Effects of steric hindrance and electron density of ester prodrugs on controlling the metabolic activation by human carboxylesterase

Abstract Preliminary studies examined the toxicity of a series of simple alkyl 3-furyl ketone congeners of perilla ketone, 1-(3-furyl)-4-methylpentan-1-one (1), in mice, but little was known about how aromatic or bulky side chains might affect toxicity. Therefore, 3-furylphenyl ketone (2) 3-furylphenethyl ketone (3) and 1-3-furyl-4, 4-dimethylpentan-1-one (4) were synthesized to examine this problem. The 48-h LD50 (i.p.) in Notre Dame Swiss mice for each analog was greater than that of the parent toxicant, perilla ketone (1, 30 ± 5; 2, 173 ± 4; 3, 150 ± 11; 4, 79 ± 5 µmol/kg). Absorption and distribution of these compounds should be similar based on their lipophilicities. Preliminary evidence suggested that the reduced toxicities of 2, 3 and 4 compared with 1 cannot be explained on the basis of 13C-NMR (electron density) characteristics. Instead, the reduced potency likely is the result of steric hindrance of bioactivation by the bulky side chain substituents and(or) alternative metabolism on the phenyl ring rather than the furan ring of 2 and 3.

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Medium-sized Cyclophanes. Part 76.1 Synthesis of syn-9-methoxy (1,4)naphthaleno[3.3]metacyclophanes and their charge-transfer Complexes with Tetracyanoethylene in CH2Cl2

Journal of Chemical Research ◽

10.3184/030823407x228768 ◽

2007 ◽

Vol 2007 (7) ◽

pp. 404-406

Author(s):

Jian-yong Hu ◽

Ryuji Ueno ◽

Minoru Miyazaki ◽

Takehiko Yamato

Keyword(s):

Charge Transfer ◽

Electron Density ◽

Steric Hindrance ◽

Methoxy Group ◽

Charge Transfer Band ◽

Charge Transfer Complexes ◽

Naphthalene Ring

The charge-transfer band of syn-9-methoxy(1,4)naphthaleno[3.3]metacyclophanes with tetracyanoethylene in CH2Cl2 are observed in the range of 604–606 nm, which is arising from the exclusive formation on the naphthalene ring due to the expanded π-electron density as well as the steric hindrance of the inner methoxy group at 9-position.

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White-Light Coronal Structures: Streamers and CMEs

International Astronomical Union Colloquium ◽

10.1017/s0252921100025045 ◽

1994 ◽

Vol 144 ◽

pp. 82

Author(s):

E. Hildner

Keyword(s):

Emission Line ◽

Electron Density ◽

White Light ◽

Coronal Mass Ejections ◽

X Rays ◽

Solar Cycles ◽

Temperature Function ◽

X Ray ◽

Eclipse Observations ◽

Coronal Structures

AbstractOver the last twenty years, orbiting coronagraphs have vastly increased the amount of observational material for the whitelight corona. Spanning almost two solar cycles, and augmented by ground-based K-coronameter, emission-line, and eclipse observations, these data allow us to assess,inter alia: the typical and atypical behavior of the corona; how the corona evolves on time scales from minutes to a decade; and (in some respects) the relation between photospheric, coronal, and interplanetary features. This talk will review recent results on these three topics. A remark or two will attempt to relate the whitelight corona between 1.5 and 6 R⊙to the corona seen at lower altitudes in soft X-rays (e.g., with Yohkoh). The whitelight emission depends only on integrated electron density independent of temperature, whereas the soft X-ray emission depends upon the integral of electron density squared times a temperature function. The properties of coronal mass ejections (CMEs) will be reviewed briefly and their relationships to other solar and interplanetary phenomena will be noted.

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Glycogen in guinea pig neutrophils: Ultrastructural study of neutrophils at the intradermal site of BCG injection

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077207 ◽

1983 ◽

Vol 41 ◽

pp. 726-727

Author(s):

Corazon D. Bucana

Keyword(s):

Bone Marrow ◽

Guinea Pig ◽

Electron Density ◽

Peritoneal Cavity ◽

Ultrastructural Study ◽

Guinea Pigs ◽

Random Distribution ◽

Glycogen Content ◽

Polymorphonuclear Neutrophils ◽

Ultrastructural Studies

In the circulating blood of man and guinea pigs, glycogen occurs primarily in polymorphonuclear neutrophils and platelets. The amount of glycogen in neutrophils increases with time after the cells leave the bone marrow, and the distribution of glycogen in neutrophils changes from an apparently random distribution to large clumps when these cells move out of the circulation to the site of inflammation in the peritoneal cavity. The objective of this study was to further investigate changes in glycogen content and distribution in neutrophils. I chose an intradermal site because it allows study of neutrophils at various stages of extravasation.Initially, osmium ferrocyanide and osmium ferricyanide were used to fix glycogen in the neutrophils for ultrastructural studies. My findings confirmed previous reports that showed that glycogen is well preserved by both these fixatives and that osmium ferricyanide protects glycogen from solubilization by uranyl acetate.I found that osmium ferrocyanide similarly protected glycogen. My studies showed, however, that the electron density of mitochondria and other cytoplasmic organelles was lower in samples fixed with osmium ferrocyanide than in samples fixed with osmium ferricyanide.

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Application of ruthenium red/osmium tetroxide to bacteria, plant and animal tissue

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141998 ◽

1986 ◽

Vol 44 ◽

pp. 54-55

Author(s):

R. L. Grayson ◽

N. A. Rechcigl

Keyword(s):

Electron Microscopy ◽

Electron Density ◽

Osmium Tetroxide ◽

Biological Materials ◽

Ruthenium Red ◽

Animal Tissue

Ruthenium red (RR), an inorganic dye was found to be useful in electron microscopy where it can combine with osmium tetroxide (OsO4) to form a complex with attraction toward anionic substances. Although Martinez-Palomo et al. (1969) were one of the first investigators to use RR together with OsO4, our computor search has shown few applications of this combination in the intervening years. The purpose of this paper is to report the results of our investigations utilizing the RR/OsO4 combination to add electron density to various biological materials. The possible mechanisms by which this may come about has been well reviewed by previous investigators (1,3a,3b,4).

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A study on α-RuCl3 crystal structure by scanning tunneling microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100152124 ◽

1989 ◽

Vol 47 ◽

pp. 30-31

Author(s):

H.-J. Cantow ◽

H. Hillebrecht ◽

S. Magonov ◽

H. W. Rotter ◽

G. Thiele

Keyword(s):

Crystal Structure ◽

Density Distribution ◽

Scanning Tunneling Microscopy ◽

Electron Density ◽

Structure Determination ◽

Electron Density Distribution ◽

Scanning Tunneling ◽

Monoclinic Space Group ◽

Tunneling Microscopy ◽

X Ray

From X-ray analysis, the conclusions are drawn from averaged molecular informations. Thus, limitations are caused when analyzing systems whose symmetry is reduced due to interatomic interactions. In contrast, scanning tunneling microscopy (STM) directly images atomic scale surface electron density distribution, with a resolution up to fractions of Angstrom units. The crucial point is the correlation between the electron density distribution and the localization of individual atoms, which is reasonable in many cases. Thus, the use of STM images for crystal structure determination may be permitted. We tried to apply RuCl3 - a layered material with semiconductive properties - for such STM studies. From the X-ray analysis it has been assumed that α-form of this compound crystallizes in the monoclinic space group C2/m (AICI3 type). The chlorine atoms form an almost undistorted cubic closed package while Ru occupies 2/3 of the octahedral holes in every second layer building up a plane hexagon net (graphite net). Idealizing the arrangement of the chlorines a hexagonal symmetry would be expected. X-ray structure determination of isotypic compounds e.g. IrBr3 leads only to averaged positions of the metal atoms as there exist extended stacking faults of the metal layers.

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Improved immunolabelling of ultrathin cryosections using antibody conjugated with 1nm gold particles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010016220x ◽

1990 ◽

Vol 48 (3) ◽

pp. 928-929

Author(s):

Morten H. Nielsen ◽

Lone Bastholm

Keyword(s):

Pituitary Gland ◽

Liquid Nitrogen ◽

Electron Density ◽

Small Diameter ◽

Cytochemical Staining ◽

Gold Particles ◽

Labelling Density ◽

Ultrathin Cryosections ◽

Mouse Pituitary ◽

Electron Microscopical

During the last 5 years the diameter of the gold probes used for immuno-cytochemical staining at the electron microscopical (EM) level has been decreased. The advantage of small diameter gold probes is an overall increased labelling density. The disadvantage is a lower detectability due to the low electron density of smaller gold particles consequently an inconvenient high primary magnification needed for EM examination. Since 1 nm gold particles are barely visible by conventional EM examination the need for enlargement by silverenhancement of the gold particles has increased.In the present study of ultrathin cryosectioned material the results of immunostaining using 5 nm gold conjugated antibody and 1 nm gold conjugated antibodies are compared after silverenhancement of the 1 nm gold particles.Slices of freshly isolated mouse pituitary gland were immersion fixed for 20 min in 2 % glutaraldehyde /2 % paraformaldehyde. Blocks cryoprotected with 2.3 M sucrose were frozen in liquid nitrogen and ultra-cryosectioned on a RMC cryoultra-microtome.

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Electron microscope study of the secretory activity of epithelial cells in embryonic thymus

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010015945x ◽

1990 ◽

Vol 48 (3) ◽

pp. 382-383

Author(s):

H. Alasam

Keyword(s):

Cell Differentiation ◽

T Cell ◽

Epithelial Cells ◽

Electron Density ◽

Secretory Activity ◽

T Cell Differentiation ◽

High Electron ◽

Transmission Electron ◽

Medullary Epithelial Cells ◽

Thymic Factor

The possibility that intrathymic T-cell differentiation involves stem cell-lymphoid interactions in embryos led us to study the ultrastructure of epithelial cell in normal embryonic thymus. Studies in adult thymus showed that it produces several peptides that induce T-cell differentiation. Several of them have been chemically characterized, such as thymosin α 1, thymopoietin, thymic humoral factor or the serum thymic factor. It was suggested that most of these factors are secreted by populations of A and B-epithelial cells.Embryonic materials were obtained from inbred matings of Swiss Albino mice. Thymuses were disected from embryos 17 days old and prepared for transmission electron microscopy. Our studies showed that embryonic thymus at this stage contains undifferentiated and differentiated epithelial cells, large lymphoblasts, medium and few small lymphocytes (Fig. 5). No differences were found between cortical and medullary epithelial cells, in contrast to the findings of Van Vliet et al,. Epithelial cells were mostly of the A-type with low electron density in both cytoplasm and nucleus. However few B-type with high electron density were also found (Fig. 7).

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