Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry, Biochemistry and Applications

386 Pages·2011·5.46 MB·english

by  Alexander F. Pozharskii

Heterocycles in Life and Society
Heterocycles in Life and Society: An Introduction to H eterocyclic Chemistry, Biochemistry and Applications ,
Second Edition. Alexander F . P ozhars kii, Anatoly T. S oldatenkov and A lan R . K atritzky.
© 2011 John Wiley & Sons, Ltd. Published 2011 by John Wiley & Sons, Ltd. ISBN: 978-0-470-71411-9
Heterocycles in Life
and Society
An Introduction to Heterocyclic Chemistry,
Biochemistry and Applications
Second Edition
by
ALEXANDER F. POZHARSKII
Soros Professor of Chemistry, Southern Federal University,
Russia
ANATOLY T. SOLDATENKOV
Professor of Chemistry, Russian People’s Friendship University,
Russia
ALAN R. KATRITZKY
Kenan Professor of Chemistry, University of Florida, Gainesville,
USA
A John Wiley & Sons, Ltd., Publication
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LibraryofCongressCataloging-in-PublicationData
Pozharskii,A.F.(AleksandrFedorovich)
Heterocyclesinlifeandsociety/AlexanderF.Pozharskii,AlanR.Katritzky,AnatolySoldatenkov.–2nded.
p.cm.
ISBN978-0-470-71411-9(hardback)–ISBN978-0-470-71410-2(paper)
1.Heterocyclicchemistry.I.Katritzky,AlanR.II.Soldatenkov,A.T.(AnatolyTimofeevich)III.Title.
QD400.P67132011
547(cid:3).59–dc22
2010054024
AcataloguerecordforthisbookisavailablefromtheBritishLibrary.
PrintISBN:978-0-470-71411-9(H/B)978-0-470-71410-2(P/B)
ePDFISBN:978-1-119-99838-9
oBookISBN:978-1-119-99837-2
ePubISBN:978-1-119-97013-2
eMobiISBN:978-1-119-97014-9
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Contents
Preface toSecond EnglishEdition ix
Preface toFirstEnglishEdition xiii
1. MolecularRingsStuddedWithJewels 1
1.1 FromHomocycletoHeterocycle 1
1.2 BuildingHeterocyclesFromBenzene 2
1.3 SomeMoreKindsof Heterocycles 6
1.4 Problems 8
1.5 SuggestedReading 8
2. Why NaturePrefers Heterocycles 11
2.1 ReactionsforallTastes 11
2.2 HeterocyclesasAcidsandBases 14
2.3 HeterocyclesandMetals 15
2.4 ‘ThereareSubtleTiesofPower...’ 17
2.4.1 Thevan der Waals-LondonInteractions 18
2.4.2 HydrogenBonding 19
2.4.3 ElectrostaticInteractions 21
2.4.4 MolecularComplexes 21
2.4.5 HydrophobicForces 25
2.5 Tautomerism:HeterocyclesandTheir ‘Masks’ 27
2.6 Problems 31
2.7 SuggestedReading 33
3. Heterocycles andHereditary Information 35
3.1 NucleicAcids 35
3.2 TheDoubleHelix 38
3.3 HowOneDNA DoublesItself 42
3.4 ProteinSynthesis,GeneticCodeand theGenome 45
3.5 Whatare Mutations? 50
3.6 MysteriousTelomeres 54
3.7 GeneExpression 55
3.8 Problems 60
3.9 SuggestedReading 61
4. Enzymes, Coenzymes andVitamins 63
4.1 MolecularRobots 63
4.2 Coenzymesand Enzymesas ‘JointMolecularVentures’ 66
vi Contents
4.2.1 Oxidative–ReductiveCoenzymes 67
4.2.2 Coenzymesas CarriersofMolecularSpecies 78
4.3 Vitamins,the‘MoleculesofHealth’ 97
4.4 Ribozymes:Vestigesofan AncientWorld 99
4.5 Problems 103
4.6 SuggestedReading 104
5. Heterocycles andBioenergetics 107
5.1 ATPas theUniversalCurrencyofEnergy 108
5.2 Breathing 111
5.2.1 Glycolysis 112
5.2.2 TheKrebsCycle,orthe‘MolecularMerry-Go-Round’ 115
5.2.3 TheRespiratoryChain 118
5.3 Problems 122
5.4 SuggestedReading 123
6. Heterocycles andPhotosynthesis 125
6.1 Chlorophyll:Sunlight-ReceivingAntennaandEnergy Carrier 126
6.2 WhatDaylightcan Achieve 130
6.3 PhotosynthesisWithoutLight 135
6.4 Problems 138
6.5 SuggestedReading 138
7. Heterocycles andHealth 139
7.1 MedicinesFromaNaturalStorehouse 139
7.2 HeterocyclesVersusInfectiousMicrobes 143
7.2.1 In Search of‘MagicBullets’ 143
7.2.2 SulfanilamidesandHeterocycles 144
7.2.3 Antibiotics 146
7.2.4 AntibioticsFromtheOcean’s Depths 152
7.2.5 HeterocyclicAntifungalAgents 155
7.2.6 HeterocyclesAgainstParasiticDiseases 155
7.3 HeterocyclesandViralInfections 158
7.4 HeterocyclesandtheDiseasesof OurCentury 162
7.4.1 HeterocyclestoCureStress,BrainDisordersand Pain 163
7.4.2 Heterocyclesand CardiovascularDiseases 169
7.4.3 Heterocyclesand MalignantTumors 173
7.5 HeterocyclicMoleculesinCombatwithUlcersand SexualDysfunctions 178
7.6 Problems 181
7.7 SuggestedReading 182
8. Heterocycles inAgriculture 185
8.1 A CenturyofChemical WarfareAgainstWeeds 186
8.2 Regulatorsof PlantGrowth 190
8.3 TheStruggleAgainstVoraciousInsects 193
8.4 ResistingtheKingdomsofMustinessand Rot 200
8.5 HeterocyclesinAnimalHusbandry 202
8.6 CombinatorialChemistryandFunctionalGenomicsintheSynthesis
ofBiologicallyActiveHeterocyclicCompounds 202
Contents vii
8.7 Problems 205
8.8 SuggestedReading 207
9. Heterocycles inIndustry andTechnology 209
9.1 HeterocyclesandNaturalColors 209
9.2 Dyes 211
9.2.1 FromImperialCloakstoJeans 211
9.2.2 ‘Cyanine’MeansAzure 214
9.2.3 Phthalocyanines:SometimesBetterthanPorphyrins 215
9.2.4 TheAnchoringof Dyes 217
9.3 FluorescentAgents 218
9.3.1 Why TheyShine 218
9.3.2 Safety andAesthetics 219
9.3.3 How toConvertWhiteintoSnow White 220
9.3.4 Markersand Tracers 221
9.3.5 Imagingand DiagnosticAgents 222
9.3.6 Lasers ContainingHeterocyclicLuminophores 226
9.4 ColorChangeCompounds 231
9.5 FireRetardancy 233
9.6 PhotographicMaterialsand RecordersofInformation 235
9.7 HeterocyclesasFoodAdditives 237
9.8 HeterocyclesasCosmeticsandPerfumery Ingredients 241
9.9 OtherApplications 243
9.10 Problems 245
9.11 SuggestedReading 246
10. Heterocycles andSupramolecularChemistry 247
10.1 MolecularRecognitionand Host–GuestInteractions 248
10.1.1 CationReceptors 248
10.1.2 Anion-,Betaine-and IonicAssociated Receptors 257
10.1.3 ReceptorsforNeutralMolecules 259
10.1.4 MolecularCarcerands 261
10.1.5 MolecularContainersfortheProton 262
10.2 Self-AssemblingMolecularSystems 267
10.3 Problems 272
10.4 SuggestedReading 274
11. Heterocycles andTwenty-FirstCentury Challenges 275
11.1 Energy Problem 275
11.1.1 Biofuels 275
11.1.2 HydrogenasaFuel 276
11.1.3 Direct UseofSolarEnergy 278
11.1.4 ConductingMaterials 286
11.2 EcologyandGreen Chemistry 293
11.3 BiotechnologyandRelated Problems 299
11.3.1 Enzyme Technologies 299
11.3.2 DNA Technologies 304
11.3.3 New TrendsinHealthCare 309
11.3.4 HeterocyclesasMolecularSensors 310
viii Contents
11.4 FromMolecularDevicestoMolecularComputer 315
11.5 Problems 321
11.6 SuggestedReading 322
12. TheOriginofHeterocycles 325
12.1 TheOriginoftheUniverseand theAppearanceof ChemicalElements 326
12.2 InterstellarMolecules 328
12.3 OrganicCompoundsinCometsand Meteorites 333
12.4 DoHeterocyclesExistontheMoonandMars? 335
12.5 TheAtmosphereof Earthand OtherPlanets 335
12.6 HeterocyclesandtheOriginoftheBiosphere 336
12.6.1 SimplePrecursorsofHeterocycles 336
12.6.2 HeterocyclicAminoAcids 338
12.6.3 Pyrrolesand Porphyrins 340
12.6.4 FuranoseSugars 341
12.6.5 Nicotinamide 344
12.6.6 Purinesand Pyrimidines 344
12.6.7 Nucleosidesand Nucleotides 345
12.6.8 PolynucleotidesandtheBirthof‘Animated’OrganicMolecules 350
12.7 Problems 358
12.8 SuggestedReading 358
Conclusion 361
AnswersandReferences toSelected Problems 363
Index 371
Preface to Second English Edition
On 7 September 2009, Chemical Abstracts Service registered its 50-millionth chemical
substance– aheterocycliccompoundofthefollowingstructure:
O
N
N
HO S N
CH
3
F
Hardly a casual coincidence: heterocyclic compounds form the largest and one of the most
importantclassesoforganiccompoundsandsome55%oforganicchemistrypublicationsinclude
the field. They include not only the many thousands of original articles and conference mate-
rials published annually but a great number of scientific monographs such as the multivolume
ComprehensiveHeterocyclicChemistry,coveringallfieldsofheterocyclicchemistry.Heterocyclic
chemistryistaughtworldwideatmostuniversitiesanditsscopeisreflectedinmanyfinetextcom-
pendia and reference sources. It is therefore very strange that many general chemistry (and even
organicchemistry)textsfailtoincludeheterocyclesanddiscussthesignificanceoftheirchemistry,
or at most only in a nonsystematic manner. Furthermore, time constraints often prevent teachers
ofchemistryfromelaboratingonthemanifoldapplicationsofheterocycles.Thisiswhyfromthe
verybeginningthemaingoalofthepresentbookanditspredecessorwastobridgethisgapandto
emphasizenotsomuch theinnumerablereactionsofthedifferentclasses ofheterocyclesastheir
practicalimportanceinlifeandsociety,especiallytheirscientificapplicationsinvariousbranches
oftechnology,medicineandagriculture.Ourhopewas,andis,thatthisapproachwillinspirethe
student to become involved in an immensely important and exciting field of modern chemical
science and technology. The 14 years that have passed since the first edition have justified this
approach. Indeed, human society, in addition to chronic old problems, now faces acute, newly
recognized dangers such as climate change and ecology degradation, energy shortages, depletion
of mineral resources, population growth, pandemic illnesses and so on. These challenges have
forced science to become more applied and expensive but at the same time more productiveand
useful.Thisproductivityresultsfromtheappearanceofnewpowerfulphysicalmethods,apparatus
aswell asfundamentaldevelopmentsincomputationaltechniques.
The past 10 years have been marked in biochemistry by such milestone achievements as
genomedecoding,clarificationofribosomestructureand itsactivitymechanism, and wideappli-
cations of imaging techniques. Further progress has been made in medicinal chemistry where
new methods of biological screening, drug delivery and drug targeting in combination with
x PrefacetoSecondEnglishEdition
innovative chemotherapy have been elaborated. An epochal event in science is the creation of
nanotechnology which, via new materials and electronic devices, is leading to revolutionary
changes in our future life. In the energy sector the growing production of biofuels, progress
in development of hydrogen as a fuel, artificial photosynthesis and dye-sensitized solar cells all
lookveryencouraging.Theseandotherlinesofdevelopmentwouldbeimpossiblewithoutorganic
chemistry and often without heterocyclic compounds. The discussion of these themes lies at the
focus of this second edition: most chapters have been substantially revised and updated, and
chapter 11iscompletelynew.
While thisbook isintended for universitylevel chemistry and biochemistrystudentsand their
instructors, it should be of interest to researchers over the whole of the chemical, biological,
medical and agricultural sciences as well as in adjacent branches of science and technology.
These assertions are well founded because the majority of known pharmaceutical preparations
(antibiotic, neurotropic, cardiovascular, anticarcinogenic) are heterocyclic in nature; because the
agriculturaluseofnewplantdevelopmentregulatorsandpesticidesbasedonheterocyclicstructures
becomesmorewidespreadeachyear;andbecausegreatattentionisbeingpaidtothesynthesisand
productionofnewkindsofthermostablepolymers,highlydurablefibers,fastpigments,colorants
and functionaldyesand oforganicconductorscontainingheterocyclicfragments.
This book consists of 12 chapters. First, chapters (1) and (2) present the elements of the
structure and properties of heterocycles and are a useful introduction to the fundamentals of
their chemistry. Next, four chapters deal in a general way with the key role of heterocyclic
molecules in life processes, including the transfer of hereditary information (3), the manner in
which enzymes function (4), the storage and transfer of bioenergy (5) and photosynthesis (6).
Chapters(7)–(9) consider the applicationsof heterocycles in medicine, agriculture,and industry,
respectively. We have now dedicated chapter (10) to supramolecular chemistry in view of its
significance. Finally, chapter (11) considers the future contribution of heterocyclic chemistry to
moderntrendsofappliedscience,thelatestdiscoveriesandtheprospectsoffindingnewspheresof
use for heterocycles. Chapter (12) deals with the past: specifically the emergence of heterocyclic
molecules on primordial Earth, which is tightly connected with the far-reaching achievements
of astrophysics. Due to modern orbital telescopes and space stations our knowledge about the
origin of the Universe and its evolution has been significantly widened and deepened. On this
basis new scientific disciplines are arising and strongly developing. In two of these, perhaps the
most fascinating (prebiotic chemistry, synthetic biology), the role of heterocyclic compounds is
especially important. In fact, a test-tube recreation of the process of molecular evolution up to
synthesisofbiologicalcellsandliveorganismsisputforwardasanotsodistantperspective.Itis
notnecessarytopossessarichimaginationtoforeseethattheconsequencesofsuchadevelopment
ofeventscouldbeeven moredramaticthenthatof nanotechnology.
Throughout this text the student will learn to apply the knowledge gained by working on
problems related to the topics covered in each chapter. Many of the 100 problems have been
chosen from scientific journals and represent areas of recent significant interest. The scientists
who solved these mysteries were yesterday’s students. Thus, the approach to the problems will
give today’s students further insight into nature and a preview of what is scientifically possible.
Each chapteralso containssuggestedfurtherreading.
Theauthorshavetriedtoorganizethisbookinassimplifiedaformaspossible,inasfarasthe
scientific language is concerned. Each chapter is preceded by a piece written by a Russian poet
(translatedintoEnglishbyE.N.Sokolyuk)or(inonecase)anAmericanpoet.Theselectedverses
maysuggestsubtlelinkswiththeconceptsandcontentsofeachchapterandwereintroducedwith
thehopeoffruitfulcross-pollinationbetweenthenaturalsciencesandhumanities,somuchneeded
inourmodern world.
PrefacetoSecondEnglishEdition xi
In conclusion, we would like to express our warm acknowledgements to many people who
helped us during the preparation of the second edition of this book. We are most grateful for
helpfuldiscussionandtechnicalassistancefromDrAnnaGulevskaya,DrValeryOzeryanskii(for
reading Chapter 11), Dr Vladimir Sorokin (who kindly supplied us with some fresh literature
sources) andDr JohnZoltewicz.
A.F.Pozharskii
A.T. Soldatenkov
A.R.Katritzky