Database: EMBASE <: international biomedical and pharmaceutical literature, 1988 - May 2000. [Trial access until 3/2001. Feedback welcome to medical.library@umich.edu] Search Strategy (You Saved Citations 1-138 From Set 102): ----------------------------------------------------------------------------- 1 Iron/ 14320 2 iron.mp. 35412 3 ferric:.mp. 6463 4 ferro:.mp. 8187 5 anemi:.mp. 31226 6 7439-89-6.rn. 13998 7 Iron derivative/ 257 8 Bleomycin iron/ 48 9 Carbonyl iron/ 76 10 Dysprosium iron hydroxide dy 165/ 11 11 Edetate iron/ 75 12 Iron absorption/ 719 13 Iron binding capacity/ 466 14 Iron binding protein/ 397 15 Iron blood level/ 1232 16 Iron chelate/ 167 17 Iron chelation/ 1070 18 Iron complex/ 606 19 Iron oxide/ 646 20 exp Antianemic agent/ 17201 21 Iron responsive element/ 152 22 Iron saccharate/ 90 23 Iron regulatory factor/ 145 24 Iron sulfur protein/ 574 25 Molybdenum iron protein/ 51 26 Nitrilotriacetate iron/ 134 27 Superparamagnetic iron oxide/ 167 28 Iron 52/ 25 29 Iron 58/ 14 30 Iron 55/ 94 31 Iron 59/ 243 32 Pentetate iron/ 6 33 Doxorubicin iron/ 10 34 Iron nickel phosphorus alloy/ 1 35 exp Iron metabolism/ 2631 36 Iron deficiency/ 1811 37 exp Anemia/ 27375 38 Iron overload/ 1602 39 Iron therapy/ 768 40 Iron transport/ 1351 41 Ferrous citrate fe 59/ 6 42 Ferrous ion/ 1423 43 Ferric citrate fe 59/ 13 44 Ferric ferrocyanide/ 122 45 Ferric hydroxide/ 366 46 Ferric ion/ 1485 47 Ferric oxide/ 294 48 Ferric phosphate/ 27 49 Ferric sulfate/ 54 50 or/1-49 84034 51 exp Tooth demineralization/ 7492 52 demineralization.mp. 879 53 caries.mp. 1798 54 caires.mp. 0 55 craies.mp. 0 56 careis.mp. 1 57 carise.mp. 0 58 (teeth adj3 cavit:).mp. 32 59 (tooth adj3 cavit:).mp. 97 60 (dental adj3 cavit:).mp. 85 61 (dentin adj3 cavit:).mp. 19 62 (enamel adj3 cavit:).mp. 10 63 (teeth adj3 decay:).mp. 58 64 (tooth adj3 decay:).mp. 58 65 (dental adj3 decay:).mp. 47 66 (dentin adj3 decay:).mp. 0 67 (enamel adj3 decay:).mp. 1 68 (active adj decay).mp. 5 69 (rampant adj3 decay:).mp. 4 70 (recurrent adj3 decay:).mp. 5 71 (white adj spot:).mp. 231 72 carious.mp. 109 73 cariology.ti,ab. 2 74 (non-cavitated adj3 lesion:).mp. 0 75 (noncavitated adj3 lesion:).mp. 1 76 Tooth remineralization/ 788 77 (dental adj3 fissure:).mp. 14 78 (tooth adj3 fissure:).mp. 8 79 (teeth adj3 fissure:).mp. 1 80 caries-free.mp. 29 81 cariesfree.mp. 0 82 Cariogenic agents/ 3 83 precavit:.mp. 2 84 (filled adj3 teeth).mp. 45 85 (filled adj3 tooth).mp. 9 86 (oral adj fissure:).mp. 17 87 (tooth adj3 remineraliz:).mp. 1 88 (teeth adj3 remineraliz:).mp. 5 89 dft.mp. 542 90 dfs.mp. 980 91 dmf:.mp. 1235 92 cariogeni:.mp. 164 93 or/51-92 12313 94 Saliva/ 2282 95 exp Salivary gland/ 5795 96 (saliva or salivary or parotid).mp. 16372 97 or/93-96 29129 98 50 and 97 458 99 limit 98 to human 320 100 from 99 keep 1-300 300 101 from 99 keep 301-320 20 102 98 not 99 138 103 from 102 keep 1-138 138 *************************** <1> UI - 2000170817 AU - Curie C AU - Alonso JM AU - Le Jean M AU - Ecker JR AU - Briat J-F IN - C. Curie, Lab. Biochim. Physiol. Mol. Plantes, CNRS/INRA/ENSAM/Univ. Montpellier, 2 Place Viala, F-34060 Montpellier CEDEX 1; France. E-Mail: curie@ensam.inra.fr. TI - Involvement of NRAMP1 from Arabidopsis thaliana in iron transport. SO - Biochemical Journal Vol 347(3) (pp 749-755), 2000. AB - Nramp genes code for a widely distributed class of proteins involved in a variety of processes, ranging from the control of susceptibility to bacterial infection in mammalian cells and taste behaviour in Drosophila to manganese uptake in yeast. Some of the NRAMP proteins in mammals and in yeast are capable of transporting metal ions, including iron. In plants, iron transport was shown to require a reduction/Fe(II) transport system. In Arabidopsis thaliana this process involves the IRT1 and Fro2 genes. Here we report the sequence of five NRAMP proteins from A. thaliana. Sequence comparison suggests that there are two classes of NRAMP proteins in plants: A. thaliana (At) NRAMP1 and Oriza saliva (Os) NRAMP1 and 3 (two rice isologues) represent one class, and AtNRAMP2-5 and OsNRAMP2 the other. AtNramp1 and OsNramp1 are able to complement the fet3fet4 yeast mutant defective both in low-and high-affinity iron transports, whereas AtNramp2 and OsNramp2 fail to do so. In addition. AtNramp1 transcript, but not ArNramp2 transcript, accumulates in response to iron deficiency in roots but not in leaves. Finally, overexpression of AtNramp1 in transgenic A. thaliana plants leads to an increase in plant resistance to toxic iron concentration. Taken together, these results demonstrate that AtNramp1 participates in the control of iron homoeostasis in plants. [References: 38] <2> UI - 2000168135 AU - Yoshizawa K IN - K. Yoshizawa, Department of Molecular Engineering, Kyoto University, Sakyo-ku, Kyoto 606-8501; Japan. E-Mail: kazunari@scl.kyoto-u.ac.jp. TI - Two-step concerted mechanism for methane hydroxylation on the diiron active site of soluble methane monooxygenase. SO - Journal of Inorganic Biochemistry Vol 78(1) (pp 23-34), 2000. AB - A new concerted mechanism is proposed for the conversion of methane to methanol on intermediate Q of soluble methane monooxygenase (sMMO), the active site of which is considered to involve an Fe2(mu-O)2 diamond core. A hybrid density functional theory (DFT) method is used for our mechanistic study on the important reactivity of the bare FeO+ complex and a diiron model of intermediate Q. The reaction pathway for the methane hydroxylation on the diiron complex is essentially identical to that for the gas-phase reaction by the bare FeO+ complex. Methane is highly activated on the dinuclear iron model through the formation of a methane complex, in which a coordinatively unsaturated iron plays a central role in the bonding interaction between the diiron model and substrate methane. A H atom abstraction via a four-centered transition state and a recombination of the OH and CH3 groups via a three-centered transition state successively occur on the dinuclear iron-oxo species, leading to the formation of a methanol complex that corresponds to intermediate T. These electronic processes take place in a concerted manner. Our mechanism for methane hydroxylation by sMMO is different from the radical mechanism that has been widely accepted for enzymatic hydrocarbon hydroxylation, especially by cytochrome P450. Copyright (C) 1999 Elsevier Science Inc. [References: 70] <3> UI - 2000145947 AU - Hallmann R AU - Savigni DL AU - Morgan EH AU - Baker E IN - R. Hallmann, Institute for Experimental Medicine, University of Erlangen-Nuernberg, Schwabachanlage 10, D-91054 Erlangen; Germany. E-Mail: rhallman@expmed.uni-erlangen.de. TI - Characterization of iron uptake from transferrin by murine endothelial cells. SO - Endothelium: Journal of Endothelial Cell Research Vol 7(2) (pp 135-147), 1999. AB - Iron is required by the brain for normal function, however, the mechanisms by which it crosses the blood-brain barrier (BBB) are poorly understood. The uptake and efflux of transferrin (Tf) and Fe by murine brain-derived (bEND3) and lymph node-derived (mlEND1) endothelial cell lines was compared. The effects of iron chelators, metabolic inhibitors and the cellular activators, lipopolysaccharide (LPS) and tumour necrosis factor-alpha (TNF-alpha), on Tf and Fe uptake were investigated. Cells were incubated with 59Fe-125I-Tf; Fe uptake was shown to increase linearly over time for both cell lines, while Tf uptake reached a plateau within 2 h. Both Tf and Fe uptake were saturable. bEND3 cells were shown to have half as many Tf receptors as mlEND1 cells, but the mean cycling times of a Tf molecule were the same. Tf and Fe efflux from the cells were measured over time, revealing that after 2 h only 25% of the Tf but 80% of the Fe remained associated with the cells. Of 7 iron chelators, only deferriprone (L1) markedly decreased Tf uptake. However, Fe uptake was reduced by more than 50% by L1, pyridoxal isonicotinoyl hydrazone (PIH) and desferrithiocin (DFT). The cellular activators TNF-alpha or LPS had little effect on Tf turnover, but they accelerated Fe uptake in both endothelial cell types. Phenylarsenoxide (PhAsO) and N-ethyl maleimide (NEM), inhibitors of Tf endocytosis, reduced both Tf and Fe uptake in both cell lines, while bafilomycin A1, an inhibitor of endosomal acidification, reduced Fe uptake but did not affect Tf uptake. The results suggest that Tf and Fe uptake by both bEND3 and mlEND1 is via receptor-mediated endocytosis with release of Fe from Tf within the cell and recycling of apo-Tf. On the basis of Tf- and Fe-metabolism both cell lines are similar and therefore well suited for use in in vitro models for Fe transport across the BBB. [References: 33] <4> UI - 2000127391 AU - Dunietz BD AU - Beachy MD AU - Cao Y AU - Whittington DA AU - Lippard SJ AU - Friesner RA IN - S.J. Lippard, Massachusetts Inst. of Technology, Cambridge, MA 02139; United States. TI - Large scale ab initio quantum chemical calculation of the intermediates in the soluble methane monooxygenase catalytic cycle. SO - Journal of the American Chemical Society Vol 122(12) (pp 2828-2839), 2000. AB - Ab initio DFT quantum chemical methods are applied to study intermediates in the catalytic cycle of soluble methane monooxygenase hydroxylase (MMOH), a dinuclear iron-containing enzyme that converts methane and dioxygen selectively to methanol and water. The quantum chemical models reproduce reliably the X-ray crystallographic coordinates of the active site for the oxidized diiron(III) and reduced diiron(II) states to a high degree of structural precision. The results inspired a reexamination of the X-ray structure of reduced MMOH and revealed previously unassigned electron density now attributed to a key structural water molecule. The quantum chemical calculations required construction of a model containing about 100 atoms, which preserved key hydrogen bonding patterns necessary for structural integrity. Smaller models were unstable for the reduced form of the enzyme, an observation with significant mechanistic implications. The large model was then used to investigate the catalytic intermediates H(peroxo), formed upon the addition of dioxygen, and Q, the active species that reacts with methane. The structures, which differ significantly from alternatives proposed in the literature, are consistent with the experimentally available information concerning the spin states, geometries, and thermodynamics of formation of these intermediates. Other models that have been proposed, particularly in the case of Q, are ruled out in our calculations by energetic considerations, which have a simple physical interpretation. A bound water molecule is critical in assembling the catalytically active species Q. <5> UI - 2000102993 AU - Nlate S AU - Ruiz J AU - Blais J-C AU - Astruc D IN - D. Astruc, Groupe de Chimie Supramoleculaire, Metaux de Transition, Universite Bordeaux I, 33405 Talence Cedex; France. E-Mail: d.astruc@lcoo.u-bordeaux.fr. TI - Ferrocenylsilylation of dendrons: A fast convergent route to redox- stable ferrocene dendrimers. SO - Chemical Communications Vol 6(5) (pp 417-418), 2000. AB - A 54-ferrocene dendrimer is synthesized by a convergent route and can be used to modify a Pt electrode in CH2Cl2; it can be reversibly oxidized in DMF in a single 54-electron wave (and with NO+). <6> UI - 2000081541 AU - Sivakolundu SG AU - Mabrouk PA IN - P.A. Mabrouk, Department of Chemistry, Northeastern University, Boston, MA 02115; United States. TI - Cytochrome c structure and redox function in mixed solvents are determined by the dielectric constant. SO - Journal of the American Chemical Society Vol 122(7) (pp 1513-1521), 2000. AB - Cyclic voltammetry (CV), UV-visible (UV-vis); circular dichroism (CD), and resonance Raman (lambda(ex) = 406.7, 413.1 nm) spectroscopy have been used to probe the structure and redox function of horse cytochrome c (cyt c) in aqueous mixtures of three water-miscible organic solvents, specifically, acetonitrile (ACN), dimethylformamide (DMF), and dimethyl sulfoxide (DMSO) containing 100-60% water. As the concentration of the organic solvent is increased, significant changes are observed in the spectroscopy of ferricytochrome c (ferricyt c) with the greatest structural changes observed for ferricyt c in mixed solvent media with the lowest dielectric constant (30% ACN in this work). In the UV-visible spectrum, the Soret band blue shifts (1 nm) and the intensity of the 695 nm band decreases. UV CD (185-240 nm) suggest that changes in the protein secondary structure on going from aqueous to nonaqueous media are relatively small and that the protein structure remains largely intact in nonaqueous media. In the visible CD spectrum, the negative 417 nm CD signal disappears, signaling significant changes in heme-polypeptide interactions. Shifts in the vibrational frequencies and changes in the relative intensities of bands in both the marker band and low frequency spectral regions of cyt c in mixed media have been attributed to mixtures of the type IVa, IVb, Va, and Vb alkaline conformers of ferricyt c in mixed media. The change in the composition of these mixtures as the dielectric constant decreases parallels closely that reported by Dopner et al. for yeast iso-1-cytochrome c in aqueous solution as the aqueous solution pH is raised from pH 7 to pH 10. The spectroscopic characteristics of the reduced form of cyt c in mixed solvents are very similar to those of native ferrous cyt c (ferrocyt c) in aqueous solution, reflecting minimal change in heme active site structure in the reduced state. Cyt c in mixed solvents exhibits a quasireversible, one-electron response at 4,4'-dipyridyl disulfide-modified Au electrodes between 5 and 200 mV/s. The redox potential for cyt c in mixed media (199-274 mV vs SHE) and the rate of heterogeneous electron transfer (0.4-3.5 x 10-3 cm/s) decrease as the organic solvent content of the solvent medium increases. Our data support the conclusion that the internal dielectric constant within the heme crevice plays the key role in determining the reduction potential of cyt c and suggest that the effects of axial ligation (Met vs Lys) may be less significant than previously believed. <7> UI - 2000040480 AU - Yoshizawa K AU - Yumura T AU - Shiota Y AU - Yamabe T IN - K. Yoshizawa, Department of Molecular Engineering, Kyoto University, Sakyo-ku, Kyoto 606-8501; Japan. TI - Formation of an iron-oxo species upon decomposition of dinitrogen oxide on a model of Fe-ZSM-5 zeolite. SO - Bulletin of the Chemical Society of Japan Vol 73(1) (pp 29-36), 2000. AB - The so-called 'a-oxygen' on Fe-ZSM-5 zeolite, a surface oxygen species responsible for high reactivity in oxidation of methane and of benzene, has been investigated. We present from density-functional-theory (DFT) calculations how such a reactive surface species is generated upon decomposition of dinitrogen oxide (N2O) and propose a possible form of 'a- oxygen' on Fe-ZSM-5 zeolite. In the initial stages of the reactions, a complex involving an Fe(ON2) moiety is formed, followed by dissociation into an iron-oxo species and N2. The activation energy for the decomposition of N2O on a possible iron active site model of Fe-ZSM-5 zeolite is predicted to be 2.4 kcal mol-1 at the B3LYP level of theory. Therefore the decomposition of N2O is expected to take place easily at a coordinatively unsaturated iron active center supported on zeolite. The iron-oxo species thus formed should play an essential role in the direct hydroxylation of methane, benzene, and other hydrocarbons if it involves a coordinatively unsaturated iron. The oxygen exchange on the iron-oxo complex was also investigated. The activation energy for the oxygen exchange on the 'a-oxygen' is predicted to be 26.8 kcal mol-1. We propose that the bare FeO+ complex and the so-called 'a-oxygen' on Fe-ZSM-5 zeolite involve similar catalytic active centers responsible for similar catalytic functions for methane and benzene. [References: 69] <8> UI - 2000019436 AU - MacDonald CLB AU - Cowley AH IN - A.H. Cowley, Dept. of Chemistry and Biochemistry, University of Texas, Austin, TX 78712; United States. TI - A theoretical study of free and Fe(CO)4-complexed borylenes (boranediyls) and heavier congeners: The nature of the iron-group 13 element bonding. SO - Journal of the American Chemical Society Vol 121(51) (pp 12113-12126), 1999. AB - The singlet and lowest-lying triplet states of the univalent group 13 ligands MeM, (eta5-C5H5)M, (eta5-C5Me5)M, and (H3Si)2NM (M = B, Al, Ga, In) have been investigated by DFT methods. Each ligand possesses a singlet ground state. Four models were considered for the interaction of these ligands with the Fe(CO)4 fragment: a purely M [right arrow] Fe sigma-bonded model (A) supplemented by one back-bonding interaction from Fe to M (B), or a M [right arrow] Fe sigma-bonded model supplemented by two back-bonding interactions from Fe to M (C), and a M=Fe double-bonded model (D). In general, the DFT calculations indicated that the RM ligands behave as two-electron donors (i.e. bonding model A). The RM ligands with non pi-bonding substitutents, R, were found to have some pi-acceptor capability that would be appropriate for iron [right arrow] ligand back-bonding. However, evidence for such an interaction was only found in the case of MeBFe(CO)4. <9> UI - 2000010771 AU - Gosmini C AU - Nedelec JY AU - Perichon J IN - C. Gosmini, Laboratoire C.N.R.S. d'Electrochimie, Catalyse et Synthese Organique 2, Rue Henri Dunant, 94320 Thiais; France. E-Mail: gosmini@glvt-cnrs.fr. TI - Electrochemical cross-coupling between functionalized aryl halides and 2-chloropyrimidine or 2-chloropyrazine catalyzed by nickel 2,2'-bipyridine complex. SO - Tetrahedron Letters Vol 41(2) (pp 201-203), 2000. AB - 2-Arylpyrimidines and 2-arylpyrazines have been obtained in good to high yields from 2-chloropyrimidine and 2-chloropyrazine and various functionalized aryl halides by electroreduction using an iron rod as the anode and a catalytic amount of nickel-bipyridine complex in a mixture of DMF and pyridine as solvent. [References: 4] <10> UI - 1999422879 AU - Bergeron RJ AU - Weimar WR AU - Wiegand J IN - Dr. R.J. Bergeron, Box 100485 JHMHC, Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610; United States. E-Mail: bergeron@mc.cop.ufl.edu. TI - Pharmacokinetics of orally administered desferrithiocin analogs in Cebus apella primates. SO - Drug Metabolism & Disposition Vol 27(12) (pp 1496-1498), 1999. AB - The pharmacokinetic behavior of three iron chelators based on the desferrithiocin (DFT) pharmacophore, (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4- thiazolecarboxylic acid (desmethyldesferrithiocin, DMDFT, 2); (S)-4,5- dihydro-2-(2,4-dihydroxyphenyl)-4-thiazolecarboxylic acid [4-(S)- hydroxydesazaDMDFT, 3); and (R)-2-(2-hydroxyphenyl)-4-oxazolinecarboxylic acid, the oxazoline analog of desazaDMDFT, 4, is described. Although 2 and 3 are comparably effective in inducing iron excretion upon oral administration, they exhibit markedly different plasma pharmacokinetics. Ligand 2 achieves a substantially higher plasma concentration than does 3, yet the renal clearance of these compounds is similar. The oxazoline analog 4 shows poor iron clearance when administered orally, although it remains in the plasma for extended periods. Chelator 4 demonstrates a marked capacity to bind to human serum albumin compared with the thiazoline derivatives. The possible implications for designing ligands for the treatment of transfusional iron overload are discussed. [References: 22] <11> UI - 1999413726 AU - Guzman RE AU - Kerlin RL AU - Zimmerman TE IN - Dr. R.E. Guzman, Dept. of Veterinary Pathobiology, University of Illinois, 2001 S. Lincoln Avenue, Urbana, IL 61801; United States. E-Mail: reguzman@students.uiuc.edu. TI - Histologic lesions in cynomolgus monkeys (Macaca fascicularis) naturally infected with Simian retrovirus type D: Comparison of seropositive, virus- positive, and uninfected animals. SO - Toxicologic Pathology Vol 27(6) (pp 672-677), 1999. AB - Simian retrovirus (SRV) type D is a common cause of simian acquired immunodeficiency syndrome (SAIDS), a usually fatal immunosuppressive disease of macaques. Associated gross and histologic lesions have been well described for the rhesus macaque (Macaca mutatta) in experimental and natural infections. However, morphologic changes induced by this virus at the gross and light-microscopic level have not been documented in the cynomolgus macaque (Macaca fascicularis). In 1996, sporadic cases of anemia, weight loss, and diarrhea were noted in a colony of cynomolgus macaques in our research facility. Out of 28 animals, 24 tested positive for SRV by serology or virus isolation. Animals could mainly be classified into 1 of 2 categories: 1) positive for virus isolation but negative for SRV antibody and 2) negative for virus isolation but antibody positive. During the process of eliminating the virus from the colony, a complete postmortem examination was performed on the 24 infected animals that had to be culled. Twelve SRV- negative animals were available as controls. Minimal to mild follicular lymphoid infiltrates were seen in various organ systems in 75% of the negative animals, compared with moderate to marked infiltrates in 83% of infected animals. Lymphoid infiltrates were more common in the brain, bone marrow, and salivary gland of viremic animals and were rare to nonexistent in seropositive or negative animals. Lymphoid hyperplasia was present in 38% of the infected animals, whereas lymphoid depletion was seen in 47% of the infected animals. Overall, lesions were of greater severity in viremic animals than in virus-negative or seropositive animals. Overall, infected animals had lower, statistically significant hematocrit and lymphocyte values. Viremic animals had significantly lower hematocrit, white blood cell, lymphocyte, and neutrophil values than did controls. Only 1 out of 24 infected animals had clinical signs that were consistent with the definition of SAIDS, and none had evidence of opportunistic infections. Lesions were similar to those already reported in other species of macaques, but the absence of severe illness that was consistent with SAIDS in most viremic animals suggests that there may be a different manifestation of disease in the cynomolgus. [References: 19] <12> UI - 1999406476 AU - Yamaguchi I AU - Osakada K AU - Yamamoto T AU - Katada M IN - I. Yamaguchi, Res. Lab. of Resources Utilization, Tokyo InStitute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503; Japan. TI - 1:2 polycondensation of 3,3',4,4'-biphenyltetramine and 1,1'- ferrocenedimethanol catalyzed by [RuCl2(PPh3)3] to give polybenzimidazole containing ferrocenylene groups. SO - Bulletin of the Chemical Society of Japan Vol 72(11) (pp 2557-2562), 1999. AB - The 1:2 polycondensation of 3,3',4,4'-biphenyltetramine and 1,1'- ferrocenedimethanol catalyzed by [RUCl2(PPh3)3] gives ferrocenylene- containing polybenzimidazole 1, (Im-Fc-CH2-O-CH2-Fc)(n) (Im = [5,5'- bi(benzimidazole)]-2,2'-diyl, Fc = 1,1'-ferrocenediyl). The reaction involves 1:2 condensation of 3,3',4,4'-biphenyltetramine and 1,1'-ferrocenedimethanol to make two imidazole rings and subsequent intermolecular dehydrating coupling of two CH2OH groups to form the CH2-O-CH2 linkage. Polymer 1 is soluble in DMF and DMSO and has molecular weights, M(n) 2. 1 x 104 and M(w) = 4.5 x 104, determined by GPC (polystyrene standards). Extremely broad 1H NMR signals and results of SQUID measurements showing paramagnetism of 1 suggest the presence of Fe(III) centers in the polymer. The content of Fe(III) is estimated as approximately 20% based on the Mossbauer spectrum of 1. An equimolar reaction of 1,2-diaminobenzene and 1,1'-ferrocenedimethanol in the presence of th(Ru(II) catalyst gives bis[1'-(benzimidazol-2- yl)ferrocen-1-ylmethyl] ether. The model compound shows reversible oxidation and reduction peaks assigned to the Fe(II)/Fe(III) redox, whereas the polymer I undergoes oxidation and subsequent irreversible deprotonation to give the electrochemically inert polymer. [References: 82] <13> UI - 1999394705 AU - Avula CPR AU - Fernandes G IN - G. Fernandes, Department of Medicine, Division of Clinical Immunology, University of Texas, 7703 Floyd Curl, San Antonio, TX 78284-7874; United States. TI - Modulation of lipid peroxidation and antioxidant enzymes in murine salivary gland by dietary fatty acid ethyl esters. SO - Life Sciences Vol 65(22) (pp 2373-2383), 1999. AB - The present study was undertaken to investigate the effect of n-9, n-6, and n-3 dietary fatty acid ethyl esters on basal (uninduced) and Fe2+/ascorbate (induced) lipid peroxidation (LPO) in salivary gland (SG) of mice. Feeding n-3 ethyl ester polyunsaturated fatty acids (PUFA) increased the uninduced and induced LPO in SG homogenates. In contrast, feeding olive oil ethyl esters (n-9) significantly lowered the induced and uninduced LPO in SG tissue. Salivary gland susceptibility to LPO increased in the order of: olive oil < corn oil < safflower oil < n-3 ethyl esters. Olive oil esters in the diet increased primarily the 18:1 levels in SG tissue. Whereas feeding n-3 PUFA notably increased the superoxide dismutase (SOD) and catalase activities in SG homogenates, no significant changes were seen between n-9 and n-6 PUFA-fed mice. Lower levels of Vitamin E (Vit E) in the tissues of n-3 PUFA-fed mice indicate that the higher the dietary lipid unsaturation, the higher the requirement for Vit E in the diet. Our results indicate that, similar to other organs, salivary gland susceptibility to uninduced or induced oxidation depends on the source of dietary PUFA. In conclusion, feeding olive oil increases the resistance of SGs to induced and uninduced LPO. [References: 50] <14> UI - 1999391667 AU - Pontillon Y AU - Akita T AU - Grand A AU - Kobayashi K AU - Lelievre-Berna E AU - Pecaut J AU - Ressouche E AU - Schweizer J IN - J. Schweizer, Commissariat a l'Energie Atomique, MDN/SPSMS/DRFMC, CEN-Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9; France. TI - Experimental and theoretical spin density in a ferromagnetic molecular complex presenting interheteromolecular hydrogen bonds. SO - Journal of the American Chemical Society Vol 121(43) (pp 10126-10133), 1999. AB - The association of phenylboronic acid (no unpaired electron, compound 1) with the free radical phenyl nitronyl nitroxide (PNN, S = [half], compound 2) constitutes an interheteromolecular hydrogen bonding system displaying ferromagnetic intermolecular interactions. We have investigated its spin density distribution to visualize the pathway of these magnetic interactions. This complex crystallizes at room temperature in the monoclinic space group P21/n. The unit cell includes one pair (1 + 2). The molecule (1) bridges two radicals (2) by hydrogen bonds OH...ON: the two different hydrogen bond lengths are quite similar (1.95 and 1.92 [Angstrom] ). Infinite chains of this run along the b-axis. In this structure the methyl groups of the PNN are randomly distributed in two different configurations. Below T = 220 K the compound undergoes a crystallographic phase transition due to the ordering of these methyl groups. We have determined the low-temperature structure using both X- ray and neutron diffraction. The new space group is P1-. The global structure is preserved and infinite chains still run along the b-axis, but the unit cell now comprises two different pairs (1 + 2) instead of one, with four different hydrogen bond OH...ON distances: 1.96 and 1.84 [Angstrom] for the first pair, 1.96 and 1.91 [Angstrom] for the second pair. The spin density of this complex was measured at T = 1.8 K (H = 4.6 T) by polarized neutron diffraction. The data were treated using both maximum entropy approach and wave function modeling. As in the isolated PNN, the main part of the spin density is located on the O-N-C-N-O fragment of each radical in the unit cell. However, compared to the isolated case, a significant difference exists: a large unbalance is observed between the two oxygen atoms of each radical. Moreover, a positive contribution is found on the two hydrogen atoms involved on the OH...ON hydrogen bonds of each phenylboronic acid molecule. The stronger contribution corresponds to the longer hydrogen bonds. On the radical the stronger reduction is observed on the oxygen atoms involved in the shorter hydrogen bonds. The experimental results are compared to those obtained by density functional theory (DFT) calculations: on the whole, the experimental effects have been reproduced. However, if there is a good qualitative agreement, from the quantitative point of view, the DFT results are still very far from the experimental ones. <15> UI - 1999386165 AU - Kuipers ME AU - De Vries HG AU - Eikelboom MC AU - Meijer DKF AU - Swart PJ IN - M.E. Kuipers, Yamanouchi Europe BV, Clinical Pharmacology Research Dept., Elisabethhof 1, 2353 EW Leiderdorp; Netherlands. E-Mail: kuipers.nl@yamanouchi-eu.com. TI - Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates. SO - Antimicrobial Agents & Chemotherapy Vol 43(11) (pp 2635-2641), 1999. AB - Because of the rising incidence of failures in the treatment of oropharyngeal candidosis in the case of severely immunosuppressed patients (mostly human immunodeficiency virus [HIV]-infected patients), there is need for the development of new, more effective agents and/or compounds that support the activity of the common antifungal agents. Since lactoferrin is one of the nonspecific host defense factors present in saliva that exhibit antifungal activity, we studied the antifungal effects of human, bovine, and iron-depleted lactoferrin in combination with fluconazole, amphotericin B, and 5-fluorocytosine in vitro against clinical isolates of Candida species. Distinct antifungal activities of lactoferrin were observed against clinical isolates of Candida. The MICs generally were determined to be in the range of 0.5 to 100 mg . ml-1. Interestingly, in the combination experiments we observed pronounced cooperative activity against the growth of Candida by using lactoferrin and the three antifungals tested. Only in a limited concentration range was minor antagonism detected. The use of lactoferrin and fluconazole appeared to be the most successful combination. Significant reductions in the minimal effective concentrations of fluconazole were found when it was combined with a relatively low lactoferrin concentration (1 mg/ml). Such combinations still resulted in complete growth inhibition, while synergy of up to 50% against several Candida species was observed. It is concluded that the combined use of lactoferrin and antifungals against severe infections with Candida is an attractive therapeutic option. Since fluconazole-resistant Candida species have frequently been reported, especially in HIV-infected patients, the addition of lactoferrin to the existing fluconazole therapy could postpone the occurrence of species resistance against fluconazole. Clinical studies to further elucidate the potential utility of this combination therapy have been initiated. [References: 42] <16> UI - 1999380257 AU - Munday R AU - Smith BL AU - Munday CM IN - R. Munday, AgResearch, Ruakura Agricultural Research Centre, Private Bag 3123, Hamilton; New Zealand. E-Mail: mundayr@agresearch.cri.nz. TI - Effect of inducers of DT-diaphorase on the toxicity of 2-methyl- and 2-hydroxy-1,4-naphthoquinone to rats. SO - Chemico-Biological Interactions Vol 123(3) (pp 219-237), 1999. AB - It has previously been shown that rats pre-treated with butylated hydroxyanisole (BHA), a well-known inducer of the enzyme DT-diaphorase, are protected against the toxic effects of 2-methyl-1,4-naphthoquinone but are made more susceptible to the harmful action of 2-hydroxy-1,4-naphthoquinone. In the present experiments, the effects of BHA have been compared with those of other inducers of DT-diaphorase. Rats were dosed with BHA, butylated hydroxytoluene (BHT), ethoxyquin (EQ), dimethyl fumarate (DMF) or disulfiram (DIS) and then challenged with a toxic dose of the naphthoquinones. All the inducers protected against the haemolytic anaemia induced by 2-methyl-1,4-naphthoquinone in rats, with BHA, BHT and EQ being somewhat more effective than DMF and DIS. A similar order of activity was recorded in the relative ability of these substances to increase hepatic activities of DT-diaphorase, consistent with a role for this enzyme in facilitating conjugation and excretion of this naphthoquinone. In contrast, all the compounds increased the haemolytic activity of 2-hydroxy-1,4-naphthoquinone. DMF and DIS were significantly more effective in this regard than BHA, BHT and EQ. DMF and DIS also caused a much greater increase in levels of DT-diaphorase in the intestine, suggesting that 2-hydroxy-1,4-naphthoquinone is activated by this enzyme in the gut. BHA, BHT and EQ had no effect on the nephrotoxicity of 2-hydroxy-1,4-naphthoquinone, but the severity of the renal lesions was decreased in rats pre-treated with DMF and DIS. The results of the present experiments show that modulation of tissue levels of DT-diaphorase may not only alter the severity of naphthoquinone toxicity in vivo, but may also change the relative toxicity of these substances to different target organs. Copyright (C) 1999 Elsevier Science Ireland Ltd. [References: 62] <17> UI - 1999355467 AU - Kodaira H AU - Ishihara K AU - Hotta K AU - Kagoshima M AU - Shimada H AU - Ishii K IN - H. Kodaira, Department of Molecular Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641; Japan. TI - Rat gastric mucous gel layer contains sialomucin not produced by the stomach. SO - Japanese Journal of Pharmacology Vol 81(1) (pp 86-93), 1999. AB - The sialylated mucus components of the normal gastric mucosa and mucous gel layer of rats were studied by using various histochemical staining methods including Maackia amurensis II (MAL-II) and Sambucus nigra (SNA) lectins, alcian blue (AB) pH 2.5 - periodic acid Schiff (PAS) and high iron diamine (HID) - AB pH 2.5. The acidic and neutral mucins characterized by the AB-PAS staining were abundantly present in the mucous gel layer as well as in the gastric mucosa. The sialomucin characterized by HID-AB was barely found in either the mucous gel layer or the mucosa. The sialomucin positive to MAL-II and SNA, which react with the N-acetyl neuraminic acid residue linked to galactose via an alpha-linkage, was moderately detected only in the mucous gel layer, but not in the entire mucosal layer. Furthermore, in animals given surgery to form an esophageal fistula through which saliva was excluded or in animals subjected to salivectomy, the mucous gel layer stained with MAL-II and SNA lectins was markedly decreased. These results indicate that a part of the sialomucin containing-mucous gel layer covering normal rat gastric mucosa originates from the saliva and that MAL-II and SNA lectins are useful for detecting this specific sialomucin. [References: 37] <18> UI - 1999290667 AU - Zhang J AU - Slevin CJ AU - Unwin PR IN - P.R. Unwin, Department of Chemistry, University of Warwick, Coventry CV4 7AL; United Kingdom. E-Mail: P.R.Unwin@warwick.ac.uk. TI - Resolution of coupled electron transfer-ion transfer processes at liquid/liquid interfaces by visualisation of interfacial concentration profiles. SO - Chemical Communications Vol 5(16) (pp 1501-1502), 1999. AB - A powerful approach for investigating heterogeneous electron transfer (ET) reactions at liquid/liquid (oil/water) interfaces is described and illustrated with studies of the reactions between IrCl62- or Fe(CN)63- in an aqueous phase and decamethylferrocene (DMFc) or ferrocene (Fc) in 1,2-dichloroethane (DCE). [References: 18] <19> UI - 1999285025 AU - Basch H AU - Mogi K AU - Musaev DG AU - Morokuma K IN - H. Basch, Cherry L. Emerson Ctr. Sci. Comp., Department of Chemistry, Emory University, Atlanta, GA 30322; United States. TI - Mechanism of the methane [right arrow] methanol conversion reaction catalyzed by methane monooxygenase: A density functional study. SO - Journal of the American Chemical Society Vol 121(31) (pp 7249-7256), 1999. AB - The hybrid density functional (DFT) method B3LYP was used to study the mechanism of the methane hydroxylation reaction catalyzed by a non-heme diiron enzyme, methane monooxygenase (MMO). The key reactive compound Q of MMO was modeled by (NH2)(H2O)Fe(m-O)2(eta2-HCOO)2Fe(NH2)(H2O), I. The reaction is shown to take place via a bound-radical mechanism and an intricate change of the electronic structure of the Fe core is associated with the reaction process. Starting with I, which has a diamond-core structure with two Fe(IV) atoms, L4F(IV)(mu-O)2Fe(IV)L4, the reaction with methane goes over the rate-determining H-abstraction transition state III to reach a bound-radical intermediate IV, L4Fe(IV)(mu-O)(mu-OH(. . . CH3))Fe(III)L4, which has a bridged hydroxyl ligand interacting weakly with a methyl radical and is in an Fe(III)-Fe(IV) mixed valence state. This short- lived intermediate IV easily rearranges intramolecularly through a low barrier at transition state V for addition of the methyl radical to the hydroxyl ligand to give the methanol complex VI, L4Fe(III)(OHCH3)(mu- O)Fe(III)L4, which has an Fe(III)-Fe(III) core. The barrier of the rate- determining step, methane H-abstraction, was calculated to be 19 kcal/mol. The overall CH4 oxidation reaction to form the methanol complex, I + CH4 [right arrow] VI, was found to be exothermic by 39 kcal/mol. <20> UI - 1999280447 AU - Cannes C AU - Bedioui F AU - Condon-Gueugnot S AU - Nedelec JY AU - Devynck J IN - F. Bedioui, Lab. d'Electrochimie/Chimie Analyt., UMR CNRS-ENSCP no. 7575, Ecole Nat. Super. de Chimie de Paris, 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05; France. E-Mail: bedioui@ext.jussieu.fr. TI - Electroassisted catalysis of the reductive coupling of 2-bromooctane and methyl vinyl ketone by a binuclear cobalt-salen-iron complex in DMF solution: Electrosynthesis and cyclic voltammetry analysis. SO - NEW J CHEM, Vol 23(5) (pp 489-494), 1999. AB - We report in this study the combined use of a CoSalen [H2 Salen = bis(salicylidene)ethane-1,2-diamine] complex and an undivided electrochemical cell process in the electroassisted reductive coupling of 2-bromooctane and methyl vinyl ketone with satisfactory results. Correlation between the electroanalytical analysis of the reactivity of CoSalen in the presence of 2- bromooctane and methyl vinyl ketone and the electrosynthesis performed in an undivided electrochemical cell with a sacrificial iron anode allows us to suggest that a heterobinuclear Co-Salen-Fe complex is the effective catalyst of the considered reaction. Stability of this intermediate during preparative electrolysis is also discussed. <21> UI - 1999280174 AU - Carpenter GH AU - Pankhurst CL AU - Proctor GB IN - Dr. G.H. Carpenter, Secretory and Soft Tissue Res. Unit, Rayne Institute, 123 Coldharbour Lane, London SE5 9NU; United Kingdom. E-Mail: guy.carpenter@kcl.ac.uk. TI - Lectin binding studies of parotid salivary glycoproteins in Sjogren's syndrome. SO - Electrophoresis Vol 20(10) (pp 2124-2132), 1999. AB - Human parotid salivas were collected from patients with secondary Sjogren's syndrome and controls without disease or with drug-induced xerostomia. Parotid glycoproteins were separated by gradient sodium dodecyl sulphate gel electrophoresis (SDS-PAGE), electroblotted onto nitrocellulose membrane and probed with biotinylated lectins of characterised sugar specificities. The binding patterns of lectins from Maclura pomifera (MPA) and Arachis hypogaea (PNA) indicated that many parotid glycoproteins have sialylated O-linked glycans and that sialylation is not affected by disease. Binding by lectins from Ricinus communis (RCA-1), Limax flayus (LFA), Lotus tetragonolobus (LTA) and Ulex europaeus (UEA-1) appeared unaltered in secondary Sjogren's syndrome, suggesting no obvious change in N-glycosylation of parotid glycoproteins. Variations in binding patterns of most lectins was attributable to subject-to-subject variations in recognised polymorphic proteins. Dolichos biflorus agglutinin (DBA) consistently showed increased binding to a 75 kDa (Mr) protein in salivas from patients with secondary Sjogren's syndrome. The binding protein was identified as lactoferrin but found not to contain N-acetylgalactosamine, the sugar to which DBA binds. Binding of DBA to lactoferrin was dependent upon its saturation with iron modified SDS-PAGE under nonreducing conditions resolved iron-free and iron- saturated lactoferrins and demonstrated increased levels of the iron- saturated form in secondary Sjogren's syndrome. Lectin binding studies of purified lactoferrins from saliva, milk, and polymorphonuclear neutrophils suggested that raised levels of lactoferrin in saliva originate from salivary cells and not from inflammatory cells. These results suggest that DBA binding provides greater specificity as an indicator of salivary gland disease than measurement of lactoferrin levels alone. [References: 33] <22> UI - 1999251416 AU - Deng L AU - Margl P AU - Ziegler T IN - T. Ziegler, Department of Chemistry, University of Calgary, Calgary, Alta. 72N 1N4; Canada. TI - Mechanistic aspects of ethylene polymerization by iron(II)-bisimine pyridine catalysts: A combined density functional theory and molecular mechanics study. SO - Journal of the American Chemical Society Vol 121(27) (pp 6479-6487), 1999. AB - We present an extensive theoretical study of the iron(II)-bisimine pyridine based ethylene-polymerization catalysts {[2,6-((R)N=C(R'))2- C5H3N]FeC3H7}+ (R = R' = H, 1a; R = 2,6-C6H4(i-Pr)2, R' = CH3, 1A) recently developed by the groups of Brookhart and Gibson. The study was based on density functional theory (DFT) for the 'generic' model system 1a and a combined DFT and molecular mechanics approach for the 'real' system 1A. It is shown that the rate-determining step for both termination and propagation in the 'real' system is the capture of ethylene by 1A. The steric bulk introduced by R = 2,6-C6H4(i-Pr)2 was found to suppress ethylene capture for the termination step and increase the rate of insertion. Termination takes place on the singlet potential energy surface (PES). For propagation the singlet and triplet PES's are close in energy and spin-state change is possible. The quintet states are too high in energy to play any role in polymerization. The model system 1a was found to form an ethylene complex that is too stable for any further chemical transformation to take place. <23> UI - 1999246532 AU - Diekwisch TGH AU - Marches F AU - Williams A AU - Luan X IN - T.G.H. Diekwisch, Baylor College of Dentistry, Texas A and M University System, 3302 Gaston Avenue, Dallas, TX 75246; United States. E-Mail: tomdkw@tambcd.edu. TI - Cloning, gene expression, and characterization of CP27, a novel gene in mouse embryogenesis. SO - Gene Vol 235(1-2) (pp 19-30), 1999. AB - We report the full-length sequencing, tissue-specific expression, and immunolocalization of cp27, a novel gene in mouse embryogenesis. The cp27 gene was isolated and cloned from a mouse E11 lambdagt11 library using a peptide antibody that recognized a distinct expression pattern in mouse craniofacial development. The cp27 gene contains an open reading frame of 295 amino acids corresponding to a predicted molecular mass of 33 kDa. On Western blots, a polyclonal antibody against CP27 detected a single epitope at 27 kDa. The putative CP27 protein has an isoelectric point of 4.75 and features a distinct helix-loop-helix structure according to prediction algorithms. We have cloned the human cp27 gene and mapped it to a locus on the human chromosome 16 which is in proximity to several loci associated with inherited craniofacial diseases such as fanconi anemia type A. Northern blot analysis of RNA from multiple mouse tissues demonstrated high levels of expression in developing mouse teeth, heart, lung, and liver of a single transcript of approx. 1.8 kbp. In situ hybridization using a radioactive RNA probe resulted in distinct signals in the developing neuroepithelium, cerebellum, heart, lung, liver, teeth, salivary glands, and periosteum of developing bones. Immunohistochemical staining of developing mouse tissues detected epitopes specific for CP27 in the mesenchyme surrounding the primary brain vesicles, in basement membranes, in the periosteum, in salivary glands, and in the stellate reticulum of teeth. Thus, CP27 represents a unique gene product involved in mouse embryogenesis. (C) 1999 Elsevier Science B.V. All rights reserved. [References: 28] <24> UI - 1999186548 AU - Dexter DT AU - Ward RJ AU - Florence A AU - Jenner P AU - Crichton RR IN - Dr. D.T. Dexter, Dept. Neurodegenerative Disorders, Imperial College, School of Medicine, Fulham Palace Road, London W6 8RF; United Kingdom. E-Mail: d.dexter@ic.ac.uk. TI - Effects of desferrithiocin and its derivatives on peripheral iron and striatal dopamine and 5-hydroxytryptamine metabolism in the ferrocene-loaded rat. SO - Biochemical Pharmacology Vol 58(1) (pp 151-155), 1999. AB - Iron overload disorders, such as beta-thalassaemia, are currently treated with the iron chelator desferrioxamine (DFO) or 1,2-dimethyl-3-hydroxypyridin-4-one (L1), which is currently under clinical evaluation. However, DFO is inactive orally and needs to be administered by intramuscular infusion, whilst there are concerns over the long-term effectiveness and toxicity of L1. In addition, both DFO and L1 affect brain dopamine (DA) and 5-hydroxytryptamine (5-HT) metabolism. In this study, the 3,5,5-trimethylhexanoyl ferrocene rat model of iron overload was used to compare the iron-chelating capabilities of a novel orally active siderophore, desferrithiocin (DFT) and its desmethyl derivatives DFT-D and DFT-L, to that of DFO, along with their ability to affect brain DA and 5-HT metabolism. Chronic administration of ferrocene produced a 12-fold increase in liver iron levels, as assessed by electrothermal atomic absorption. Subsequent treatment with DFT over a two-week period produced a 37% reduction in liver iron levels, whereas similar treatment with DFT-D and DFT-L produced a more marked reduction in these levels (65% and 59%, respectively) in the ferrocene-treated animals. In contrast, using the same dosing regimen, DFO and L1 only produced a 16% and 18% reduction, respectively, in liver iron levels. Both DFT and its derivatives failed to affect either striatal DA or 5-HT metabolism when assessed by HPLC. In view of the previously described oral bioavailability of DFT, the marked ability of DFT and its derivatives to chelate hepatic iron, and their inability to affect brain DA or 5-HT metabolism, such siderophores appear potentially useful clinical iron chelators. Copyright (C) 1999 Elsevier Science Inc. [References: 25] <25> UI - 1999183065 AU - Spatafora GA AU - Moore MW IN - Dr. G.A. Spatafora, Department of Biology, Middlebury College, Middlebury, VT 05753; United States. E-Mail: spatafor@panther.middlebury.edu. TI - Growth of Streptococcus mutans in an iron-limiting medium. SO - Methods in Cell Science Vol 20(1-4) (pp 217-221), 1998. AB - Microbial pathogens require iron to survive and promote disease. Reports in the literature indicate that iron can potentiate infection in the human host by triggering the expression of bacterial virulence determinants. Streptococcus mutans is a prevalent microorganism in dental plaque and the principal causative agent of human dental caries. This oral pathogen may respond to the changing availability of iron in the plaque environment brought about by conditions of feast or famine. Our understanding of a role for iron in S. mutans-induced caries formation is limited, however, by the lack of an appropriate test medium. In this study we applied batch chromatography to remove iron from a chemically-defined medium which we subsequently reconstituted with manganese and/or magnesium. The final metal ion concentrations in this medium were confirmed by inductively coupled argon plasma (ICAP) analysis. Importantly, the iron-depleted medium supported the growth of S. mutans only when supplemented with 0.01 to 10 muM iron, concentrations which are consistent with those found in human saliva. The practical applications of this medium are far-reaching and include the identification of iron sources, and iron-responsive genes and their products which may promote streptococcal pathogenesis. Other trace metals may be altered in this medium to promote investigations of their putative effect(s) on streptococcal growth and expression. [References: 9] <26> UI - 1999176343 AU - Chart H AU - Jenkins C IN - Dr. H. Chart, Laboratory of Enteric Pathogens, Central Public Health Laboratory, 61 Colindale Avenue, Colindale, London NW9 5HT; United Kingdom. TI - The serodiagnosis of infections caused by verocytotoxin-producing Escherichia coli. SO - Journal of Applied Microbiology Vol 86(5) (pp 731-740), 1999. AB - Patients with haemolytic uraemic syndrome (HUS) and haemorrhagic colitis (HC) produce serum antibodies to the lipopolysaccharides (LPS) of Escherichia coli O157 and certain other E. coli serogroups. Patients may also make salivary antibodies to the LPS of E. coli O157. Serological tests based on these antibodies can be used to provide evidence of infection in the absence of culturable VTEC or the toxins they produce. Serum antibodies to LPS persist for several months following onset of disease, enabling both current and retrospective serological testing. The LPS of E. coli O157 shares epitopes with strains of Brucella abortus, Yersinia enterocolitica O9, Vibrio cholerae O1 Inaba, group N Salmonella and certain strains of Citrobacter freundii and E. hermanni. Serological tests for serum antibodies to E. coli O157 should be evaluated in the light of these cross-reactions. Serological tests to supply evidence of infection with E. coli O157 have been shown to provide a valuable adjunct to bacteriological procedures for detecting culturable VTEC and VT. The use of well characterized LPS antigens in association with the techniques of ELISA and immunoblotting provide valuable procedures for detecting evidence of infection with E. coli O157 and possibly other VTEC. [References: 88] <27> UI - 1999175685 AU - Kaneko Y AU - Yuda M AU - Iio T AU - Murase T AU - Chinzei Y IN - Y. Chinzei, Department Medical Zoology, School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-0001; Japan. E-Mail: chinzei@doc.medic.mie-u.ac.jp. TI - Kinetic analysis on nitric oxide binding of recombinant Prolixin-S, a nitric oxide transport protein from the bloodsucking bug, Rhodnius prolixus. SO - Biochimica et Biophysica Acta - Protein Structure & Molecular Enzymology Vol 1431(2) (pp 492-499), 1999. AB - Kinetics of the NO binding and removal reaction of recombinant Prolixin-S (rProlixin-S) were analyzed using stopped-flow spectrophotometry. The reaction was observed as a biphasic process. The rate constant of the fast phase increased linearly as NO concentration increased. The rate constant at the slow phase increased as NO concentrations increased at low NO concentration, then reached a plateau at high NO concentration. These NO dependencies of the reaction are characteristic of a bimolecular two-step consecutive reaction. The reaction consisted of the fast NO binding reaction of rProlixin-S and the following slow structural change of NO-protein complex. Kinetic studies revealed that the NO binding rate constant was independent of pH, but the rate constant of the NO removal reaction increased as pH increased. The apparent NO dissociation constant (K(d)) of rProlixin-S was also calculated from the values of the kinetic parameters obtained in this work. The K(d) value increased as pH and temperature increased. The K(d) value of rProlixin-S and NO was 10-300 nM in regular physiological condition, which is 103 higher and 103 lower than those of the other ferric and ferrous hemoproteins and NO, respectively. These results indicate that Prolixin-S is one of NO transport proteins regulating blood pressure. Copyright (C) 1999 Elsevier Science B.V. [References: 31] <28> UI - 1999162025 AU - Drouin BJ AU - Kukolich SG IN - S.G. Kukolich, Chemistry Department, University of Arizona, Tucson, AZ 85721; United States. TI - Microwave spectra and the molecular structure of tetracarbonylethyleneiron. SO - Journal of the American Chemical Society Vol 121(16) (pp 4023-4030), 1999. AB - Microwave spectra of seven isotopomers of tetracarbonylethyleneiron were recorded using a Pulse-Beam Fourier Transform Microwave Spectrometer. Rotational transitions for a 'c' dipole moment with J' [left arrow] J from 2 [left arrow] I to 6 [left arrow] 5 were measured in the 4-12 GHz range. Rotational constants were determined by fitting the measured microwave spectra to a Watson 'A' reduced Hamiltonian with centrifugal distortion parameters. The measured rotational constants of the main isotopomer are A = 1031.1081(4) MHz, B = 859.8055(4) MHz, and C = 808.5675(3) MHz. Data were also obtained for three 13C- substituted species and two 18O-substituted species in natural abundance. Additional spectra were measured for an isotopically enriched sample of perdeuterated tetracarbonylethyleneiron. The moments of inertia of the seven isotopomers were used in a Kraitchman analysis and in two different least- squares fitting analyses to determine the molecular structure of the compound. The ethylene ligand exhibits significant structural changes upon complexation to iron, primarily an increase in C-C bond length with movement of the hydrogen atoms away from the metal center. The CC and CH bond lengths were found to be r(o) = 1.419(7) and = 1.072(4) [Angstrom], respectively. The CCH angle and the FeCCH dihedral angle were found to be <(CCH)(o) = 120.6(5) [degree] and <(Fe-CCH)(o) = 103.6(9) [degree], respectively. The plane of the hydrogen atoms is displaced 0.217(2) [Angstrom] above the ethylene carbon atoms, along the c axis. Extensive DFT calculations were carried out prior to the experimental research. The calculated structure proved extremely valuable in obtaining accurate predictions for the spectra, and provided structural parameters in excellent overall agreement with measured parameters. <29> UI - 1999162022 AU - Niu S AU - Thomson LM AU - Hall MB IN - M.B. Hall, Department of Chemistry, Texas A and M University, College Station, TX 77843; United States. TI - Theoretical characterization of the reaction intermediates in a model of the nickel iron hydrogenase of Desulfovibrio gigas. SO - Journal of the American Chemical Society Vol 121(16) (pp 4000-4007), 1999. AB - The catalytic cycle for H2 oxidation in [NiFe] D. gigas hydrogenase has been investigated through density functional theory (DFT) calculations on a wide variety of redox and protonated structures of the active site model, (CO)(CN)2Fe(mu-SMe)2Ni(SMe)2. DFT calculations on a series of known LFe(CO)(CN)(L')(n-) (L = Cp or Cp*, L' = CN, CO, CNCH3; n = 0, 1, 2) complexes are used to calibrate the calculated CO bond distances with the measured IR stretching frequency. By combining this calibration curve with the energy and CO bond distance of the DFT calculations on the active site model and the experimental IR frequencies on the enzyme, the redox states and structures of active site species have been determined: Ni-B is a Ni(III)- Fe(II) species, Ni-SI(a) is a Ni(II)-Fe(II) species, Ni-SI(b) has a protonated terminal sulfur (Ni bound), Ni-R is a Ni(II)-Fe(II) dihydrogen complex with H2 bound at Fe, and Ni-C is a Ni(III)-Fe(II) species with an FeH-Ni bridge. The latter species returns to Ni-SI through a Ni(I)-Fe(II) intermediate, which is potentially observable. Protonation of the Ni bound terminal sulfur results in a folding of the Fe(mu-S)2Ni framework. Dihydrogen activation is more exothermic on the Ni(III) species than on the corresponding Ni(II) or Ni(I) species. Our final set of proposed structures are consistent with IR, EPR, ENDOR, and XAS measurements for these species, and the correlation coefficient between the measured CO frequency in the enzyme and the CO distance calculated for the model species is 0.905. <30> UI - 1999162003 AU - Godbout N AU - Sanders LK AU - Salzmann R AU - Havlin RH AU - Wojdelski M AU - Oldfield E IN - E. Oldfield, Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801; United States. TI - Solid-state NMR, Mossbauer, crystallographic, and density functional theory investigation of Fe-O2 and Fe-O2 analogue metalloporphyrins and metalloproteins. SO - Journal of the American Chemical Society Vol 121(16) (pp 3829-3844), 1999. AB - We have synthesized and studied via solid-state NMR, Mossbauer spectroscopy, single-crystal X-ray diffraction, and density functional theory the following Fe-O2 analogue metalloporphyrins: Fe(5,10,15,20- tetraphenylporphyrinate) (nitrosobenzene)(1-methylimidazole); Fe(5,10,15,20- tetraphenylporphyrinate) (nitrosobenzene)(pyridine); Fe(5,10,15,20- tetraphenylporphyrinate)(4-nitroso-N,N-dimethylaniline)(pyridine); Fe(2,3,7,8,12,13,17,18-octaethylporphyrinate) (nitrosobenzene)(1- methylimidazole) and Co(2,3,7,8,12,13,17,18-octaethylporphyrinate)(NO). Our results show that the porphyrin rings of the two tetraphenylporphyrins containing pyridine are ruffled while the other three compounds are planar: reasons for this are discussed. The solid-state NMR and Mossbauer spectroscopic results are well reproduced by the DFT calculations, which then enable the testing of various models of Fe-O2 bonding in metalloporphyrins and metalloproteins. We find no evidence for two binding sites in oxypicket fence porphyrin, characterized by very different electric field gradients. However, the experimental Mossbauer quadrupole splittings can be readily accounted for by fast axial rotation of the Fe-O2 unit. Unlike oxymyoglobin, the Mossbauer quadrupole splitting in PhNO . myoglobin does not change with temperature, due to the static nature of the Fe . PhNO subunit, as verified by 2H NMR of Mb . [2H5]PhNO. Rotation of O2 to a second (minority) site in oxymyoglobin can reduce the experimental quadrupole splittings, either by simple exchange averaging, or by an electronic mechanism, without significant changes in the Fe-O-O bond geometry, or a change in sign of the quadrupole splitting. DFT calculations of the molecular electrostatic potentials in CO, PhNO, and O2-metalloporphyrin complexes show that the oxygen sites in the PhNO and O2 complexes are more electronegative than that in the CO system, which strongly supports the idea that hydrogen bonding to O2 will be a major contributor to O2/CO discrimination in heme proteins. <31> UI - 1999162002 AU - Salzmann R AU - McMahon MT AU - Godbout N AU - Sanders LK AU - Wojdelski M AU - Oldfield E IN - E. Oldfield, Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801; United States. TI - Solid-state NMR, crystallographic and density functional theory investigation of Fe-CO and Fe-CO analogue metalloporphyrins and metalloproteins. SO - Journal of the American Chemical Society Vol 121(16) (pp 3818-3828), 1999. AB - We have synthesized and characterized the following four metalloporphyrins: Fe(OEP)(CO)(1-MeIm), Ru(OEP)(CO)(1-MeIm), Os(OEP)(CO)(1- MeIm), and Fe(TPP)(iPrNC)(1-MeIm), where OEP = 2,3,7,8,12,13,17,18- octaethylporphyrinate, TPP = 5,10,15,20-tetraphenylporphyrinate, and 1-MeIm = 1-methylimidazole, using single-crystal X-ray diffraction, solid-state nuclear magnetic resonance (NMR), and density functional theory (DFT) methods. Unlike the situation found with the Fe-, Ru-, Os(TPP)(CO)(1-MeIm) analogues, which have ruffled porphyrins, all four systems here have essentially planar porphyrin rings, and a rule is developed that successfully predicts the presence or absence of ring distortion in a broad range of metalloporphyrins. In each of the three CO complexes, the M-C-O bond is close to linear and untilted, but with the iPrNC adduct, there are noticeable ligand distortions supporting the idea that RNC groups (but not CO) may be distorted in metalloproteins. Solid-state 13C, 15N, and 17NMR shifts and shifts and tensors determined experimentally are in generally good agreement with those computed via DFT. For isocyanide binding to proteins, the experimental shifts are more deshielded than in the model system, and the effects which might contribute to this difference are explored theoretically. Unlike CO, electrostatic field effects are unlikely to make a major contribution to protein shielding. Neither are Fe-C-N tilt-bend distortions, although a bend at nitrogen is energetically feasible and also gives a large deshielding, as seen with proteins. <32> UI - 1999166822 AU - Beissel T AU - Powers RE AU - Parac TN AU - Raymond KN IN - K.N. Raymond, Department of Chemistry, University of California, Berkeley, CA 94720; United States. TI - Dynamic isomerization of a supramolecular tetrahedral M4L6 cluster. SO - Journal of the American Chemical Society Vol 121(17) (pp 4200-4206), 1999. AB - The bis-hydroxamate ligand isophthal-di-N-(4-methylphenyl)hydroxamate (E) forms tetrahedral clusters of the type M4E6 (M = Ga(III), Fe(III)). The syntheses of these and several other tetrahedral metal clusters have illustrated a general approach to the design of supramolecular metal clusters based on incommensurate coordination number interactions. In each case, rigid spacers separate bidentate units and preclude formation of metal coordination species other than the one targeted. For the Ga4E6 cluster described here each vertex is a chiral metal center (Delta or Delta) that generates clusters with T (DeltaDeltaDeltaDelta or DeltaDeltaDeltaDelta), C3 (DeltaDeltaDeltaDelta or DeltaDeltaDeltaDelta), or S4 (DeltaDeltaDeltaDelta) symmetry. The rigid ligand spacer is bimodal, accommodating either mixed or homochiral metal centers at either end, but locks in the chirality of the complex once formed. Therefore all three isomers are seen in solution and their interconversion, although still on the NMR time scale, is significantly slower than isomerization of similar unimolecular hydroxamate complexes. The distribution of the isomers in aqueous solution for the T, C3, and S4 isomers is 4, 58, and 38%, respectively. The barrier to the interconversions, which occur through a nondissociative trigonal twist at the metal centers, is 58 kJ mol-1 for each of the isomerization steps. The syntheses of the ligand and corresponding iron and gallium complexes are described. The compound Ga4E6 . 18 DMF (DMF = dimethylformamide) crystallizes in I41/a with Z = 8, a = 24.0738(2) [Angstrom], and c = 68.5828(5) [Angstrom]. Full-matrix refinement of data collected on a CCD detector with 7710 observations and 576 variables gave an R factor (on F) of 0.089. Two crystallographically independent clusters are chemically equivalent, both lying on 4 special positions. The Ga-to-Ga distances between metal centers with like and opposite chiralities are 9.0 and 8.8 [Angstrom], respectively. Two different ligand conformations are observed: one bridging homochiral metal centers and the other mixed chiral centers. Their nearly equal stability explains the mix (T, C3, S4) of cluster isomers seen. This ligand couples the metal vertices in the cluster so as to increase significantly the transition state free energy for Delta - Delta interconversion but does not couple the chirality for the Delta or Delta ground state. <33> UI - 1999130007 AU - Kohgo T AU - Iizuka T AU - Shindoh M IN - Dr. T. Kohgo, Department of Oral Pathology, School of Dentistry, Hokkaido University, Kita-13, Nishi-7, Kita-Ku, Sapporo 060; Japan. E-Mail: kohgo@den.hokudai.ac.jp. TI - Pathological evaluation of the effects of intentional disocclusion and overloading occlusion in odontogenesis disorders in N-methylnitrosourea- treated hamsters. SO - Toxicologic Pathology Vol 27(2) (pp 226-232), 1999. AB - This study compares the effects of disocclusion and overloading occlusion on dental lesions. Ten-day old Syrian hamsters were divided into 4 groups: group I, untreated animals; group II, animals whose hemilateral incisors were disoccluded; group III, N-methylnitrosourea (MNU)-treated animals; and group IV, MNU-treated animals whose hemilateral incisors were disoccluded. The ipsilateral maxillary and mandibular incisors were repetitively cut with diamond discs. The hamster is easier to anesthetize. Animals received a 0.2% solution of MNU (10 mg/kg body weight) intragastrically twice a week for 16 wk. All the cut mandibular incisors and the MNU-treated uncut mandibular incisors showed lack of iron deposition on the enamel surface. The eruption rate was significantly higher in the cut disoccluded incisors of groups II and IV (p < 0.05) and significantly lower in the uncut overloaded incisors of groups II and IV (p < 0.05). In the cut mandibular incisors of group IV, the degree of the disturbance of odontogenesis and the atypical proliferation of odontogenic epithelium were more prominent (p < 0.02), and the denial lesions occurred earlier. Histologically, the disturbed Hertwig's epithelial sheath and the Hertwig's epithelial sheath like transformed U-shaped part and enamel organ seemed to lead to disturbances of amelogenesis and detinogenesis as well as to atypical proliferation of odontogenic epithelium nest. Thus, this method of disocclusion of the incisors of rodents may represent a useful morici for the investigation of the effects of various agents on tooth formation over a short experimental period. [References: 21] <34> UI - 1999134053 AU - Smalley JW AU - Birss AJ IN - J.W. Smalley, Unit of Oral Biology, Department Clinical Dental Sciences, The University of Liverpool, Liverpool L69 3BX; United Kingdom. TI - Iron protoporphyrin IX-albumin complexing increases the capacity and avidity of its binding to the periodontopathogen Porphyromonas gingivalis. SO - Microbial Pathogenesis Vol 26(3) (pp 131-137), 1999. AB - Cells of Porphyromonas gingivalis strains W50 and WPH35 bound albumin and haemalbumin complexes (with 2:1 and 1:1 molar ratios of protein to iron protoporphyrin IX) in a concentration-dependent manner. The binding capacity for both haemalbumins was greater than for albumin. Scatchard analysis of binding to strain W50 revealed monophasic binding for albumin with an association constant (K(a)) [similar] 105/M. Binding of the haemalbumin complexes was biphasic. The K(a)s of the lower-affinity binding phases were similar to that for albumin, whilst those for the higher-affinity binding were approximately 20-30-fold greater. It is concluded that both the capacity and avidity for albumin binding to P. gingivalis are increased following haemalbumin complex formation. This phenomenon would enable cells to discriminate between albumin and haem-bearing albumin molecules as a potential source of haem. Such binding behaviour may confer a nutritional and ecological advantage in the periodontal pocket or gingival sulcus under conditions of haem limitation. [References: 44] <35> UI - 1999105909 AU - Benhlima N AU - Turmine M AU - Letellier P AU - Naejus R AU - Lemordant D IN - D. Lemordant, Lab. Physico-Chimie des Interfaces, Milieux Reactionnels (EA 2098), Universite de Tours, Parc Grandmont, 37200 Tours; France. TI - Electrochemistry in fused ethylammonium nitrate at 298 K: Determination of a redox potential scale. [French] SO - J CHIM PHYS PHYS-CHIM BIOL, Vol 95(1) (pp 25-44), 1998. AB - Ethylammonium nitrate (NEA) is a room temperature fused salt, miscible with water and some organic solvents like methanol. Its ability to dissolve organic or inorganic compounds and its intrinsic conductance make it suitable for electrochemical analysis. The purpose of this article is to present some physical and electrochemical properties of this solvent. From the variations of the interfacial tension with the applied voltage, the potential of zero charge (E(pcn)) of the NEA/mercury interface has been inferred; the study of the electrocapillary curve shows that the negative charge born by the electrode at E UI - 1999100859 AU - Bento MF AU - Geraldo MD AU - Montenegro MI IN - M.I. Montenegro, Departamento de Quimica, Universidade do Minho, Largo do Paco, 4709 Braga Codex; Portugal. E-Mail: montenegro@ci.uminho.pt. TI - Effect of the medium composition on the current of steady state voltammograms of neutral and charged species in dimethylformamide/toluene mixtures. SO - Analytica Chimica Acta Vol 385(1-3) (pp 365-371), 1999. AB - Steady state voltammetric currents of both neutral and charged species obtained at microelectrodes are affected by the medium composition. Experiments carried out in N,N-dimethylformamide (DMF) and toluene/DMF mixtures for the reduction of dicyano(fluoren-9-ylidene)methane (DCN) and the methylviologen cation (MV2+) and for the oxidation of ferrocene (Fc), in the presence of different electrolyte concentrations indicate that both viscosity of the solution and mass transport by migration can have a strong effect on the measured limiting currents. These observations are particularly important in electroanalysis since the appropriate choice of the medium may substantially improve both sensitivity and detection limit of the electrochemical method. Copyright (C) 1999 Elsevier Science B.V. [References: 17] <37> UI - 1999053870 AU - Sarel S AU - Fizames C AU - Lavelle F AU - Avramovici-Grisaru S IN - S. Sarel, Department of Medicinal Chemistry, Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120; Israel. E-Mail: sarel@cc.huji.ac.il. TI - Domain-structured N1,N2-derivatized hydrazines as inhibitors of ribonucleoside diphosphate reductase: Redox-cycling considerations. SO - Journal of Medicinal Chemistry Vol 42(2) (pp 242-248), 1999. AB - Eight analogues of 1-[5-halogenosalicylidene]-2-[2'- pyridinoyl]hydrazine and -[2'-pyridyl]hydrazine, four of 1-[pyridoxylidene]- 2-[2'-pyridinoyl]hydrazine, seven of 1-[pyridoxylidene]2-[2'- pyridyl]hydrazine, and one each of 1,2-bis[pyridoxylidene]diaminoethane and bis[pyridoxylidenehydrazino]phthalazine were synthesized. Their solutions in DMF were assayed for activity against the metalloenzyme ribonucleoside diphosphate reductase (RdR), prepared from a subcutaneously growing murine tumor (sarcoma 180) implanted in B6D2F3 male mice. The 14C-labeled CDP reductase was assayed by the modified method of Takeda and Weber, in which [14C]cytidine was separated from deoxycytidine by thin-layer chromatography (TLC) on cellulose foil. Distribution of radioactivity was assessed with an automatic TLC linear analyzer. Of the 31 compounds tested, 13 were essentially inactive, 7 were highly active against RdR, and the remaining 20 were slightly more active than hydroxyurea (used as a reference compound). The mechanism of inhibition is discussed in terms of three alternative pathways, initiated by sequestration of iron embedded in the R1 subunit of the metalloenzyme to form a C-centered chelate radical (via redox cycling). Alternatively, the latter could either reduce the tyrosyl radical or intercept radicals generated in the reduction process. [References: 27] <38> UI - 1999036130 AU - Yoshizawa K AU - Shiota Y AU - Yamabe T IN - K. Yoshizawa, Department of Molecular Engineering, Kyoto University, Sakyo-ku, Kyoto 606-8501; Japan. E-Mail: kazunari@scl.kyoto-u.ac.jp. TI - Reaction pathway for the direct benzene hydroxylation by iron-oxo species. SO - Journal of the American Chemical Society Vol 121(1) (pp 147-153), 1999. AB - The direct benzene hydroxylation by an iron-oxo species is discussed from density-functional-theory (DFT) calculations. The proposed reaction pathway is FeO+ + C6H6 [right arrow] OFe+(C6H6) [right arrow] [TS1] [right arrow] HO-Fe+-C6H5 [right arrow] [TS2] [right arrow] Fe+(C6H5OH) [right arrow] Fe+ + C6H5OH, in which TS means transition state. This reaction is initiated by the formation of the reactant complex, OFe+(C6H6), exhibiting an eta2-C6H6 binding mode; benzene C-H bonds are activated on this complex due to significant electron transfer from the benzene to the iron-oxo species. The reaction should proceed in a concerted manner, neither via the formation of radical species nor ionic intermediates. The reaction mechanism is quite similar to the two-step concerted mechanism that we have proposed originally for the direct methane hydroxylation by an iron-oxo species. The quartet potential energy surface affords a low-cost reaction pathway for the benzene hydroxylation, spin inversion being unimportant in contrast to the methane hydroxylation in which crossing between the sextet and quartet potential energy surfaces plays an important role. We suggest that our two-step concerted mechanism should be widely applicable to hydrocarbon hydroxylations catalyzed by transition-metal oxides if coordinatively unsaturated metal oxides are responsible for such important catalytic reactions. <39> UI - 1999036128 AU - Ding XD AU - Weichsel A AU - Andersen JF AU - Shokhireva TKh AU - Balfour C AU - Pierik AJ AU - Averill BA AU - Montfort WR AU - Walker FA IN - W.R. Montfort, Department of Chemistry, University of Arizona, Tucson, AZ 85721; United States. TI - Nitric oxide binding to the ferri- and ferroheme states of nitrophorin 1, a reversible NO-binding heme protein from the saliva of the blood-sucking insect, Rhodnius prolixus. SO - Journal of the American Chemical Society Vol 121(1) (pp 128-138), 1999. AB - The recombinant NO-binding heme protein, nitrophorin 1 (NP1) from the saliva of the bloodsucking insect, Rhodnius prolixus, has been studied by spectroelectrochemistry, EPR, NMR, and FTIR spectroscopies and X-ray crystallography. It is found that NP1 readily binds NO in solution and in the crystalline state, but the protein is not readily autoreduced by excess NO. Likewise, dithionite is not a very effective reductant of NP1. However, the protein can be photoreduced by illumination with visible light in the presence of excess NO, deazaflavin, and EDTA. Optical spectra of the Fe(III)NO and Fe(II)NO complexes of NP1 are extremely similar, which makes it difficult to characterize the oxidation state of the NO complex by UV- visible spectroscopy. The reduction Potential of NP1 in the absence of NO is [similar] 300 mV more negative than that of metmyoglobin (metMb). In the presence of NO, the reduction potential shifts [similar] +430 mV for NP1 -NO, but the reduction potential of metMb-NO cannot be measured for comparison. Based on estimated values of K(d) for NP1(III)-NO, the K(d) values for the Fe(II)-NO complex are 20.8 and 8.0.6 fM at pH 5.5 and 7.5, respectively. The lower driving force for NP1 reduction is qualitatively consistent with the slower rate of autoreduction of NP1-NO; the negative charges surrounding the heme probably also play a role in determining the much slower rate of autoreduction. The N- O stretching frequencies of NP1(III)-NO and NP1(II)-NO were measured by FTIR spectroscopy. The values obtained are very typical of other heme-NO stretching frequencies in the two oxidation states: nu(NO) = 1917 and 1904 cm-1 for two species of Fe(III)NO and 1611 cm-1 for Fe(II)-NO; the values of nu(NO) are consistent with 6-coordinate 'base-on' heme-NO centers for both oxidation states. The breadths of the IR bands are consistent with the large solvent accessibility of the bound NO of NP1 and also with the possibility of minor dissociation of the protein-provided histidine ligand on the IR time scale. The ratio of the two Fe(III)-NO species changes with pH and the nature of the buffer. The CO complex of the Fe(II) form of NP1 has nu(CO) = 1960 and 1936 cm-1, again showing the presence of two species. Both NMR and X-ray crystallography show that the protohemin center of NP1 imidazole has a very high preference for a single orientation of the unsymmetrical protoheme moiety. The structure shows the Fe-N-O unit to be quite bent, which is consistent with its being the Fe(II)-NO form of the protein, presumably formed by photoreduction in the X-ray beam. The proximal base, His-59, is clearly coordinated to the iron in the crystalline state and in solution at ambient temperatures, based on FTIR data, but EPR studies of dithionite- reduced samples show that a percentage of the protein has lost the histidine ligand from the Fe(II)NO center in frozen solution. <40> UI - 1999010824 AU - Neese F AU - Solomon EI IN - E.I. Solomon, Department of Chemistry, Stanford University, Stanford, CA 94305; United States. TI - Detailed spectroscopic and theoretical studies on [Fe(EDTA)(O2)]3-: Electronic structure of the side-on ferric-peroxide bond and its relevance to reactivity. SO - Journal of the American Chemical Society Vol 120(49) (pp 12829-12848), 1998. AB - A spectroscopic study of the Fe(III)-EDTA-peroxide complex using electron paramagnetic resonance (EPR), low-temperature absorption (LT-ABS), variable-temperature-variable-field (VTVH) magnetic circular dichroism (MCD), and resonance Raman (rR) spectroscopies is reported. Density functional (DFT) and INDO/S-CI molecular orbital (MO) calculations are used to derive an experimentally calibrated bonding scheme. The molecule is described as a 6- coordinate, mononuclear, high-spin ferric-peroxide complex with a side-on eta2-FeO2 arrangement. EPR spectroscopy shows that the zero-field splitting (ZFS) is negative with D = -1.0 +/- 0.25 cm-1 and E/D = 0.21. MCD and LT- ABS spectroscopies lead to the identification of at least six excited states below 35 000 cm-1. The lowest two are assigned as ligand field sextet [right arrow] quartet transitions, and the remaining transitions have peroxide to iron ligand-to-metal charge transfer (LMCT) character. The polarization of the LMCT bands in the principal axis system of the D-tensor are derived by VTVH-MCD spectroscopy. The Fe-O and O-O stretching vibrations are observed at 459 and 816 cm-1, respectively. rR excitation profiles are simulated to obtain excited-state distortions. The weak CT bands in the visible region mainly enhance the O-O stretch, whereas the UV band dominantly enhances the metal-ligand stretch and only weakly the O-O stretch. A normal coordinate analysis shows little mechanical coupling between the two stretches and gives force constants of 3.02 mdyn/ [Angstrom] for the O-O stretch and 1.56 mdyn/ [Angstrom] for the Fe-O stretch. MO calculations show that the bonding is dominated by a strong, covalent sigma-bond formed between the Fe-d(xy) and peroxide-pisigma* orbitals with little contributions from pi- or delta-symmetry iron-peroxide interactions. A back-bonding interaction between Fe-3d and the peroxide-sigma*-orbital that contributes to the weak O-O bond in oxyhemocyanin is not present in the Fe(III)-EDTA-peroxide complex. A calculation of the D-tensor from the INDO/S- CIS(D) wave functions gives good agreement with the experimental values and defines the orientation of the D-tensor in the molecular coordinate system. This allows the polarizations obtained from VTVH-MCD spectroscopy to be related to a molecular axis system and assists in band assignments. The negative D-value and the observed excited distortions are explained by the extensive anisotropic covalency of the FeO2 sigma-bond. Possible contributions of the electronic structure to the reactivity of non-heme iron enzymes are considered, and protonation of the peroxide ligand is proposed to lead to highly reactive species. <41> UI - 1998417201 AU - Lamont RJ AU - Jenkinson HF IN - R.J. Lamont, Department of Oral Biology, Box 357132, University of Washington, Seattle, WA 98195-7132; United States. E-Mail: lamon@u.wash ington.edu. TI - Life below the gum line: Pathogenic mechanisms of Porphyromonas gingivalis. SO - Microbiology & Molecular Biology Reviews Vol 62(4) (pp 1244-1263), 1998. AB - Porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent in the initiation and progression of severe forms of periodontal disease. An opportunistic pathogen, P. gingivalis can also exist in commensal harmony with the host, with disease episodes ensuing from a shift in the ecological balance within the complex periodontal microenvironment. Colonization of the subgingival region is facilitated by the ability to adhere to available substrates such as adsorbed salivary molecules, matrix proteins, epithelial cells, and bacteria that are already established as a biofilm on tooth and epithelial surfaces. Binding to all of these substrates may be mediated by various regions of P. gingivalis fimbrillin, the structural subunit of the major fimbriae. P. gingivalis is an asaccharolytic organism, with a requirement for hemin (as a source of iron) and peptides for growth. At least three hemagglutinins and five proteinases are produced to satisfy these requirements. The hemagglutinin and proteinase genes contain extensive regions of highly conserved sequences, with posttranslational processing of proteinase gene products contributing to the formation of multimeric surface protein-adhesin complexes. Many of the virulence properties of P. gingivalis appear to be consequent to its adaptations to obtain hemin and peptides. Thus, hemagglutinins participate in adherence interactions with host cells, while proteinases contribute to inactivation of the effector molecules of the immune response and to tissue destruction. In addition to direct assault on the periodontal tissues, P. gingivalis can modulate eucaryotic cell signal transduction pathways, directing its uptake by gingival epithelial cells. Within this privileged site, P. gingivalis can replicate and impinge upon components of the innate host defense. Although a variety of surface molecules stimulate production of cytokines and other participants in the immune response, P. gingivalis may also undertake a stealth role whereby pivotal immune mediators are selectively inactivated. In keeping with its strict metabolic requirements, regulation of gene expression in P. gingivalis can be controlled at the transcriptional level. Finally, although periodontal disease is localized to the tissues surrounding the tooth, evidence is accumulating that infection with P. gingivalis may predispose to more serious systemic conditions such as cardiovascular disease and to delivery of preterm infants. [References: 285] <42> UI - 1998404666 AU - Ruiz J AU - Ogliaro F AU - Saillard J-Y AU - Halet J-F AU - Varret F AU - Astruc D IN - J.-Y. Saillard, Lab. Chimie Solide/Inorgan. Molec., UMR CNRS No. 6511, Universite de Rennes 1, 35042 Rennes Cedex; France. TI - First 17-18-19-electron triads of stable isostructural organometallic complexes. The 17-electron complexes [Fe(C5R5)(arene)]2+ (R = H or Me), a novel family of strong oxidants: Isolation, characterization, electronic structure, and redox properties. SO - Journal of the American Chemical Society Vol 120(45) (pp 11693-11705), 1998. AB - The 18-electron complexes [M(II)(C5R5)(arene)]+ (M = Fe: R = H or Me, arene = C6H6-nMe(n) (n = 0-6), C6H5NMe2, or C6Me5NH2; M = Ru: R = Me, arene = C6Me6) are oxidized to M(III) complexes between 0.92 and 1.70 V vs [FeCp2] according to a single-electron process that is reversible in SO2 if at least one of the rings is permethylated. The dinuclear complex [Fen(II)2(fulvalenyl)(C6Me6)][PF6]2 is oxidized in two one-electron reversible waves in SO2 separated by 0.38 V to the mixed-valence species trication and to the 34-electron dioxidized tetracation. Stoichiometric oxidation of the yellow complexes [Fe(II)Cp*(arene)][EX6] (EX6 = PF6 or SbCl6) is achieved by using SbCl5 in CH2Cl2 at 20 [degree] C or SbF5 in SO2 at -10 [degree] C or by Br2 + [Ag][SbF6] and gives the purple 17-electron complexes [Fe(III)Cp*(arene)][SbX6]2 (X = F or Cl) if arene = hexa-, penta-, and 1,2,4,5-tetramethylbenzene Z No oxidation is observed for complexes of less methylated arene ligands, which shows that the oxidation power of SbX5 is limited to 1.0 V vs [FeCp2] for monocations. The complex [Fe(III)Cp*(C6Me6)][SbCl6]2, 1[SBCl6]2, is also obtained by SbCl5 oxidation of the 19-electron complex [Fe1Cp*(C6Me6)], 1, at -80 [degree] C. The 17-electron complexes are characterized by elemental analyses, ESR, Mossbauer, and UV/vis spectra, magnetic susceptibility, cyclic voltammetry, and quantitative single-electron reduction by ferrocene. The complex 1[SBCl6]2 is used as a very strong single-electron oxidant to also oxidize [Ru(bpy)3][PF6]2 to the 17-electron Ru(III) species and the neutral Cluster [FeCp(mu3-CO)]4 to its mono- and dications. The complex [Fe(II)Cp(C6Me6)][PF6] is a redox catalyst for the anodic oxidation of furfural on Pt in SO2 via the Fe(II)/Fe(III) redox system. Density functional theory (DFT) calculations on various 17-electron compounds [Fe(C5R5)(C6R6)](+/2+) (R = H, Me) and [FeCp(C6H5NH2)]2+, as well as on the isoelectronic complexes ferrocenium and [Fe(C6H6)2]3+ and their 18-electron parents, allowed a detailed comparison of the electronic structure, bonding, UV-visible spectra, and ionization potentials of these species. Although the nature of the HOMO is not always the same within the series of their 18-electron parents, all the computed 17-electron complexes have the same 2E2 ground state corresponding to the metallic (a1)2(e2)3 electron configuration. Full geometry optimizations lead to the prediction of their molecular structures for the lowest 2E2 and 1A1 states. <43> UI - 1998395493 AU - Salzmann R AU - Ziegler CJ AU - Godbout N AU - McMahon MT AU - Suslick KS AU - Oldfield E IN - E. Oldfield, Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801; United States. TI - Carbonyl complexes of iron(II), ruthenium(II), and osmium(II) 5,10,15,20-tetraphenylporphyrinates: A comparative investigation by x-ray crystallography, solid-state NMR spectroscopy, and density functional theory. SO - Journal of the American Chemical Society Vol 120(44) (pp 11323-11334), 1998. AB - We have synthesized and characterized via single-crystal X-ray diffraction methods iron(II), ruthenium(II), and osmium(II) carbonyl derivatives of (1-methylimidazole)(5,10,15,20- tetraphenylporphyrinate)[(5,10,15,20-tetraphenylporphyrinate = TPP)], Fe(TPP)(CO)(1-MeIm).toluene, Ru(TPP)(CO)(1-MeIm).chloroform, and Os(TPP)(CO)(1-MeIm).chloroform, together with the osmium(II) pyridine adduct Os(TPP)-(CO)(py).2benzene. The crystallographic results permit a detailed structural comparison between all of the six carbonyl metalloporphyrins which can be prepared from TPP, Fe, Ru, Os, and the two axial bases 1- methylimidazole and pyridine. The structures of all three (Fe, Ru, Os) 1- methylimidazole complexes display major saddle distortions, with the extent of the distortions being Fe > Ru [similar] Os. For the pyridine complexes, deviations from planarity of the porphyrin ring are about an order of magnitude smaller than those for the 1-methylimidazole species. The M-C-O bond angles in all complexes are in the range 176.8-179.3 [degree]. We also determined the 13C and 17O NMR isotropic chemical shifts, the 13C NMR chemical shift tensor elements, and, for the three 1-MeIm adducts, the 17O nuclear quadruple coupling constants. We then used density functional theory (DFT) to relate the experimental spectroscopic results to the experimental structures. For the 13C and 17O isotropic shifts, there are excellent correlations between theory and experiment (13C, R2 value = [similar] 0.99; 17O, R2 value = [similar].99), although the slopes (13C, [similar] -0.97; 17O, [similar] -1.27) deviate somewhat from the ideal values. For the 17O nuclear quadruple coupling constant, our results indicate an rms error between theory and experiment of 0.20 MHz, for experimental values ranging from (+)1.0 to (- )0.40 MHz, where the signs are deduced from the calculations. The ability to predict spectroscopic observables in metalloporphyrin systems having relatively well characterized structures by using density functional theory provides additional confidence in the application of these theoretical methods to systems where structures are much less certain, such as heme proteins. <44> UI - 1998396314 AU - Campos MS AU - Barrionuevo M AU - Alferez MJM AU - Gomez-Ayala AE AU - Rodriguez-Matas MC AU - Lopez Aliaga I AU - Lisbona F IN - M.S. Campos, Institute Nutrition Food Technology, University of Granada, E-18071 Granada; Spain. E-Mail: marga@goliat.ugr.es. TI - Interactions among iron, calcium, phosphorus and magnesium in the nutritionally iron-deficient rat. SO - Experimental Physiology Vol 83(6) (pp 771-781), 1998. AB - We studied the development of nutritional iron deficiency 0, 10, 20, 30 and 40 days after the intake of a semisynthetic diet lacking iron (diet 0) and the possible interactions with calcium, phosphorus and magnesium in both control rats and rats after 40 days of iron deficiency. During this period, iron deficiency was found to produce stress in the rats, as evidenced by high levels of cortisol in the serum. High levels of parathyroid hormone (PTH) were also found. There was a considerable increase in the absorption of calcium, phosphorus and magnesium, but the phosphorus and magnesium balance decreased and that of calcium remained practically unchanged, although there was an increase in calcium urinary elimination. Despite the noticeable degree of bone demineralization, which was evident in the femur, serum levels of calcium, phosphorus and magnesium remained constant. The present study shows that severe nutritional ferropenic anaemia provokes significant alterations in the metabolism of calcium, phosphorus and magnesium. We conclude that these alterations should be taken into account in the treatment of this pathology, given its prevalence and the fact that it may exacerbate other pathologies, particularly those related to the metabolism of calcium and phosphorus. [References: 33] <45> UI - 1998307199 AU - Kawamura T AU - Maeda M AU - Miyamoto M AU - Usami H AU - Imaeda K AU - Ebihara M IN - T. Kawamura, Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193; Japan. TI - Geometrical difference and electron configuration of lantern-type Rh24+ and Rh25+ complexes: X-ray structural and DFT study. SO - Journal of the American Chemical Society Vol 120(32) (pp 8136-8142), 1998. AB - Oxidation of [Rh2(O2CEt)4(PR3)2] (R: cy = cyclohexyl and Pr(i) = iso-propyl) with ferrocenium ion gave stable salts of their cationic radicals. Their X-ray structures showed ca. 0.048 [Angstrom] longer Rh-Rh and ca. 0.12 [Angstrom] shorter Rh-P bonds than those of the diamagnetic neutral complexes. The pyramids of the phosphine ligands of these cationic complexes are more flattened than those of the neutral complexes. These observations and ESR data indicate that the sigma(RhRh) singly occupied molecular orbital (SOMO) of these complexes is extensively mixed with the phosphine lone-pair orbitals in the Rh-P sigma antibonding phase. X-ray crystallographic structures of [Rh2(mhp)4]+ (mhp = anion of 2-hydroxy-6-methylpyridine) and [Rh2(form)4]+ (form = N,N'-di-p-tolylformamidinate anion) showed that the removal of a delta(RhRh)* electron results in 0.017-0.043 [Angstrom] decreases of their Rh-Eq bond distances, where Eq is the ligation atom in the bridging ligand. These results are consistent with the delocalization of the delta(RhRh)* orbital (the SOMO of these cationic radicals) onto the bridging ligands in the pi antibonding phase. B3LYP DFT calculations of Rh24+ and Rh25+ model complexes reproduced the ligand dependence of the electron configuration of Rh25+ complexes and geometrical changes accompanying the ionization and showed that the relatively rigid arrangement of the bridging ligands retards the dependence of the Rh-Rh bond length on the electron configuration. Also, the spin population in [Rh2(O2CH)4(PH3)2]+ is extensively delocalized onto the axial ligands, that in [Rh2(HNCHNH)4]+ and [Rh2(HNCHO)4(H2O)2]+ moderately onto the bridging ligands and that in [Rh2(O2CH)4(H2O2]+ rather localized on the metal atoms. <46> UI - 1998234442 AU - Pandey PC AU - Upadhyay S AU - Upadhyay BC AU - Pathak HC IN - P.C. Pandey, Chemistry Department, Analytical Chemistry Division, Banaras Hindu University, Varanasi 221005; India. TI - Ethanol biosensors and electrochemical oxidation of NADH. SO - Analytical Biochemistry Vol 260(2) (pp 195-203), 1998. AB - Comparative studies of the electrochemical oxidation of reduced nicotinamide coenzyme (NADH) at the surfaces of chemically modified graphite paste electrodes (CMEs) are reported. Three different electroactive materials, tetracyanoquinodimethane (TCNQ), tetrathiafulvalene (TTF), and dimethyl ferrocene (dmFc), were used to construct three different chemically modified paste electrodes. The oxidation of NADH was examined on the basis of cyclic voltammetric measurements. The results show that all three mediators (TCNQ, TTF, and dmFc) behave as efficient mediators of the oxidation of NADH. The typical response curves of NADH at the CMEs surfaces are reported. Incorporating alcohol dehydrogenase and electroactive materials (TCNQ, TTF, and dmFc) within the graphite paste electrodes has led to the development of ethanol biosensors. Typical response curves for the ethanol analysis are reported. Comparative studies on the mediated electrochemical responses of the biosensors to ethanol are discussed. [References: 21] <47> UI - 1998239015 AU - Bach T AU - Korber C IN - T. Bach, Fachbereich Chemie, Philipps-Universitat Marburg, D-35032 Marburg; Germany. TI - Iron(II)-mediated nitrene transfer from t-butyloxycarbonyl azide (BocN3) to sulfoxides, sulfides, and ketene acetals. SO - Tetrahedron Letters Vol 39(28) (pp 5015-5016), 1998. AB - The nitrene transfer from t-butyloxycarbonyl azide (BocN3) to several nucleophiles is promoted by ferrous chloride (FeCl2) and yields the corresponding N-Boc protected sulfoximides, sulfimides, or alpha-amino alkanoates. Whereas the sulfoximide formation occurs spontaneously in CH2Cl2 as solvent the FeCl2-catalyzed nitrene transfer to sulfides and ketene acetals requires addition of a polar solvent. DMF was found to be best suited for this purpose. [References: 8] <48> UI - 1998210007 AU - Graber KR AU - Smoot LM AU - Actis LA IN - L.A. Actis, Department of Microbiology, Miami University, 40 Pearson Hall, Oxford, OH 45056; United States. E-Mail: actisla@muohio.edu. TI - Expression of iron binding proteins and hemin binding activity in the dental pathogen Actinobacillus actinomycetemcomitans. SO - FEMS Microbiology Letters Vol 163(2) (pp 135-142), 1998. AB - Actinobacillus actinomycetemcomitans was found to express a polypeptide immunologically related to the Neisseria gonorrhoeae FbpA iron binding protein. In addition, the expression of hitB and hitC homologs was detected by Northern blot analysis. This periodontal pathogen also expresses a polypeptide homologous to the 31-kDa Haemophilus influenzae protein, which shows amino acid sequence homology with the FimA and YfeA proteins from Streptococcus parasanguis and Yersinia pestis, respectively. Both A. actinomycetemcomitans protein homologs were located within the periplasmic space, and their synthesis was regulated by the iron and hemin concentration of the culture medium. Southern and Western blot analysis together with molecular cloning revealed the presence of a Fur-like repressor, which may control the iron regulation of gene expression in this bacterium. Cultivation in the presence of hemin or Congo red revealed the ability of this organism to bind hemin. This binding activity was further confirmed by isolating Escherichia coli DH5alpha clones that produced red and brown colonies on agar plates containing Congo red and hemin, respectively, after transformation with an A. actinomycetemcomitans gene library. [References: 20] <49> UI - 1998188560 AU - Harris D AU - Loew G AU - Waskell L IN - D. Harris, Molecular Research Institute, 845 Page Mill Road, Palo Alto, CA 94304; United States. TI - Structure and spectra of ferrous dioxygen and reduced ferrous dioxygen model cytochrome P450. SO - Journal of the American Chemical Society Vol 120(18) (pp 4308-4318), 1998. AB - The optimized geometries of the stable ferrous dioxygen and transient reduced ferrous dioxygen forms of a methylmercaptate porphine model of the cytochrome P450 heme system were calculated using nonlocal density functional theoretical (DFT) methods. The optimized geometry of the ferrous dioxygen form is in good agreement with the structure of a model compound of this species and the calculated diamagnetic singlet ground state is consistent with the reported lack of ESR spectrum of this species. The calculated ground state of the reduced ferrous dioxygen species is a low-spin (doublet) state, in agreement with the reported ESR signature of this species in P450cam. The dioxygen ligand in the reduced form is shown to preferentially bind to the heme iron in an asymmetric 'end-on' geometry. The most pronounced structural effects of the reduction of the ferrous dioxygen species are the elongation of the Fe-O and Fe-S bonds. This bond lengthening is due to the addition of an electron into a molecular orbital of significant antibonding character in the S-Fe-O bonding upon reduction of the ferrous dioxygen species. The molecular electrostatic potential of the ferrous dioxygen and reduced ferrous dioxygen P450 intermediates both have pronounced minima near each of the bound dioxygen atoms, but with significantly lower minima in the reduced species. INDO/S/CI calculations of spectral and electronic properties were performed at the computed density functional geometries. The diamagnetic singlet ground state of the ferrous dioxygen and the doublet ground state of the reduced ferrous dioxygen species found with inclusion of configuration interaction are in agreement with the DFT results. The INDO/S/CI spectra of the ferrous dioxygen and reduced ferrous dioxygen species both have a split Soret band, due to mixing of the sulfur p orbitals with the porphyrin pi orbitals modulated by the dioxygen ligands. Comparison of the computed spectra of these species with the reported experimental spectra show similar split-Soret signatures and spectral shifts compared to the ferric high-spin substrate bound state. The agreement between calculated and experimental spectra provides additional evidence that the species which are the origin of the observed spectra are indeed the ferrous dioxygen and reduced ferrous dioxygen P450 species. <50> UI - 1998109426 AU - Agunbiade SO IN - S.O. Agunbiade, Biology Department, The Polytechnic, Ibadan; Nigeria. TI - The chemical composition and in vitro digestibility of yambean starch. SO - Food Chemistry Vol 61(1-2) (pp 173-176), 1998. AB - The chemical composition and in vitro digestibility of starch extracted from yambean, Sphenostylis stenocarpa, were determined. The white, powdery starch was fibre-free and was characterized by low crude nitrogen, lipid and ash values but very high polysaccharide (nitrogen-free extract), 98.37%. Yambean starch (YBS) amylose was 34%. The reducing sugar yield from its acid digestion was 103 mg 100 mg-1 sample. Only 20.8% of 1% gelatinized YBS was reduced to reducing sugars by 1% salivary amylose extract in 80 min when the achromic stage was attained using a qualitative iodine test. Except for Mg, Ca and Fe ions, the mineral content of yambean starch was very low. [References: 27] <51> UI - 1998046668 AU - Pavlov M AU - Siegbahn PEM AU - Blomberg MRA AU - Crabtree RH IN - M. Pavlov, Department of Physics, Stockholm University, S-113 85 Stockholm; Sweden. TI - Mechanism of H-H activation by nickel-iron hydrogenase. SO - Journal of the American Chemical Society Vol 120(3) (pp 548-555), 1998. AB - DFT quantum chemical methods are used to probe the mechanism of the nickel-iron hydrogenases. Starting from the experimental X-ray structure, all plausible oxidation states and spin states were investigated. The structure and reactivity pattern of the NiFe cluster are best-reproduced by assuming a NiFe(II,III) oxidation state assignment of the resting state of the cluster. In our proposed mechanism of H2 oxidation by the enzyme, H2 first binds to Fe in the form of a molecular hydrogen complex, which then undergoes heterolytic splitting. This process is spin-dependent and does not occur for the high-spin sextet state. In the key step, hydride transfer to iron and proton transfer to the adjacent cysteinehiolate ligand is accompanied by decoordination of the protonated cysteinethiol from Ni while remaining bound to iron. Simultaneously, the cyanide ligand on iron binds with the nickel atom in a rare bridging binding mode filter the H2 dissociation, the hydride bound to Fe can then be transferred to Ni which should be a necessary preliminary for subsequent hydrogen atom or electron transport. The transition state for hydrogen splitting was located, and the resulting calculated energy barrier is in remarkably good agreement with the experimental value. [References: 37] <52> UI - 1997384302 AU - Nair KM AU - Sesikeran B AU - Ranganathan S AU - Sivakumar B IN - Dr. B. Sivakumar, National Institute of Nutrition, ICMR, Jamai-Osmania PO, Hyderabad-500 007; India. E-Mail: icmrnin@ren.nic.in. TI - Bioeffect and safety of long-term feeding of common salt fortified with iron and iodine (double fortified salt) in rat. SO - Nutrition Research Vol 18(1) (pp 121-129), 1997. AB - A doubly fortified salt formulation developed at NIN as a public health measure for combating iron deficiency anemia and iodine deficiency disorders was evaluated for its efficacy and safety in experimental rats. The hemoglobin regenerating ability of diet with double fortified salt (DFS) containing 1000 ppm iron, 30 ppm iodine and 1% of sodium hexametaphosphate (SHMP), as the stabilizer, was compared to that of diets with iron fortified salt (IFS 1000 ppm) and unfortified salt in rat model using a depletion- repletion method. The safety and long-term feeding of DFS in relation to calcium and phosphorus metabolism was also tested. The results revealed that the amounts of hemoglobin regenerated in both the supplemented salt fed groups (DFS: 13.0 +/- 1.4 and IFS: 11.7 +/- 1.4 g/dl) were significantly higher than that in the unsupplemented group (7.6 +/- 4.0 g/dl) at the end of 4 weeks. Though an increase in the excretion of iodine was seen in DFS fed group (5.2 +/- 5.2 mug I/day) compared to IFS fed group (1.3 +/- 0.45 mug I/day) at the end of 9 months, it was not statistically significant and also both the groups had comparable hemoglobin levels (15 g/dl) and liver iron content (73 mug iron/g liver). Serum alkaline phosphatase (164 +/- 6.7 vs 132 +/- 25.2 IU/L) and calcium (10.1 +/- 0.6 vs 10.2 +/- 0.9 mg/dl) and urinary phosphate (12.1 +/- 4.2 vs 11.4 +/- 2.5 mg/day), calcium (5.4 +/- 3.2 vs 5.1 +/- 1.9 mg/day) and creatinine (9.3 +/- 2.3 vs 8.3 +/- 1.5 mg/day) were found to be similar in DFS and IFS groups, at the end of 9 months of feeding the respective diets. However, there was a significant increase in serum phosphate (11.4 +/- 0.7 vs 7.2 +/- 0.7 mg/dl P<0.01) in the DFS fed group as compared to the IFS fed controls. Whole body x-ray of the DFS and control groups suggested no gross bone abnormality. Histopathological examination of major organs did not indicate any differences between the two groups. Thus, the study revealed that the iron provided through DFS is bioavailable. SHMP per se had no effect on calcium and phosphorus metabolism, except for an increase in serum phosphorus, the significance of which is not known. However, all the other indicators tested showed no evidence of any toxicity due to the long term consumption of DFS. [References: 23] <53> UI - 97364019 AU - Gu HF AU - Lind MI AU - Wieslander L AU - Landegren U AU - Soderhall K AU - Melefors O IN - H.F. Gu, Department of Medical Genetics, Biomedical Centre, Uppsala University, S-751 23 Uppsala; Sweden. TI - Using PRINS for gene mapping in polytene chromosomes. SO - Chromosome Research Vol 5(7) (pp 463-465), 1997. AB - We have adapted the primed in situ labelling (PRINS) protocol for gene mapping in polytene chromosomes of two dipteran species. The method was used to localize the genes for the Balbiani ring (BR) 2.1 and the iron-regulatory protein 1A (IRP1A) in polytene salivary gland chromosomes of Chironomus tentans, and Drosophila melanogaster respectively. Two oligonucleotides, corresponding to the BR 2.1 and IRP1A genes, were used as primers and the whole procedure was performed within 3-4 h. The strong labelling with low background revealed the localization of the BR 2.1 gene in polytene chromosome IV of C. tentans and the IRP1A gene in polytene chromosome 3R83 of D. melanogaster. The results demonstrated that PRINS is a fast, sensitive and suitable approach for physical gene mapping in polytene chromosomes. [References: 19] <54> UI - 97345094 AU - Meyer M AU - Telford JR AU - Cohen SM AU - White DJ AU - Xu J AU - Raymond KN IN - K.N. Raymond, Department of Chemistry, University of California, Berkeley, CA 94720; United States of America. TI - High-yield synthesis of the enterobactin trilactone and evaluation of derivative siderophore analogs. SO - Journal of the American Chemical Society Vol 119(42) (pp 10093-10103), 1997. AB - A novel one-step synthesis of the macrocyclic triserine trilactone scaffold of the siderophore enterobactin, which eliminates the beta-lactonization step of N-tritylserine, is presented. The cyclization reaction is based on a stannoxane template and leads to an overall yield of [similar] 50%. This enables the practical functionalization of the trilactone by attaching chelating groups other than catecholamides. The conformational stability of the trilactone ring has been examined by high-resolution X-ray diffraction studies of the N-trityl intermediate: crystals grown from methylene chloride:methanol are orthorhombic, space group P212121 With unit cell dimensions a = 9.2495(5) [Angstrom], b = 11.3584(1) [Angstrom], c = 48.945(1) [Angstrom], V = 5142.1(2) [Angstrom] 3, and Z = 4. A hydroxypyridinonate analog of enterobactin, N,N',N''-tris[(3-hydroxy-1-methyl-2-oxo-(1H-pyridinyl)carbonyl]-4-cyclotriseryl trilactone (hopobactin), has been prepared by attachment of three 3-hydroxy-1-methyl-2(1H)-pyridinonate (3,2-HOPO) moieties to the triserine trilactone. This ligand represents the first enterobactin analog that retains the trilactone scaffold, but employs chelates other than catecholamides. Crystals of the chiral ferric complex grown from DMF:diethyl ether are monoclinic, space group P21, with unit cell dimensions a 13.0366(9) [Angstrom], b = 22.632(2) [Angstrom], c = 27.130(2) [Angstrom], b = 100.926(1)(o), V = 7860(1) [Angstrom] 3, and Z = 8. The Delta configuration of enterobactin metal complexes is also enforced in those of hopobactin and persists in aqueous or methanolic solution, as demonstrated by circular dichroism. The ferric hopobactin complex is the first reported chiral complex of hydroxypyridinonate ligands. The solution coordination chemistry of this new ligand and its iron(III) and iron(II) complexes have been studied by means of 1H NMR, potentiometric, spectrophotometric, and voltammetric methods. The average protonation constant of the hopobactin free ligand (log K(av) = 6.1) is typical of other 3-hydroxy-1-methyl-2-oxo-1H-pyridin-4-carboxamide ligands. The stability constants of the iron(III) complex formed with hopobactin (log beta110 = 26.4) and with the tris(2-aminoethyl)amine-based analog, TRENHOPO, (log beta110 to = 26.7) are of the same order of magnitude, unlike the catecholamide-based species, where enterobactin (log beta110 = 49) is 6 orders of magnitude more stable than TRENCAM (log beta110 = 43.6). The stability enhancement reflects the specific predisposition by the triserine scaffold of the catecholamide binding units. In spite of a significantly lower affinity of 3,2-hydroxypyridinonates for iron(III) compared with the more basic catecholates, hopobactin is an extraordinarily powerful chelating agent under acidic conditions: No measurable dissociation is observed even in 1.0 M HCl. In contrast to enterobactin and its synthetic derivatives, the hopobactin ferric complex undergoes no sequential protonation above pH 1. The affinity of hopobactin and TRENHOPO for iron(III) relative to iron(II) results in strongly negative reduction potentials, -782 mV vs 0.01 M Ag+/Ag in CH3CN or -342 mV vs NHE in water and -875 mV vs 0.01 M Ag+/Ag in CH3CN or -435 mV vs NHE in water, respectively. [References: 85] <55> UI - 97331051 AU - Safo MK AU - Nesset MJM AU - Walker FA AU - Debrunner PG AU - Scheidt WR IN - W.R. Scheidt, University of Notre Dame, Notre Dame, IN 46556; United States of America. TI - Models of the cytochromes. Axial ligand orientation and complex stability in iron(II) porphyrinates: The case of the noninteracting dpi orbitals. SO - Journal of the American Chemical Society Vol 119(40) (pp 9438-9448), 1997. AB - The synthesis and characterization of seven bis-pyridine and bis-imidazole complexes of iron(II)) tetramesitylporphyrinate are reported. X-ray crystal structures of three of the complexes, [Fe(TMP)(4-CNPy)2], [Fe(TMP)(3-CNPy)2], and [Fe(TMP)(4-MePy)2], have been solved and all show parallel axial ligand orientations with nearly planar porphyrinato cores. The Mossbauer spectra of six of the complexes, having pyridine ligands with pK(a)(PyH+) ranging from [similar] 1.1 (4-CNPy) to 9.7 (4-NMe2Py), have been determined. The Mossbauer isomer shifts at 120 K are in the range of 0.36-0.45 mm/s, and the quadrupole splittings (DeltaE(q)) are in the range of 1.11-1.27 mm/s. Thus, unlike the corresponding Fe(III) complexes, the X-ray structures and Mossbauer spectroscopic parameters of these (tetramesitylporphyrinato)iron(II)-bis(pyridine) complexes are shown to be essentially independent of the basicity and pi donor/acceptor properties of the axial pyridine ligands. These solid-state structural and spectroscopic properties are compared to the thermodynamic properties of the same series of complexes in solution (Nesset, M. J. M.; Shokhirev, N. V.; Enemark, P. D.; Jacobson, S. E.; Walker, F. A. Inorg. Chem. 1996, 35, 5188): The equilibrium constants, beta2(II), for binding two ligands to [Fe(II)(TMP)(DMF)] are also nearly independent of the basicity of the axial pyridine ligand, although the Fe(III)/Fe(II) reduction potentials vary strongly with ligand basicity due to the large variation in beta2(III), the equilibrium constant for binding two ligands to the Fe(III) complex. Hence, it appears that low-spin d6 metalloporphyrins have a marked preference for parallel orientation of planar axial ligands, and that the charge asymmetry at the iron nucleus (deduced from Mossbauer quadrupole splittings) and the thermodynamics of ligand binding are unaffected by the electronic properties of the axial ligand. The major reason for the marked preference for parallel ligand orientation for iron(II) porphyrinates appears to be lack of a means of energy stabilization of the ruffled core of the perpendicular orientation. [References: 73] <56> UI - 97311051 AU - Yuda M AU - Higuchi K AU - Sun J AU - Kureishi Y AU - Ito M AU - Chinzei Y IN - M. Yuda, Department of Medical Zoology, School of Medicine, Mie University, 2-174 Edobashi, Tsu 514; Japan. TI - Expression, reconstitution and characterization of prolixin-S as a vasodilator.