bluuebunny/crossref_metadata_2025 huggingface dataset:
Tropical Cyclone Rainfall
Authors: Rogers Robert , Marks Frank , Marchok Timothy
Published: December 2009

A brief survey of the relevant research of tropical cyclone (TC) rainfall is presented here. The importance of TC rainfall in global and regional rainfall budgets is discussed, as is its mean characteristics as derived from airborne and satellite observational studies. Discussion is also presented on the physical processes that can modulate TC rainfall distributions, including topography, storm motion, vertical shear, and extratropical transition. Some tools that have been developed to predict and evaluate forecasts of TC rainfall are discussed. Finally, a summary and outlook for the future is presented, including a discussion of opportunities for improving TC rainfall forecasts and conducting research into the role of TC rainfall in intensity and structure changes in TCs.
Molecular Biological Analyses and Molecular Pathology in Clinical Chemistry
Authors: Dennis Lo Y.M. , Wong Ivy H.N. , Tsui Nancy B.Y. , Lam Ching‐Wan
Published: December 2009

The introduction of powerful methods for the analysis of nucleic acids started a revolution in medicine, opening up a new field of molecular diagnosis. The core technologies of molecular diagnosis involve techniques for the amplification and characterization of nucleic acids. These techniques have enabled the diagnosis of many diseases with unprecedented sensitivity and specificity. As research tools, these methods have increased our understanding of many diseases on a molecular level, with the unraveling of the molecular pathology of many common disorders. The foundation for the rapid and continual development of molecular pathology received a boost from the genome‐wide scale analyses of the human genome, such as the Human Genome Project (HGP) and the HapMap Project, which have provided the essential genetic blueprint for future investigations.
Pesticides (New Generation) and Related Compounds, Analysis of
Authors: Picó Yolanda
Published: December 2009

Miscellaneous pesticides and related compounds comprise substances that can neither be included in the classical chemical category of pesticides nor classified by their mode of action. They are a heterogeneous group of substances, the most representative of which are macrocyclic lactones, chloronicotinyls, tetranortriterpenoids, ammonium quaternary salts, dinitroanilines, acetamides, oximes, triazoles, and pyridine‐based molecules. The pesticides covered in this article have hardly changed in the last years. However, their analytical determination has undergone significant improvements. This article provides a well‐defined and critical compilation of the sample treatment and clean‐up procedures, as well as determination techniques applied to miscellaneous pesticides. The new approaches in sample preparation in environmental matrices, such as air, water, soil, food and biological samples, are described. Analytical techniques for characterizing these compounds, which mostly include gas chromatography (GC) and high‐performance liquid chromatography (HPLC) coupled to mass spectrometry (MS), are discussed. Both techniques have almost completely displaced other chromatographic methods. However, in the frontier between chemical and biological techniques, the development of biosensor techniques is very promising. Here, analytical methods applied to the field of real samples are also presented.
Pharmacogenomics
Authors: Melanson Stacy E.F.
Published: December 2009

Adverse drug reactions occur in 5–10% of hospitalized patients and are one of the leading causes of death in the United States. 1, 2 The field of pharmacogenomics explores the relationship between a patient's genetics and his/her response to drugs. If a patient's response to a drug can be predicted by his/her genetics, then the right drug at the right dose can be administered. Additionally, harmful side effects and toxicity can be avoided. Pharmacogenomic genotyping offers the advantage that it only needs to be performed once and can provide unequivocal genetic information. However, the complexity of gene regulation and gene–environment interaction can complicate pharmacogenomic testing. This article provides an overview of pharmacogenomics and examples of pharmacogenomic applications.
Conformational and Chiroptical Properties of Alkyl Halides
Authors: Brewster James H.
Published: December 2009

Introduction

Properties of Atoms and Bonds

Conformational Properties of Alkyl Halides

Chiroptical Properties of Alkyl Halides
The Formation of the
C

F
Bond: The Last Twelve Years
Authors: Rozen Shlomo
Published: December 2009

Introduction

Nucleophilic Fluorinating Reagents

Electrophilic Fluorinating Reagents

Synthesis of Compounds Containing The
18
F
Isotope For Use In Positron‐Emitting Tomography

Recent Reviews on Selective Fluorination Methods
Recent Advances in the Organic Chemistry of Astatine
Authors: Berei Klara , Vasáros László
Published: December 2009

Introduction

Physical and Chemical Properties of Astatine

Synthesis and Identification of Organic Astatine Compounds

Physicochemical Properties of Organic Astatine Compounds

Biomedical Applications
Prologue: History of Cyclopropane Derivatives Before 1916
Authors: Conant James Bryant
Published: December 2009

PART
I
General and Theoretical Aspects of the Cyclopropyl Group
Authors: Cremer Dieter , Kraka Elfi , Szabo Kalman Josef
Published: December 2009

Introduction

Structure and Topology

Electronic Structure—Orbital Description

Electron Density Distribution and Chemical Bonding

Energy and Stability

Geometry

Vibrational Spectra

One‐Electron Properties

NMRSpectra

Excited States and Ultraviolet Absorption Spectra

Charged Cyclopropyl Groups

The Cyclopropyl Radical

Fused Cyclopropanes

Formation and Reactivity

Acknowledgements
Cyclopropane Photochemistry
Authors: Zimmerman Howard E.
Published: December 2009

Introduction

Reactions Giving Rise to Three‐Membered Ring Photoproducts

Photochemical Reactions of Three‐Membered Ring Compounds

Acknowledgements
Photochemistry of Nitro and Nitroso Compounds
Authors: Ho Tong‐Ing , Chow Yuan L.
Published: December 2009

Introduction

Photochemistry of Aromatic Nitro Compounds

Photochemistry of Nitro‐Olefins

Photochemistry of Aliphatic Nitro Compounds

Photochemistry of
C
‐Nitroso Compounds

Photochemistry of Alkyl Nitrites

Photochemistry of

N

‐Nitro and

N

‐Nitroso Compounds
The Electrochemistry of Nitro, Nitroso, and Related Compounds
Authors: Fry Albert J.
Published: December 2009

Introduction

General Considerations

Substituted Nitroaromatics

Aromatic Dinitro Compounds

Aliphatic Nitro Compounds

Related Processes

Nitroso Compounds

Acknowledgments
Nitric Oxide from Arginine: A Biological Surprise
Authors: Mehler Alan H.
Published: December 2009

Abbreviations and Designations Used in Biochemistry

Introduction

IndividualNOS

Localization of the Human Gene

Formation ofNOand Citrulline

Complexities ofNOS

Physiological Functions ofNOS

Conclusions
Reactions of Nitrosoarenes with SH Groups
Authors: Eyer P. , Gallemann D.
Published: December 2009

Introduction and Historical Remarks

Reaction Products and Pathways

Biological Significance
Conformation and Chiroptical Properties of Dienes and Polyenes
Authors: Salvadori Piero , Carlo Rosini , di Bari Lorenzo
Published: December 2009

Introduction

Conjugated Dienes

Polyenes

Oligoenes

Appendix
Ultraviolet/Visible, Infrared and Raman Spectra
Authors: Furukawa Yukio
Published: December 2009

Introduction

Electronic and Vibrational Spectroscopies

Electronic Spectra

Vibrational Spectra
Analysis of Dienes and Polyenes and Their Structure Determination
Authors: Aizenshtat Zeev
Published: December 2009

Introduction

Spectroscopic Methods

Separation and Chromatography of Dienes and Polyenes

Thermal Desorption and Electron Energy Loss Spectroscopy

Mass Spectrometry

Chemical Derivatizations

Selected Examples of Multi‐Parameter Analysis for Dienes and Polyenes: Structure Determination

Analysis of Carotenoids as an Example of Polyene Studies

Acknowledgements
The Chiroptical Properties of the Carbon–Carbon Double Bond
Authors: Gedanken Aharon
Published: December 2009

Introduction

The Spectroscopy of the Olefinic Chromophore

The Planar
C

C
Chromophore

Sector Rules for Chiral Olefins

Isotope Effect

Linear Dichroism Measurements
The Electrochemistry of the CC, CO and CN Groups
Authors: Fry Albert J.
Published: December 2009

Introduction

General Considerations

Alkenes (CCCompounds)

CNCompounds

Carbonyl (CO) Compounds

Acknowledgments
Photochemistry of Compounds Containing CC Double Bonds
Authors: Haddad Nizar
Published: December 2009

Introduction

Excited States

Z–EIsomerizations

[2 + 2] Photodimerizations

[2 + 2] Photocycloadditions of Alkenes to Enones

DI‐π‐Methane Rearrangement
Some Synthetic Uses of Double‐Bonded Functional Groups
Authors: Hoyle Jeff
Published: December 2009

Introduction

Oxidation

Reduction

CCBond‐Forming Reactions

Preparation of Heterocycles

Acknowledgments
Hydrogenation of Compounds ContainingCC,COandCNBonds
Authors: Wills Martin
Published: December 2009

Introduction

Hydrogenation ofCCBonds

Hydrogenation ofCOBonds

Hydrogenation ofCNBonds

Conclusions
Strained Olefins
Authors: Sandström Jan
Published: December 2009

Basic Concepts

Tetrasubstituted Ethylenes

Push–Pull Systems

Bis‐Tricyclic Ethylenes

Medium‐Sizedtrans‐Cycloalkenes and Analogues

Bi‐ and Polycyclic Bridgehead Olefins

Miscellaneous Compounds

Conclusions
Advances in the Metathesis of Olefins
Authors: Ivin K. J.
Published: December 2009

Introduction

Catalysts, Intermediates, Initiator Efficiencies

Acyclic Monoenes not Containing Functional Groups

Acyclic Monoenes Containing Functional Groups

The Carbonyl–Olefination Reaction

Acyclic Diene Metathesis (ADMET)

Ring‐Opening Metathesis Polymerization (ROMP) Of Cycloalkenes

Copolymerization

Polymerization of Acetylenes by Olefin Metathesis Catalysts

Intramolecular Metathesis Reactions of Enynes and Dienynes

Metathesis Reactions of Alkynes Involving Total Cleavage of theCCBond
N‐Oxidative Transformations ofCNGroups as Means of Toxification and Detoxification
Authors: Hlavica Peter , Lehnerer Michael
Published: December 2009

Introduction

Chemical Aspects of theN‐Oxygenation of theCNFunctionality

Occurrence ofN‐OxygenatedCNFunctionalities in Natural and Synthetic Compounds and Biological Activity

Metabolic in Vivo and in Vitro Formation ofN‐OxygenatedCNFunctionalities

Enzymology of the Formation ofN‐OxygenatedCNFunctionalities

Further Transformations ofN‐OxygenatedCNFunctionalities

Conclusions
Thermochemistry of Azo, Hydrazo, Azoxy and Related Species†Dedicated to Charles G. Overberger, pioneering investigator of cycle azo componds.
Authors: Liebman Joel F. , Afeefy Hussein Y. , Slayden Suzanne W.
Published: December 2009

Introduction: Scope and Definitions

Azo Compounds

Hydrazines

Hydrazides

Azoxy Compounds

Azodioxy Compounds

Acknowledgements
The Photoelectron Spectroscopy of Hydrazo, Azo and Azoxy Compounds
Authors: Novak Igor , Kovač Branka
Published: December 2009

Introduction

Pes of Azo Compounds

Pes of Azoxy Compounds

Pes of Hydrazo Compounds

Conclusion

Acknowledgements
Acidity, Basicity and Complex Formation
Authors: KlapÖtke Thomas M
Published: December 2009

Outline

Introduction

Hydrazo Compounds

Azo Compounds

Azoxy Compounds

Acknowledgements
Cathodic and Anodic Behaviour of Organic Compounds Possessing 
N

N
 or >
N

N
< Linkages
Authors: Simonet Jacques , Gueguen‐simonet Noëlle
Published: December 2009

Introduction

Reduction—Cathodic Electron Transfers

Oxidation

Acknowledgements
Radical Reactions of Azo, Hydrazo and Azoxy Compounds
Authors: Koga Gen , Warner John C. , Anselme J.‐P
Published: December 2009

Introduction

Radical Reactions of Azo Compounds

Radical Reactions of Hydrazo Compounds

Radical Reactions of Azoxy Compounds
Silyl‐Substituted Carbocations
Authors: Siehl Hans‐Ullrich , Müller Thomas
Published: December 2009

Introduction

Calculational Results

Gas Phase Studies

Solvolytic Studies

Stable Ion Studies

Conclusions

Acknowledgements
Silicon‐Substituted Carbenes
Authors: Maas Gerhard
Published: December 2009

Introduction

Geometric and Electronic Structure: Theory and Experiment

Silicon‐Substituted Carbenes in Synthesis

Concluding Remarks

Acknowledgments
The Photochemistry of Organosilicon Compounds
Authors: Brook A. G.
Published: December 2009

Introduction

Compounds Containing a Single Silicon Atom

Compounds Containing Two Silicon Atoms Disilanes

Tri‐, Tetra‐ and Polysilanes

Acylsilane Photochemistry

Silyldiazoalkanes and Silylcarbenes

Photochemical Routes to Silenes, Silylenes and Disilenes

Photochemical Rearrangements of Silenes, Silylenes and Disilenes

Other Photolyses Leading to Multiply Bonded Silicon

Photolysis of Miscellaneous Compounds

Addendum

Photochemical Routes to Silenes, Silylenes and Disilenes
Synthetic Applications of Allylsilanes and Vinylsilanes
Authors: Luh Tien‐Yau , Liu Shiuh‐Tzung
Published: December 2009

Introduction

Electrophilic Substitution ofCSiBonds

Organometallic Reagents PromotedCSiCleavage Reactions

MiscellaneousCSiCleavage Reactions

Reactions of Allylsilanes and Vinylsilanes without Cleavage of theCSiBond
Cyclic Polychalcogenide Compounds with Silicon
Authors: Choi Nami , Ando Wataru
Published: December 2009

Introduction

Monocyclosilachalcogenides

Bicyclosilachalcogenides

Tricyclosilachalcogenides

Polycyclosiloxanes
Cyclopentadienyl Silicon Compounds
Authors: Jutzi Peter
Published: December 2009

Introduction

Compounds Containing Cyclopentadienyl‐Siliconσ‐Bonds

Compounds Containing Cyclopentadienyl–Siliconπ‐Bonds

Acknowledgements
Chirality in Bioorganosilicon Chemistry
Authors: Tacke Reinhold , Wagner Stephan A.
Published: December 2009

Introduction

Biological Recognition of Enantiomeric Organosilicon Drugs

Biocatalysis as a Method for the Preparation of Optically Active Organosilicon Compounds

Concluding Remarks

Acknowledgments
General and Theoretical Aspects of Organic Gold Compounds†This chapter is dedicated to the memory of Prof. Saul Patai, a humane person, educator and outstanding scientist.
Authors: Hoz Tova , Basch Harold
Published: December 2009

Introduction

AuL+Complexes,L = Neutral Ligand

AuXCompounds,X = Negatively Charged Ligand

LAuL′+Complexes

XAuLComplexes

YAuX−Complexes

AuL3+andAuL2L′+Complexes

AuL4+Complexes
Thermochemistry of the Organometallic Compounds of Silver and Gold
Authors: Liebman Joel F. , Simões José Martinho , Slayden Suzanne W.
Published: December 2009

Introduction

Silver Acetylides

Silver Cyano Derivatives

Silver(I) Olefin Complexes in the Condensed Phase

Silver Complexes with Acetylenes

Organogold Derivatives in the Condensed Phase

Organosilver Species in the Gas Phase

Organogold Species in the Gas Phase

Acknowledgments
Analytical Aspects of Organogold and Organosilver Compounds
Authors: Zabicky Jacob , Grinberg Sarina
Published: December 2009

Introduction

Elemental Analysis of Gold and Silver

Characterization and Determination of Organogold and Organosilver Compounds

Self‐Assembled Monolayers
The Organic Photochemistry of Silver and Gold
Authors: Horspool William M.
Published: December 2009

Introduction

Reactions Involving Silver as Films or in Solution

Photochemistry of Silver Complexes of Alkenes

Silver–Carbon Bond Fission on Photolysis

Silver Salts of Carboxylic Acids

Reactions with Silver Triflate

Amine Complexes of Silver

Miscellaneous Reactions Involving Silver

Monolayers on Gold

Gold Complexes

Gold as a Catalyst

Carbon–Gold Bond Fission

Miscellaneous Reactions Involving Gold
Medicinal Chemistry of Gold Compounds
Authors: Fricker Simon P.
Published: December 2009

Metals in Biology

Historical Use of Gold in Medicine

Gold Therapy for Rheumatoid Arthritis

Mechanism of Action of Antiarthritic Gold Drugs

Antitumour

Anti‐Infective

Conclusion

Acknowledgement
NMR
Spectroscopy of Dienes and Polyenes
Authors: Takeuchi Yoshito , Takayama Toshio
Published: December 2009

Introduction

Theory of
NMR
Chemical Shifts of Polyenes

Recent Applications

Special Topics
IntermolecularCyclization Reactions to form Carbocycles
Authors: Beusker Patrick H , Scheeren Hans W
Published: December 2009

General Introduction

[2 + 2] Cycloaddition Reactions

Diels–Alder Reactions

[6 + 4] Cycloaddition Reactions

[8 + 2] Cycloaddition Reactions

[2 + 2 + 2] Cycloaddition Reactions
Electrophilic Additions to Dienes and Polyenes
Authors: Chiappe Cinzia , Ruasse Marie‐Françoise
Published: December 2009

Introduction

Electrophilic Hydrogen

Electrophilic Carbenium Ions

Electrophilic Halogens and Positive Halogen Donors

Electrophilic Sulfur and Selenium

Electrophilic Mercury

Conclusions

Acknowledgements
Rearrangements of Dienes and Polyenes
Authors: Lukyanov Sergei M. , Koblik Alla V.
Published: December 2009

Introduction

Rearrangements of Allenes and Cumulenes

Rearrangements of Conjugated Dienes and Polyenes

Rearrangements of Non‐Conjugated Dienes and Polyenes
Recent Advances in the Chemistry of Silicon–Silicon Multiple Bonds
Authors: Weidenbruch Manfred
Published: December 2009

Introduction

Acyclic Disilenes

Tetrasilabuta‐1,3‐Diene

Cyclic Disilenes

Disilynes

Conclusion

Acknowledgments
Recent Developments in the Chemistry of Compounds with Silicon–Nitrogen Bonds
Authors: Neugebauer Peter , Jaschke Bettina , Klingebiel Uwe
Published: December 2009

Introduction

Preparation and Properties of theSiNBond

Aminosilanes

Lithium Derivatives of Silylamines

Lithium Derivatives of Hydrazines

Iminosilanes

Cyclic Silicon–Nitrogen Compounds

Cyclodisilazanes

Cyclotrisilazanes

Cyclotetrasilazanes

Application of Cyclosilazanes as Precursors for Silicon‐Based Ceramics
Silicon‐Based Dendrimers and Hyperbranched Polymers
Authors: Son David Y
Published: December 2009

Introduction

Silicon‐Based Dendrimers

Silicon‐Based Hyperbranched Polymers

Concluding Remarks
Silyl Migrations
Authors: Kira Mitsuo , Iwamoto Takeaki
Published: December 2009

Introduction

1,2‐Silyl Migrations

1,3‐Silyl Migrations

1,N‐Silyl Migrations (n ≥ 4)
Kinetic Studies of the Reactions ofSiCandSiSiBonds
Authors: Morkin Tracy L. , Owens Thomas R. , Leigh William J.
Published: December 2009

Introduction

Experimental Methods

Kinetics and Mechanisms of the Reactions of Silenes

Kinetics and Mechanisms of the Reactions of Disilenes

Conclusions
Recent Advances in Structural Chemistry of Organic Germanium, Tin and Lead Compounds
Authors: Klinkhammer Karl W
Published: December 2009

Introduction

Tetrylenes (Tetrelanediyls)R2Eand their Derivatives

Multiple‐Bonded Systems
Gas‐Phase Chemistry and Mass Spectrometry ofGe‐,Sn‐ andPb‐Containing Compounds
Authors: Riveros José M. , Takashima Keiko
Published: December 2009

Introduction

Mass Spectrometry ofGe,SnandPbDerivatives

Gas‐Phase Ion Chemistry

Gas‐Phase Chemistry of NeutralGe,SnandPbSpecies

Acknowledgments
Synthetic Uses ofR3MH(M = Ge,Sn,Pb)
Authors: Carland Michael W. , Schiesser Carl H.
Published: December 2009

Introduction

The Preparation of Novel Trialkylgermanes and Stannanes

Trialkyltin Hydrides as Reagents in Radical Chain Reactions

Trialkyltin Hydrides in Non‐Radical Chemistry

Trialkylgermanium and Lead Hydrides in Synthesis

Acknowledgement
Trichlorogermane, a New Superacid in Organic Chemistry
Authors: Kolesnikov Stanislav , Tandura Stanislav N. , Nefedov Oleg M.
Published: December 2009

Introduction

Synthesis, Structure and Physical Properties of Trichlorogermane

Acidic and Superacidic Properties of Trichlorogermane

Electrochemical Investigation ofHGeCl3andGeCl4

Reactions of Trichlorogermane with Organic Halides

Reactions of Trichlorogermane with Unsaturated Compounds

Double Germylation

Reactions ofHGeCl3with Aromatic Compounds

Conclusions
The Photochemistry of Organometallic Compounds of Germanium, Tin and Lead
Authors: Long Conor , Pryce Mary T.
Published: December 2009

Introduction

Saturated Oligomeric Systems

Alkyl Compounds

Aryl Compounds

Conjugated Catenates

Metal Oxanes

Photoinduced Electron Transfer

Metal–Metal Multiple‐Bonded Systems

Systems Involving Transition Metal Fragments
Biological Activity of Organotin and Organolead Compounds
Authors: Lukevics Edmunds , Pudova Olga
Published: December 2009

Tin

Lead
Analytical Aspects of Organolithium Compounds
Authors: Zabicky Jacob
Published: December 2009

Introduction

Quantitative Analysis

Characterization Methods

Association

Analysis by Inference After Quenching
α‐Amino‐Organolithium Compounds
Authors: Gawley Robert E. , Coldham Iain
Published: December 2009

Introduction to α‐Amino‐Organolithium Compounds

Unstabilized α‐Amino‐Organolithium Compounds

Dipole‐Stabilized α‐Amino‐Organolithium Compounds

Dipole‐andHeteroatom‐Stabilized α‐Amino‐Organolithium Compounds

Mesomerically Stabilized α‐Amino‐Organolithium Compounds

Dipole‐andMesomerically Stabilized α‐Amino‐Organolithium Compounds

Acknowledgments
Stereochemical Aspects—Conformation and Configuration
Authors: Berg Ulf
Published: December 2009

Introduction

Conformation

Resolution and Determination of Configuration

Cyclobutane in Bicyclic Systems

Cyclobutane in Polycyclic Systems

Stereochemistry Of Ring Closure and Ring‐Opening Reactions

Natural Products
Acidity and Basicity of Cyclobutanes
Authors: Quintanilla Esther , Dávalos Juan Z. , Abboud José Luis M. , Alkorta Ibon
Published: December 2009

Introduction

Geometrical Structures

Some Consequences of the Geometrical Structures

Selected Reactions

CBandCUBas Bases

Hydrogen Bonding (HB)

CBandCUBas Substituents

Acknowledgments
NMR
Spectroscopy of Cyclobutanes
Authors: Seidl Peter Rudolf , Dias Jacques Fernandes
Published: December 2009

Introduction

Structural and Conformational Effects

Spectral Parameters

Substituted Cyclobutanes

Cyclobutanes as Part of Ring Systems
Cation Radicals in the Synthesis and Reactions of Cyclobutanes
Authors: Bauld Nathan L.
Published: December 2009

Introduction

Historical

Energetic Considerations for Cation Radical/Neutral Cycloaddition Reactions

Novel Cation Radical Structures Encountered in Cation Radical/Neutral Cycloadditions

Mechanistic Considerations

Stereochemistry of Cation Radical Cyclobutanation

Other Early Cation Radical Cyclobutanation Precedents

Mechanistic Diversity

The Concerted (or Quasi‐Concerted) Cycloaddition Mechanism

Mechanistic Considerations in Aminium Salt Initiated Cyclobutadimerizations

Cross Cyclobutanation

Cyclobutane Periselectivity in Cross Additions to Conjugated Dienes

The Competition between Cation Radical Cyclobutanation and
D
iels–
A
lder Cycloaddition

Steric Effects in Cation Radical Cyclobutanation

D
iels–
A
lder Periselectivity in Reactions with Acyclic Dienes

D
iels–
A
lder/Cyclobutanation Competition in Cation Radical Cycloadditions to Styrenes

Conformational Effects upon Periselectivity in Cation Radical/Neutral Cycloaddition Reactions

The Cation Radical
Vinylcyclobutane
(

VCB

) Rearrangement

Stereochemistry of the Cation Radical Vinylcyclobutane Rearrangement

The Cation Radical Arylcyclobutane Rearrangement

Intramolecular Cation Radical Cyclobutanation

Natural Product Synthesis via Cation Radical Cyclobutanation

Cation Radical Chain Cycloaddition Polymerization

Retrocyclobutanation

Cation Radical Cycloadditions Involving Alkynes

Cation Radical Chain Reactions of Alkene Cation Radicals with Dioxygen

Retroelectrocyclic Reactions of Cyclobutene Cation Radicals
Organometallic Derivatives
Authors: Butenschön Holger
Published: December 2009

Introduction and Scope

Cyclobutanes

Cyclobutenes

Cyclobutadienes

Benzocyclobutenes and Related Systems

Benzocyclobutadienes
Solvent‐Free Photosynthesis of Cyclobutanes: Photodimerization of Crystalline Olefins
Authors: Natarajan Arunkumar , Ramamurthy V.
Published: December 2009

Introduction

Photodimerization of Cinnamic Acids: Emergence of Topochemical Postulates

Photodimerization of Coumarins, Styrylcoumarins and Benzylidenecyclopentanones

Reaction Cavity Concept: Role of Empty Space and Immediate Neighbors

Fine Tuning of Topochemical Postulates

Impact of Excitation on Molecular Geometry and Intermolecular Arrangement

Crystal Engineering

Does Dimerization Precede Geometric Isomerization?

Single Crystal to Single Crystal Photodimerization of Olefins

Concluding Remarks

Appendix: More Examples of Solid State Photodimerization of Olefins

Acknowledgment
Fluorinated Cyclobutanes and Their Derivatives
Authors: Lemal David M. , Chen Xudong
Published: December 2009

Cyclobutanes

Cyclobutenes

Other Unsaturated Cyclobutanes

Perfluoroalkyl‐Substituted Systems

Afterword

Acknowledgments
Thermochemistry of Peroxides
Authors: Slayden Suzanne W. , Liebman Joel F.
Published: December 2009

Introduction, Scope and Definitions

Hydrocarbon‐Substituted Peroxides

Peroxides with Single‐Bonded Oxygen Functional Groups

Peroxycarboxylic Acids and Their Derivatives

Cyclic Peroxides and Multiply‐Linked Peroxides
17ONMRSpectroscopy of Organic Compounds Containing the OOgroup
Authors: Cerioni Giovanni , Mocci Francesca
Published: December 2009

Introduction

Organic Peroxides

A Brief Look at Metallo‐Organic and Biological Systems
Peroxides in Biological Systems
Authors: Cadet Jean , Di Mascio Paolo
Published: December 2009

Introduction

DNAHydroperoxides

Lipid Hydroperoxides

Protein Hydroperoxides

Cellular Indicators of Hydroperoxides

Conclusions

Acknowledgments
Contemporary Trends in Dioxetane Chemistry*This chapter is dedicated to our appreciated friend and esteemed colleague, Professor Rostislav F. Vasil'ev, for his pioneering work on the chemical generation of electronically excited states
Authors: Adam Waldemar , Trofimov Alexei V.
Published: December 2009

Introduction

Stereoselective Synthesis of Chiral Dioxetanes and their Transformations

α‐Peroxy Lactone as Oxidant

Chemiluminescent Decomposition of 1,2‐Dioxetanes

Bioanalytical Application of the Dioxetane Chemiluminescence

Photooxidation ofDNAby 1,2‐Dioxetanes

Conclusions

Acknowledgment
Mass Spectrometry of Organozinc Compounds
Authors: Palii Sergiu P. , Zagorevskii Dmitri V.
Published: December 2009

Introduction

Mass Spectrometry of Organozinc Compounds

Dialkylzinc and Dihaloalkylzinc Compounds

Other Organozinc Compounds with the General Formula
Zn
R
2

Miscellaneous Complexes Containing a
Zn

C
Bond

Organozinc Ion Structure and Energetics

Energetics and Photodissociation Studies

Gas Phase Ion/Molecule Reactions

In silico
Studies of Organozinc Ion Structures

Other Studies Involving Mass Spectrometry

Mass Spectrometric Investigation of Pyrolysis of Zinc‐Containing Species

Monitoring of Organometallic Vapor Phase Epitaxy by Mass Spectrometry

Conclusions
Synthesis and Reactions of Allenylzinc Reagents
Authors: Marshall James A.
Published: December 2009

Zincation of Propargylic Bromides

Mechanistic Studies

Regiochemistry of Additions to Aldehydes and Ketones

Stereochemistry of Additions

Transition State Calculations

Reagent Regioselectivity

Iodoallene‐Derived Reagents

Configurational Stability

Allenyl Alkylzinc Reagents

Coupling of Allenylzinc Bromide Reagents with Aryl and Vinyl Halides

Palladiozincation of Propargylic Mesylates

Double Diastereoselection

Applications to Natural Product Synthesis

Additions to Imines and Aldehydes

Kinetic Resolution of Chiral Allenylzinc Reagents

Amine‐Substituted Allenylzinc Reagents

Additions to Sulfoximines

Additions of Chloroallenylzinc Reagents to Aldehydes and Imines
The Chemistry of Organozincate Compounds
Authors: Harada Toshiro
Published: December 2009

Introduction

Preparation of Zincates

Reaction of Zincates

Concluding Remarks
The Chemistry of Zinc Enolates
Authors: Lombardo Marco , Trombini Claudio
Published: December 2009

General and Theoretical Aspects

The Reformatsky Reaction

The Gilman–Speeter Reaction

Further Electrophiles for Reformatsky Reagents

Alternative Routes to Zinc Enolates

Zinc Dienolates

Conclusions
Toxicological and Environmental Aspects of Anilines
Authors: Travis Anthony S.
Published: December 2009

Introduction

Cyanosis

Analytical Methods for Environmental Detection and Sampling of Anilines

Carcinoma

Mechanism of Bladder Cancer

Specific Aromatic Amines

Environmental Fate

Regulation and Legislation

Aromatic Amines as Dietary Carcinogens

Conclusion
Electrochemistry of Organomagnesium Compounds
Authors: Jaworski Jan S.
Published: December 2009

Introduction

Electrochemical Synthesis of Organomagnesium Compounds

Conductivity of Solutions of Organomagnesium Compounds

Anodic Oxidation of Organomagnesium Compounds

Cathodic Reduction of Organomagnesium Compounds

Organomagnesium Compounds as Intermediates in Electrode Reactions

Concluding Remarks: Electrochemical Data in the Elucidation of Reactivity of
G
rignard Reagents
Carbomagnesiation Reactions
Authors: Itami Kenichiro , Yoshida Jun‐Ichi
Published: December 2009

Introduction

Carbomagnesiation Reactions of Alkynes

Carbomagnesiation Reactions of Alkenes

Carbomagnesiation Reactions of Aromatics
Acute Toxicity
Authors: Andrew David J.
Published: December 2009

Testing for acute toxicity is the most fundamental of toxicological investigations and is routinely performed as a regulatory requirement for a number of different substance and product types in order to ensure human safety. The results of these studies are used to characterize the hazard, to assign the substance to a classification category, to provide information on the likely medical treatment of an overexposure and to inform the design of subsequent longer‐term toxicity studies where these are required. The relative simplicity of the study design and the endpoints investigated makes acute toxicity studies obvious candidates for replacement by alternative (in silicoandin vitro) methods, and while there has been some progress in the development of these alternatives, regulatory acceptance is currently limited. Incorporation of the use of read‐across and the availablein vitroandin silicomethods, within vivostudies performed only when required, is recommended in order to give an intelligent and integrated strategy to the assessment of acute toxicity.
Repeated Exposure Toxicity
Authors: Ballantyne Bryan
Published: December 2009

Acute toxicity studies are essential preliminaries to repeated‐dosing studies, but the former give limited information about organ‐specific toxicity. Many toxic effects are not detected in acute studies because of the need for cumulative toxicity to develop or because of a long latency to development of toxicity. Evaluation of repeated‐exposure toxicity requires that studies be conducted by an appropriate route for a sufficient number of exposures. The initial concentrations or doses chosen will be determined by findings from acute studies, when these permit the detection of toxicity. Short‐term repeated‐dose studies vary in length from a few (5‐9) days to 28 days, while subchronic studies are usually 90 days, and chronic studies 18 months or more, in rodents. The material to be tested should be of known purity. Most repeated‐exposure studies are conducted using rats or mice, with some regulatory agencies also requiring the use of a larger species (e.g. dog), for subchronic studies. The choice of species is heavily constrained by regulatory authorities and the requirement for normative data. Dosing may be by various routes, that chosen depending largely on the likely route of human exposure. Oral dosing can be gavage, or incorporation of test material into the diet or drinking water. In‐life observations include clinical observation, food and water consumption and body weight determinations. Standard haematology, clinical chemistry and urinalysis measurements are necessary in all studies. At termination, necropsy is carried out, selected organs are weighed and selected organs processed for histopathology.
Physiologically Based Pharmacokinetic Modelling
Authors: Leung Hon‐Wing
Published: December 2009

This chapter presents the readers with a primer on the subject of physiologically based pharmacokinetic (PBPK) modelling. It discusses the theory and principles of PBPK modelling, and compares and contrasts it with classical pharmacokinetic modelling. It describes the multiple steps involved in developing PBPK models, and includes a compilation, with complete referencing, of published PBPK models for environmental chemicals that have been developed to date. The many applications of PBPK modelling to address issues in toxicology and health risk assessment are discussed with relevant examples. It concludes with some discussion of the problems and limitations in PBPK modelling, and offers some observations about future directions for this rapidly emerging field.
Effects of Chirality on Toxicity
Authors: Nilos Mae Grace , Gan Jay , Schlenk Daniel
Published: December 2009

Chirality is a prominent feature of the living world, and also occurs in man‐made chemicals, especially pharmaceuticals and agrochemicals. The significance of chirality has long been recognized in relation to the biological activity of natural compounds and synthetic drugs. At a molecular level, chirality is ubiquitous in the building blocks of proteins, carbohydrates, nucleic acids, lipids and steroids. Thus, stereoselectivity can be expected in the interactions of chiral chemicals with biological molecules. It is not uncommon in racemic mixtures of chiral drugs or agrochemicals to have only one of its two (or more) enantiomers responsible for most or all of the desired activity. The other enantiomer(s) are all too often assumed to be inactive of little or no important activity. The last 30 years has seen a significant increase in published work highlighting the important relationship between molecular geometry and bioactivity, particularly for chiral pharmaceuticals and agrochemicals. However, a sizable number of chiral drugs and agrochemicals are still available as racemates with relatively little or no information with regard to the toxicological properties of the individual enantiomers. The persistent reluctance to acknowledge the risks associated with the chirality of a chemical is no longer justified. Chiral technology has developed to a point where we are allowed several options in enantiomer resolution and preparation techniques, which in turn offer new avenues for human and environmental toxicologists to explore the stereochemical properties of these ubiquitous agents. This chapter discusses some of the toxicological complexities that could result from chirality, in the hope of highlighting the importance of enantioselective considerations in both mammalian and ecotoxicology.
The Influence of Temperature on Toxicity
Authors: Gordon Christopher J. , Rowsey Pamela J.
Published: December 2009

Our understanding of the effects of temperature on toxic response has seen resurgence in the past several decades, with the development of better methods to study the integration of autonomic and behavioural thermoregulatory responses in rodents and other species. Radiotelemetry provides researchers with the best tool to study the thermoregulatory responses in undisturbed rodents exposed chronically or acutely to toxic chemicals. The thermoregulatory response to acute exposure to many toxic chemicals involves a regulated hypothermic response, characterized by an increase in autonomic thermoeffectors to increase heat loss and a behavioural preference for cooler temperatures. This thermoeffector response is quickly manifested by a marked drop in the core temperature in rodents. However, in humans and other large mammals, the hypothermic response is meagre due to their large thermal inertia. A combination of exposure to cool temperatures and a moderate hypothermic response has been found to benefit survival with a variety of toxic agents. Thus, the integrated thermoregulatory response of rodents to lower their core temperature seems to be an adaptive response. On the other hand, fever or hyperthermia is often seen in humans and other large mammals exposed to various toxicants. A fever is also seen in rodents provided that core temperature is monitored without disturbing the animal (e.g. telemetry). The universal effects of temperature on chemical toxicity calls for researchers to have a better understanding of the thermoregulatory effects of environmental toxicants.
Development of Tolerance to the Toxicity of Xenobiotics
Authors: Fonnum Frode
Published: December 2009

The development of tolerance to xenobiotics usually involves the inactivation of receptors or the induction of enzymes that bind or inactivate the xenobiotics. This review showns, as the main example, anticholinesterase, the effect of which is modified in several different ways. Tolerance depends on the internalization or inactivation of the muscarinic receptor or the nicotinic receptor. Also mentioned is the interaction of the adenosine receptor with the cholinergic system. Further, the importance of carboxylesterases, butyrylcholinesterase and phosphoric hydrolases in tolerance is discussed. An interesting topic included is the survival of acetylcholinesterase knock‐out animals. Finally the mechanism of tolerance to morphine in the locus coerulus is discussed as an example.
Pathological Techniques in Toxicology
Authors: Greaves Peter
Published: December 2009

Histopathological evaluation remains an important part of the assessment of the adverse effects of xenobiotics on the whole organism. In addition to conventional special staining techniques and electron microscopy, new techniques involving immunocytochemistry, molecular biology and novel visualization procedures have provided additional objective techniques that have enabled better functional and morphological characterization of induced alterations in organs of the body. This chapter covers both conventional and new methods involved in the microscopical assessment of tissue changes induced by xenobiotics.
Clinical Chemistry in Toxicity Testing: Scope and Methods
Authors: Gosselin Sylvie , Ramaiah Lila , Earl Lesley
Published: December 2009

Noncellular blood compartment (plasma or serum) and urine biochemical components are important indicators of overall animal health and can be used in conjunction with other parameters to investigate the toxicity of drugs and chemicals. This chapter describes the measurement and interpretation of clinical chemistry tests employed in toxicology studies in commonly used laboratory species. The introductory sections delineate methods for sample collection and data generation, and provide a general approach for data interpretation and reporting, with emphasis on distinguishing pre‐analytical/analytical variations from test material‐related changes. The following sections are organized by organ system, describing core clinical chemistry tests used in routine toxicology studies. These include protein, lipid and carbohydrate metabolisms, liver and kidney functions and electrolyte balance. Nonroutine tests evaluating cardiac and skeletal muscle, bone, blood vessels, the endocrine system, the nervous system are also presented. Because few clinical chemistry parameters are specific indicators of single organ toxicity, each section emphasizes the integrated interpretation of biochemistry changes with other study endpoints such as clinical signs, food consumption and bodyweight, haematology, electrocardiography, blood pressure and histopathology. Patterns of change are presented in the context of identifying organ toxicity.
Imaging Techniques in Neurotoxicology Research and Development
Authors: Hantson Philippe , Duprez Thierry
Published: December 2009

The impact of neuroimaging techniques in the work up of intoxicated patients is nowadays increasing regarding both macroscopic anatomical damage (CT and MR) and ultrastructural damage (DWI), but also regarding metabolic (MR spectroscopy) and functional impairment (fMRI). Perfusional status of diseased areas may also be investigated by magnetic resonance imaging (MRI) using exogenous or even endogenous tracers, and the density of membrane receptors can be investigated using isotopic techniques (positron emission tomography (PET), single photon emission computed tomography (SPECT)). There is growing evidence for elective sensitivity of defined brain areas like basal ganglia towards toxic exposure and for relative specificity of topographical brain damage for some substances, but with significant overlapping between toxins. Uncertain relationships between severity of brain abnormalities on CT or MR images at an acute phase and functional clinical outcome renders mandatory the investigation of better early prognostic parameters which could mainly involve DWI and1H‐MRS data in clinical routine, and fMRI data, perfusion parameters, and receptors density in the investigational field.
Nanotoxicology—The Toxicology of Nanomaterials
Authors: Gellein Kristin , Syversen Tore
Published: December 2009

Nanotoxicology is a new and fast‐growing discipline that deals with the interaction between engineered nanostructures and biological systems. Because of their size, these materials have unusual physicochemical properties that make them different from bulk materials of the same chemical composition. However, the same properties that make these materials very attractive in a range of technological applications, also raise concern about adverse effects in biological systems. Today, a limited amount of data is available on possible effects on man and the environment. Nanomaterials (NMs) are currently available in a wide variety of compositions, and traditional approaches of toxicity testing are often not directly applicable. Studies so far, bothin vivoandin vitro,indicate that these materials have the potential to cause adverse effects. As both the production volume and application range of NMs expands rapidly there is an urgent need to develop adequate toxicity testing and evaluation of these products.
Antidotal Studies
Authors: Bateman D. Nicholas , Marrs Timothy C.
Published: December 2009

Antidotes for poisons may act in a variety of ways and, in some cases, two (or more) antidotes using different antidotal approaches, are used together. Antidote development depends on an extensive knowledge of the action of the poison, which the antidote is expected to counteract. Poisons and their antidotes may be studiedin vitro,in experimental animals or in humans. The design of experimental studies in animals and experimental and observational ones in humans presents major challenges. In the case of animal studies, the aim is to simulate realistic treatment scenarios.
Ophthalmic Toxicology
Authors: Ballantyne Bryan
Published: December 2009

Ophthalmic toxicology is a specialist area that deals with potentially adverse effects on the eye from chemicals and their metabolites, reaching the eye by local contact and from the systemic circulation, and also covers the effects that may be produced systemically by chemicals that have been absorbed into the circulation following topical contact with the eye. This chapter reviews, with illustrative examples, all these aspects of ophthalmic toxicology, with particular reference to causation, mechanisms of production of lesions, relevantin vivoandin vitrolaboratory testing procedures, the significance and clinical relevance of the observed effects. Site‐specific lesions and functional disturbances in the eye that are discussed in detail are those to the cornea, iris, ciliary body, aqueous humour production, the lens, retina, optic nerve and extraocular muscles. Systemic effects following topical contamination of the eye are discussed particularly for chemicals and drugs, and discussed in terms of the sites of absorption.
Cutaneous Toxicology
Authors: Hermansky Steven J.
Published: December 2009

The skin is the largest organ of the body. It serves many functions one of which is protection from the outside world, including chemical and microbiological insults. Skin ailments represent one of the most common complaints of patients in medical settings and account for significant loss of productivity in the workplace. Cutaneous toxicity from chemical exposures is responsible for many of these complaints. Skin reactions to chemicals often appear similar, but have many biological causes, including chemical irritation and sensitization (allergies). A primary goal of the cutaneous toxicologist is to predict the potential irritant and/or sensitization potential of chemicals. This chapter summarizes the varied effects that chemicals may have on the skin, including acute and chronic conditions. The chapter also describes the multiple methods to predict potential cutaneous chemical hazards that may be produced in the workplace or via consumer exposure to topical drugs and cosmetics. Important human, animal andin vitromethods to predict a chemical hazard are described.
Hepatotoxicity
Authors: Hinton Richard H. , Grasso Paul , Marrs Timothy C.
Published: December 2009

The liver has many physiological roles and is a key organ in detoxication. Furthermore, the liver is affected by a very large number of xenobiotics. The liver also has an immense capacity for self‐repair, so that the many abnormalities of structure or function in the liver reverse rapidly on cessation of xenobiotic exposure. Nevertheless the liver's defences can be overwhelmed. Acute liver failure can be caused by many compounds e.g. paracetamol (acetaminophen), while repeated liver damage, for example from ethanol, may lead to cirrhosis. While primary liver cancer is rare in Western Europe and North America, it is common in other parts of the world such as sub‐Saharan Africa, alcohol and aflatoxins being amongst the aetiological factors. Non‐dose‐dependent adverse effects on the liver are common with many classes of drug and may be sufficiently severe to require cessation of treatment. In the regulatory context it is important to recognize the difference between adaptive and toxic effects.
Toxicology of the Exocrine Pancreas
Authors: Foster John R.
Published: December 2009

The exocrine pancreas is not a common target organ for toxic drugs and chemicals. It is however the fifth most common human cancer in the western world, and acute and chronic pancreatitis, through various identifiable and unidentified causes, is a common disease in both the developed and developing countries of the world. Both inflammatory disease and cancer of the pancreas is correlated to lifestyle with poor diet and habits, such as moderate to high alcohol intake and smoking, having positive correlations to developing the disease. The chapter describes the functional anatomy of the organ together with its biochemistry that determines toxicity, in particular the role of oxidant damage in the development of cell and tissue damage is thought to be important. The consequences of toxic damage to the acinar cells are severe and primarily result from the auto‐activation and hence autodigestion of the tissue by the digestive enzymes normally contained within the exocrine cells, a cascade of apoptosis/necrosis and fibrosis with the ultimate collapse of the organ, subsequent shock, multi‐organ collapse and death. The organ has complex molecular mechanisms to prevent premature activation of the digestive enzymes and also has defence mechanisms present to neutralise any premature enzyme activation but these can be rendered ineffectual by factors such as alcohol abuse and a poor diet.

Chemical exposure, through both occupational and consumer product usage, has been associated with the development of both pancreatic neoplastic and non‐neoplastic disease but the relationship between exposure and disease has never developed further than a simple association and it is likely that the development of pancreatic disease is a multi‐faceted combination of inter‐related events, none of which in isolation can induce disease. The pancreas has its own array of phase 1 and 2 metabolic enzyme systems and the role of pancreatic drug and chemical activation and detoxification in inducing toxicity is discussed together with the possible secondary effects of hepatic drug/chemical activation and detoxification.

Finally the role of animal models of pancreatic disease is discussed in terms of their contribution to understanding the aetiology of the human conditions and the possible use of therapeutic intervention in treating the disease.