bluuebunny/crossref_metadata_2025 huggingface dataset:
Alteration of the Substrate Specificity of Benzoylformate Decarboxylase from Pseudomonas putida by Directed Evolution
Authors: Lingen Bettina , Kolter‐Jung Doris , Dünkelmann Pascal , Feldmann Ralf , Grötzinger Joachim , Pohl Martina , Müller Michael
Published: July 2003

Alteration of the substrate specificity of thiamin diphosphate (ThDP)‐dependent benzoylformate decarboxylase (BFD) by error‐prone PCR is described. Two mutant enzymes, L476Q and M365L‐L461S, were identified that accept ortho‐substituted benzaldehyde derivatives as donor substrates, which leads to the formation of 2‐hydroxy ketones. Both variants, L476Q and M365L‐L461S, selectively catalyze the formation of enantiopure (S)‐2‐hydroxy‐1‐(2‐methylphenyl)propan‐1‐one with excellent yields, a reaction which is only poorly catalyzed by the wild‐type enzyme. Different ortho‐substituted benzaldehyde derivatives, such as 2‐chloro‐, 2‐methoxy‐, or 2‐bromobenzaldehyde are accepted as donor substrates by both BFD variants as well and conversion with acetaldehyde resulted in the corresponding (S)‐2‐hydroxy‐1‐phenylpropan‐1‐one derivatives. As deduced from modeling studies based on the 3D structure of wild‐type BFD, reduction of the side chain size at position L461 probably results in an enlarged substrate binding site and facilitates the initial binding of ortho‐substituted benzaldehyde derivatives to the cofactor ThDP.
Structural Investigation of the HIV‐1 Envelope Glycoprotein gp160 Cleavage Site, 2: Relevance of an N‐Terminal Helix
Authors: Oliva Romina , Falcigno Lucia , D′Auria Gabriella , Dettin Monica , Scarinci Claudia , Pasquato Antonella , Di Bello Carlo , Paolillo Livio
Published: July 2003

Proteolytic activation of the HIV‐1 envelope glycoprotein gp160 is selectively performed by the proprotein convertase furin at the C‐terminus of the sequence R508–E–K–R511 (site 1), in spite of the presence of another consensus sequence, Lys500–Ala–Lys–Arg503 (site 2). On the basis of the solution structural analysis of the synthetic peptide p498, spanning the gp160 sequence Pro498–Gly516, we previously suggested a possible role of an N‐terminal helix in regulating the exposure and accessibility of the gp160 physiological cleavage site, enclosed in a loop. Here we report on the activity and conformation of the 23‐residue peptide h‐REKR, designed to exhibit a large N‐terminal helix, followed by the gp160 native sequence, Arg508–Gly516. h‐REKR is digested by furin with high efficiency, comparable to the full native p498. Circular dichroism analyses, in mixtures from pure water to 98 % trifluoroethanol, outline a significant content of helical structure in the peptide conformation. The molecular model obtained from NMR data collected in trifluoroethanol/water, by means of DYANA and AMBER simulations, indeed has helical structure on a large N‐terminal segment. Such a long helix does not seem to affect the loop conformation of the C‐terminal site 1‐containing sequence, which exhibits the same proton chemical shifts already observed for the full native p498.
Tamoxifen Derivatives for Delivery of the Antitumoral (DACH)Pt Group: Selective Synthesis by McMurry Coupling, and Biochemical Behaviour
Authors: Top Siden , Kaloun El Bachir , Vessières Anne , Leclercq Guy , Laïos Ioanna , Ourevitch Michèle , Deuschel Christine , McGlinchey Michael J. , Jaouen Gérard
Published: July 2003

The goal of our study was to potentiate the effects of the ((R,R)‐trans‐1,2‐diaminocyclohexane)‐platinum(II) fragment [(DACH)Pt], known for its cytotoxic properties, either with tamoxifen (Tam), the most widely used antiestrogen in the treatment of hormone‐dependent breast cancers, or with its active metabolite hydroxytamoxifen (hydroxy‐Tam). We coupled Tam or hydroxy‐Tam derivatives bearing a malonato group at the para position of the β aromatic ring with the (DACH)Pt fragment. The malonato‐Tam and malonato‐hydroxy‐Tam compounds were prepared through McMurry coupling of the appropriate ketones. The presence of the malonate group resulted in a pronounced stereospecificity in the reaction, since malonato‐Tam was obtained only as the Z isomer, while malonato‐hydroxy‐Tam was obtained as an 80/20 E/Z mixture. Attribution of the isomeric structures was achieved by 2D NMR spectroscopy. The platinum complexes (DACH)Pt‐malonato‐Tam and (DACH)Pt‐malonato‐hydroxy‐Tam were then prepared by coupling the barium salts derived from the malonato‐Tam and malonato‐hydroxy‐Tam with the nitrate derived from (DACH)PtCl2. Study of the biochemical properties of these two platinum complexes showed that, while the hydroxy‐Tam complex is satisfactorily recognized by the estrogen receptor (relative binding affinity, RBA=6.4 %), the Tam complex is less well recognized (RBA=0.5 %). The effects of these complexes on two hormone‐dependent breast cancer cell lines (MCF7 and MVLN) were studied in vitro. Both complexes showed an antiproliferative effect on MCF7 cells, and an antiestrogenic effect on MVLN cells. The observed effects appear to be essentially antihormonal, since incorporation of the (DACH)Pt fragment into the tamoxifen skeleton did not cause an increase in the cytotoxicity of the complexes.
Photoreversible Inhibition of Cholinesterases: Catalytic Serine‐Labeled Caged Butyrylcholinesterase
Authors: Loudwig Sandra , Nicolet Yvain , Masson Patrick , Fontecilla‐Camps Juan C. , Bon Suzanne , Nachon Florian , Goeldner Maurice
Published: July 2003

The photoregulation of the catalytic activity of butyrylcholinesterase (BChE) was investigated by treating the enzyme with a newly developed carbamylating reagent, N‐methyl‐N‐(2‐nitrophenyl)carbamoyl chloride, which has proved to be an efficient photoremovable alcohol‐protecting group. BChE was efficiently inhibited in a time‐ and concentration‐dependent manner, and the enzyme could be protected against inhibition by active‐site‐specific ligands (that is, tacrine). The inactivation kinetics showed a biphasic character, which can be analyzed as the result of the existence of two conformational states in solution. Pseudo‐irreversible inactivation of BChE, which results from catalytic serine carbamylation, was suggested by recovery of the enzyme activity after dilution and was demonstrated by X‐ray crystallography. Remarkably, the 3D structure of the carbamylated BChE conjugate showed a nonambiguous carbamylation of the catalytic serine residue as the only chemical modification on the protein. The photoreversibility of the enzyme inactivation was analyzed by irradiating the inactivated enzyme at 365 nm and was shown to reach completion in some conditions. The efficient and specific “caging” of BChE, together with the availability of carbamylated BChE crystals, will offer a unique possibility to study the catalytic properties of this enzyme by kinetic crystallography after cryophotolytic uncaging of the enzyme conjugate crystals.
Protein Stabilisation by Compatible Solutes: Effect of Mannosylglycerate on Unfolding Thermodynamics and Activity of Ribonuclease A
Authors: Faria Tiago Q. , Knapp Stefan , Ladenstein Rudolf , Maçanita António L. , Santos Helena
Published: July 2003

Differential scanning calorimetry, optical spectroscopy, and activity measurements were used to investigate the effect of mannosylglycerate, a negatively charged osmolyte widely distributed among thermophilic and hyperthermophilic archaea and bacteria, on the thermal unfolding of ribonuclease A (RNase A). For comparison, assays in the presence of trehalose, a canonical solute in mesophiles, and potassium chloride were also carried out. A thermodynamic analysis was performed by using differential scanning calorimetry data. The changes in the heat capacity for unfolding were similar for the different solutes examined. Mannosylglycerate was an efficient thermostabiliser of RNase A and induced an increase of 6 °C mole‐1 in the melting temperature. Moreover, the performance of mannosylglycerate as a stabiliser depended on the net charge of the molecule, with the maximal effect being observed at pH values above 4.5. Analysis of the enthalpic and entropic contributions to unfolding, derived from calorimetric data, revealed that the stabilisation rendered by mannosylglycerate is primarily achieved through a decrease in the unfolding entropy. Also, the number of protons taken up by RNase A upon denaturation in the presence of mannosylglycerate was considerably higher than with other solutes, a result consistent with a more rigid structure of the native protein. Mannosylglycerate (potassium salt) inhibited the activity of RNase A, albeit to a smaller extent than KCl, and acted as an efficient suppressor of aggregation of the denatured protein, thereby having a remarkable beneficial effect on the inactivation of RNase A upon thermal denaturation. The results are discussed in view of the physiological role of this charged compatible solute.
Direct Visualization of DNA Duplex Formation on the Surface of a Giant Liposome
Authors: Shohda Koh‐ichiroh , Toyota Taro , Yomo Tetsuya , Sugawara Tadashi
Published: July 2003

Corrigendum published online September 4, 2003. 10.1002/cbic.200390107.
Comparative Study of Purine and Pyrimidine Nucleoside Analogues Acting on the Thymidylate Kinases of Mycobacterium tuberculosis and of Humans
Authors: Pochet Sylvie , Dugué Laurence , Labesse Gilles , Delepierre Muriel , Munier‐Lehmann Hélène
Published: July 2003

Thymidine monophosphate kinase (TMPK) from Mycobacterium tuberculosis (TMPKmt) is an attractive target for the design of specific inhibitors. This fact is the result of its key role in the thymidine pathway and of unique structural features in the active site observed by X‐ray crystallography, especially in comparison to its human counterpart (TMPKh). Different 5‐modified thymidine derivatives, as well as purine and pyrimidine analogues or C‐nucleosides were tested on TMPKmt and TMPKh, and the results were rationalized by docking studies. 5‐Halogenated 2′‐deoxyuridines are the best inhibitors of TMPKmt found and present the highest selectivity indexes in favor of TMPKmt.
CloN6, a Novel Methyltransferase Catalysing the Methylation of the Pyrrole‐2‐carboxyl Moiety of Clorobiocin
Authors: Westrich Lucia , Heide Lutz , Li Shu‐Ming
Published: July 2003

The aminocoumarin antibiotic clorobiocin contains a 5‐methylpyrrole‐2‐carboxylic acid unit. This pyrrole unit is derived from L‐proline, and it would be expected that its 5‐methyl group should be introduced by a methylation reaction. However, sequence analysis of the clorobiocin biosynthetic gene cluster did not reveal a gene with sequence similarity to the SAM‐dependent methyltransferases that could be assigned to this reaction. This study, however, has provided evidence that the gene cloN6 is involved in this methylation reaction. Its gene product CloN6 shares conserved sequence motifs with the recently identified radical SAM protein superfamily, and it has been suggested that members of this family can catalyse methylcobalamin‐dependent methylation reactions. cloN6 was inactivated in the clorobiocin producer Streptomyces roseochromogenes var. oscitans DS 12.976 by use of the PCR‐targeting method. The cloN6− mutants accumulated, instead of clorobiocin, a derivative lacking the 5′′′‐methyl group of the pyrrole moiety (termed novclobiocin 109). A structural isomer carrying the pyrrole‐2‐carboxyl moiety at 2″‐OH rather than at the 3″‐OH of the deoxysugar (novclobiocin 110), and a derivative completely lacking the pyrrole unit (novclobiocin 104) were also identified. The structures of the metabolites were confirmed by NMR and MS analysis. Antibacterial activity tests against Bacillus subtilis showed that novclobiocin 109 and novclobiocin 110 have antibacterial activities about eight times less than that of clorobiocin, whereas novclobiocin 104 showed no activity under the test conditions.
Selection of D‐Amino‐Acid Peptides That Bind to Alzheimer's Disease Amyloid Peptide Aβ1–42 by Mirror Image Phage Display
Authors: Wiesehan Katja , Buder Katrin , Linke Reinhold P. , Patt Stephan , Stoldt Matthias , Unger Eberhard , Schmitt Bettina , Bucci Enrico , Willbold Dieter
Published: July 2003

A mirror image phage display approach was used to identify novel and highly specific ligands for Alzheimer's disease amyloid peptide Aβ(1–42). A randomized 12‐mer peptide library presented on M13 phages was screened for peptides with binding affinity for the mirror image of Aβ(1–42). After four rounds of selection and amplification the peptides were enriched with a dominating consensus sequence. The mirror image of the most representative peptide (D‐pep) was shown to bind Aβ(1–42) with a dissociation constant in the submicromolar range. Furthermore, in brain tissue sections derived from patients that suffered from Alzheimer's disease, amyloid plaques and leptomeningeal vessels containing Aβ amyloid were stained specifically with a fluorescence‐labeled derivative of D‐pep. Fibrillar deposits derived from other amyloidosis were not labeled by D‐pep. Possible applications of this novel and highly specific Aβ ligand in diagnosis and therapy of Alzheimer's disease are discussed.
Macrophomate Synthase: The First Structure of a Natural Diels–Alderase
Authors: Pohnert Georg
Published: July 2003

An enzyme‐catalyzed Diels–Alder reaction in the formation of macrophomic acid can be deduced from the crystal structure of macrophomate synthase. The active site of the Diels–Alderase allows to explain how the single enzyme promotes two carbon–carbon bond formations, two decarboxylations and a dehydration step (see scheme).
Cover Picture: Direct Visualization of DNA Duplex Formation on the Surface of a Giant Liposome (ChemBioChem 8/2003)
Authors: Shohda Koh‐ichiroh , Toyota Taro , Yomo Tetsuya , Sugawara Tadashi
Published: July 2003

The cover picture shows the phase‐contrast microscopy image (top left) and the fluorescent microscopy image (bottom left) of a giant liposome stained with a green fluorescent probe on the surface of the membrane (right diagram). This process occurs by hybridization of a fluorescent‐tagged DNA 15mer (green) and a conjugate DNA molecule, the latter of which is composed of a DNA 15mer (orange ribbon), a polyethyleneglycol spacer (orange ball), and cholesterol (orange rugby ball). Since the conjugate molecule is firmly anchored to the membrane of the giant liposome, it will become a bridging molecule between the world of RNA and lipids. Further details can be found in the article by T. Sugawara et al. on p. 778 ff.
The First Successful Crystallographic Characterization of a Cyclodextrin Dimer: Efficient Synthesis and Molecular Geometry of a Doubly Sulfur‐Bridgedβ‐Cyclodextrin
Authors: Yuan De‐Qi , Immel Stefan , Koga Katzutaka , Yamaguchi Masatoshi , Fujita Kahee
Published: July 2003

β‐Cyclodextrin is transannularly disulfonylated at the 6A‐ and 6B‐positions, and then converted to the corresponding 6A,6B‐diiodide and 6A,6B‐dithiol. Cross‐coupling of the latter two species yields a single head‐to‐head‐coupledβ‐cyclodextrin dimer5with two sulfur linkers at adjacent 6‐methylene carbons. NMR and X‐ray analysis revealed thetrans‐type (“aversive”) linkage of bothβ‐cyclodextrin units. In the solid‐state structure of5⋅5 MeOH⋅23 H2O, the undistorted cyclodextrin macrocycles feature almost parallel ring planes pointing away from each other, leaving5with a “handcuff‐like” appearance of approximateC2symmetry. This work represents the first successful crystallographic study on a cyclodextrin dimer.
Tuning the Redox Potentials of Dinuclear Tungsten Oxo Complexes [(Cp*W(4,4′‐R,R‐2,2′‐bpy)(μ‐O))2][PF6]2 Toward Photochemical Water Splitting
Authors: Cremer Christian , Burger Peter
Published: July 2003

A series of novel dinuclear tungsten(IV) oxo complexes with disubstituted 4,4′‐R,R‐2,2′‐bipyridyl (R2bpy) ligands of the type [(Cp*W(R2bpy)(μ‐O))2][PF6]2 (R=NMe2, tBu, Me, H, Cl) was prepared by hydrolysis of the tungsten(IV) trichloro complexes [Cp*W(R2bpy)Cl3]. Cyclic voltammetry measurements for the tungsten(IV) oxo compounds provided evidence for one reversible oxidation and two reversible reductions leading to the oxidation states WVWIV, WIVWIII and WIIIWIII. The corresponding complexes [(Cp*W(R2bpy)(μ‐O))2]n+ [PF6]n (n=0 for R=Me, tBu, and 1, 3 for both R=Me) could be isolated after chemical oxidation/reduction of the tungsten(IV) oxo complexes. The crystal structures of the complexes [(Cp*W(R2bpy)(μ‐O))2][BPh4]2 (R=NMe2, tBu) and [(Cp*W(Me2bpy)(μ‐O))2]n+[PF6]n (n=0, 1, 2, 3) show a cis geometry with a puckered W2O2 four‐membered ring for all compounds except [(Cp*W(Me2bpy)(μ‐O))2] which displays a trans geometry with a planar W2O2 ring. Examining the interaction of these novel tungsten oxo complexes with protons, we were able to show that the WIVWIV complexes [(Cp*W(R2bpy)(μ‐O))2][PF6−]2 (R=NMe2, tBu) undergo reversible protonation, while the WIIIWIII complexes [(Cp*W(R2bpy)(μ‐O))2] transfer two electrons forming the WIVWIV complex and molecular hydrogen.
Synthesis of a New Potential Tridentate Anthracene Ligand Bearing Deprotectable Methoxymethoxy (OMOM) Group at 1,8‐Positions: Attempt To Synthesize Anionic Hypervalent Carbon Compounds
Authors: Yamashita Makoto , Mita Yukari , Yamamoto Yohsuke , Akiba Kin‐ya
Published: July 2003

A novel potential tridentate ligand bearing deprotectable coordinating atoms, 1,8‐bis(methoxymethoxy)‐9‐bromoanthracene (15), was synthesized. The key steps are as follows: 1) stepwise mono‐oxygenation from 1,8‐dibromo‐9‐methoxyanthracene by use of electrophilic oxaziridine and gaseous dioxygen, and 2) selective reduction of the methoxy group by LDBB (lithium di‐tert‐butylbiphenylide) followed by treatment with BrCF2CF2Br. The corresponding 1,8‐bis(methoxymethoxy)‐9‐lithio‐anthracene (14), which should be a useful versatile trianion equivalent, could be generated by treatment of the bromide with one equivalent of nBuLi. The lithioanthracene reacted with hexafluoroacetone to give the deprotected ether 17 together with the adduct alcohol 16. The ether could easily be deprotected to give 1,2‐dihydro‐1,1‐bis(trifluoromethyl)‐2‐oxa‐9‐hydroxyanthrylene (8), which was deprotonated with KH in the presence of [18]crown‐6 to give the corresponding anion (9‐K([18]crown‐6)). The X‐ray structure and NMR spectra of 9‐K([18]crown‐6) showed that it has an unsymmetrical structure probably due to the interaction between the oxygen atom of the phenoxide and the potassium cation surrounded by the crown ether.
On the Electronic Structures of the 1,3‐Diboracyclobutane‐1,3‐diyls and Their Valence Isomers with a B2E2 Skeleton (E=N, P, As)
Authors: Schoeller Wolfgang W. , Rozhenko Alexander , Bourissou Didier , Bertrand Guy
Published: July 2003

The concept of through‐space versus through‐bond interactions on the stabilization of biradical structures with a singlet or triplet ground state is evaluated for the 1,3‐diboracyclobutane‐1,3‐diyls and related congeners. Singlet biradicals are favored when the intermediate units E feature singlet character (PH2+, AsH2+), while E fragments with triplet character (NH2+) induce small energy separations between the lowest singlet and triplet states. These considerations are supported by quantum chemical calculations with energy optimization at 1) MCSCF level plus MR‐MP2 correction, 2) MR‐MP2 level, and 3) two different types of density functional levels for the planar (D2h) geometries. The singlet–triplet energy separations in the planar compounds increase with increasing singlet stability of the corresponding E fragments. In addition to this newly developed principal features for singlet stabilization, which primarily occurs in bonded structures with higher main‐group elements, the corresponding valence isomers with bicyclobutane, cyclobutene and cis‐butadiene structures are investigated.
Vibrational and Quantum‐Chemical Study of Push–Pull Chromophores for Second‐Order Nonlinear Optics from Rigidified Thiophene‐Based π‐Conjugating Spacers
Authors: Ruiz Delgado Mari Carmen , Hernández Víctor , Casado Juan , López Navarrete Juan T. , Raimundo Jean‐Manuel , Blanchard Philippe , Roncali Jean
Published: July 2003

Two types of push–pull chromophores built around thiophene‐based π‐conjugating spacers rigidified by either covalent bonds or noncovalent intramolecular interactions have been analysed by means of IR and Raman spectroscopical measurements in the solid state as well as in a variety of solvents. Comparison of the Raman features of NLO‐phores based on a covalently rigidified dithienylene (DTE) spacer with those of their open chain DTE analogues shows that the bridging of the central double bond of DTE with the nearest β‐positions of the thienyl units through two ethylene bridges significantly improves the intramolecular charge transfer. This also occurs for NLO‐phores based on a 2,2′‐bi(3,4‐ethylenedioxythiophene) (BEDOT) spacer as compared with their corresponding parent compounds based on an unsubstituted bithiophene (BT) spacer. For NLO‐phores based on a BEDOT spacer, noncovalent intramolecular interactions between sulfur and oxygen atoms are responsible for the rigidification of the spacer. The Raman spectra of these NLO‐phores obtained in the form of solutes in dilute solutions reveal two different behaviours: i) chromophores based on covalently bridged or open chain DTE spacers display Raman spectral profiles in solution quite similar to those of the corresponding solids, with a very little dependence on the polarity of the solvent, while ii) larger spectral changes are noticed for NLO‐phores built around BEDOT or BT spacers on going from solids to solutions. In the second case, spectral changes must be ascribed not solely to conformational distortions of the donor and acceptor end groups with respect to the π‐conjugated backbone mean‐square‐plane (as for the DTE‐based NLO‐phores) but also to distortions of the thienyl units of the π‐conjugating spacer from coplanarity. The insertion of vinylenic bridges between the thienyl units of the π‐conjugating spacer and between the spacer and the donor and acceptor end groups is a suitable strategy to reach a fairly large intramolecular charge transfer both in polar and nonpolar solvents. Density functional theory (DFT) calculations have been carried out to assign the relevant electronic and vibrational features and to derive useful information about the molecular structure of these NLO‐phores.
Stabilization of CoI by ZnII in Pure Acetonitrile and its Reaction with Aryl Halides
Authors: Seka Sylvaine , Buriez Olivier , Périchon Jacques
Published: July 2003

The study of the electrochemical behavior of cobalt(II) bromide (CoBr2) in pure acetonitrile allowed us to demonstrate that Co2+ is the catalyst precursor involved in the electrochemical and chemical conversions of arylhalides, ArX, to arylzinc compounds in that solvent. The reduction of Co2+ leads to the Co+ species, which disproportionates too rapidly to react further with aryl halides. However, the presence of zinc(II) bromide allows us to stabilize the electrogenerated cobalt(I) and to observe it on the timescale of slow cyclic voltammetry. Under such conditions, the CoI species has time to react with aryl halides and produce [CoIIIArX]+ complexes that are reduced into [CoIIArX] by a single electron uptake at the same potential at which Co2+ is reduced. Rate constants for the oxidative addition of ArX to CoI have been determined for various aryl halides and compared to the values obtained in an acetonitrile (ACN)/pyridine (9:1, v/v) mixture. It is shown that CoI is stabilized more by ZnBr2 than by pyridine. A transmetallation reaction between [CoIIArX] and ZnBr2 has also been observed. We finally propose a mechanism for the cobalt‐catalyzed electrochemical conversion of aryl bromides into organozinc species in pure acetonitrile.
GdIII Complexes with Fast Water Exchange and High Thermodynamic Stability: Potential Building Blocks for High‐Relaxivity MRI Contrast Agents
Authors: Laus Sabrina , Ruloff Robert , Tóth Éva , Merbach André E.
Published: July 2003

On the basis of structural considerations in the inner sphere of nine‐coordinate, monohydrated GdIII poly(aminocarboxylate) complexes, we succeeded in accelerating the water exchange by inducing steric compression around the water binding site. We modified the common DTPA5− ligand (DTPA=(diethylenetriamine‐N,N,N′,N″,N″‐pentaacetic acid) by replacing one (EPTPA5−) or two (DPTPA5−) ethylene bridges of the backbone by propylene bridges, or one coordinating acetate by a propionate arm (DTTA‐prop5−). The ligand EPTPA5− was additionally functionalized with a nitrobenzyl linker group (EPTPA‐bz‐NO25−) to allow for coupling of the chelate to macromolecules. The water exchange rate, determined from a combined variable‐temperature 17O NMR and EPR study, is two orders of magnitude higher on [Gd(eptpa‐bz‐NO2)(H2O)]2− and [Gd(eptpa)(H2O)]2− than on [Gd(dtpa)(H2O)]2− (k${_{{\rm ex}}^{\,298}}$=150×106, 330×106, and 3.3×106 s−1, respectively). This is optimal for attaining maximum proton relaxivities for GdIII‐based, macrocyclic MRI contrast agents. The activation volume of the water exchange, measured by variable‐pressure 17O NMR spectroscopy, evidences a dissociative interchange mechanism for [Gd(eptpa)(H2O)]2− (ΔV ≠=(+6.6±1.0) cm3 mol−1). In contrast to [Gd(eptpa)(H2O)]2−, an interchange mechanism is proved for the macrocyclic [Gd(trita)(H2O)]− (ΔV ≠=(−1.5±1.0) cm3 mol−1), which has one more CH2 group in the macrocycle than the commercial MRI contrast agent [Gd(dota)(H2O)]−, and for which the elongation of the amine backbone also resulted in a remarkably fast water exchange. When one acetate of DTPA5− is substituted by a propionate, the water exchange rate on the GdIII complex increases by a factor of 10 (k${_{{\rm ex}}^{\,298}}$=31×106 s−1). The [Gd(dptpa)]2− chelate has no inner‐sphere water molecule. The protonation constants of the EPTPA‐bz‐NO25− and DPTPA5− ligands and the stability constants of their complexes with GdIII, ZnII, CuII and CaII were determined by pH potentiometry. Although the thermodynamic stability of [Gd(eptpa‐bz‐NO2)(H2O)]2− is reduced to a slight extent in comparison with [Gd(dtpa)(H2O)]2−, it is stable enough to be used in medical diagnostics as an MRI contrast agent. Therefore both this chelate and [Gd(trita)(H2O)]− are potential building blocks for the development of high‐relaxivity macromolecular agents.
From Supramolecular Block Copolymers to Advanced Nano‐Objects
Authors: Gohy Jean‐François , Lohmeijer Bas G. G. , Schubert Ulrich S.
Published: July 2003

The formation of asymmetric bis‐complexes, based on terpyridine ligands and ruthenium ions, is described as a powerful tool for the self‐assembly of polymer blocks end‐functionalized with terpyridine units. This is illustrated in this contribution for the synthesis of amphiphilic metallo‐supramolecular block copolymers, which are further used to produce aqueous micelles. Finally, the reversibility of the supramolecular bond opens new avenues for the preparation and manipulation of these nano‐objects.
Synthesis and Properties of the First Stable Silylene–Isocyanide Complexes
Authors: Takeda Nobuhiro , Kajiwara Takashi , Suzuki Hiroyuki , Okazaki Renji , Tokitoh Norihiro
Published: July 2003

The first stable silylene–isocyanide complexes, [Tbt(Mes)SiCNAr] (5 c: Ar=Tip, 5 d: Ar=Tbt, 5 e: Ar=Mes*; Tbt=2,4,6‐tris[bis(trimethylsilyl)methyl]phenyl, Mes=mesityl, Tip=2,4,6‐triisopropylphenyl, Mes*=2,4,6‐tri‐tert‐butylphenyl) were successfully synthesized by the reaction of a kinetically stabilized disilene, [Tbt(Mes)SiSi(Mes)Tbt] (1), with bulky isocyanides, ArNC (3c–e). The spectroscopic data of 5 c–e and theoretical calculations for a model molecule indicated that 5 c–e are not classical cumulative compounds but the first stable silylene–Lewis base complexes. The reactions of 5 c–e with triethylsilane and 1,3‐dienes gave the corresponding silylene adducts, and they underwent isocyanide‐exchange reactions in the presence of another isocyanide at room temperature. These results indicate dissociation of complexes 5 c–e to the corresponding silylene 2 and isocyanides 3 c–e under very mild conditions. The reaction of 5 c with methanol gave the MeOH adduct 16, [Tbt(Mes)SiHC(OMe)NTip], which has a hydrogen atom on the silicon atom. This regioselectivity can be explained in terms of the contribution of zwitterionic resonance structures D and E, which have an anion on the silicon atom. This result indicates that 5 c is not a classical cumulene having SiC double bonds that should react with methanol to give adducts bearing a methoxyl group on the silicon atom. Although the reactions of 5 c–e with electrophilic reagents such as methanol, hydrogen chloride, and methyl iodide gave the formal silylene adducts, the studies on the reaction mechanism by trapping experiments and the observation of the intermediate suggested that the reaction mainly or partially proceeds by initial nucleophilic attack of the silicon atom, as is the case in the formation of 16 in the reaction of 5 c with methanol. It was revealed that 5 c–e show the nucleophilicity of the silicon atom, most likely resulting from the contribution of the zwitterionic resonance structures D and E.
Synthesis and Reactivity of Calix[4]arene‐Supported Group 4 Imido Complexes
Authors: Dubberley Stuart R. , Friedrich Andreas , Willman David A. , Mountford Philip , Radius Udo
Published: July 2003

New mononuclear titanium and zirconium imido complexes [M(NR)(R′2calix)] [M=Ti, R′=Me, R=tBu (1), R=2,6‐C6H3Me2 (2), R=2,6‐C6H3iPr2 (3), R=2,4,6‐C6H2Me3 (4); M=Ti, R′=Bz, R=tBu (5), R=2,6‐C6H3Me2 (6), R=2,6‐C6H3iPr2 (7); M=Zr, R′=Me, R=2,6‐C6H3iPr2 (8)] supported by 1,3‐diorganyl ether p‐tert‐butylcalix[4]arenes (R′2calix) were prepared in good yield from the readily available complexes [MCl2(Me2calix)], [Ti(NR)Cl2(py)3], and [Ti(NR)Cl2(NHMe2)2]. The crystallographically characterised complex [Ti(NtBu)(Me2calix)] (1) reacts readily with CO2, CS2, and p‐tolyl‐isocyanate to give the isolated complexes [Ti{N(tBu)C(O)O}(Me2calix)] (10), [{Ti(μ‐O)(Me2calix)}2] (11), [{Ti(μ‐S)(Me2calix)}2] (12), and [Ti{N(tBu)C(O)N(‐4‐C6H4Me)}(Me2calix)] (13). In the case of CO2 and CS2, the addition of the heterocumulene to the TiN multiple bond is followed by a cycloreversion reaction to give the dinuclear complexes 11 and 12. The X‐ray structure of 13⋅4(C7H8) clearly establishes the N,N′‐coordination mode of the ureate ligand in this compound. Complex 1 undergoes tert‐butyl/arylamine exchange reactions to form 2, 3, [Ti(N‐4‐C6H4Me)(Me2calix)] (14), [Ti(N‐4‐C6H4Fc)(Me2calix)] (15) [Fc=Fe(η5‐C5H5)(η5‐C5H4)], and [{Ti(Me2calix)}2{μ‐(N‐4‐C6H4)2CH2}] (16). Reaction of 1 with H2O, H2S and HCl afforded the compounds [{Ti(μ‐O)(Me2calix)}2] (11), [{Ti(μ‐S)(Me2calix)}2] (12), and [TiCl2(Me2calix)] in excellent yields. Furthermore, treatment of 1 with two equivalents of phenols results in the formation of [Ti(O‐4‐C6H4R)2(Me2calix)] (R=Me 17 or tBu 18), [Ti(O‐2,6‐C6H3Me2)2(Me2calix)] (19) and [Ti(mbmp)(Me2calix)] (20; H2mbmp=2,2′‐methylene‐bis(4‐methyl‐6‐tert‐butylphenol) or CH2({CH3}{C4H9}C6H2‐OH)2). The bis(phenolate) compounds 17 and 18 with para‐substituted phenolate ligands undergo elimination and/or rearrangement reactions in the nonpolar solvents pentane or hexane. The metal‐containing products of the elimination reactions are dinuclear complexes [{Ti(O‐4‐C6H4R)(Mecalix)}2] [R=Me (23) or tBu (24)] where Mecalix=monomethyl ether of p‐tert‐butylcalix[4]arene. The products of the rearrangement reaction are [Ti(O‐4‐C6H4Me)2 (paco‐Me2calix)] (25) and [Ti(O‐4‐C6H4tBu)2(paco‐Me2calix)] (26), in which the metallated calix[4]arene ligand is coordinated in a form reminiscent of the partial cone (paco) conformation of calix[4]arene. In these compounds, one of the methoxy groups is located inside the cavity of the calix[4]arene ligand. The complexes 24, 25 and 26 have been crystallographically characterised. Complexes with sterically more demanding phenolate ligands, namely 19 and 20 and the analogous zirconium complexes [Zr(O‐4‐C6H4Me)2(Me2calix)] (21) and [Zr(O‐2,6‐C6H3Me2)2(Me2calix)] (22) do not rearrange. Density functional calculations for the model complexes [M(OC6H5)2(Me2calix)] with the calixarene possessing either cone or partial cone conformations are briefly presented.
Electron Delocalization in Cross‐Conjugated p‐Phenylenevinylidene Oligomers
Authors: Klokkenburg Mark , Lutz Martin , Spek Anthony L. , van der Maas John H. , van Walree Cornelis A.
Published: July 2003

The synthesis, structure, and electronic properties of a series of cross‐conjugated p‐phenylenevinylidene oligomers with one to four double bonds are reported. The X‐ray crystal structure of the compound with two double bonds reveals a nonplanar conformation with torsion angles about the C(phenylene)–C(vinylidene) and C(phenyl)–C(vinylidene) formal single bonds of 39.5(2)° and 30.5(2)°, respectively. Admixture of quinoid character in the ground state is observed. Infrared and Raman spectroscopy do not provide a clear picture of the degree of electron delocalization in the series, since the CC stretching mode does not adequately reflect the CC bond order and has a local nature. In contrast, electronic spectra and electrochemical data, as well as AM1 and PPP/SCF calculations, reveal that the cross‐conjugated compounds basically behave as linearly π‐conjugated systems in the sense that molecular orbitals are delocalized over the entire structure and systematically change in energy. The electronic interaction between the repeating units is, however, not very strong, which has the consequence that spatial extension of the molecular orbitals does not lead to a red shift of the highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) electronic transition. This is related to the feature that the modest narrowing of the HOMO–LUMO gap with the chain length is accompanied by a relatively large reduction of electron repulsion. This finding implies that care should be taken in the use of electronic spectra for the evaluation of conjugation phenomena.
High‐Pressure Preparation, Crystal Structure, and Properties of α‐(RE)2B4O9 (RE=Eu, Gd, Tb, Dy): Oxoborates Displaying a New Type of Structure with Edge‐Sharing BO4 Tetrahedra
Authors: Emme Holger , Huppertz Hubert
Published: July 2003

High‐pressure/high‐temperature conditions of 10 GPa and 1150 °C were used to synthesize the new rare‐earth oxoborates α‐(RE)2B4O9 (RE=Eu, Gd, Tb, Dy) in a Walker‐type multianvil apparatus. Single‐crystal X‐ray structure determination of α‐(RE)2B4O9 (RE=Eu, Gd, Tb) revealed: C2/c, Z=20, α‐Eu2B4O9: a=2547.9(5), b=444.3(1), c=2493.8(5) pm, β=99.82(3)°, R1=0.0277, wR2=0.0693 (all data); α‐Gd2B4O9: a=2539.0(1), b=443.3(1), c=2490.8(1) pm, β=99.88(1)°, R1=0.0457, wR2=0.0643 (all data); α‐Tb2B4O9: a=2529.4(1), b=441.6(1), c=2484.3(1) pm, β=99.88(1)°, R1=0.0474, wR2=0.0543 (all data). The isotypic compounds exhibit a new type of structure that is built up of BO4 tetrahedra to form a network that incorporates the rare‐earth cations. The most important feature is the existence of the new structural motif of edge‐sharing BO4 tetrahedra next to the known motif of corner‐sharing BO4 tetrahedra, which is realized in the presented compounds α‐(RE)2B4O9 (RE=Eu, Gd, Tb, Dy) for the second time. Furthermore, we report the temperature‐resolved in‐situ powder‐diffraction measurements, DTA, IR/Raman spectroscopic investigations, and magnetic properties of the new compounds.
Comparison of Side‐On and End‐On Coordination of E2 Ligands in Complexes [W(CO)5E2] (E=N, P, As, Sb, Bi, Si−, Ge−, Sn−, Pb−)
Authors: Esterhuysen Catharine , Frenking Gernot
Published: July 2003

Complexes of W(CO)5 with neutral diatomic pnictogen ligands N2, P2, As2, Sb2, and Bi2 and anionic Group 14 ligands Si22−, Ge22−, Sn22−, and Pb22− coordinated in both side‐on and end‐on fashion have been optimized by using density functional theory at the BP86 level with valence sets of TZP quality. The calculated bond energies have been used to compare the preferential binding modes of each respective ligand. The results were interpreted by analyzing the nature of the interaction between the ligands and the metal fragment using an energy partitioning method. This yields quantitative information regarding the strength of covalent and electrostatic interactions between the metal and ligand, as well as the contributions by orbitals of different symmetry to the covalent bonding. Results show that all the ligands studied bind preferentially in a side‐on coordination mode, with the exception of N2, which prefers to coordinate in an end‐on mode. The preference of the heavier homologues P2–Bi2 for binding in a side‐on mode over the end‐on mode in the neutral complexes [(CO)5WE2] comes mainly from the much stronger electrostatic attraction in the former species. The energy difference between the side‐on and end‐on isomers of the negatively charged complexes with the ligands Si22−, Ge22−, Sn22−, and Pb22− is much less and it cannot be ascribed to a particular bonding component.
N‐Heterocyclic Carbene Functionalized Iridium Phosphinidene Complex [Cp*(NHC)IrPMes*]: Comparison of Phosphinidene, Imido, and Carbene Complexes
Authors: Termaten Arjan T. , Schakel Marius , Ehlers Andreas W. , Lutz Martin , Spek Anthony L. , Lammertsma Koop
Published: July 2003

The novel phosphinidene complex [Cp*(NHC)IrPMes*] (3; NHC=1,3‐diisopropyl‐4,5‐dimethylimidazol‐2‐ylidene) was prepared in high yield from [Cp*(NHC)IrCl2] (2) and [LiPHMes*]⋅3 THF. It represents the first example of an NHC ligated transition metal phosphinidene complex. The X‐ray crystal structure for 3 is also reported. DFT calculations on the N‐heterocyclic carbene containing parent complexes [Cp(NHC)IrE] (E=PH, NH, CH2) show that the NHC ligand acts as good σ‐donor/weak π‐acceptor ligand and forms strong IrC(NHC) single bonds. The IrE double bonds result from strong triplet–triplet interactions between [Cp(NHC)Ir] and E.
Covalent Chemistry and Conformational Dynamics of Topologically Chiral Amide‐Based Molecular Knots
Authors: Lukin Oleg , Müller Walter M. , Müller Ute , Kaufmann Astrid , Schmidt Claus , Leszczynski Jerzy , Vögtle Fritz
Published: July 2003

The readily available in gram quantities tris(allyloxy)knot of the amide‐type 5 (knotane) can be completely and partially deprotected with nBu3SnH in the presence of a palladium catalyst resulting in hydroxyknotanes 7–9. These, in turn, react with diethylchlorophosphate giving rise to knotanes equipped with between one and three phosphoryl groups. Sulfonylation of bis(allyloxy)monohydroxyknotane 8 with p‐toluenesulfonyl chloride and, following removal of one or two allyl groups from the intermediate monosulfonate 13, give rise to sulfonyloxy‐allyloxy‐hydroxy‐ and sulfonyloxy‐dihydroxy‐knotanes 15 and 14, respectively. This provides a convenient method for the preparation of knotanes with any substitution pattern. All new knotanes have been isolated in preparative amounts and as highly pure substances with an exception of allyloxy‐dihydroxyknotane 9. This compound could only be obtained as a mixture with the corresponding monohydroxy‐derivative 8. The structures of all synthesized compounds were established by means of FAB and MALDI TOF mass spectrometry, 1H and 31P NMR spectroscopy. The triphosphorylated knotane 10 exhibits high solubility in alcohols, allowing its complete enantiomeric resolution with a commercially available chiral HPLC column. 1H,1H DQF‐COSY correlation spectroscopy along with H/D exchange experiments and ab initio calculations provided the first detailed 1H NMR signal assignments of knotanes in [D6]DMSO solution. The combination of variable temperature 1H and 31P NMR spectroscopy and molecular modeling has been applied to study the conformational behavior of the new knotanes in different solvents. It has been shown that in DMSO solution at room temperature knotanes exist in a relatively rigid nonsymmetrical conformation similar to that found in the solid state while faster conformational exchange leading to the average D3 symmetrical structure was detected in a number of other solvents.
Lipopeptaibol Metabolites of Tolypocladium geodes: Total Synthesis, Preferred Conformation, and Membrane Activity
Authors: Rainaldi Mario , Moretto Alessandro , Peggion Cristina , Formaggio Fernando , Mammi Stefano , Peggion Evaristo , Galvez José Antonio , Díaz‐de‐Villegas Maria Dolores , Cativiela Carlos , Toniolo Claudio
Published: July 2003

We have synthesized by solution methods and characterized the lipopeptaibol metabolite LP237‐F8 extracted from the fungus Tolypocladium geodes and five selected analogues with the Etn→Aib or Etn→Nva replacement at position 8 and/or a triple Gln→Glu(OMe) replacement at positions 5, 6, and 9 (Etn=Cα‐ethylnorvaline, Aib=α‐aminoisobutyric acid, Nva=norvaline). Conformation analysis, performed by FT‐IR absorption, NMR, and CD techniques, strongly supports the view that the six terminally blocked decapeptides are highly helical in solution. Helix topology and amphiphilic character are responsible for their remarkable membrane activity. At position 8 the combination of high hydrophobicity and Cα tetrasubstitution, as in the Etn‐containing LP237‐F8 metabolite, has a positive effect on membrane interaction.
Cofactor Recycling Mechanism in Asymmetric Biocatalytic Reduction of Carbonyl Compounds Mediated by Yeast: Which is the Efficient Electron Donor?
Authors: Zhang Ben‐Li , Pionnier Sébastien
Published: July 2003

In asymmetric reduction of carbonyl compounds mediated by microorganisms, the cofactors that transfer hydride should be regenerated by using a recycling system. In most cases, this recycling system consists of carbohydrate molecules, especially glucose or sucrose. Other molecules such as ethanol and acetate have been used as electron donors too. The reduction can even be conducted without added electron donors. To improve biocatalytic synthesis, it is important to understand the cofactor recycling mechanism. In this work, the hydride‐transfer mechanism in cofactor regeneration, which takes place in bioreduction mediated by yeast, was studied by means of an isotope tracing technique. The results show that, when glucose was used, the NADH involved in the glycolysis was consumed directly in the formation of ethanol and was not used in the bioreduction. Hence, the regeneration of cofactors in the reduction is not coupled with glycolysis. Nevertheless, glucose is an efficient electron donor that transfers hydride through the hexose monophosphate (HMP) pathway in which the main hydrogen source is C‐1 and C‐3 hydrogen of glucose. Ethanol is not a good electron donor, since, when it was used, only a small quantity of hydrogen was transferred from this molecule, and the main hydrogen source was water. Therefore, the ethanol oxidation pathway may not be efficient. In the absence of added auxiliary substrates, the yeast cells may use electron donors stored in its cellules. However, in this case we observed that the main hydrogen source for cofactor recycling was water, while only very few hydrogen atoms were from unexchangeable sites. This is similar to the case in which ethanol is used, and is in contradiction with the HMP pathway if stored glucose was the electron donor. The question that remains to be investigated is “what is the efficient electron donor recycling mechanism in the yeast cellules?”
Formation of Dinuclear Titanium and Zirconium Complexes by Olefin Metathesis—Catalytic Preparation of Organometallic Catalyst Systems
Authors: Cano Sierra Jesus , Hüerländer Doris , Hill Michael , Kehr Gerald , Erker Gerhard , Fröhlich Roland
Published: July 2003

The titanium complex [(C5H4allyl)TiCl3] (2) undergoes olefin metathesis coupling when treated with 3 mol % of [Cl2(L1)(L2)RuCHPh] (L1=L2=PCy3, 4 a; L1=PCy3, L2=(H2IMes), 4 b) to yield the dimetallic complex [Cl3Ti(C5H4)‐CH2CHCHCH2‐(C5H4)TiCl3] (5). The allyl‐substituted titanocene complex [Cp(C5H4allyl)TiCl2] (3) analogously yields the dimetallic system 6 when treated with 4. The ansa‐zirconocene complex [Me2Si(C5H4)(C5H3allyl)ZrCl2] (7) cleanly yields the analogous dimetallic coupling product 8 (>95 % isomerically pure), when treated with catalytic amounts of 4 b in toluene. Complex 8 gives an active homogeneous ethene or propene polymerization catalyst, especially at elevated temperatures, when treated with excess methylalumoxane.
Synthesis and Solid‐State Organization of Coil–Ring–Coil Block Copolymers
Authors: Rosselli Silvia , Ramminger Anne‐Désirée , Wagner Thomas , Lieser Günter , Höger Sigurd
Published: July 2003

Shape‐persistent macrocycles based on the phenyl‐ethynyl‐butadienyl backbone containing two extraannular hydroxyl groups were prepared by the oxidative coupling of the appropriate phenylethynyl oligomers. Carbodiimide‐directed coupling with independently synthesized polystyrene carboxylic acid oligomers led to ABA coil–ring–coil block copolymers in which the central macrocycle serves as rigid and the polystyrene oligomers as flexible elements. Depending on the size of the coil blocks, these structures aggregate in cyclohexane into supramolecular hollow cylindrical brushes in which the rigid core is surrounded by the flexible matrix. However, in the solid state it is not possible to identify a morphology in which isolated channels based on aggregated macrocycles are embedded in a matrix of polystyrene. Detailed X‐ray and electron diffraction studies on samples prepared from a solution in cyclohexane under equilibrium conditions show that the material adopts a lamellar morphology in the solid state in which columns of macrocycles are aggregated into layers which are separated by polystyrene.
The Synthesis of Acid‐ and Base‐Labile Lipopeptides on Solid Support
Authors: Ludolph Björn , Waldmann Herbert
Published: July 2003

Lipidated peptides, including characteristic partial structures of human Ras proteins, were synthesized by means of a new solid‐phase technique in 22–68 % yield. This technique gives access to farnesylated, palmitoylated, and doubly lipidated peptides as methyl esters or carboxylic acids carrying a fluorescent tag or a maleimide moiety for coupling to proteins. The peptide backbones were built up on the resin by using 9‐fluorenylmethoxycarbonyl chemistry together with the oxidatively cleavable hydrazide linker. As a key step, the acid‐labile farnesyl and basic‐labile palmitoyl lipid groups were introduced onto the resin after the cleavage of appropriate acid‐ or reduction‐sensitive protecting groups from the cysteine residues. Optional introduction of different fluorescent tags or a maleimide group into the peptide was followed by release of the resin‐bound target peptide as the methyl ester or carboxylic acid by very mild copper(II)‐mediated oxidation in slightly acidic or basic media. This new methodology should substantially facilitate the access to lipidated peptides for the study of important biological phenomena like biological signal transduction, localization, and vesicular transport.
Characteristics of Organic Transformations in a Confined Dendritic Core: Studies on the AIBN‐Initiated Reaction of Dendrimer Cobalt(II) Porphyrins with Alkynes
Authors: Uyemura Makoto , Aida Takuzo
Published: July 2003

Cobalt(II) complexes of poly(aryl ester) dendrimer porphyrins [(m‐[Gn]TPP)CoII] (generation number n=0–4), in the presence of azobisisobutyronitrile (AIBN) at 60 °C, underwent alkenylation with several alkynes at the metal center. A complete inhibition of double‐bond migration (secondary transformation) was observed for [(m‐[Gn]TPP)CoII] (n=3 and 4), which gave [(m‐[Gn]TPP)CoIIIC(CH2)R] (n=3 and 4) exclusively. Overall reaction rates for [(m‐[Gn]TPP)CoII] (n=0–3) were hardly dependent on the size of the dendritic substituents, while a notable retardation was observed for the largest dendrimer, [(m‐[G4]TPP)CoII]. Mechanistic studies on double‐bond migration with pure [(m‐[Gn]TPP)CoIIIC(CH2)Bu] (n=0–4) demonstrated that the secondary transformation involves participation of [(m‐[Gn]TPP)CoIIIH] (n=0–4), derived from [(m‐[Gn]TPP)CoII] and AIBN, rather than [(m‐[Gn]TPP)CoII] alone. Crossover experiments using [(m‐[Gn]TPP)CoIIIC(CH2)Bu] (n=2–4), in combination with nondendritic [(m‐[G0]TPP)CoII] and AIBN, indicated a high level of steric protection of the active center by a robust [G4]‐dendritic cage, as suggested by a 1H NMR pulse relaxation time profile of m‐[G4]TPPH2.