersystem crossing from the singlet excited sate to the triplet excited state occurs followed by intramolecular photoinduced electron transfer from the triplet excited state of the Sn(IV)-TMPP(Ph)(8) moiety to the α-[PW(12)O(40)](3-) moiety in the 1:1 complex in benzonitrile.     

Molecular-level helical stack of a nucleotide-appended oligo(p-phenylenevinylene) directed by supramolecular self-assembly with a complementary oligonucleotide as a template

The nucleotide-appended oligo(p-phenylenevinylene), {bis[2,5-bis(2-methoxyethoxy)-1,4-phenylene]bis(2,1-ethenediyl-1,4-phenylenemethylene)}bis(2'-deoxy-3'-thymidylic acid) (8), has been synthesized, and self-assembly of the single-component 8 and binary self-assembly of 8 with a complementary single-stranded 20-meric oligodeoxyadenylic acid (9) have been examined in aqueous solutions. Atomic force microscopy (AFM), UV-visible (UV-vis), and circular dichroism (CD) measurements revealed that right-handed helical stacks with 6.4- and 5.1-nm diameters self-assemble from the binary components of 8 and 9 as a template depending on the residual stoichiometry of the two components (thymine (T):adenine (A) = 1:1 and T:A = 2:1, respectively). The concentration of 9 was found to strongly influence the CD spectra of 8 in aqueous solutions. Consequently, we concluded that the one side of the thymine moieties in the stacked assemblies of 8 complexes with a single chain of 9. Complementary T-A base pairs thus formed and induced helical stack of the oligo(p-phenylenevinylene)s in the binary self-assembly. In contrast, self-assembly of the single-component 8 and binary self-assembly of 8 with the noncomplementary 20-meric oligothymidylic acid (10) produced no remarkable formation of fibrous structures like helical stacks.     

Redox-induced coordination isomerization of a phosphoniobenzophospholide

1-Triphenylphosphoniobenzo[c]phospholide 1 reacts with [M(CO)(5)Br] (M = Mn, Re) and [Mn(CO)(3)(naphthalene)][BF(4)] to give complexes cis-[M(CO)(4)(1)Br] (5 a,b) and [Mn(CO)(3)(1)][BF(4)] (6 a[BF(4)]), respectively, featuring eta(1)(P)- and eta(5)(pi)-coordination of the phosphole ring. The corresponding reactions with [M(2)(CO)(10)] proceed with conservation of the metal-metal bond and yield, depending on the reaction temperature, dinuclear complexes [M(2)(CO)(8)(1)] (M=Mn, 7 a) or [M(2)(CO)(6)(1)(2)] (M=Mn, Re, 8 a,b) with mu(2)-bridging eta(1)(P):eta(2)(Pdbond;C) coordination of the phosphole moiety. All complexes formed were characterized by spectroscopic data; 5 b, 6 a[BF(4)], and 8 a,b were characterized by X-ray diffraction studies as well. The structural and (31)P NMR data of the dinuclear manganese complex 8 a suggest that the interaction between the metal atoms and the eta(2)-bound Pdbond;C double bond moieties is dominated by the L-->M charge-transfer contribution; this hints at a very low back-donation ability of the central M(2)(CO)(6) fragment. Investigation of the reactions of the Mn complexes 6 a and 8 a with Mg or ferrocenium hexafluorophosphate ([Fc][PF(6)]), respectively, revealed that the chemically reversible mutual interconversion between both species was feasible. Likewise, oxidation of the rhenium complex 8 b with [Fc][PF(6)] gave spectroscopic evidence for the formation of a Re analogue of 6 a. Electrochemical studies suggested that the oxidation 8 a-->2 6 a involves two consecutive single-electron-transfer steps, the first of which is electrochemically reversible and produces a metastable radical cation that is detectable by ESR spectroscopy. The mutual interconversion between 6 a and 8 a represents the first case of a reversible coordination isomerization of a phosphaarene that is triggered by a redox process and might stimulate further studies directed at the use of dinuclear phosphaarene complexes in redox-catalysis.     

Reactions of a new optically active arylperhydronaphthalenol based chiral auxiliary

(1 ,4a ,8 ,8a )-8-(5′-methoxy-2′-methylpheny])-8-methyldecahydro-1-naphthalenol is a chiral auxiliary more efficient than 8-phenylmenthol in the Diels-Alder reaction of its acrylate ester with cyclopentadiene and in the diisobutylaluminium hydride reduction of its phenylglyoxylate ester.     

Crystal-to-crystal transformation from a chain polymer to a two-dimensional network by thermal desolvation

Single-crystal to single-crystal transformation of a new lead(II) coordination polymer with ligands 8-hydroxyquinoline (8-Quin) and nitrate, [Pb2(8-Quin)2(NO3)2(MeOH)] () to [Pb(8-Quin)(NO3)] (1beta), is reported and the structures of and determined by X-ray crystallography.     

Inclusion of a Cu2+ ion by a large-cavity crown ether dibenzo-24-crown-8 through supramolecular interactions

A supramolecular copper-aqua-crown ether complex, [Cu(II)(H2O)4(dibenzo-24-crown-8]2+ (1c) is stabilized with a Lindqvist-type polyoxometalate anion, [Mo(VI)6O19]2- (1a), in an ion-pair compound [Cu(II)(H2O)4(dibenzo-24-crown-8][Mo(VI6O19] identical with [1c][1a] identical with 1. In the crystal, 1c and 1a assemble to a chainlike structure in which each polyoxoanion 1a is sandwiched by two 1c cations. 1c is a structurally characterized dibenzo-24-crown-8 (a larger-cavity crown ether) supramolecular complex that shows encapsulation of a small cation at the center of its internal cavity, and compound 1 represents a unique example of a first-row transition metal-crown ether inclusion complex that interacts with a polyoxometalate anion.     

Oxidation of a guanine derivative coordinated to a Pt(IV) complex initiated by intermolecular nucleophilic attacks

In this study we report that fac-[Pt(IV)(dach)(9-EtG)Cl(3)](+) (dach = d,l-1,2-diaminocyclohexane, 9-EtG = 9-ethylguanine) in high pH (pH 12) or phosphate solution (pH 7.4) produces 8-oxo-9-EtG and Pt(II) species. The reaction in H(2)(18)O revealed that the oxygen atom in hydroxide or phosphate ends up at the C8 position of 8-oxo-G. The kinetics of the redox reaction was first order with respect to both Pt(IV)-G and free nucleophiles (OH(-) and phosphate). The oxidation of G initiated by hydroxide was approximately 30～50 times faster than by phosphate in 100 mM NaCl solutions. The large entropy of activation of OH(-1) (ΔS(?) = 26.6 ± 4.3 J mol(-1) K(-1)) due to the smaller size of OH(-) is interpreted to be responsible for the faster kinetics compared to phosphate (ΔS(?) = -195.5 ± 11.1 J mol(-1) K(-1)). The enthalpy of activation for phosphate reaction is more favorable relative to the OH(-) reaction (ΔH(?) = 35.4 ± 3.5 kJ mol(-1) for phosphate vs. 96.6 ± 11.4 kJ mol(-1) for OH(-1)). The kinetic isotope effect of H8 was determined to be 7.2 ± 0.2. The rate law, kinetic isotope effect, and isotopic labeling are consistent with a mechanism involving proton ionization at the C8 position as the rate determining step followed by two-electron transfer from G to Pt(IV).     

Determination of some catechol derivatives by a flow injection electrochemiluminescent inhibition method

A flow injection electrochemiluminescent inhibition method has been developed for the determination of some catechol derivatives based on studying the inhibition phenomena of these compounds to the electrochemiluminescence of luminol. The linear calibration range of 5x10(-8) to 1x10(-5), 5x10(-8) to 1x10(-5) and 1x10(-8) to 5x10(-5) mol l(-1(,)) the detection limit of 1.2x10(-8), 2.1x10(-8) and 5.2x10(-9) mol l(-1)were obtained for catechol, 3,4-dihydroxybenzoic acid and chlorogenic acid, respectively. The method has higher sensitivity and wider dynamic range than conventional spectrophotometric method or chemiluminescent method. The method has been successfully applied to determine chlorogenic acid in cigarettes. The mechanism of the inhibition effect was proposed. Catechol derivatives mostly react with the freshly electrogenerated oxygen species on the electrode surface and lead to the inhibition of electrochemiluminescence.     

Membrane transducing activity of recombinant Hoxc8 protein and its possible application as a gene delivery vector

In order to examine whether the Hoxc8 protein can deliver nucleic acid into mammalian cells, we designed several Hoxc8-derived recombinant proteins to be synthesized as glutathione S-transferase (GST) fused forms in E. coli (GST-Hoxc8(1-242), containing a full length of Hoxc8; GST-Hoxc8(152-242), possessing a deletion of the acidic N-terminus of Hoxc8; GST-Hoxc8(149-208), which contained the homeodomain only). After labeling these proteins with Oregon 488, we examined their membrane transduction ability under the fluorescence microscope and verified that all three proteins showed similar transduction efficiency. The ability of the proteins to form in vitro protein-DNA complexes was analyzed on agarose gel; both GST-Hoxc8(1-242) and GST-Hoxc8(149-208) formed complexes. In contrast, the GST-Hoxc8(152-242) protein did not form a complex. The GST-Hoxc8(149-208) protein formed a complex with DNA at a mass ratio of 1ú1 (DNAúprotein), and GST-Hoxc8(1-242) formed a complex at a mass ratio of 1ú5. When the DNA (pDsRed1-C1) and protein complexes were added to culture media containing mammalian cells, the cells uptook the complexes, which was indicated by red fluorescence expression under the fluorescent microscope. These results indicate that recombinant Hoxc8 derivatives that harbor a homeodomain are able to traverse the mammalian cellular membrane. DNA that is bound to the recombinant derivatives can be carried across the membrane as well. This process could be applied in the development of a useful delivery vector for gene therapy in the future.     

Alkali metal complexes of a naphthylamine-substituted phosphanide

The reaction between {(Me3Si)2CH}PCl2 and one equivalent of [C10H6-8-NMe2]Li, followed by in situ reduction with LiAlH4, gives the secondary phosphane {(Me3Si)2CH}(C10H6-8-NMe2)PH(1) in good yield as a colourless crystalline solid. Metalation of 1 with Bu(n)Li in diethyl ether gives the lithium phosphanide [{[{(Me3Si)2CH}(C10H6-8-NMe2)P]Li}2(OEt2)](2), which undergoes metathesis with either NaOBu(t) or KOBu(t) to give the heavier alkali metal derivatives [[{(Me3Si)2CH}(C10H6-8-NMe2)P]-Na(tmeda)](3) and [[{(Me3Si)2CH}(C10H6-8-NMe2)P]K(pmdeta)](4), after recrystallisation in the presence of the corresponding amine co-ligand [tmeda = N,N,N',N'-tetramethylethylenediamine, pmdeta = N,N,N',N",N"-pentamethyldiethylenetriamine]. Compounds 2-4 have been characterised by 1H, 13C{1H} and 31P{1H} NMR spectroscopy, elemental analyses and X-ray crystallography. Dinuclear 2 crystallises with the phosphanide ligands arranged in a head-to-head fashion and is subject to dynamic exchange in toluene solution; in contrast, compounds 3 and 4 crystallise as discrete monomers which exhibit no dynamic behaviour in solution. DFT calculations on the model compound [{[(Me)(C10H6-8-NMe2)P]Li},(OMe2)] (2a) indicate that the most stable head-to-head form is favoured by 15.0 kcal mol(-1) over the corresponding head-to-tail form.     

New sphingolipids and a sterol from a lobophytum species of the Indian ocean

Chemical investigation of a soft coral species of the genus Lobophytum has resulted in the isolation of three new sphingolipids--(2S,3S,4R)-2-nonadecanoylamino-octadecane-1,3,4-triol (1), (2S,3R,4E,8E)-[(2'R)-2'-hydroxyheptadecanoylamino]-4,8-octadecadiene-1,3-diol (2), 1-O-(beta-D-glucopyranosyl)-(2S,3R,4E,8E)-2-[(2'R)-2'-hydroxynonadecanoylamino]-9-methyl-4,8-octadecadiene-1,3-diol (3) and a sterol--(24S)-ergost-5-en-3beta,7beta-diol (4) along with the known sphingolipid--(2S,3R,4E,8E)-2-hexadecanoylamino-4,8-octadecadien-1,3-diol (5) which showed cytotoxicity against human peripheral blood mononuclear cells (PBMC).     

Serendipitous synthesis of a ditwistane: a one-step access!

4-tert-Butyl-2-cyclohexen-1-one dimerizes in THF solution via its kinetic enolate, leading to di-tert-butylditwistane 8 in up to 36% yield (−78 °C → room temp., protonolysis, flash chromatography). X-ray crystallography shows that 8 incorporates one R and one S enantiomer of the starting ketone; none of the diastereomeric ditwistanes epi-8, epi’-8 or iso-8 was isolated. This means that the formation of 8 proceeds with mutual kinetic resolution and 100% induced diastereoselectivity.     

Heterocirculenes as a new class of organic semiconductors

We report a fabrication of field-effect transistors using the new organic semiconductors octathio[8]circulene and tetrathiotetraseleno[8]circulene . The maximum hole mobility of 9 x 10(-3) cm(2) V(-1) s(-1) is, most likely, limited by one-dimensional growth of and in thin films.     

Electrochemical determination of 8-hydroxydeoxyguanosine using a carbon nanotube modified electrode

In this work, a multi-wall carbon nanotube (MWNT) film-modified glassy carbon electrode (GCE) was constructed for the determination of 8-hydroxydesoxyguanosine (8-OHdG). The electrochemical behaviors of 8-OHdG were examined using cyclic voltammetry (CV) and linear sweep voltammetry (LSV), suggesting that MWNT film facilitates the electron transfer of 8-OHdG and then significantly enhances the oxidation peak current of 8-OHdG. Finally, a sensitive and simple electrochemical method with a good linear relationship in the range of 8.0 × 10⁻⁸ ∼ 5.0 × 10⁻⁶ mol 1⁻¹, was developed for the determination of 8-OHdG. The detection limit is 9.0 × 10⁻⁹ mol 1⁻¹ for 6-min accumulation. This newly-proposed method was successfully used to detect 8-OHdG in urine samples. Published in Russian in Elektrokhimiya, 2008, Vol. 44, No. 3, pp. 351–356. The text was submitted by the authors in English.