bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thalidomide-Induced Sinus Bradycardia
Authors: Kaur Amandeep , Yu Susan S , Lee Audrey J , Chiao Teresa B 
Published: May 2003

OBJECTIVE: To report a case of thalidomide-induced sinus bradycardia in an elderly man. CASE SUMMARY: A 72-year-old white man, with transfusion-dependent refractory anemia with ringed sideroblasts and hypertension treated with atenolol, was started on thalidomide 100 mg at bedtime. During the dose titration period (maximum dose 400 mg/d), his heart rate decreased from a baseline of 63 beats/min to as low as 44 beats/min with positive electrocardiogram findings of sinus bradycardia. After discontinuation of atenolol, the patient's heart rate increased to 68 beats/min, but symptoms of bradycardia persisted. Due to the patient's continued dizziness and lightheadedness, thalidomide was discontinued. In the 3 months following discontinuation of thalidomide, the patient's heart rate increased to an average of 74 beats/min. DISCUSSION: Clinical trials and postmarketing surveillance suggest that the incidence of thalidomide-induced bradycardia is low. The mechanism of this effect is unknown. Concurrent medications affecting the heart rate may also increase the risk of thalidomide-induced bradycardia. Following titration of thalidomide to a maximum dose of 400 mg/d, our patient's heart rate decreased markedly, resulting in intermittent symptoms of lightheadedness and dizziness. He may have been at higher risk of thalidomide-induced bradycardia because of concurrent administration of atenolol. An objective causality assessment revealed that the adverse event was probable. CONCLUSIONS: Despite the low incidence of thalidomide-induced bradycardia, it appears to be an important adverse effect, particularly in patients with comorbidities or concurrent medications that decrease heart rate. Therefore, providers should monitor these patients closely for signs and symptoms of bradycardia during the administration of thalidomide.
Chemical Neuroimmunology: Health in a Nutshell Bidirectional Communication between Immune and Stress (Limbic‐Hypothalamic‐Pituitary‐Adrenal) Systems
Authors: Lozovaya Natalya , Miller Andrew D. 
Published: June 2003

AbstractStress is a ubiquitous and pervasive part of modern life that is frequently blamed for causing a plethora of diseases and other discomforting medical conditions. All higher organisms, including humans, experience stress in the form of a wide variety of stressors that range from environmental pollutants and drugs to traumatic events or self‐induced trauma. Stressors registered by the central nervous system (CNS) generate physiological stress responses in the body (periphery) by means of the limbic‐hypothalamic‐pituitary‐adrenal (LHPA) axis. This LHPA axis operates through the use of chemical messengers such as the stress hormones corticotropin‐releasing hormone (CRH) and glucocorticoids (GCs). Under conditions of frequent exposure to acute stress and/or chronic, long‐term exposure to stress, the LHPA axis becomes dysfunctional and in the process frequently overproduces both CRH and GCs, which results in many mild to severely toxic side effects. Bidirectional communication between the LHPA axis and immune/inflammatory systems can dramatically potentiate these side effects and create environments in the CNS and periphery ripe for the triggering and/or promotion of tissue degeneration and disease. This review aims to present as far as possible a molecular view of the processes involved so as to provide a bridge from the diffuse range of studies on molecular structure and receptor interactions to the burgeoning biological and medical literature that describes the empirical interplay between stress and disease. We hope that our review of this fast‐growing field, which we christen chemical neuroimmunology, will give a clear indication of the striking range and depth of current molecular, cellular and medical evidence linking stress hormones to degeneration and disease. In so doing, we hope to provide encouragement for others to become interested in this critical and far‐reaching field of research, which is very much at the heart of many important disease processes and very much a critical part of the crucial interface between chemistry and biology.
A Molecular Mechanism of Enantiorecognition of Tertiary Alcohols by Carboxylesterases
Authors: Henke Erik , Bornscheuer Uwe T. , Schmid Rolf D. , Pleiss Jürgen 
Published: June 2003

AbstractCarboxylesterases containing the sequence motif GGGX catalyze the hydrolysis of esters of chiral tertiary alcohols, albeit with only low to moderate enantioselectivity, for three model substrates (linalyl acetate, methyl‐1‐pentin‐1‐yl acetate, 2phenyl‐3‐butin‐2‐yl acetate). In order to understand the molecular mechanism of enantiorecognition and to improve enantioselectivity for this interesting substrate class, the interaction of both enantiomers with the substrate binding sites of acetylcholinesterases and p‐nitrobenzyl esterase from Bacillus subtilis was modeled and correlated to experimental enantioselectivity. For all substrate–enzyme pairs, enantiopreference and ranking by enantioselectivity could be predicted by the model. In p‐nitrobenzyl esterase, one of the key residues in determining enantioselectivity was G105: exchange of this amino acid for an alanine residue led to a sixfold increase of enantioselectivity (E=19) towards 2phenyl‐3‐butin‐2‐yl acetate. However, the effect of this mutation is specific: the same mutant had the opposite enantiopreference towards the substrate linalyl acetate. Thus, depending on the substrate structure, the same mutant has either increased enantioselectivity or opposite enantiopreference compared to the wild‐type enzyme.
Mollusk Shell Acidic Proteins: In Search of Individual Functions
Authors: Gotliv Bat‐Ami , Addadi Lia , Weiner Steve 
Published: June 2003

AbstractAcidic proteins play a major role in the biomineralization process. These proteins are generally thought to control mineral formation and growth. Thus, characterization of individual acidic proteins is important as a first step toward linking function to individual proteins, which is our ultimate goal. In order to characterize the protein(s) responsible for the assemblage of biominerals, a new gel electrophoresis fixing and staining protocol was developed and many, if not all of the acidic proteins were visualized on the gel for the first time. In an in vitro assay we show that proteins extracted from an aragonitic shell layer induce the formation of amorphous calcium carbonate prior to its transformation into the aragonitic crystalline form. This study removes some major obstacles in the characterization of acidic proteins and sheds more light on the functions of these proteins in the biomineralization process.
One‐Pot TiO2‐Catalyzed Synthesis of Nucleic Bases and Acyclonucleosides from Formamide: Implications for the Origin of Life
Authors: Saladino Raffaele , Ciambecchini Umberto , Crestini Claudia , Costanzo Giovanna , Negri Rodolfo , Di Mauro Ernesto 
Published: June 2003

AbstractA novel one‐pot TiO2‐catalyzed synthesis of nucleobases and acyclonucleosides from formamide is reported. Since formamide can be formed under prebiotic conditions, these reactions have implications for the origin of life. While a number of purine derivatives have been found as products of non‐TiO2‐catalyzed reactions, important compounds that would not otherwise occur (namely, thymine, 5hydroxymethyluracil, and acyclonucleosides) are formed in acceptable yields by TiO2‐catalyzed reactions. Moreover, TiO2 selectively affects the rates of degradation of nucleobases, as single units and when embedded in polynucleotides.
Cover Picture: Selective Protein Degradation by Ligand‐Targeted Enzymes: Towards the Creation of Catalytic Antagonists (ChemBioChem 6/2003)
Authors: Davis Benjamin G. , Sala Rafael F. , Hodgson David R. W. , Ullman Astrid , Khumtaveeporn Kanjai , Estell David A. , Sanford Karl , Bott Richard R. , Jones J. Bryan 
Published: June 2003

AbstractThe cover picture shows a ligand‐targeted proteinase enzyme or “catalytic antagonist” acting as a molecular angler fish: By precisely positioning different binding ligands (L) around the active site “mouth” of a degradative proteinase enzyme, target proteins (TP) can be plucked from solution, locked in position adjacent to the catalytic triad “jaws”, and in this way readily and specifically degraded. The hunting strategy of the deep sea angler fish, which uses a lure above its mouth, illustrates this principle. Further details can be found in the article by B. Davis, R. R. Bott, J. B. Jones et. al. on pp. 533–537.
Synthesis and Properties of [CoCp*(2,5‐PC4tBu2H2)]: The First Monophosphacobaltocene
Authors: Burney Claire , Carmichael Duncan , Forissier Kareen , Green Jennifer C. , Mathey François , Ricard Louis 
Published: June 2003

AbstractThe reduction of the phosphacobaltocenium salt [CoCp*(2,5‐PC4tBu2H2)]+[BPh4]− (3; Cp*=pentamethylcyclopentadienyl) by magnesium in tetrahydrofuran (THF) furnishes the stable air‐sensitive phosphacobaltocene [CoCp*(2,5‐PC4tBu2H2)] (4) in yields of up to 80 %. The crystal structure of 4 shows long CoCα and short CαCβbonds in the phospholyl ligand, consistent with a semi‐occupied molecular orbital (SOMO) having a″ symmetry. A combined Amsterdam density functional (ADF)/photoelectron spectroscopic study, which confirms this assignment, gives ionisation energies (IE) of 5.02 eV from the SOMO and 8.89 eV from the phosphorus “lone pair”. A comparison of cyclovoltammograms for 3 and the corresponding cyclopentadienyl complex [CoCp*(1,3‐C5tBu2H3)]+ [BPh4]− (5) shows that replacing a CH group by an sp2 phosphorus atom results in an anodic first reduction potential shift of 0.29 V.
Interplay between Solvent and Counteranion Stabilization of Highly Unsaturated Rhodium(III) Complexes: Facile Unsaturation‐Induced Dearomatization
Authors: Gandelman Mark , Konstantinovski Leonid , Rozenberg Haim , Milstein David 
Published: June 2003

AbstractAbstraction of the chloride ligand from the PCN‐based chloromethylrhodium complex 2 by AgX (X=BF4−, CF3SO3−) or a direct C–C cleavage reaction of the PCN ligand 1 with [(coe)2Rh(solv)n]+X− (coe=cyclooctene) lead to the formation of the coordinatively unsaturated rhodium(III) complexes 3. Compound 3 a (X=BF4−) exhibits a unique medium effect; the metal center is stabilized by reversible coordination of the bulky counteranion or solvent as a function of temperature. Reaction of [(PCN)Rh(CH3)(Cl)] with AgBArf in diethyl ether leads to an apparent rhodium(III) 14‐electron complex 4, which is stabilized by reversible, weak coordination of a solvent molecule. This complex coordinates donors as weak as diethyl ether and dichloromethane. Upon substitution of the BF4− ion in [(PCN)Rh(CH3)]BF4 by the noncoordinating BArf− ion in a noncoordinating medium, the resulting highly unsaturated intermediate undergoes a 1,2‐metal‐to‐carbon methyl shift, followed by β‐hydrogen elimination, leading to the Rh‐stabilized methylene arenium complex 5. This process represents a unique mild, dearomatization of the aromatic system induced by unsaturation.
Photoinduced Electron Transfer between the Interlocked Components of Porphyrin Catenanes: Effect of the Presence of Nonequivalent Reduction Sites on the Charge Recombination Rate
Authors: Flamigni Lucia , Talarico Anna Maria , Serroni Scolastica , Puntoriero Fausto , Gunter Maxwell J. , Johnston Martin R. , Jeynes Tyrone P. 
Published: June 2003

Abstract[2]Catenanes made up of several polyether‐strapped porphyrin macrocycles interlinked with the cyclic electron acceptor cyclobis(paraquat‐p‐phenylene) were spectroscopically, photophysically, and electrochemically characterized. The catenanes exhibit very rich redox behavior due to the presence of several different and interacting electro‐active subunits. The redox patterns represent useful “fingerprints” that provide detailed information on the electronic interactions and the chemical environments that the electroactive subunits experience in the supramolecular arrays. A photoinduced electron transfer from the porphyrin excited state (charge separation CS) occurs with τ=20 ps in the catenanes with a larger strap and faster than 20 ps (instrumental resolution) in the catenanes with a shorter strap. The resulting charge‐separated state recombines to the ground state (charge recombination CR) with lifetimes similar in all cases, 41±4 ps. Comparison of the electron transfer rates CS and CR in the host–guest complexes of the same porphyrins with the noncyclic electron acceptor paraquat, indicate slower reactions in the [2]catenanes. This behavior is assigned to the different separation between reacting partners determined by the type of bond (weak interaction or mechanical) and to a two‐step consecutive electron transfer to different sites of the macrocyclic electron acceptor in the catenanes which retards charge recombination.
The 1Δg Dioxygen Ene Reaction with Propene: A Density Functional and Multireference Perturbation Theory Mechanistic Study
Authors: Maranzana Andrea , Ghigo Giovanni , Tonachini Glauco 
Published: June 2003

AbstractThis study aims to determine whether a balance between concerted and non‐concerted pathways exists, and in particular to ascertain the possible role of diradical/zwitterion or peroxirane intermediates. Three non‐concerted pathways, via 1) diradical or 2) peroxirane intermediates, and 3) by means of hydrogen‐abstraction/radical recoupling, plus one concerted pathway (4), are explored. The intermediates and transition structures (TS) are optimized at the DFT(MPW1K), DFT(B3LYP) and CASSCF levels of theory. The latter optimizations are followed by multireference perturbative CASPT2 energy calculations. 1) The polar diradical forms from the separate reactants by surmounting a barrier (ΔE${^{\ne }_{{\rm MPW}1{\rm K}}}$=12, ΔE${^{\ne }_{{\rm B}3{\rm LYP}}}$=14, and ΔE${^{\ne }_{{\rm CASPT}2}}$=16 kcal mol−1 and can back‐dissociate through the same TS, with barriers of 11 (MPW1K) and 8 kcal mol−1 (B3LYP and CASPT2). The diradical to hydroperoxide transformation is easy at all levels (ΔE${^{\ne }_{{\rm MPW}1{\rm K}}}$<4, ΔE${^{\ne }_{{\rm B}3{\rm LYP}}}$=1 and ΔE${^{\ne }_{{\rm CASPT}2}}$=1 kcal mol−1). 2) Peroxirane is attainable only by passing through the diradical intermediate, and not directly, due to the nature of the critical points involved. It is located higher in energy than the diradical by 12 kcal mol−1, at all theory levels. The energy barrier for the diradical to cis‐peroxirane transformation (ΔE≠=14–16 kcal mol−1) is much higher than that for the diradical transformation to the hydroperoxide. In addition, peroxirane can very easily back‐transform to the diradical (ΔE≠<3 kcal mol−1). Not only the energetics, but also the qualitative features of the energy hypersurface, prevent a pathway connecting the peroxirane to the hydroperoxide at all levels of theory. 3) The last two‐step pathway (hydrogen‐abstraction by 1O2, followed by HOO‐allyl radical coupling) is not competitive with the diradical mechanism. 4) A concerted pathway is carefully investigated, and deemed an artifact of restricted DFT calculations. Finally, the possible ene/[π2+π2] competition is discussed.
Palladium(0)‐Catalyzed Intramolecular [2+2+2] Alkyne Cyclotrimerizations with Electron‐Deficient Diynes and Triynes
Authors: Yamamoto Yoshihiko , Nagata Asako , Nagata Hitomi , Ando Yoji , Arikawa Yasuhiro , Tatsumi Kazuyuki , Itoh Kenji 
Published: June 2003

AbstractIn the presence of 2.5 mol % of [Pd2(dba)3] (dba=dibenzylideneacetone) and 5 mol % of PPh3, nearly equimolar amounts of dimethyl nona‐2,7‐diyne‐1,9‐dioate derivatives (diyne diesters) and dialkyl acetylenedicarboxylates were allowed to react in toluene at 110 °C to afford [2+2+2] cycloadducts in moderate‐to‐good yields. Similarly, dimethyl trideca‐2,7,12‐triyne‐1,13‐dioate derivatives (triyne diesters) were catalytically transformed into phthalic acid ester analogues in excellent yields. To gain insight into the mechanism of these intramolecular alkyne cyclotrimerizations, stoichiometric reactions of [Pd2(dba)3] with a diyne diester and a triyne diester bearing ether tethers were conducted in acetone at room temperature to furnish an oligomeric bicyclopalladacyclopentadiene and a Pd0 triyne complex, respectively. The structures of these novel complexes were unequivocally determined by Xray structure analysis. The isolated triyne complex was heated at 50 °C or treated with PPh3 in acetone at room temperature to afford the arene product. Furthermore, the same complex catalyzed the triyne cyclization with or without PPh3.
Columnar Mesomorphism from Hemi‐Disklike Metallomesogens Derived from 2,6‐Bis[3′,4′,5′‐tri(alkoxy)phenyliminomethyl]pyridines (L): Crystal and Molecular Structures of [M(L)Cl2] (M=Mn, Ni, Zn)
Authors: Morale Francesca , Date Richard W. , Guillon Daniel , Bruce Duncan W. , Finn Rachel L. , Wilson Claire , Blake Alexander J. , Schröder Martin , Donnio Bertrand 
Published: June 2003

AbstractFour new series of non‐disklike complexes of general formula [MCl2(Ln)] based upon substituted 2,6‐bis(3′,4′,5′‐trialkoxyphenyliminomethyl)pyridine ligands (Ln) and with M=ZnII, CoII, MnII, and NiII have been prepared and examined for liquid crystallinity. A complete analysis of the thermal behavior by polarized‐light optical microscopy, differential scanning calorimetry, and small‐angle Xray scattering revealed a rich and varied mesomorphism. Moreover, the high thermal stability of the compounds leads to rather extended mesomorphic ranges. The nature and thermal stability of each mesophase depend on both the length of the six terminal alkoxy chains, n (n=8, 10, 12, 14, 16), and on the metal ions. As demonstrated by small‐angle Xray diffraction experiments, the mesomorphism of these complexes is solely of the columnar type. One compound shows an oblique columnar phase, while most of them show a hexagonal columnar phase, Colh, and several types of rectangular columnar phase, Colr. Xray single‐crystal structures obtained for three methoxy derivatives confirm the 1:1 metal–ligand stoichiometry of the complexes, in which the metal is pentacoordinate with a distorted, trigonal bipyramidal geometry. The crystalline structures also reveal the existence of some columnar organization in the solid state, the columns resulting from an alternated stacking of the complexes in one direction. By combining these results with those obtained from dilatometry experiments, a model for the molecular organization within the mesophases is proposed in which an antiparallel arrangement of the metallomesogens is retained in the mesophase.
Electronic Coupling in a Highly Preorganized Bimetallic Complex Comprising Pyrazolate‐Bridged CpMn(CO)2 Moieties
Authors: Röder Jens C. , Meyer Franc , Hyla‐Kryspin Isabella , Winter Rainer F. , Kaifer Elisabeth 
Published: June 2003

AbstractBy means of a multistep synthetic procedure a dimanganese complex has been prepared, in which a N,N′‐bridging pyrazolate ligand spans two CpMn(CO)2 subunits in a highly preorganized chelate arrangement. The Xray crystallographic analyses of the MnIMnI complex K+1− and of its non‐chelate precursor complex elucidate details of the molecular structure, in particular an unusual pyrazolate binding mode in the solid state and intertwining of the CO ligands in the crowded bimetallic array 1−. The MnIMnI compound (1−), the mixed‐valent MnIMnII (1), and the oxidized MnIIMnII form (1+) have been characterized by various analytical and spectrosopic methods, such as electrochemistry, variable‐temperature EPR spectroscopy, IR spectroelectrochemistry, and UV/Vis/NIR spectroelectrochemistry as well as by DFT and TD‐DFT calculations. Strong electronic coupling in the mixed‐valent complex is observed, but time‐ (and temperature‐) dependent valence detrapping occurs, thus placing 1 in class II according to the Robin and Day assignment, close to the class II/III transition. From variable‐temperature EPR spectroscopy a rough estimate of the activation energy and rate for thermal electron transfer can be deduced, with Eth≠=13.6 kJ mol−1 and kth=2.6×1010 s−1 at 298 K. Unexpectedly, no intervalence CT transition for 1 is detected in solution, but one appears in the optical spectrum of solid 1. The conclusions drawn from experiments are fully supported by DFT calculations that were carried out for all three forms of the dimanganese complex. A broken symmetry treatment for mixed‐valent 1 reveals almost perfect localization of both spin and charge on one Mn center. According to TD‐DFT the first excited states of 1 give rise to the IT processes in the NIR‐energy region, as observed in the solid‐state spectrum. The HOMOs are located at the Mn ions and are favorably arranged for π interactions with the bridging pyrazolate.
Rhodium(I) and Rhodium(III) Complexes Formed by Coordination and CH Activation of Bulky Functionalized Phosphanes
Authors: Canepa Giuseppe , Brandt Carsten D. , Ilg Kerstin , Wolf Justin , Werner Helmut 
Published: June 2003

AbstractThe reaction of [{RhCl(C8H14)2}2] (2) with iPr2PCH2CH2C6H5 (L1) led, via the isolated dimer [{RhCl(C8H14)(L1)}2] (3), to a mixture of three products 4 a–c, of which the dinuclear complex [{RhCl(L1)2}2] (4 a) was characterized by Xray crystallography. The mixture of 4a–c reacts with CO, ethene, and phenylacetylene to give the square‐planar compounds trans‐[RhCl(L)(L1)2] (L=CO (5), C2H4 (6), CCHPh (9)). The corresponding allenylidene(chloro) complex trans‐[RhCl(CCCPh2)(L1)2] (11), obtained from 4 a–c and HCCC(OH)Ph2 via trans‐[RhCl{CCHC(OH)Ph2}(L1)2] (10), could be converted stepwise to the related hydroxo, cationic aqua, and cationic acetone derivatives 12—14, respectively. Treatment of 2 and [{RhCl(C2H4)2}2] (7) with two equivalents of tBu2PCH2CH2C6H5 (L2) gave the dimers [{RhCl(C8H14)(L2)}2] (15) and [{RhCl(C2H4)(L2)}2] (16), which both react with L2 in the molar ratio of 1:2 to afford the five‐coordinate aryl(hydrido)rhodium(III) complex [RhHCl(C6H4CH2CH2PtBu2‐κ2C,P)(L2)] (17) by CH activation. The course of the reactions of 17 with CO, H2, PhCCH, HCl, and AgPF6, leading to the compounds 19–21, 24, and 25 a, respectively, indicate that the coordinatively unsaturated isomer of 17 with the supposed composition [RhCl(L2)2] is the reactive species. Labeling experiments using D2, DCl, and PhCCD support this proposal. With either [Rh(C8H14)(η6‐L2‐κP]PF6 or [Rh(C2H4)(η6‐Ln‐κP]PF6 (n=1 and 2) as the starting materials, the corresponding halfsandwich‐type complexes 27, 28, and 32 were obtained. The nonchelating counterpart of the dihydrido compound 32 with the composition [RhH2(PiPr3)(η6‐C6H6)]PF6 (35) was prepared stepwise from [Rh(C2H4)(PiPr3)(η6‐C6H6)]PF6 and H2 in acetone via the tris(solvato) species [RhH2(PiPr3)(acetone)3]PF6 (34) as intermediate. The synthesis of the bis(chelate) complex [Rh(η4‐C8H12)(C6H5OCH2CH2PtBu2‐κ2O,P)]BF4 (39) is also described. Besides 4 a, the compounds 17, 25 a, and 39 have been characterized by Xray crystal structure analysis.
Reaction of Enol Ethers with Alkynes Catalyzed by Transition Metals: 5exo‐digversus 6endo‐digCyclizations via Cyclopropyl Platinum or Gold Carbene Complexes
Authors: Nevado Cristina , Cárdenas Diego J. , Echavarren Antonio M. 
Published: June 2003

AbstractThe intramolecular reaction of enol ethers with alkynes in methanol is catalyzed by electrophilic PtII, PdII, and AuIIIchlorides and by a CuIcomplex to give five‐ or six‐membered rings bearing dimethyl acetals. The reaction takes place by anantiaddition of the enol ether and the metal to the alkyne. The possible involvement of vinylidene complexes in this reaction is excluded. In addition to the usual 5exo‐dig(or 6exo‐dig) pathways, a 6endo‐digpathway has also been found to take place with certain enynes. One case of 5endo‐digcyclization has also been found. A general scheme for the alkoxycyclization of enynes catalyzed by transition metals based on DFT calculation of PtCl2and AuCl3complexes that includesexoandendocyclizations is presented.