bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Metal Ions on Photoinduced Electron Transfer in Zinc Porphyrin–Naphthalenediimide Linked Systems
Authors: Okamoto Ken , Mori Yukie , Yamada Hiroko , Imahori Hiroshi , Fukuzumi Shunichi
Published: January 2004

Zinc porphyrin–naphthalenediimide (ZnP–NIm) dyads and zinc porphyrin–pyromellitdiimide–naphthalenediimide (ZnP–Im–NIm) triad have been employed to examine the effects of metal ions on photoinduced charge‐separation (CS) and charge‐recombination (CR) processes in the presence of metal ions (scandium triflate (Sc(OTf)3) or lutetium triflate (Lu(OTf)3), both of which can bind with the radical anion of NIm). Formation of the charge‐separated states in the absence and in the presence of Sc3+ was confirmed by the appearance of absorption bands due to ZnP.+ and NIm.− in the absence of metal ions and of those due to ZnP.+ and the NIm.−/Sc3+ complex in the presence of Sc3+ in the time‐resolved transient absorption spectra of dyads and triad. The lifetimes of the charge‐separated states in the presence of 1.0×10−3 M Sc3+ (14 μs for ZnP–NIm, 8.3 μs for ZnP–Im–NIm) are more than ten times longer than those in the absence of metal ions (1.3 μs for ZnP–NIm, 0.33 μs for ZnP–Im–NIm). In contrast, the rate constants of the CS step determined by the fluorescence lifetime measurements are the same, irrespective of the presence or absence of metal ions. This indicates that photoinduced electron transfer from 1ZnP* to NIm in the presence of Sc3+ occurs without involvement of the metal ion to produce ZnP.+–NIm.−, followed by complexation with Sc3+ to afford the ZnP.+–NIm.−/Sc3+ complex. The one‐electron reduction potential (Ered) of the NIm moiety in the presence of a metal ion is shifted in a positive direction with increasing metal ion concentration, obeying the Nernst equation, whereas the one‐electron oxidation potential of the ZnP moiety remains the same. The driving force dependence of the observed rate constants (kET) of CS and CR processes in the absence and in the presence of metal ions is well evaluated in terms of the Marcus theory of electron transfer. In the presence of metal ions, the driving force of the CS process is the same as that in the absence of metal ions, whereas the driving force of the CR process decreases with increasing metal ion concentration. The reorganization energy of the CR process also decreases with increasing metal ion concentration, when the CR rate constant becomes independent of the metal ion concentration.
Stabilization of p‐Block Organoelement Terminal Hydroxides, Thiols, and Selenols Requires Newer Synthetic Strategies
Authors: Roesky Herbert W. , Murugavel Ramaswamy , Walawalkar Mrinalini G.
Published: January 2004

Metal hydroxides represent a very interesting and highly useful class of compounds that have been known to chemists for a very long time. While alkali and alkaline earth metal hydroxides (s‐block) are commonplace chemicals in terms of their abundance and their use in a chemical laboratory as bases, the interest in Brønsted acidic molecular terminal hydroxides of p‐block elements, such as aluminum and silicon, has been of recent origin, with respect to the variety of applications these compounds can offer both in materials science and catalysis. Moreover, these systems are environmentally friendly, relative to the metal halides, owing to their ‐OH functionality (resembling that of water). Design and conceptualization of the corresponding terminal thiols, selenols, and tellurols (MSH, MSeH, and MTeH) offer even more challenging problems to synthetic inorganic chemists. This concept summarizes some of the recent strategies developed to stabilize these otherwise very unstable species. The successful preparation of a number of silicon trihydroxides a few years back resulted in the generation of several model compounds for metal–silicates. The recent synthesis of unusual aluminum compounds such as RAl(OH)2, RAl(SH)2, and RAl(SeH)2 with terminal EH (E=O, Se, or Se) groups is likely to change the ways in which some of the well‐known catalytic conversions are being carried out. The need for very flexible and innovative synthetic strategies to achieve these unusual compounds is emphasized in this concept.
Benzofuran Trimers for Organic Electroluminescence
Authors: Anderson Sally , Taylor Peter N. , Verschoor Geraldine L. B.
Published: January 2004

Four linear benzofuran trimers have been prepared by a two‐stage synthetic procedure. They were tested as materials for organic electroluminescence (OEL). Precursor phenylene ethynylene oligomers were formed in the first stage, then after removal of the phenolic hydroxyl protecting groups, a base was used to promote the cyclization of ortho‐hydroxy phenylene ethynylenes to benzofurans. Both acetate esters and tert‐butyl carbonates were employed as protecting groups. tert‐Butyl and n‐hexyl substituents on the benzofurans were used to modulate solubility, aggregation, and film‐forming properties; two tert‐butyl groups prevented aggregation in the solid state, thus maintaining emission in the blue region of the visible spectrum. The OEL characteristics of the tert‐butyl‐substituted benzofuran trimer were explored, and blue emission was observed. The two‐stage synthetic procedure employed for the preparation of these benzofuran trimers may be applied to a wide variety of benzofuran oligomer and polymer targets.
Insertion of Alkynes into the PtSi Bond of Silylplatinum Complexes Leading to the Formation of 4‐Sila‐3‐platinacyclobutenes and 5‐Sila‐2‐platina‐1,4‐cyclohexadienes
Authors: Tanabe Makoto , Osakada Kohtaro
Published: January 2004

The reaction of dimethyl acetylenedicarboxylate (DMAD) with [Pt(SiHPh2)2(PMe3)2] produces cis‐[Pt(CZCZSiHPh2)(SiHPh2)(PMe3)2] (cis‐1, Z = COOMe) and [Pt(CZCZSiPh2)(PMe3)2] (2) depending on the reaction conditions. cis‐1 and 2 are equilibrated in solution at room temperature, and they are isolated by recrystallization of the mixtures. cis‐1 is converted slowly in solution into trans‐[Pt(CZCZSiHPh2)(SiHPh2)(PMe3)2] (trans‐1) via intermediate 2 followed by reaction with H2SiPh2. DMAD also reacts with [Pt(SiHPh2)2(dmpe)] (dmpe = 1,2‐bis(dimethylphosphino)ethane) to afford [Pt(CZCZSiHPh2)(SiHPh2)(dmpe)] (3). Conversion of 3 into 4‐sila‐3‐platinacyclobutene [Pt(CZCZSiPh2)(dmpe)] (4) takes place, accompanied by formation of H2SiPh2, to give an equilibrated mixture of the two complexes. Crystallographic and spectroscopic data of cis‐1, trans‐1, and 3 suggest the presence of an intramolecular interaction between the SiH group of the 3‐sila‐1‐propenyl ligand and Pt via an SiHPt three‐center‐four‐electron bond in the solid state and in solution. DMAD reacts with 2 to give 5‐sila‐2‐platina‐1,4‐cyclohexadiene with π‐coordinated DMAD, [Pt(CZCZSiPh2CZCZ)(DMAD)(PMe3)2] (5), which is also obtained from the reaction of excess DMAD with [Pt(SiHPh2)2(PMe3)2]. Unsymmetrical six‐membered silaplatinacycles without π‐coordinated alkyne, [Pt(CZCZSiPh2CHCX)(PMe3)2] (6: X = COOMe; 7: X = Ph), are prepared analogously from the respective reactions of phenyl acetylene and of methyl acetylene carboxylate with 2. Methyl 2‐butynolate reacts with 2 at 50 °C to form a mixture of the regioisomers [Pt(CZCZSiPh2CMeCZ)(PMe3)2] (8) and [Pt(CZCZSiPh2CZCMe)(PMe3)2] (9).
Palladium‐Catalyzed Cross‐Coupling Reactions of Amines with Alkenyl Bromides: A New Method for the Synthesis of Enamines and Imines
Authors: Barluenga José , Fernández M. Alejandro , Aznar Fernando , Valdés Carlos
Published: January 2004

The palladium‐catalyzed cross‐coupling reaction of alkenyl bromides with secondary and primary amines gives rise to enamines and imines, respectively. This new transformation expands the applicability of palladium‐catalyzed CN bond forming reactions (the Buchwald–Hartwig amination), which have mostly been applied to aryl halides. After screening of different ligands, bases, and solvents, the catalytic combination [Pd2(dba)3]/BINAP in the presence of NaOtBu in toluene gave the best results in the cross‐coupling of secondary amines with 1‐bromostyrene (dba=dibenzylideneacetone, BINAP=2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl). The corresponding enamines are obtained cleanly and in nearly quantitative yields. However, steric hindrance seems to be a limitation of the reaction, as amines carrying large substituents are not well converted. The same methodology can be applied to the coupling of secondary amines with 2‐bromostyrene. Moreover, the reaction with substituted 2‐bromopropenes allows regioselective synthesis of isomerizable terminal enamines without isomerization of the double bond. The best catalytic conditions for the cross‐coupling of 1‐bromostyrene with primary amines include again the use of the Pd0/BINAP/NaOtBu system. The reaction gives rise to the expected imines in very short times and with low catalyst loadings. A set of structurally diverse imines can be prepared by this methodology through variations in the structure of both coupling partners. However, 2‐bromostyrene failed to give good results in this coupling reaction, probably due to product inhibition of the catalytic cycle. Competition experiments of vinyl versus aryl amination reveal that the reaction occurs preferentially on vinyl bromides.
Evidence That Protons Can Be the Active Catalysts in Lewis Acid Mediated Hetero‐Michael Addition Reactions
Authors: Wabnitz Tobias C. , Yu Jin‐Quan , Spencer Jonathan B.
Published: January 2004

The mechanism of Lewis acid catalysed hetero‐Michael addition reactions of weakly basic nucleophiles to α,β‐unsaturated ketones was investigated. Protons, rather than metal ions, were identified as the active catalysts. Other mechanisms have been ruled out by analyses of side products and of stoichiometric enone–catalyst mixtures and by the use of radical inhibitors. No evidence for the involvement of π‐olefin–metal complexes or for carbonyl–metal‐ion interactions was obtained. The reactions did not proceed in the presence of the non‐coordinating base 2,6‐di‐tert‐butylpyridine. An excellent correlation of catalytic activities with cation hydrolysis constants was obtained. Different reactivities of mono‐ and dicarbonyl substrates have been rationalised. A 1H NMR probe for the assessment of proton generation was established and Lewis acids have been classified according to their propensity to hydrolyse in organic solvents. Brønsted acid‐catalysed conjugate addition reactions of nitrogen, oxygen, sulfur and carbon nucleophiles are developed and implications for asymmetric Lewis acid catalysis are discussed.
Enantioselective Synthesis of Non‐Natural Aromatic α‐Amino Acids
Authors: Krebs Andreas , Ludwig Verena , Pfizer José , Dürner Gerd , Göbel Michael W.
Published: January 2004

We present two complementary methods for the stereoselective synthesis of non‐natural α‐amino acids with aromatic or heteroaromatic side chains. One approach is based on the chemical transformation of methionine, whereas the other applies the stereoselective Myers alkylation of glycine. The resulting product types differ in the linker length between glycine and the aromatic substituent. Since methionine and pseudoephedrine are available in both absolute configurations, R‐ or S‐configured enantiopure amino acids with either C2 or C3 linkers can be obtained on gram scales. In each case the key step of the synthesis is hydroboration of the unsaturated building blocks 9 and 17, followed by palladium‐catalyzed Suzuki cross‐coupling with aryl halides. Attention must in certain cases be paid to the stereochemical integrity when basic Suzuki conditions are applied. Our initial difficulties are reported as well as the final “racemization‐proof” procedures. The protecting groups chosen for the α‐amino acids should be compatible with solid‐phase peptide synthesis. This was confirmed by the successful synthesis of a series of tripeptides.
Extension of Conjugation Leading to Bathochromic or Hypsochromic Effects in OPV Series
Authors: Meier Herbert , Gerold Jürgen , Kolshorn Heinz , Mühling Bastian
Published: January 2004

Four OPV series 1–4 (a–d) with a terminal dialkylamino group as electron donor were prepared by Wittig–Horner reactions. To study the influence of the push–pull effect on the long‐wavelength absorption, three of the four series contained terminal acceptor groups (CN, CHO, NO2). The length of the chromophores strongly affects the intramolecular charge transfer (ICT)—an effect which superimposes upon the extension of the conjugation. Increasing numbers n of repeat units cause an overall bathochromic shift for the purely donor‐substituted series 1 a–4 a and the series 1 b–4 b with CN as weak acceptor. The two effects annihilate each other in the series 1 c–4 c with terminal CHO groups, so that the absorption maxima are almost independent of the length of the chromophore. A hypsochromic shift is observed for the series 1 d–4 d, which contains the strong acceptor group NO2. This anomaly disappears on protonation of the dialkylamino group because the push–pull effect disappears in the ammonium salts. The results can be explained by semiempirical quantum mechanics (AM1, INDO/S). The HOMO–LUMO transition, which is mainly responsible for the ICT, becomes less important in the electron transitions S0→S1 when the distance between donor and acceptor is increased. The commonly used VB model, which contains an electroneutral and a zwitterionic resonance structure, is contrasted with a MO model with dipole segments at both ends of the OPV chains. The latter model turned out to be more appropriate—at least for donor–acceptor‐substituted OPVs with n ≥ 2.
First Structural Characterization of Binary AsIIIand SbIIIAzides
Authors: Haiges Ralf , Vij Ashwani , Boatz Jerry A. , Schneider Stefan , Schroer Thorsten , Gerken Michael , Christe Karl O.
Published: January 2004

The highly explosive molecules As(N3)3and Sb(N3)3were obtained in pure form by the reactions of the corresponding fluorides with (CH3)3SiN3in SO2and purification by sublimation. The crystal structures and14N NMR, infrared, and Raman spectra were determined, and the results compared to ab initio second‐order perturbation theory calculations. Whereas Sb(N3)3possesses a propeller‐shaped, pyramidal structure with perfectC3symmetry, the As(N3)3molecule is significantly distorted fromC3symmetry due to crystal packing effects.
Interactions Between Organic Molecules and Water: Rotational Spectrum of the 1:1 Oxetane–Water complex
Authors: Ottaviani Paolo , Giuliano Michela , Velino Biagio , Caminati Walther
Published: January 2004

The 1:1 molecular complex between oxetane and water has been investigated by using free‐jet millimeter‐wave spectroscopy. The rotational spectra of five isotopomers (with H2O, D2O, DOH, HOD and H218O) have been assigned. Partial r0 and rs structures of the complex have been derived. The water moiety lies in the plane of symmetry of oxetane, with the “free” hydrogen E with respect to the ring. The oxetane ring appears to be slightly nonplanar, with the Cβ carbon tilted on the opposite side of the water unity. The three atoms involved in the hydrogen bond adopt a linear arrangement with an Oring⋅⋅⋅H distance of about 1.86 Å, and the angle between the COC bisector and the Oring⋅⋅⋅H bond being ≅106°. Additionally, quantum‐chemical calculations for the complex were performed and were found to be in agreement with the experimental results.
Enzyme‐catalyzed hydrolysis of 18‐methyl eicosanoic acid‐cysteine thioester
Authors: Ganske Franka , Meyer Hartmut H. , Deutz Herbert , Bornscheuer Uwe
Published: January 2004

18‐Methyleicosanoic acid (18‐MEA) is the major fatty acid component linked by a cysteine thioester bond within the cuticle at the surface of hair of humans and animals. An excess of 18‐MEA results in fatty hair and a mild method for enzymatic removal was investigated using a range of commercially available hydrolases. Pure 18‐MEA is available from natural sources only in μg quantities, so it was synthesized in gram‐amounts in a 7‐step chemical synthesis at an overall yield of 34%. Starting from 18‐MEA the corresponding thioester with cysteine (Cys‐18‐MEA) serving as model compound was obtained at a yield of 85%. The detection of hydrolases acting on Cys‐18‐MEA was performed using Ellmanns reagent followed by spectrophotometric quantification of 5‐thio‐2‐nitrobenzoic acid at 410 nm. This led to the identification of 6 enzymes with lipase from Pseudomonas cepacia (Amano PS) as the most active one. With Amano PS, 60% conversion of Cys‐18‐MEA was achieved within 5 h‐reaction time at 30 °C. Preliminary results using samples of human hair were also performed and showed that hydrolytic activity is detectable after incubation of the hair with Amano PS.
The role of pancreatic lipase C2‐like domain in enzyme interaction with a lipid‐water interface
Authors: Chahinian Henri , Belle Valérie , Fournel André , Carrière Frédéric
Published: January 2004

Human pancreatic lipase (HPL) consists of two functional domains: an N‐terminal catalytic domain (N‐HPL), and a β‐sandwich C‐terminal domain (C‐HPL) involved in the binding process between HPL and colipase. Structural similarities between C‐HPL and C2 domains have suggested another function in lipase‐lipid interactions. C2 domains occur in a wide range of proteins involved in phospholipid interactions, in signal transduction (phosphoinositide‐specific phospholipase C, protein kinase C, cytosolic phospholipase A2), membrane traffic (synaptotagmin I, rabphilin), and membrane disruption (perforin).

In this paper, we review experiments supporting an absolute requirement of C‐HPL for interfacial binding of HPL. N‐HPL and C‐HPL were produced as individual polypeptides, and their partitioning between the water phase and a lipid interface was assessed using trioctanoin emulsions or the monomolecular film technique. Using monoclonal antibodies and site‐directed mutagenesis, the contribution to lipase‐lipid interactions of an exposed hydrophobic loop (β5') present in C‐HPL was investigated. The β5' loop is located on the same side of HPL as the hydrophobic loops surrounding the active site, and has the same topology as the CBR3 loop found in C2 domains. Based on structural homology between C‐HPL and C2 domains, a model of HPL orientation at a lipid interface is proposed.
An integrated microbial/enzymatic process for production of rhamnolipids and L‐(+)‐rhamnose from rapeseed oil with Pseudomonas sp. DSM 2874
Authors: Trummler Klaus , Effenberger Franz , Syldatk Christoph
Published: January 2004

The object of this paper is the development of a biotechnological process for production of rhamnolipids by Pseudomoas sp. DSM 2874. The product obtained from rapeseed oil was found to be a mixture of up to four glycolipids (rhamnolipid 1 ‐ 4), L‐(+)rhamnose and (R, R)‐3‐(3‐hydroxydecanoyloxy) decanoic acid. An HPLC‐method was developed for identification and quantification of rhamnolipids and fatty acids, using an evaporative light scattering detector. Growing cells under nitrogen limiting conditions and resting cells were used for rhamnolipid production with triglycerides as C‐source. Best results and product yields (up to 45 g l‐1 of mixtures of rhamnolipid 1 and rhamnolipid 3) were obtained using resting cells in a fed batch process with rapeseed oil as C‐source. Product composition was found to be strongly dependent on the process conditions. Using the fungal enzyme Naringinase it was possible to cleave the glycosidic bond between the two rhamnose units of rhamnolipid 3, and the bond between L‐(+)‐rhamnose and (R, R)‐3‐(3‐hydroxydecanoyloxy) decanoic acid of rhamnolipid 1. The latter reaction occurred at a much lower rate. Direct addition of Naringinase to resting cells in an integrated microbial/enzymatic process was possible and resulted in an alteration of product composition from a rhamnolipid 1 and rhamnolipid 3 mixture to rhamnolipid 1 only.
Improvement of lipase stability in the presence of commercial triglycerides
Authors: Pirozzi Domenico
Published: January 2004

Several compounds generated by atmospheric oxidation of triglycerides, such as hydroperoxides and secondary products, may cause significant lipase inactivation in low‐water medium. Activity decay is usually time‐dependent and shows a non‐linear dependence on inactivating compound concentration.

As the effect of very dilute poisons becomes much more significant in continuous operations, stability tests were performed in the presence of oxidized oils in batch and continuous reactors. Experimental results show that the stability of Novozyme 435 is affected by secondary products of oxidation more than by hydroperoxides.

Involvement of sulphydryl groups in the mechanism of lipase interaction with two aldehydes, 4‐hydroxynonenal (4‐HNE) and malondialdehyde (MDA), has been demonstrated by blocking the lipase sulphydryl groups with pHMB pre‐treatment. The preliminary neutralization 4‐HNE and MDA with albumin also increased enzyme stability.
Lipase‐catalyzed synthesis of designer acylglycerols rich in residues of eicosapentaenoic, docosahexaenoic, conjugated linoleic, and/or stearic acids
Authors: Torres Carlos F. , Lin Betty , Moeljadi Marlina , Hill, Jr. Charles G.
Published: January 2004

Lipase‐catalyzed glycerolysis of a commercial acylglycerol (TG500), rich in eicosapentaenoic residues, and subsequent reaction of the product acylglycerols via esterification and/or transesterification reactions were investigated for the purpose of preparing acylglycerols enriched in particular fatty acid residues. An immobilized lipase from Candida antarctica (fraction B) was employed as biocatalyst for these reactions. The effects of enzyme loading, molar ratio of substrates, type of acyl donor, and use of a continuous purge stream of nitrogen were evaluated. The transesterification reactions were carried out using the ethyl esters of 3 different fatty acids, namely stearic, conjugated linoleic, and docosahexaenoic acids. Final yields of triacylglycerols of 75‐80% were obtained for the transesterification reactions with the 3 different types of fatty acid ethyl esters.
Thermomyces lanuginosus lipase catalyzed transesterification of sterols by methyl oleate
Authors: Weber Nikolaus , Weitkamp Petra , Mukherjee Kumar D.
Published: January 2004

Plant steryl and stanyl esters are effective in lowering plasma cholesterol concentration by inhibiting the absorption of cholesterol from small intestine. They are, therefore, used as constituents of special margarines, which are commercially available as functional foods with the ability to reduce blood cholesterol levels. An enzymatic method has been developed for the preparation of oleic acid esters of sterols and stanols in high yield by transesterification of methyl oleate with the 3‐hydroxy group in vacuo (20‐40 hPa) at moderate temperature (80 °C) using immobilized lipase preparation from Thermomyces lanuginosus (Lipozyme TL IM®) as biocatalyst. Neither an organic solvent nor a drying agent are required. Cholesterol and stanols such as 5α‐cholestanol and sitostanol have been converted at similar rates and in near‐quantitative yields (>95%) to the corresponding oleic acid esters.
Enzymatic fatty acid exchange in glycero‐phospholipids
Authors: Adlercreutz Patrick , Lyberg Ann‐Marie , Adlercreutz Dietlind
Published: January 2004

Lipases can be used to exchange fatty acids in the sn‐1 position of glycerophospholipids and phospholipase A2 is useful for the corresponding exchange reaction in the sn‐2 position. In both cases, the exchange can be done in a one‐step acidolysis process or in a two‐step process. In the latter case, the original fatty acid in the desired position is removed by enzymatic hydrolysis or alcoholysis and after isolation of the resulting lysophospholipid, the new fatty acid is introduced, using the same enzyme, in an esterification reaction. Several synthesis examples from the literature are reviewed. Incorporation of a new fatty acid into the sn‐1 position is more favourable than incorporation into the sn‐2 position because of the magnitudes of the equilibrium constants of the reactions and because lipases can be used at much lower water activity than phospholipase A2. With the consecutive use of both enzymes highly pure products with defined fatty acids in both positions can be obtained.
In vitro and in vivo biosynthesis of wax diesters by an unspecific bifunctional wax ester synthase/acyl‐CoA:diacylglycerol acyltransferase from Acinetobacter calcoaceticus ADP1
Authors: Kalscheuer Rainer , Uthoff Stefan , Luftmann Heinrich , Steinbüchel Alexander
Published: January 2004

Acinetobacter calcoaceticus ADP1 possesses a bifunctional wax ester synthase/acyl‐CoA:diacylglycerol acyltransferase (WS/DGAT) catalyzing the biosynthesis of wax esters and triacylglycerols. The unspecificity of WS/DGAT was used for in vitro and in vivo biosynthesis of wax diesters consisting of 1, 16‐hexadecanediol esterified with longchain fatty acids. An in vitro assay employing the membrane fraction of recombinant Escherichia coli XL1‐Blue expressing wax/dgat coding for WS/DGAT and using 1, 16‐hexadecanediol and 1‐14 C‐palmitoyl‐CoA as substrates resulted in the production of 2 radiolabeled substances as revealed by autoradiography suggesting the acylation of one or both hydroxy groups of 1, 16‐hexadecanediol by WS/DGAT. For in vivo biosynthesis of wax diesters, the knock‐out mutant A. calcoaceticus ADP1acr1 | Km was generated by disruption of acr1 coding for acyl‐CoA reductase which caused the inability to synthesize fatty alcohols and, thus in consequence, wax esters. Co‐cultivation of A. calcoaceticus ADP1acr1 | Km on gluconate and 1, 16‐hexadecanediol in nitrogen‐limited mineral salts medium resulted in the accumulation of a mixture of wax diesters of 1, 16‐hexadecanediol esterified with palmitic and oleic acid as revealed by electron impact ionization mass spectrometry. 1‐Monopalmitoylglycerol could also be utilized as an alternative acyl acceptor by the unspecific WS/DGAT in vitro resulting in the synthesis of 1, 2‐ and 1, 3‐dipalmitoylglycerol, whereas 1‐oleoylglycerol‐3‐phosphate (lysophosphatidic acid) was not accepted.
N‐[4‐(dicyanomethylazo)phenyl]‐2‐saccharin‐2‐ylacetamide in the synthesis of pyridazine and pyrimidine derivatives
Authors: Aly A. A. , Nassar S. A.
Published: January 2004

N‐[4‐(Dicyanomethylazo)phenyl]‐2‐saccharin‐2‐ylacetamide (2) proved to be a convenient precursor for the synthesis of a variety of pyridazine and pyrimidine derivatives 4a,b,6, and 7. Also a series of substituted pyrimidines 10–16 were prepared from the reaction of N‐[4‐(2‐amino‐1‐cyano‐2‐substitutedvinylazo)phenyl]‐2‐(saccharin‐2‐yl)acetamide 9a,b with different reagents via initial addition to either the cyano or amino group, followed by cyclization. Some of the synthesized heterocycles were screened for their biological activity. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 15:2–8, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10194
Experimental and theoretical studies on some new pyrrol‐2,3‐diones formation
Authors: Yildirim Ismail , Kandemirli Fatma
Published: January 2004

4‐Benzoyl‐5‐phenyl‐2,3‐furandione (1) reacts with asymmetric disubstituted urea derivatives like 1,1‐dimethylurea (2a) and 1,1‐diethylurea (2b) by the elimination of a H2O molecule to give the 4‐benzoyl‐1‐(N,N‐dialkylcarbamyl)‐5‐phenyl‐2,3‐pyrroldiones 3a and 3b. The structures of 3a,b were determined by the 13C NMR, 1H NMR, IR spectroscopic data and elemental analyses. The electronic structures of the reactants, their transition states, intermediate states, and final products of the reactions were investigated on the basis of AM1 and ab initio (DFT) methods. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 15:9–14, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10204
Heterobimetallic heterocyclic derivatives of indium(III)
Authors: Bansal Seema , Singh Yashpal , Singh Anirudh
Published: January 2004

Reactions of InCl3 with potassium salts of bifunctional tridentate (L1H2HOC6H4CH NCH2CHMeOH) and monofunctional bidentate (L2HHOC6H4CHN‐i‐Bu) Schiff bases in 1:1 and 1:2 molar ratio in benzene afford complexes In(L1)Cl and In(L2)2Cl, respectively. On reaction with potassium isopropoxymetallates KB(O‐i‐Pr)4, KAl(O‐i‐Pr)4, KTi(O‐i‐Pr)5, and KNb(O‐i‐Pr)6, they produce interes‐ ting heterobimetallic heterocyclic complexes. These are characterized by elemental (N, B, Al, Ti, and Nb) analyses, molecular weight measurements, and spectral [IR, NMR (1H, 13C, 11B, and 27Al)] studies. Probable structures are suggested for them. © 2003 Wiley Periodicals, Inc. 15:21–25, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10206
Cyclobutane‐substituted diacetamido sulfides and 2,5‐diacylthiophenes
Authors: Koparır Metin , Cansız Ahmet , Ahmedzade Misir , Çetin Ahmet
Published: January 2004

A general and convenient route for the synthesis of 2,5‐di[1‐methyl‐1‐arylcyclobutane‐3‐yl]‐ thiophenes 4a–c and bis[1‐methyl‐1‐arylcyclobutane‐3‐yl]‐2‐(2‐oxyethtylamido)thiazole sulfides 7a–c is reported. The characterization of these compounds was obtained by elemental analyses, IR, 13C, and 1H NMR techniques. © 2003 Wiley Periodicals, Inc. 15:26–31, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10207
Synthesis and in vitro antitumor activity of some triarylantimony di(N‐phenylglycinates)
Authors: Yu Lin , Ma Yong‐Qiang , Wang Guo‐Cang , Li Jin‐Shan
Published: January 2004

Triarylantimony(V) di(N‐phenylglycinates) (PhNHCH2COO)2SbAr3 (Ar = Ph, p‐CH3C6H4, p‐ClC6H4, and p‐FC6H4) have been synthesized and characterized by elemental analysis, IR, 1H NMR, and mass spectra. The crystal structure of (PhNHCH2COO)2Sb(C6H4F‐p)3 has been determined by X‐ray diffraction. The in vitro antitumor activities of these compounds against three cancer cell lines are reported. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 15:32–36, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10208
Bromination of silatranyl‐, germatranyl‐, silyl‐, and germyl‐phenylacetylenes
Authors: Selina Anastasia A. , Karlov Sergey S. , Gauchenova Ekaterina V. , Churakov Andrei V. , Kuz'mina Lyudmila G. , Howard Judith A. K. , Lorberth Jörg , Zaitseva Galina S.
Published: January 2004

Reactions of element‐substituted alkynes R3MCCPh (R3M = Me3Si, Et3Si, Ph3Si, Et3Ge, n‐Bu3Sn, N(CH2CH2O)3Si, N(CH2CH2O)3Ge, N(CH2‐CHMeO)3Ge, and N(CH2CH2O)2(CH2CHPhO)Ge) with bromine, tetra‐n‐butylammonium tribromide (TBAT), and N‐bromosuccinimide (NBS)/DMSO were investigated. The Z,E‐ratio of isomeric dibromoalkenes formed in bromination reaction with Br2 and TBAT are discussed. The crystal structures of N(CH2CH2O)3SiCCPh and N(CH2CHMeO)3GeX (X = C CPh, C(Br)C(Br)Ph, C(Br2)C(O)Ph), and Ph3SiC(Br)C(Br)Ph are reported. © 2003 Wiley Periodicals, Inc. 15:43–56, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10211
Antimicrobial activity of amino acid, imidazole, and sulfonamide derivatives of pyrazolo[3,4‐d]pyrimidine
Authors: Ghorab M. M. , Ismail Zeinab H. , Abdel‐Gawad Soad M. , Aziem Anhar Abdel
Published: January 2004

Derivatives of pyrazolo[3,4‐d]pyrimidine with amino acid 3a–d, imidazole 4a–d, carbonyl 6–9, pyrazole 10, pyrazolone 11, and sulfonamide 12–17 moieties were synthesized. Structure of the new compounds were established by their elemental analyses and spectral data. Some of the synthesized compounds were tested in vitro for their antimicrobial activity. Compounds 4b, 12, and 16 were almost as potent as the standard antibiotic Chloramphenicol as positive control. Also, compounds 3b, 3c, 12, and 16 were nearly as active as Terbinafine as positive control. © 2003 Wiley Periodicals, Inc. 15:57–62, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10212
Phenylbiguanide as electron donor in heterocyclic synthesis
Authors: El‐Shaieb Kamal M. , Mourad Aboul‐Fetouh E. , Hassan Alaa A.
Published: January 2004

Phenylbiguanide reacts with some π‐acceptors such as TCNE, TCNQ, CNIND, DCNQ, and CHL‐o, if any. opy; 2003 Wiley Periodicals, Inc. Heteroatom Chem 15:63–66, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10213
Synthesis and herbicidal activity of (Z)‐ethoxyethyl 2‐cyano‐3‐(2‐methylthio‐5‐pyridylmethylamino)acrylates
Authors: Wang Qing Min , Sun Hui Kai , Huang Run Qiu
Published: January 2004

2‐Methylthio‐5‐pyridinemethylene amine was prepared from 2‐chloro‐5‐methylpyridine. Ethoxyethyl 2‐cyano‐3,3‐dimethylthioacrylate was prepared from ethoxyethyl cyanoacetate, carbon disulfide, and dimethyl sulfate in 86.2% yield. Its reaction with 2‐methylthio‐5‐pyridinemethylene amine yielded (Z)‐ethoxyethyl 2‐cyano‐3‐methylthio‐3‐(2‐methylthio‐5‐pyridylmethylamino)acrylate. Ethoxyethyl (Z+E)‐2‐cyano‐3‐ethoxyacrylate was synthesized from ethoxyethyl 2‐cyanoacetate and triethyl or‐ thoacetate in 90.7% yield, and its reaction with 2‐ methylthio‐5‐pyridinemethylene amine yielded (Z)‐ethoxyethyl 2‐cyano‐3‐methyl‐3‐(2‐methylthio‐5‐pyri‐dylmethylamino)acrylate. The structures of all of the products were confirmed by 1H NMR, elemental analysis, IR, and mass spectroscopy. The herbicidal activities of the products were evaluated, and the results of bioassay showed that (Z)‐ethoxyethyl 2‐cyano‐3‐methyl‐3‐(2‐methylthio‐5‐pyridylmethylamino)acrylate exhibits good herbicidal activity on rape (Brassica napus) at a dose of 1.5 kg/ha. © 2003 Wiley Periodicals, Inc. 15:67–70, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10214
Promotion of 1,3‐dithiolanes using a bentonitic clay as catalyst
Authors: Aceves J. M. , Arroyo G. A. , Vargas Y. M. , Miranda R. , Cabrera A. , Delgado F.
Published: January 2004

The reactions between 1,2‐ethandithiol with several carbonylic compounds to form the corresponding 1,3‐dithiolanes were performed using a natural clay as promotor. The target molecules are used as reagents to obtain fine chemicals, herbicides, fungicides, and pharmaceutical compounds among others applications. A kinetic study of camphorquinone and 1,2‐ethandithiol showed a first‐order dependence with 1,2‐ethandithiol as well as with camphorquinone. The substrate transformation in percent was found to be dependent with the reaction time, the amount of catalyst, and the reagents concentration. © 2003 Wiley Periodicals, Inc. 15:71–76, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.10215
Phosphono‐substituted isoindolines and indoles from 2,3‐ and 2,4‐benzoxazin‐1‐ones
Authors: Abdou Wafaa M. , Kamel Azza A. , Khidre Maha D.
Published: January 2004

Reactions of 2,3‐benzoxazinone 1 and 2,4‐benzoxazinone 2, with trialkyl phosphites 3a–c provide access to new phosphono‐substituted isoindolines 6a–f and indoles 19a–e, respectively. Phosphono‐substituted 2,3‐benzoxazines 5a–c were also obtained in the first reaction. Bisisoindolinylidene (7) was, however, isolated in low yields when 1 was heated with triethyl or triisopropyl phosphite at 100deg;C whereas at 170deg;C 7 was obtained as the major product (∼53%). On the other hand, the reaction of 1 or 2 with dialkyl phosphonates 4a–c proceeded in the presence of aqueous solution of NaOH (5%) to give the respective alkylated product 14a–c or 20a–c. © 2003 Wiley Periodicals, Inc. 15:77–84, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.10216
Benzofuranyl‐pyran‐2‐ones, ‐pyridazines, and ‐pyridones from naturally occurring furochromones (visnagin and khellin)
Authors: Keshk Eman M.
Published: January 2004

The novel and versatile enaminones 2a,b were synthesized by treatment of visnaginone methyl ether 1a or khellinone methyl ether 1b with N,N‐dimethylformamide dimethylacetal. They were reacted with hippuric acid or N‐acetylglycine to yield benzofuran‐5‐yl‐2H‐pyran‐2‐ones 3a–d. The reaction of 2a,b with cyanoacetamide and malononitrile dimer in sodium ethoxide gave benzofuran‐5‐yl‐pyridones 4a,b and [benzofuran‐5‐yl‐1H‐pyridine‐2‐ylidene] malononitrile 5a, respectively. Refluxing 2a,b with hydrazine hydrate or with hydroxyla‐ mine afforded benzofuran‐5‐yl‐1H‐pyrazoles 6a,b and benzofuran‐5‐yl‐isoxazoles 7a,b, respectively. Moreover, 2a,b coupled with aryl diazonium salt in the presence of sodium hydroxide to yield 3‐(benzofuran‐5‐yl)‐2‐aryl‐hydrazono‐3‐oxo‐propanals 8a,b which were excellent precursors for the synthesis of pyridazines 9–12. © 2003 Wiley Periodicals, Inc. 15:85–91, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10219
Phenylarsenic(III) complexes of 2‐(2‐hydroxyphenyl)benzothiazolines
Authors: Sharma Simpal , Sharma Rajendra K. , Rai Audhesh K. , Singh Yashpal
Published: January 2004

Equimolar reactions of PhAs(OMe)2 (prepared in situ) and 2‐(2‐hydroxyphenyl)benzothiazolines LH2 give the addition products PhAs(OMe)2LH2, while equimolar reactions of PhAsCl2 with Na2L yield substitution products PhAsL. All these derivatives have been characterized by elemental analyses and their plausible structures have been established on the basis of physico‐chemical, IR, and NMR (1H and 13C) spectral studies. © 2003 Wiley Periodicals, Inc. 15:92–96, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.10220
Pathophysiology of acute graft‐versus‐host disease
Authors: Reddy Pavan
Published: January 2004

Graft‐versus‐host disease (GVHD) has been the primary limitation to the wider application of allogeneic bone marrow transplantation (BMT). The pathophysiology of acute GVHD is complex and can be conceptualized to be a three‐step process based on murine studies. In step 1, the conditioning regimen leads to the damage and activation of host tissues and induces the secretion of inflammatory cytokines. As a consequence, the expression of MHC antigens and adhesion molecules is increased enhancing the recognition of host alloantigens by donor T cells. Donor T‐cell activation in step 2 is characterized by donor T cell interaction with host APCs and subsequent proliferation, differentiation and secretion of cytokines. Cytokines such as IL‐2 and IFN‐γ enhance T‐cell expansion, induce cytotoxic T cells (CTL) and natural killer (NK) cell responses and prime additional mononuclear phagocytes to produce TNF‐α and IL‐1. These inflammatory cytokines in turn stimulate production of inflammatory chemokines, thus recruiting effector cells into target organs. In step 3, effector functions of mononuclear phagocytes are triggered via a secondary signal provided by lipopolysaccaride (LPS) that leaks through the intestinal mucosa damaged during step 1. This mechanism may result in the amplification of local tissue injury and further promotion of an inflammatory response, which, together with the CTL and NK components, leads to target tissue destruction in the transplant host. The following review discusses the three‐step process of the pathophysiology of experimental acute GVHD. Copyright © 2003 John Wiley & Sons, Ltd.
Low dose 2‐CdA schedule activity in splenic marginal zone lymphomas
Authors: Riccioni R. , Caracciolo F. , Galimberti S. , Cecconi N. , Petrini M.
Published: January 2004

Splenic Marginal Zone Lymphoma (SMZL) is a rare clinicopathological entity among marginal zone lymphomas. SMZL is an indolent lymphoma usually treated by splenectomy. A subset of patients is characterized by a more aggressive clinical course and poor prognosis. Treatment of these cases and second‐line therapy for relapsed patients have not been yet identified. We report 10 cases treated with cladribrine (5 mg/m2/week) for six courses. Six patients (60%) achieved partial response, two patients (20%) achieved a complete response and the two remaining patients did not respond and died as a result of progression of the disease. The treatment was well tolerated. A total of 60% of the patients had an overall survival rate of 48 months and 24 months progression‐free‐survival was achieved by 37% with a median time of progression‐free‐survival of 17 months. Interestingly, in addition to a relevant percentage of hematological remission, some patients also experienced a molecular remission. We conclude that this treatment is safe and well tolerated and is able to induce a substantial number of responses. Our results suggest that this schedule is well tolerated and could be an useful alternative to splenectomy. Copyright © 2003 John Wiley & Sons, Ltd.
Epoetin alfa corrects anemia and improves quality of life in patients with hematologic malignancies receiving non‐platinum chemotherapy
Authors: Littlewood Timothy J. , Nortier Johan , Rapoport Bernardo , Pawlicki Marek , De Wasch Gilbert , Vercammen Els , Schuette Wolfgang , Wils Jacques , Freund Mathias
Published: January 2004

Anemia, a commonly occurring morbidity in patients with cancer, often leads to diminished quality of life (QOL). Numerous clinical trials have shown that epoetin alfa treatment improves hematologic and QOL variables in cancer patients. The clinical trial analysis reported here was performed to assess response to epoetin alfa in patients with hematologic malignancies. Cancer patients with anemia undergoing non‐platinum‐based chemotherapy who were enrolled in a multinational, randomized (2:1), double‐blind, placebo‐controlled trial were prospectively stratified by tumor type (hematologic, solid). Efficacy endpoints included proportion of patients transfused after day 28; change in hemoglobin (Hb) level from baseline to last assessment; proportion of treatment responders (increase in Hb ≥2 g/dl unrelated to transfusion) and correctors (patients whose Hb levels reached ≥12 g/dl during the study); and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study, and survival for the full study cohort was estimated using Kaplan–Meier techniques. Efficacy analyses of hematologic and QOL variables, as well as Kaplan–Meier estimates of survival, were performed post hoc for the hematologic tumor stratum. Among patients with hematologic malignancies, the mean increase in Hb levels was greater with epoetin alfa than with placebo treatment (2.2 vs. 0.3 g/dl). Transfusion requirements were lower in patients who received epoetin alfa versus placebo (25.2 vs. 43.1%), and the proportion of responders and correctors was higher with epoetin alfa than with placebo (75.2 vs. 16.7% and 72.6 vs. 14.8%, respectively). Patients who received epoetin alfa had improved QOL while patients who received placebo had decreased QOL. These results are similar to those seen in the full study cohort, where differences between epoetin alfa and placebo were significant (P<0.05) for all five primary cancer‐ and anemia‐specific QOL domains evaluated. Although the study was not powered for survival, Kaplan–Meier estimates showed a trend in overall survival favoring epoetin alfa in both the full study cohort and the hematologic subgroup. Epoetin alfa treatment was well tolerated. Epoetin alfa therapy increased Hb levels, reduced transfusion requirements, and improved QOL in patients with anemia undergoing non‐platinum chemotherapy for hematologic malignancies. Copyright © 2004 John Wiley & Sons, Ltd.
Glutathione S‐transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokers
Authors: Sikdar Nilabja , Paul Ranjan Rashmi , Roy Bidyut
Published: January 2004

Polymorphism in glutathione S‐transferase (GST) genes, causing variations in enzyme activities, may influence susceptibility to oral cancer and leukoplakia in smokers and/or smokeless tobacco users. In this case‐control study consisting of 109 leukoplakia and 256 oral cancer patients and 259 controls, genotype frequencies at GSTM1, GSTT1, GSTM3 and GSTP1 loci were determined by polymerase chain reaction‐restriction fragment length polymorphism methods and analyzed by multiple logistic regression to determine the risks of the diseases. There were no significant differences in the distributions of GSTM1, GSTM3 and GSTT1 genotypes in patients and controls when all individuals were compared. In contrast, frequencies of ile/ile genotype at codon 105 and variant val‐ala haplotype of GSTP1 was significantly higher (OR = 1.5; 95% CI = 1.0–2.0) and lower (OR = 1.4; 95% CI = 1.0–1.9) in oral cancer patients compare to controls, respectively. The impacts of all genotypes on risks of oral cancer and leukoplakia were also analyzed in patients with different tobacco habits and doses. Increased risks of cancer and leukoplakia were observed in tobacco smokers with GSTM3 (A/A) genotype (OR = 2.0, 95% CI = 1.0–4.0; OR = 2.0, 95% CI = 1.0–4.4, respectively). So, GSTM3 (A/A) genotype could become one of the markers to know which of the leukoplakia would be transformed into cancer. Heavy tobacco chewing (> 124 chewing‐year) increased the risk of cancer in individuals with GSTT1 homozygous null genotype (OR = 3.0; 95% CI = 1.0–9.8). Furthermore, increased lifetime exposure to tobacco smoking (> 11.5 pack‐year) increased the risk of leukoplakia in individuals with GSTM1 homozygous null genotype (OR = 2.4; 95% CI = 1.0–5.7). It may be suggested that polymorphisms in GSTP1, GSTM1, GSTM3 and GSTT1 genes regulate risk of cancer and leukoplakia differentially among different tobacco habituals. © 2003 Wiley‐Liss, Inc.
Parvovirus H‐1 infection of human glioma cells leads to complete viral replication and efficient cell killing
Authors: Herrero y Calle Marta , Cornelis Jan J. , Herold‐Mende Christel , Rommelaere Jean , Schlehofer Joerg R. , Geletneky Karsten
Published: January 2004

The extremely poor prognosis of malignant gliomas requires the investigation of other than standard therapies, i.e., the application of oncolytic viruses. In our study, we evaluated the effects of the oncosuppressive parvovirus H‐1 on different established glioblastoma cell lines of rat and human origin and on short‐term/low‐passage cultures of human glioblastoma cells. We observed an efficient and dose‐dependent killing of all glioma cell cultures at low multiplicities of infectious particles (MOI) per cell. Southern blot analysis of viral DNA amplification, RT‐PCR analysis of viral RNA expression and Western blot analysis of the expression of viral structural (VP‐1/VP‐2) and nonstructural (NS‐1) proteins demonstrated the biosynthesis of these viral macromolecular components in all of the cultures. Moreover, all the glioma cells were proficient for the production of infectious H‐1 virus particles. The amount of virus production differed between a several fold increase of the input virus titer in most of the short‐term/low‐passage cultures up to 1,000‐fold in one short‐term glioma and in the rat cells. Glioma cells lines and, more importantly, short‐term/low‐passage cultures of human glioblastomas were found to be highly susceptible target cells for H‐1 virus mediated cytotoxicity. The formation of fully infectious progeny particles in infected glioma cells offers the chance for the induction of secondary rounds of infection resulting in an advanced cytotoxic effect. These advantageous characteristics of H‐1 virus infection of glioma cells, combined with the known low toxicity of H‐1 virus in nontransformed cells, make parvovirus H‐1 a promising candidate for oncolytic glioma therapy. © 2003 Wiley‐Liss, Inc.