bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of α‐Nitro‐α‐diazocarbonyl Derivatives and Their Applications in the Cyclopropanation of Alkenes and in OH Insertion Reactions
Authors: Charette André B. , Wurz Ryan P. , Ollevier Thierry
Published: January 2003

A facile and highly efficient method for the preparation of α‐nitro‐α‐diazocarbonyl derivatives by a diazo‐transfer reaction involving (trifluoromethyl)sulfonyl azide has been developed. These substrates undergo a rhodium‐catalyzed cyclopropanation reaction with a variety of alkenes. A systematic study of the reaction indicated that the diastereoselectivity of the cyclopropanation could be effectively controlled through the modification of the steric bulk of the diazo reagent. A novel OH insertion reaction of the metalcarbene complex derived from the α‐nitro‐α‐diazocarbonyl reagent afforded the corresponding novel α‐nitro‐α‐alkoxy carbonyl derivatives.
Toward an Understanding of the Chemical Etiology for DNA Minor‐Groove Recognition by Polyamides
Authors: Marques Michael A. , Doss Raymond M. , Urbach Adam R. , Dervan Peter B.
Published: January 2003

Crescent‐shaped polyamides composed of aromatic amino acids, i.e., 1‐methyl‐1H‐imidazole Im, 1‐methyl‐1H‐pyrrole Py, and 3‐hydroxy‐1H‐pyrrole Hp, bind in the minor groove of DNA as 2 : 1 and 1 : 1 ligand/DNA complexes. DNA‐Sequence specificity can be attributed to shape‐selective recognition and the unique corners or pairs of corners presented by each heterocycle(s) to the edges of the base pairs on the floor of the minor groove. Here we examine the relationship between heterocycle structure and DNA‐sequence specificity for a family of five‐membered aromatic amino acids. By means of quantitative DNase‐I footprinting, the recognition behavior of polyamides containing eight different aromatic amino acids, i.e., 1‐methyl‐1H‐pyrazole Pz, 1H‐pyrrole Nh, 5‐methylthiazole Nt, 4‐methylthiazole Th, 3‐methylthiophene Tn, thiophene Tp, 3‐hydroxythiophene Ht, and furan Fr, were compared with the polyamides containing the parent‐ring amino acids Py, Im, and Hp for their ability to discriminate between the four WatsonCrick base pairs in the DNA minor groove. Analysis of the data and molecular modeling showed that the geometry inherent to each heterocycle plays a significant role in the ability of polyamides to differentiate between DNA sequences. Binding appears sensitive to changes in curvature complementarity between the polyamide and DNA. The Tn/Py pair affords a modest 3‐fold discrimination of T⋅A vs. A⋅T and suggests that an S‐atom in the thiophene ring prefers to lie opposite T not A.
Lewis Base Catalyzed Aldol Reaction of Trimethylsilyl Enolates with Aldehydes
Authors: Mukaiyama Teruaki , Fujisawa Hidehiko , Nakagawa Takashi
Published: January 2003

A new Lewis base catalyzed aldol reaction of trimethylsilyl enolates with aldehydes is established in DMF or pyridine solvent by using a Lewis base such as lithium diphenylamide (Tables 4 and 5) or lithium 2‐pyrrolidone (Tables 6–8). The effect of solvent suggests that this reaction proceeds via the pentacoordinated hypervalent silicate generated by the coordination of the above Lewis base to a trimethylsilyl enolate. Successive coordination of the solvent to the thus‐formed pentacoordinated silicate leads to an active enolate intermediate having hexacoordinated silicate, which, in turn, attacks carbonyl compounds to form the desired aldols (Scheme 5).
The Development of a Convergent and Efficient Enantioselective Synthesis of the Bengamides via a Common Polyol Intermediate
Authors: Boeckman, Jr. Robert K. , Clark Tammy J. , Shook Brian C.
Published: January 2003

An efficient, general synthetic route to the bengamide family of antitumor agents from a common polyol thioester is described. Consecutive aldol condensations afford the protected polyol thioester side chain suitable for coupling to the bengamides. A novel chiral‐phase‐transfer‐catalyzed enantioselective alkylation affords the properly functionalized caprolactams required for the synthesis of more‐complex members of the bengamide family. Use of the methyl 2‐naphthyl ether protecting group, compatible with the boron Lewis acids required for enantioselective aldol condensation, allows direct access to all the bengamides.
Synthesis of Cyclic Peptides by Photochemical Decarboxylation of N‐Phthaloyl Peptides in Aqueous Solution
Authors: Griesbeck Axel G. , Heinrich Thomas , Oelgemöller Michael , Molis Arne , Heidtmann Axel
Published: January 2003

The synthesis of a variety of cyclic peptides from N‐phthaloyl‐protected di‐, tri‐, tetra‐, and pentapeptides with different aminocarboxylic acid tethers by photodecarboxylation – initiated by intramolecular electron transfer – has been explored in aqueous media. The progress and the chemoselectivity of the follow‐up processes after CO2 extrusion were traced by the respective pH/time‐profiles, as well as by the overall change in pH after completion of the reaction. The competition between cyclization and simple oxidative decarboxylation depends on spacer length and geometry, H‐bonding interaction between the electron accepting phthalimide CO groups and amide H‐atoms, as well as the geometric reorganization coupled with the radical combination step and the formation of the lactam rings. With progressing reaction, hydrolysis of the phthalimide chromophore becomes an increasingly important side reaction due to the constant increase in pH. The use of phosphate‐buffered aqueous media consequently improved the cyclization yields. The ground‐state interactions between amide groups and the terminal COO− group with the imide CO groups were studied for the model system [N‐(phthaloyl)glycyl]sarcosine (1) by NMR spectroscopy where the amide (E/Z)‐equilibrium depends on the presence of carboxylate vs. free carboxylic acid, demonstrating the role of H‐bonding and metal coordination.
Rationale for active vitamin D and analogs in the treatment of osteoporosis
Authors: Nishii Yasuho
Published: January 2003

In 1981, Chugai Pharmaceutical succeeded in marketing alfacalcidol, a prodrug of calcitriol, as a therapeutic agent for renal osteodystrophy. In 1983, Chugai succeeded in extending the application of alfacalcidol to the treatment of osteoporosis as well. Clinicians in Japan have accepted alfacalcidol as a remedy for osteoporosis. However, the use of calcitriol and its analogs for the treatment of osteoporosis is still controversial. Some misunderstandings exist internationally about the efficacy of the active form of vitamin D for the treatment of osteoporosis. It is important to emphasize that patients with osteoporosis have intestinal calcium malabsorption and dysfunction in renal activation of vitamin D. When massive doses of parent vitamin D were administered to OVX rats, bone mass increased, but surprisingly, many porotic area were observed in the cortical bone. On the other hand, administration of alfacalcidol increased physiological bone without porotic observation. It is necessary to give the active form of vitamin D, D‐hormone, with an RDA‐equivalent supply of calcium. Alfacalcidol forms physiological strong bones that are hardly fractured by regulating calcium and bone metabolism. We proposed a new vitamin D analog, 2β (3‐hydroxypropoxy)calcitriol [ED‐71] as a therapeutic drug for osteoporosis, which is more potent than calcitriol. ED‐71 is now being investigated in phase 2 clinical studies in Japan. ED‐71 will appear as more improved drugs for osteoporosis until 2010. J. Cell. Biochem. 88: 381–386, 2003. © 2002 Wiley‐Liss, Inc.
A new active vitamin D analog, ED‐71, causes increase in bone mass with preferential effects on bone in osteoporotic patients
Authors: Kubodera N. , Tsuji N. , Uchiyama Y. , Endo K.
Published: January 2003

As a candidate for active vitamin D analogs that have selective effects on bone, 1α,25‐dihydroxy‐2β‐(3‐hydroxypropoxy)vitamin D3 (ED‐71) has been synthesized and is currently under clinical trials. In ovariectomized rat model for osteoporosis, ED‐71 caused an increase bone mass at the lumbar vertebra to a greater extent than 1α‐hydroxyvitamin D3 (alfacalcidol), while enhancing calcium absorption and decreasing serum parathyroid hormone levels to the same degree as alfacalcidol. ED‐71 lowered the biochemical and histological parameters of bone resorption more potently than alfacalcidol, while maintaining bone formation markers.An early phase II clinical trial was conducted with 109 primary osteoporotic patients. The results indicate that oral daily administration of ED‐71 (0.25, 0.5, 0.75, and 1.0 μg) for 6 months increased lumbar bone mineral density in a dose‐dependent manner without causing hypercalcemia and hypercalciuria. ED‐71 also exhibited a dose‐dependent suppression of urinary deoxypyridinoline with no significant reduction in serum osteocalcin. These results demonstrate that ED‐71 has preferential effects on bone with diminished effects on intestinal calcium absorption. ED‐71 offers potentially a new modality of therapy for osteoporosis with selective effects on bone. J. Cell. Biochem. 88: 286–289, 2003. © 2002 Wiley‐Liss, Inc.
Conventional and tissue‐specific inactivation of the 25‐hydroxyvitamin D‐1α‐hydroxylase (CYP27B1)
Authors: St‐Arnaud René , Dardenne Olivier , Prud'homme Josée , Hacking S. Adam , Glorieux Francis H.
Published: January 2003

Mutations in the human 25‐hydroxyvitamin‐D3‐1α‐hydroxylase (CYP27B1) gene cause pseudo vitamin D deficiency rickets (PDDR). The kidney is the main site of expression of the CYP27B1 gene, but expression has been documented in other cell types, including chondrocytes. We engineered a tissue‐specific and a conventional knockout of CYP27B1 in mice. The conventional knockout strain reproduced the PDDR phenotype. Homozygote mutant animals were treated with 1,25(OH)2D3 or fed a high‐calcium diet (2% calcium, 1.25% phosphate, 20% lactose) for 5 weeks post‐weaning. Blood biochemistry revealed that both rescue treatments corrected the hypocalcemia and secondary hyperparathyroidism. Bone histomorphometry confirmed that rickets were cured. The rescue regimen restored the biomechanical properties of the bone tissue. Mice carrying the loxP‐bearing allele were bred to transgenic animals expressing the Cre recombinase in chondrocytes under the control of the collagen type II promoter. Genotyping confirmed excision of exon 8 in chondrocytes. Serum biochemistry revealed that mineral ion homeostasis is normal in mutant animals. Preliminary observation of bone tissue from mutant mice did not reveal major changes to the growth plate. Precise histomorphometric analysis will be required to assess the impact of chondrocyte‐specific inactivation of CYP27B1 on the maturation and function of growth plate cells in vivo. J. Cell. Biochem. 88: 245–251, 2003. © 2002 Wiley‐Liss, Inc.
Morphometry of macaca mulatta forelimb. III. moment arm of shoulder and elbow muscles
Authors: Graham Kirsten M. , Scott Stephen H.
Published: January 2003

The conversion of muscle activity into smooth, purposeful movement of the limb depends complexly on the morphometry of muscles and their mechanical action on the skeleton. Although nonhuman primates are common subjects in motor control experiments (Scott [2000] Can J Physiol Pharmacol 78:923–933), little information is available on the morphometric properties of their upper limbs. One key variable is muscle moment arm, or mechanical advantage, which defines how linear motion or force of a muscle is translated into angular motion or torque at a joint. This study reports moment arm values with respect to joint angle (flexion/extension) of 14 muscles spanning the shoulder and elbow in Macaca mulatta. The magnitude of moment arm values ranged widely across muscles. In some muscles mechanical advantage remained constant with joint angle, whereas the moment arm of others varied strongly. The angle (Θ) at which optimal fascicle length (L) occurred showed strong trends, where the elbow‐spanning muscles had Θ values clustered at mid‐flexion and the shoulder musculature Θ values tended to be grouped around the neutral joint angle of 0°. Estimates of peak muscle torque for flexor and extensor muscle groups at each joint were surprisingly similar in both magnitude and dependency on joint angle. The present study, along with the previous two in this series (Cheng and Scott [2000] J Morphol 245:206–224; Singh et al. [2002] J Morphol 251:323–332), provides a comprehensive description of the morphology of the proximal portion of the limb suitable for the development of a musculoskeletal model of the M. mulatta upper limb. J. Morphol. 255:301–314, 2003. © 2003 Wiley‐Liss, Inc.
Cytological evaluation of spermatogenesis and organization of the germinal epithelium in the male slider turtle, trachemys scripta
Authors: Gribbins Kevin M. , Gist Daniel H. , Congdon Justin D.
Published: January 2003

The germ cell development in the slider turtle (Trachemys scripta) testis was investigated by viewing the histology of the seminiferous epithelium in plastic sections with a light microscope. Germ cell morphologies in the slider turtle testis were similar to the morphologies of other vertebrate germ cell types. However, the slider turtle seminiferous epithelium contained germ cells that progress through spermatogenesis in a temporal rather than a spatial pattern, resulting in a single spermatogenic event that climaxed with one massive sperm release in November. Mature sperm then are stored within the epididymis until breeding commences in the following spring. The germ cell development strategy in the slider turtle is different from that of other amniotes and is more reminiscent of the developmental strategy found in the anamniotic testis. This temporal progression of germ cells through spermatogenesis within a tubular testis represents a transitional model that may be evolutionarily significant. J. Morphol. 255:337–346, 2003. © 2003 Wiley‐Liss, Inc.
Orthogonal grids around convex bodies using foliations
Authors: Herrera B. , Grau F. X. , Giralt Francesc
Published: January 2003

A new technique for the construction of orthogonal grids around convex bodies is presented. The method, which is analytical or numerical depending on how the body boundary is expressed, is based on the development of geometric foliations that follow a prescribed direction (for instance, the prevailing direction of flow) around convex bodies of arbitrary shape. The construction of these foliations is straightforward and does not require the solution of any system of algebraic or differential equations, nor the use of iterative procedures. The method is applicable both to two‐ and three‐dimensional domains since it is based solely on the concept of local curvature. The lines or surfaces given by the foliations of first and second order, together with the complementary orthogonal lines, respectively, define the orthogonal two‐ or three‐dimensional grids. Copyright © 2002 John Wiley & Sons, Ltd.
Computational form‐finding of tension membrane structures—Non‐finite element approaches: Part 1. Use of cubic splines in finding minimal surface membranes
Authors: Brew J. S. , Lewis W. J.
Published: January 2003

This paper, presented in three parts, discusses a computational methodology for form‐finding of tension membrane structures (TMS), or fabric structures, used as roofing forms. The term ‘form‐finding’ describes a process of finding the shape of a TMS under its initial tension. Such a shape is neither known a priori, nor can it be described by a simple mathematical function. The work is motivated by the need to provide an efficient numerical tool, which will allow a better integration of the design/analysis/manufacture of TMS. A particular category of structural forms is considered, known as minimal surface membranes (such as can be reproduced by soap films). The numerical method adopted throughout is dynamic relaxation (DR) with kinetic damping.

Part 1 describes a new form‐finding approach, based on the Laplace–Young equation and cubic spline fitting to give a full, piecewise, analytical description of a minimal surface. The advantages arising from the approach, particularly with regard to manufacture of cutting patterns for a membrane, are highlighted.

Part 2 describes an alternative and novel form‐finding approach, based on a constant tension field and faceted (triangular mesh) representation of the minimal surface. It presents techniques for controlling mesh distortion and discusses effects of mesh control on the accuracy and computational efficiency of the solution, as well as on the subsequent stages in design.

Part 3 gives a comparison of the performance of the initial method (Part 1) and the faceted approximations (Part 2). Functional relations, which encapsulate the numerical efficiency of each method, are presented. Copyright © 2002 John Wiley & Sons, Ltd.
Computational form‐finding of tension membrane structures—Non‐finite element approaches: Part 2. Triangular mesh discretization and control of mesh distortion in modelling minimal surface membranes
Authors: Brew J. S. , Lewis W. J.
Published: January 2003

This paper, presented in three parts, discusses a computational methodology for form‐finding of tension membrane structures (TMS), or fabric structures, used as roofing forms. The term ‘form‐finding’ describes a process of finding the shape of a TMS under its initial tension. Such a shape is neither known a priori, nor can it be described by a simple mathematical function. The work is motivated by the need to provide an efficient numerical tool, which will allow a better integration of the design/analysis/manufacture of TMS. A particular category of structural forms is considered, known as minimal surface membranes (such as can be reproduced by soap films). The numerical method adopted throughout is dynamic relaxation (DR) with kinetic damping.

Part 1 gave a background to the problem of TMS design, described the DR method, and presented a new form‐finding methodology, based on the Laplace–Young equation and cubic spline fitting to give a full, piecewise, analytical description of the surface.

Part 2 describes an alternative and novel form‐finding method, based on a constant tension field and faceted (triangular mesh) representation of the minimal surface. Techniques for controlling mesh distortion are presented, and their effects on the accuracy and computational efficiency of the solution, as well as on the subsequent stages in design, are examined.

Part 3 gives a comparison of the performance of the initial method (Part 1) and the faceted approximations (Part 2). Functional relations, which encapsulate the numerical efficiency of each method, are presented. Copyright © 2002 John Wiley & Sons, Ltd.
Computational form‐finding of tension membrane structures—Non‐finite element approaches: Part 3. Comparison of mesh constraint methods
Authors: Brew J. S. , Lewis W. J.
Published: January 2003

This paper, presented in three parts, discusses a computational methodology for form‐finding of tension membrane structures (TMS), or fabric structures, used as roofing forms. The term ‘form‐finding’ describes a process of finding the shape of a TMS under its initial tension. Such a shape is neither known a priori, nor can it be described by a simple mathematical function. The work is motivated by the need to provide an efficient numerical tool, which will allow a better integration of the design/analysis/manufacture of TMS. A particular category of structural forms is considered, known as minimal surface membranes (such as can be reproduced by soap films). The numerical method adopted throughout is dynamic relaxation (DR) with kinetic damping.

Part 1 gave a background to the problem of TMS design, described the DR method, and presented a new form‐finding methodology based on the Laplace–Young equation and the use of cubic splines to give a full, piecewise, analytical description of the surface.

Part 2 described an alternative and novel approach to form‐finding, based on a constant tension field and faceted (triangular mesh) representation of the minimal surface. Techniques for controlling mesh distortion were presented, and the effects of mesh control on the accuracy and computational efficiency of the solution, as well as on the subsequent stages in design, were examined.

Part 3 gives a comparison of the performance of the initial method (Part 1) and the faceted approximations (Part 2). Functional relations, which encapsulate the numerical efficiency of each method, are presented. Copyright © 2002 John Wiley & Sons, Ltd.
Filling domains with disks: an advancing front approach
Authors: Feng Y. T. , Han K. , Owen D. R. J.
Published: January 2003

An advancing front‐based algorithm is proposed to constructively generate a random initial packing for disks with different radii within a 2D domain, which is often required in discrete element methods (DEM). Depending on whether the domain boundary is included in the initial front and how the front is formed, two different versions of the algorithm, termed the closed and open form, respectively, are presented. The open form version has an inherent linear complexity. The closed form can achieve the same complexity under a relatively weak condition. The generated packing is not a globally optimal arrangement but achieves a locally highest density from the algorithmic point of view. The performance of the algorithm is illustrated in several examples. The major benefit of this development is the significant reduction of CPU time required for the preparation of an initial discrete object configuration in DEM simulations. It is demonstrated that it takes only 3.77 s for the proposed algorithm to generate one million disks on a PC with a one 1 GHz processor. Copyright © 2002 John Wiley & Sons, Ltd.
A hierarchical finite element for geometrically non‐linear vibration of doubly curved, moderately thick isotropic shallow shells
Authors: Ribeiro Pedro
Published: January 2003

A p‐version, hierarchical finite element for doubly curved, moderately thick, isotropic shallow shells is derived and geometrically non‐linear free vibrations of panels with rectangular planform are investigated. The geometrical non‐linearity is due to large displacements, and the effects of the rotatory inertia and transverse shear are considered. The time domain equations of motion are obtained by applying the principle of virtual work and the d'Alembert's principle. These equations are mapped to the frequency domain by the harmonic balance method, and are finally solved by a predictor–corrector method. The convergence properties of the element proposed and the influence of several parameters on the dynamic response are studied. These parameters are the shell's thickness, the width‐to‐length ratio, the curvature‐to‐width ratio and the ratio between curvature radii. The first and higher order modes are analysed. Some results are compared with results published or calculated using a commercial finite element package. It is demonstrated that with the proposed element low‐dimensional, accurate models are obtained. Copyright © 2002 John Wiley & Sons, Ltd.
An assessment of using the predictor–corrector technique to solve reactive transport equations
Authors: Cheng Hwai‐Ping , Li Ming‐Hsu , Cheng Jing‐Ru
Published: January 2003

We examined, through comparison among the full‐coupling (FC), operator‐splitting (OS), and predictor–corrector (PC) techniques, the effectiveness of using the PC technique to solve depth‐averaged reactive transport equations in the shallow water domain. Our investigation has led to three major conclusions. Firstly, both the OS and PC techniques can efficiently solve reactive transport equations because the advection–diffusion transport equations are solved outside the non‐linear iteration loop and the reaction equations are solved node by node. However, these two techniques may risk sacrificing computational accuracy. Secondly, the OS or PC technique incorporated with the Lagrangian–Eulerian (LE) approach can handle boundary sources more precisely than alternatively with the conventional Eulerian (CE) approach. Thirdly, with the LE approach incorporated, the numerical results from the three techniques agreed highly with one another except when diffusion became significant. In this case, the PC technique's result still matched well with the FC technique's result, but differences between the OS and FC techniques' results arose as diffusion increased. Based on this study, we recommend to apply as a first step the PC technique to solving reactive transport equations with respect to both computational efficiency and accuracy. Copyright © 2002 John Wiley & Sons, Ltd.
Distinctive and fuzzy failure probability analysis of an anisotropic rock mass to explosion load
Authors: Wu Chengqing , Hao Hong , Zhou Yingxin
Published: January 2003

This paper estimates failure probability of an anisotropic rock mass with random initial damage and random critical tensile strain to explosion loads. The initial random damage and critical tensile strain of the rock mass are estimated by approximate statistical methods. They are incorporated into the constitutive law of the anisotropic damage model. The statistical estimation of the rock‐mass response to underground explosion is evaluated by the Rosenblueth's point estimate method. A statistical anisotropic continuum damage model considering both the anisotropic initial damage and cumulative damage dependent on tensile strain is suggested. A beta distribution is proposed to represent the probabilistic distribution of the damage variable of the rock mass under blasting loads. Using the theory of reliability, failure probabilities are calculated according to different levels of failure criteria of the rock mass. A fuzzy definition is also proposed to describe the fuzzy nature of failure phenomenon of the rock mass. Based on the fuzzy random probabilistic theory, a model including both the effects of randomness of the rock‐mass properties and fuzziness of its failure criterion is proposed for the failure analysis of the rock mass. The suggested models are coded and linked with an available computer programe Autodyn3D as its user's subroutines. Using the Autodyn3D together with the suggested model, a series of field blasting tests are simulated. Numerical results of stress wave propagation are compared with field‐recorded data. The failure probabilities of the rock mass around the charge hole are estimated. Copyright © 2002 John Wiley & Sons, Ltd.
Stages in learning to pronounce Chinese characters
Authors: Chen Xi , Shu Hua , Wu Ningning , Anderson Richard C.
Published: January 2003

This article reviews research examining whether children can use information in the Chinese writing system to pronounce characters. The studies reviewed suggest that children making good progress in learning to read are attending to the cues to pronunciation in fully regular characters, semiregular characters, and phonetic families. Fully regular characters provide complete information about pronunciation. Semiregular characters contain partial information about pronunciation. Phonetic families consist of characters sharing the same phonetic that are usually related in pronunciation. Based on the findings, we argue that the overarching graphophonological insight in reading Chinese characters is “the phonetic principle”—the principle that the phonetic components of compound characters provide information about character pronunciation. Children's use of the principle appears to develop in stages. © 2003 Wiley Periodicals, Inc. Psychol Schs 40: 115–124, 2003.
Is the atmospheric pressure chemical ionisation and collisionally induced methanol loss from protonated dehydroamino acids a retrosynthetic process?
Authors: Tubaro Michela , Fedrigo Maria Anna , Cativiela Carlos , Jiménez Ana Isabel , Traldi Pietro
Published: January 2003

Unsaturated 5(4H)‐oxazolones lead, by methanolysis, to the corresponding dehydroamino acid derivatives. Interestingly, under atmospheric pressure chemical ionisation (APCI) conditions, the latter give rise, aside from abundant [M+H]+ ions, to [MHCH3OH]+ species, formally corresponding to the protonated oxazolones employed for their synthesis. Retrosynthetic processes have often been described as energetically favoured decompositions of odd‐electron molecular ions but never invoked in APCI‐activated fragmentations. To investigate this possible retrosynthetic process, occurring also under collisional conditions, some experiments on the deuterated analogues have been undertaken. The breakdown curves of [M+H]+ of oxazolones and [MHCH3OH]+ of the dehydroamino acid derivatives are superimposable, proving their structural identity and giving experimental evidence of the occurrence of a real retrosynthetic process from even‐electron protonated molecules. Copyright © 2002 John Wiley & Sons, Ltd.
Metal ion complexes in the structural analysis of phospholipids by electrospray ionization tandem mass spectrometry
Authors: Ho Yen‐Peng , Huang Ping‐Chen , Deng Kuang‐Hao
Published: January 2003

The effects of metal cationization on collisionally activated dissociation (CAD) of phospholipids were investigated by electrospray ionization with quadrupole ion trap tandem mass spectrometry. The metal ions include Li+, Na+, K+, Sr2+, Ba2+, and the first transition series. CAD of the transition metal ion‐bound lipid complexes gave significant yields of product ions that identify the positions of the two fatty acyl substituents on the glycerophospholipid backbone. The cobalt(II) ion, which has a single naturally occurring isotope, was expected to be a better cationization reagent as it produces simpler mass spectra than other transition metal ions. CAD of the cobalt(II) ion complexes of glycerophosphoethanolamines, glycerophosphoglycerols and glycerophosphoserines yielded product ions that revealed information regarding both the lipid classes and the regiospecific positions of the two fatty acyl substituents. Copyright © 2002 John Wiley & Sons, Ltd.
Study of the attachment of Na+ on glucose and on some of its methylated derivatives
Authors: Antonopoulos A. , Bonnet P. , Botek E. , Debrun J. L. , Hakim B. , Herbreteau B. , Morin‐Allory L.
Published: January 2003

The mechanism of attachment of Na+ on glucose, methyl‐α‐D‐glucose, methyl‐β‐D‐glucose, 3‐O‐methylglucose, tetra‐O‐methylglucose, and also on galactose and methyl‐β‐D‐galactose, was studied. For this we measured the ion yields for the complex [sugar–Na+] formed by ionisation by matrix‐assisted laser desorption/ionisation (MALDI) and ionspray. These data were compared with the relative volatilities and hydrophobicities of the sugars, measured by evaporative light scattering and reversed‐phase liquid chromatography, respectively. Some formation enthalpies for the complexes [sugar–Na+], starting from the sugar and the cation, were obtained by ab initio calculations. No simple correlations could be observed between the ion yields and the parameters studied, so that the cationisation mechanism of the sugars remains unclear. Copyright © 2002 John Wiley & Sons, Ltd.
Fragmentation study of salinomycin and monensin A antibiotics using electrospray quadrupole time‐of‐flight mass spectrometry
Authors: Miao Xiu‐Sheng , March Raymond E. , Metcalfe Chris D.
Published: January 2003

The fragmentation pathways of two selected ionophore antibiotics, salinomycin and monensin A, were studied using electrospray (ES) orthogonal acceleration quadrupole time‐of‐flight mass spectrometry in positive‐ion mode. The identity of fragment ions was determined by accurate‐mass measurements. In ES mass spectra, ion signals of relatively high intensity were observed for [M+Na]+ and [M−H+2Na]+ for each antibiotic. Each of the ion species [M+Na]+ and [M−H+2Na]+ for salinomycin and [M−H+2Na]+ for monensin A were isolated in turn and subjected to fragmentation. In the fragmentation of [M+Na]+ and [M−H+2Na]+ from salinomycin, only CC single bond cleavage and dehydration were observed. Product ion mass spectra obtained from [M−H+2Na]+ of monensin A showed that ether ring opening, CC single bond cleavage and dehydration fragmentations had occurred. Fragment ions containing two sodium atoms were observed in the product ion mass spectrum of [M−H+2Na]+ from salinomycin, but not from monensin A. Both type A (containing the terminal carboxyl group) and type F (containing the terminal hydroxyl group) fragment ions were observed in the product ion mass spectra of sodium adduct ions of salinomycin and monensin A. Copyright © 2002 John Wiley & Sons, Ltd.
An improved liquid chromatography/tandem mass spectrometry method for the determination of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine in DNA samples using immunoaffinity column purification
Authors: Singh Rajinder , McEwan Michael , Lamb John H. , Santella Regina M. , Farmer Peter B.
Published: January 2003

The analysis of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG) represents an important biomarker of oxidative stress. A sensitive method for the detection of 8‐oxodG in DNA samples has been developed that utilizes immunoaffinity column purification of 8‐oxodG followed by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) multiple reaction monitoring (MRM) mode analysis. An internal standard of stable‐isotopically labelled 8‐oxodG containing [15N5] was added prior to the enzymatic digestion of DNA to deoxynucleosides, which was then subjected to immunoaffinity column purification followed by microbore positive ion LC/MS/MS MRM. The 8‐oxo‐7,8‐dihydroguanine (8‐oxoG) base product ion at m/z 168 was monitored following cleavage of the glycosidic bond of the 8‐oxodG [M+H]+ ion at m/z 284. Similar determinations were made for [15N5]8‐oxodG by monitoring the [15N5]8‐oxoG base product ion at m/z 173 formed from the [M+H]+ ion at m/z 289. The introduction of the immunoaffinity column purification step into the method represents a significant improvement for the accurate determination of 8‐oxodG since all artefactual peaks that are observed following the direct injection of digested DNA onto the LC/MS/MS system are removed. The identity of these artefactual peaks has been confirmed to be 2′‐deoxyguanosine (dG), thymidine (dT) and 2′‐deoxyadenosine (dA). The presence of these artefactual peaks in MRM mode analysis can be explained as a consequence of a concentration effect due to their considerably higher relative abundance in DNA compared to 8‐oxodG. The highest signal intensity was observed for the artefactual peak for dA due to the fact that the adenine base formed an adduct with methanol, which is a constituent of the mobile phase. The resulting [M+H]+ ion at m/z 284 (dA m/z 252 + CH3OH m/z 32) gave rise to a product ion at m/z 168 following the loss of deoxyribose in MRM mode analysis. Control calf thymus DNA was digested to deoxynucleosides and unmodfied deoxynucleosides were removed by immunoaffinity column purification; the enriched 8‐oxodG was determined by LC/MS/MS MRM. The level of 8‐oxodG in control calf thymus DNA was determined to be 28.8 ± 1.2 8‐oxodG per 106 unmodified nucleotides (n = 5) using 5 μg of digested DNA. The limit of detection of the microbore LC/MS/MS MRM for 8‐oxodG was determined to be 25 fmol on‐column with a signal‐to‐noise ratio of 3.5. Copyright © 2002 John Wiley & Sons, Ltd.
A top down approach to protein structural studies using chemical cross‐linking and Fourier transform mass spectrometry
Authors: Kruppa Gary H. , Schoeniger Joseph , Young Malin M.
Published: January 2003

Mass spectrometric analysis of wild‐type proteins that have been covalently modified by bifunctional cross‐linking reagents and then digested proteolytically can be used to obtain low‐resolution distance constraints, which can be useful for protein structure determination. Limitations of this approach include time‐consuming separation steps, such as the separation of internally cross‐linked protein monomers from covalent dimers, and a susceptibility to artifacts due to low levels of natural and man‐made peptide modifications that can be mistaken for cross‐linked species. The results presented here show that when a crude cross‐linked protein mixture is injected into an electrospray ionization Fourier transform mass spectrometry (ESI‐FTMS) instrument, the cross‐link positions can be localized by fragmentation and mass spectrometry on the ‘gas‐phase purified’ singly internally cross‐linked monomer. Our results show that reaction of ubiquitin with the homobifunctional lysine‐lysine cross‐linking reagent dissuccinimidyl suberate (DSS) resulted in two cross‐links consistent with the known ubiquitin tertiary structure (K6‐K11 and K48‐K63). Because no protein or peptide chemistry steps are needed, other than the initial cross‐linking, this new top down approach appears well suited for high‐throughput experiments with multiple cross‐linkers and reaction conditions. Published in 2002 by John Wiley & Sons, Ltd.
Classification of green coffee beans by differences in protein composition obtained by matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Procida Giuseppe , Campisi Barbara , Seraglia Roberta , Traldi Pietro
Published: January 2003

It is well known that proteins and peptides play an important role in the flavour of roasted coffee, but little is reported in the literature about their characterization. In view of the potential of matrix‐assisted laser desorption/ionization mass spectrometry in the analysis of proteins in complex mixtures, two varieties of coffee green beans, Arabicas and Robustas, were analyzed by this technique, in order to obtain fingerprints of their native proteins. Differences were observed between Arabicas and Robustas green beans, and cluster analysis allows differentiation of samples of the same variety from different plantations. Copyright © 2002 John Wiley & Sons, Ltd.
Quantitative analysis of clindamycin in human plasma by liquid chromatography/electrospray ionisation tandem mass spectrometry using d1‐N‐ethylclindamycin as internal standard
Authors: Rechberger Gerald N. , Fauler Günter , Windischhofer Werner , Köfeler Harald , Erwa Wolfgang , Leis Hans‐Jörg
Published: January 2003

A new method for the quantitative analysis of clindamycin in human plasma by liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/ESI‐MS/MS) is presented. Recently published methods possess a disadvantage because of their use of internal standards with extraction and ionisation properties different from those of clindamycin. To avoid these problems, d1‐N‐ethylclindamycin was synthesised for use as internal standard by N‐demethylation and subsequent d1‐N‐ethylation. Plasma sample preparation was done by an easy and rapid liquid–liquid extraction using ethyl acetate. The method was validated in the expected concentration range for a pharmacokinetic study. Calibration graphs were linear within the range 0.05–3.2 μg/mL plasma. Intra‐day precision was between 0.90% (2.8 μg/mL) and 3.25% (0.05 μg/mL), inter‐day variability was found to be between 1.33% (0.7 μg/mL) and 2.60% (0.05 μg/mL). Inter‐day accuracy showed deviations between 0.4% (0.05 μg/mL) and −4.8% (0.2 μg/mL). The method is simple and robust, and has been applied to the batch analysis of clindamycin during a pharmacokinetic study. Copyright © 2002 John Wiley & Sons, Ltd.
Performance of an ultra‐low elution‐volume 96‐well plate: drug discovery and development applications
Authors: Mallet Claude R. , Lu Ziling , Fisk Ray , Mazzeo Jeffrey R. , Neue Uwe D.
Published: January 2003

Recently, sample preparation has been considered to be the major cause of bottlenecks during high‐throughput analysis. With the assistance of robotic liquid handlers and the 96‐well plate format, more samples can be prepared for subsequent liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. Protein precipitation is still widely used despite potential loss of sensitivity or variable results due to ion suppression. The use of solid‐phase extraction (SPE) clearly gives superior results but may not be as cost effective as protein precipitation due to the labor and material costs associated with the process. Here, a novel 96‐well SPE plate is described that was designed to minimize the elution volume required for quantitative elution of analytes. The plate is packed with 2 mg of a high‐capacity SPE sorbent that allows loading of up to 750 μL of plasma, while the novel design permits elution with as little as 25 μL. Therefore, the plate offers up to a 15‐fold increase in sample concentration. The evaporation and reconstitution step that is typically required in SPE is avoided due to the concentrating ability of the plate. Examples of applications in drug discovery/development are shown and results are compared to protein precipitation. Excellent sensitivity and linearity are demonstrated. Copyright © 2002 John Wiley & Sons, Ltd.
Analysis of isomeric long‐chain hydroxy fatty acids by tandem mass spectrometry: application to the diagnosis of long‐chain 3‐hydroxyacyl CoA dehydrogenase deficiency
Authors: Johnson David W. , Trinh Minh‐Uyen
Published: January 2003

Acetyl trimethylaminoethyl ester iodide derivatives have been used to selectively analyze isomeric long‐chain hydroxy fatty acids by electrospray ionization tandem mass spectrometry (ESI‐MS/MS). The binary derivatives of 2‐, 3‐, 12‐ and 16‐hydroxypalmitic acids afford remarkably different product ion spectra. Further discrimination between isomers is possible by acylating with pivaloyl chloride. 2‐ and ω‐Hydroxy long‐chain fatty acids form pivaloyl esters in quantitative yield whereas other secondary alcohols only partially react. Cotton‐based filter paper used for blood collection contains substantial amounts of esterified long‐chain hydroxy fatty acids. From the product ion spectra of the acetyl trimethylaminoethyl esters the hydroxydocosanoic and ‐tetracosanoic acids are >90% ω‐hydroxy. All remaining saturated and unsaturated hydroxy acids are >90% 2‐hydroxy acids. A method for the quantification of free 3‐hydroxypalmitic acid in plasma by ESI‐MS/MS for the diagnosis of long‐chain 3‐hydroxyacyl CoA dehydrogenase deficiency (LCHAD) is described. Median plasma concentrations of 0.43 μmol/L (control, n = 22) and 12.2 μmol/L (LCHAD, n = 3) were obtained from 5 μL plasma samples. Copyright © 2002 John Wiley & Sons, Ltd.
In situ capping design of a pyrite cinder pile in the St. Lawrence river for metal containment
Authors: Thibodeaux Louis J.
Published: January 2003

A pile of pyrite cinders discharged from a former manufacturing facility rest upon the bottom of the St.
Lawrence River adjacent to Clark Island. In situ capping was the selected remedy to control both
the fine particle resuspension that produced a red mud cloud in the water, commonly formed on windy days, and the
soluble metals concentrations originating from the pyrite pile. Metal mass balances around the pile allowed
estimates of the pre‐capping release rates. Elevated concentrations above the pile were observed for eight
metals; these included iron, lead, mercury, selenium, arsenic, copper, cadmium, and zinc. After iron, the
highest concentration in the pyrite particles were cadmium and zinc present in the 1,000 mg/kg range. Mercury
was the lowest at the 10 mg/kg level in the pyrite solids. For iron the soluble release rate was estimated to
be 0.08 g/s, and the particle release was 0.8 to 1.2 g/s. A 30 cm cap consisting of particles 19 to 40 mm
in diameter is proposed for the site. Its placement covers a ten‐hectare area and is expected to isolate
the fine pyrite particles and prohibit their resuspension into the water column. Design estimates of steady state
flux reduction efficiencies range from a low of 99.21 percent for iron to a high of 99.96 percent for copper.
Breakthrough times to achieve these steady state flux reductions range from 100 to 3,800 years and metal porewater
concentrations at 5 cm below the cap surface are estimated to be reduced by 83 percent. Although soluble metals
will continue to be released from the pile zone, the flux of all the metals will be significantly reduced. ©
2002 Wiley Periodicals, Inc.
Combining Ion‐exchange (IX) technology and biological reduction for perchlorate removal
Authors: Batista Jacimaria R. , Gingras Tina M. , Vieira Adriano R.
Published: January 2003

Ion‐exchange (IX) resin is perhaps the most promising technology to remove the contaminant
perchlorate (ClO4−) from waters. However, ion exchange is only a separation
technology that transfers the perchlorate from waters to the waste solutions used to regenerate the resins. The
waste solutions contain high perchlorate concentrations, and treatment technologies for these regenerant
solutions are needed. In this article, we review the latest knowledge on perchlorate removal by
ion‐exchange resins; propose three systems that combine ion‐exchange resins (for
perchlorate removal) and biological reduction for treating the waste solutions resulting from resin
regeneration; and discuss the challenges and research needed to fully develop the proposed technology.
© 2002 Wiley Periodicals, Inc.
Choosing remediation and waste management options at hazardous and radioactive waste sites
Authors: Greenberg Michael , Burger Joanna , Powers Charles , Leschine Thomas , Lowrie Karen , Friedlander Barry , Faustman Elaine , Griffith William , Kosson David
Published: January 2003

This article discusses a process for finding insights that will allow federal agencies and environmental
professionals to more effectively manage contaminated sites. The process is built around what Etzioni
(1968) called mixed‐scanning, that is, perpetually doing both comprehensive and detailed
analyses and periodically re‐scanning for new circumstances that change the decision‐making
environment. The article offers a checklist of 127 items, which is one part of the multiple‐stage
scanning process. The checklist includes questions about technology; public, worker, and ecological
health; economic cost and benefits; social impacts; and legal issues. While developed for a DOE
high‐level radioactive waste application, the decision‐making framework and specific questions can
be used for other large‐scale remediation and management projects. © 2002 Wiley Periodicals,
Inc.
Field analyses of RDX and TCE in groundwater during a GCW pilot study
Authors: Elmore Andrew C. , Travaglin Lisa A. , Triplett Jennifer L.
Published: January 2003

Contaminant concentrations in groundwater are typically analyzed using traditional laboratory analytical
procedures approved by the Environmental Protection Agency (EPA) or state regulatory agencies. The use
of off‐site laboratories provides very high‐quality water quality data at a relatively high cost in
terms of time and money. Yet there are many instances when it is desirable to have water quality data measured in
the field. The field methods for measuring water quality typically cost much less than the corresponding
laboratory methods. However, the usability of the field data may be uncertain when the results are qualitatively
compared to duplicate laboratory results. Groundwater samples collected during a groundwater circulation well
pilot study were analyzed using field kits to measure concentrations of trichloroethylene (TCE) and the
explosive compound known as RDX. A subset of the samples was split for duplicate laboratory analysis. Linear
regression analysis and relative percent difference analysis were performed on the duplicate results to evaluate
the comparability of the field and laboratory data. The data analyses were also used to evaluate the concept that
the field kits were more accurate for specific concentration ranges, as well as the concept the field kit results
would improve as field personnel gained experience with the field analysis procedures. © 2002 Wiley
Periodicals, Inc.