Biochemistry

Professor Michael B. Smith was born in Detroit, Michigan, and moved toMadison Heights, Virginia, in 1957. He graduated from Amherst CountyHigh School in 1964. He worked at Old Dominion Box Factory for a yearafter graduation and then started college at Ferrum Jr. College in 1965. Hegraduated in 1967 with an A.A. and began studies at Virginia Tech later thatyear, graduating with a B.S. in Chemistry in 1969. He worked as a chemist atthe Newport News Shipbuilding & Dry Dock Co, Newport News, Virginia,from 1969 until 1972. In 1972 he began studies in graduate school at PurdueUniversity in West Lafayette, Indiana, working with Prof. Joseph Wolinsky.He graduated in 1977 with a Ph.D. in Organic Chemistry. He took a postdoctoralposition at Arizona State University in Tempe, Arizona, working on the isolation of anti-canceragents from marine animals with Professor Bob Pettit. After one year, he took another postdoctoralposition at MIT in Cambridge, Massachusetts, working on the synthesis of the anti-cancer drugbleomycin with Professor Sidney Hecht.Professor Smith began his independent career as an assistant professor in the Chemistry departmentat the University of Connecticut, Storrs, Connecticut, in 1979. He received tenure in 1986, andspent six months on sabbatical in Belgium, with Professor Leon Ghosez at the Universite Catholiquede Louvain in Louvain la Neuve, Belgium. He was promoted to full professor in 1994 and spent hisentire career at UCONN. Prof. Smith’s research involved the synthesis of biologically interestingmolecules. His most recent work involved the preparation of functionalized indocyanine dyes forthe detection of hypoxic cancerous tumors (breast cancer). Another project involved the synthesis ofinflammatory lipids derived from the dental pathogen, Porphyromonas gingivalis.He has published 26 books, including Organic Chemistry: An Acid-Base Approach, 2nd edition(Taylor & Francis), the 5th–8th editions of March’s Advanced Organic Chemistry (Wiley), andOrganic Synthesis, 4th edition (Elsevier), winner of a 2018 Texty Award. Prof. Smith published 96peer-reviewed research papers and retired from UCONN in January of 2017.

• ContentsPreface...............................................................................................................................................xiAuthor............................................................................................................................................. xiiiCommon Abbreviations....................................................................................................................xvChapter 1 Fundamental Principles of Organic Chemistry............................................................11.1 Bonding and Orbitals.........................................................................................11.2 Ionic versus Covalent Chemical Bonds..............................................................21.3 Breaking Covalent Bonds...................................................................................31.4 Polarized Covalent σ-Bonds...............................................................................41.5 Reactive Intermediates.......................................................................................51.6 Alkanes and Isomers..........................................................................................71.7 The IUPAC Rules of Nomenclature...................................................................81.8 Rings Made of Carbon: Cyclic Compounds..................................................... 111.9 Hydrocarbon Functional Groups...................................................................... 111.10 Heteroatom Functional Groups........................................................................ 131.10.1 C—X Type Functional Groups........................................................... 131.10.2 C=X Type Functional Groups............................................................. 171.11 Hydrogen-Bonding and Solubility.................................................................... 211.12 Rotamers and Conformation............................................................................241.13 Conformations with Functional Groups...........................................................301.14 Conformation of Cyclic Molecules.................................................................. 311.15 Stereogenic Carbons and Stereoisomers.......................................................... 371.16 Absolute Configuration [(R) and (S) Nomenclature]........................................ 391.17 Specific Rotation..............................................................................................441.18 Diastereomers...................................................................................................461.19 Alkene Stereoisomers: (E) and (Z)-Isomers..................................................... 51Homework...................................................................................................................54Chapter 2 The Importance of Water in Biochemical Systems..................................................... 552.1 Hydrogen Bonding............................................................................................ 552.2 Solubility.......................................................................................................... 582.3 Water Molecules in Biological Systems........................................................... 592.4 Acid-Base Equilibria in Water......................................................................... 612.5 Buffers..............................................................................................................652.6 Structural Features That Influence Acid Strength............................................662.7 Acid and Base Character of Alcohols, Thiols, Amines and Carbonyls........... 672.7.1 Acids.................................................................................................... 672.7.2 Bases....................................................................................................692.8 Elimination Reactions of Alkyl Halides (E2 and E1 Reactions)..................... 712.9 Acid-Base Equilibria in Amino Acids............................................................. 742.10 Directionality.................................................................................................... 78Homework...................................................................................................................80Chapter 3 Nucleophiles and Electrophiles...................................................................................833.1 Nucleophiles and Bimolecular Substitution (the SN2 Reaction).......................833.2 Nucleophilic Substitution with Alcohols, Ethers, Amines, or Phosphines......853.3 Carbocations and the SN1 Reaction..................................................................883.4 Ethers and Thioethers as Nucleophiles............................................................903.5 Chemical Reactions of Carbonyl Groups.........................................................933.6 Biochemical Reactions of Ketones and Aldehydes..........................................963.7 Carboxylic Acid Derivatives and Acyl Substitution.........................................973.8 Biological Hydrolysis...................................................................................... 102Homework................................................................................................................. 106Chapter 4 Radicals..................................................................................................................... 1094.1 Structure of Radicals...................................................................................... 1094.2 Formation of Radicals in Organic Chemistry................................................ 1104.3 Reactions of Radicals..................................................................................... 1114.4 Formation of Radicals in Biological Systems................................................ 1124.5 Radicals in Biological Systems...................................................................... 1144.6 Radical Reactions in Biochemical Systems................................................... 1164.7 Radicals and Cancer....................................................................................... 118Homework................................................................................................................. 119Chapter 5 Dienes and Conjugated Carbonyl Compounds in Biochemistry............................... 1215.1 Conjugated Dienes and Conjugated Carbonyl Compounds........................... 1215.2 Reactions of Conjugated Compounds............................................................1245.3 Conjugate (Michael) Addition........................................................................ 1275.4 Enzyme-Mediated Conjugate Additions........................................................ 1285.5 Sigmatropic Rearrangement Reactions.......................................................... 1295.6 Enzyme-Mediated Sigmatropic Rearrangements........................................... 132Homework................................................................................................................. 133Chapter 6 Enolates and Enolate Anions.................................................................................... 1356.1 Aldehydes and Ketones Are Weak Acids....................................................... 1356.2 Formation of Enolate Anions......................................................................... 1366.3 The Aldol Condensation................................................................................. 1376.4 Enzyme-Mediated Aldol Condensations........................................................ 1386.5 The Claisen Condensation.............................................................................. 1416.6 Enzyme-Mediated Claisen Condensation...................................................... 1426.7 Decarboxylation............................................................................................. 143Homework................................................................................................................. 144Chapter 7 Enzymes.................................................................................................................... 1477.1 Enzyme Kinetics............................................................................................ 1477.1.1 Kinetics in Organic Chemistry......................................................... 1477.1.2 Catalysts and Catalytic Reactions..................................................... 1497.1.3 Enzyme Kinetics............................................................................... 1497.2 Enzymes and Enzyme Classes....................................................................... 1537.3 Oxidoreductases (EC 1).................................................................................. 1577.3.1 Chemical Oxidation of Alcohols....................................................... 1577.3.2 Oxidases............................................................................................ 1597.3.3 Chemical Reduction of Carbonyl Compounds.................................. 1617.3.4 Reductases......................................................................................... 1627.4 Transferases (EC 2)........................................................................................ 1637.4.1 Chemical Reactions That Incorporate Methyl, Hydroxyl,Glycosyl or Amino Groups into New Molecules.............................. 1637.4.2 Methyl, Hydroxyl, Thiol, and Glycosyl Transferases........................ 1667.5 Hydrolyases (EC 3)......................................................................................... 1687.5.1 Chemical Hydrolysis......................................................................... 1697.5.2 Esterases............................................................................................ 1707.5.3 Other Hydrolyases............................................................................. 1717.6 Lyases (EC 4)................................................................................................. 1747.6.1 Bond Cleavage in Organic Chemistry............................................... 1747.6.1.1 Decarboxylation................................................................. 1747.6.1.2 Enol Formation and the Acid-Catalyzed Aldol................. 1757.6.1.3 Dehydration Reactions....................................................... 1767.6.1.4 [2+2]-Photocycloaddition................................................... 1777.6.2 Lyase Reactions................................................................................. 1787.7 Isomerases (EC 5).......................................................................................... 1807.7.1 Chemical Isomerization Reactions.................................................... 1817.7.2 Isomerase Reactions.......................................................................... 1847.8 Ligases (EC 6)................................................................................................ 1857.8.1 Chemical Methods for Carboxylation and Nucleotide Synthesis..... 1857.8.1.1 Reactions with Carbon Dioxide......................................... 1857.8.1.2 Synthesis of Polynucleotides and Polynucleosides............ 1867.8.2 Enzymatic Coupling.......................................................................... 1877.9 Translocases (EC 7)........................................................................................ 1897.9.1 Enzymatic Transport Reactions........................................................ 1897.9.2 Transport of Organic Materials......................................................... 189Homework................................................................................................................. 190Chapter 8 Lipids......................................................................................................................... 1938.1 Carboxylic Acids and Esters.......................................................................... 1938.2 Nitrate Esters, Sulfate Esters, and Phosphate Esters...................................... 1968.3 Lipid Classes.................................................................................................. 1998.4 Chemical Synthesis of Esters.........................................................................2038.5 Biosynthesis and Biodegradation of Esters....................................................205Homework.................................................................................................................209Chapter 9 Aromatic Compounds and Heterocyclic Compounds............................................... 2119.1 Benzene and Aromaticity............................................................................... 2119.2 Benzene Is a Carcinogen................................................................................ 2139.3 Functionalized Benzene Derivatives.............................................................. 2149.4 Electrophilic Aromatic Substitution: The SEAr Reaction.............................. 2169.5 Enzymatic SEAr Reactions............................................................................. 2199.6 Reduction of Aromatic Compounds...............................................................2229.7 Biological Reduction of Aromatic Rings.......................................................2249.8 Nucleophilic Aromatic Substitution. The SNAr Reaction..............................2259.9 Enzymatic SNAr Reactions.............................................................................2269.10 Polynuclear Aromatic Hydrocarbons.............................................................2279.11 Heteroaromatic Compounds: Nitrogen, Oxygen, or Sulfur............................2309.12 Reactions of Heteroaromatic Compounds...................................................... 2339.13 Enzymatic Reactions That Generate Heterocyclic Compounds....................2349.14 Reduced Forms of Nitrogen, Oxygen, and Sulfur Heterocycles....................2389.15 Heteroaromatic Compounds with More Than One Ring............................... 239Homework.................................................................................................................240Chapter 10 Carbon–Metal Bonds, Chelating Agents and Coordination Complexes................... 24310.1 Organometallics............................................................................................. 24310.2 Organometallics in Organic Chemistry......................................................... 24310.3 Biologically Relevant Metals..........................................................................24610.4 Chelating Agents............................................................................................248Homework................................................................................................................. 251Chapter 11 Amino Acids............................................................................................................. 25311.1 Characteristics of Amino Acids..................................................................... 25311.2 Structure of α-Amino Acids........................................................................... 255Homework................................................................................................................. 259Chapter 12 Peptides and Proteins................................................................................................ 26112.1 Reactions and Synthesis of α-Amino Acids................................................... 26112.2 Amino Acid Biosynthesis............................................................................... 26712.3 Peptides Are Poly(amides) of Amino Acid Residues.....................................26812.4 Chemical Synthesis of Peptides...................................................................... 27412.5 Peptide Biosynthesis.......................................................................................27712.6 Proteins and Enzymes Are Poly(peptides).....................................................28012.7 Peptide Degradation and End Group Identification.......................................28012.8 Peptidases.......................................................................................................284Homework.................................................................................................................285Chapter 13 Carbohydrates...........................................................................................................28713.1 (Poly)hydroxy Carbonyl Compounds.............................................................28713.2 Monosaccharides............................................................................................28813.3 Mutarotation...................................................................................................29313.4 The Anomeric Effect......................................................................................29413.5 Ketose Monosaccharides................................................................................295Homework.................................................................................................................297Chapter 14 Glycosides.................................................................................................................29914.1 Monosaccharides............................................................................................29914.2 Disaccharides, Trisaccharides, Oligosaccharides, and Polysaccharides........30014.3 Reactions of Carbohydrates............................................................................ 30114.4 Biologically Important Glycosides.................................................................30514.5 Biosynthesis of Carbohydrates and Glycosides..............................................30814.6 Biodegradation of Carbohydrates and Glycosides......................................... 313Homework................................................................................................................. 316Chapter 15 Nucleic Acids, Nucleosides and Nucleotides............................................................ 31715.1 Nucleosides and Nucleotides.......................................................................... 31715.2 Polynucleotides............................................................................................... 32015.3 Chemical Synthesis of Nucleotides................................................................ 32515.4 Biosynthesis of Nucleotides............................................................................ 32815.5 Ribozymes...................................................................................................... 33015.6 Hydrolysis of RNA and DNA......................................................................... 33215.7 RNA-Mediated Programmable DNA Cleavage............................................. 33315.8 Restriction Enzymes....................................................................................... 334Homework................................................................................................................. 336Chapter 16 Answers to Homework Problems.............................................................................. 337Chapter 1................................................................................................................... 337Chapter 2................................................................................................................... 338Chapter 3................................................................................................................... 339Chapter 4................................................................................................................... 341Chapter 5................................................................................................................... 343Chapter 6...................................................................................................................344Chapter 7................................................................................................................... 345Chapter 8...................................................................................................................349Chapter 9................................................................................................................... 350Chapter 10................................................................................................................. 352Chapter 11................................................................................................................. 353Chapter 12................................................................................................................. 354Chapter 13................................................................................................................. 356Chapter 14................................................................................................................. 358Chapter 15................................................................................................................. 361Index............................................................................................................................................... 363

Describing an interesting way to teach biochemistry, especially in conjunction with organic chemistry, this textbook should find application at many schools. The first of 15 chapters is a review of the fundamentals of an organic chemistry course, but a full course may be necessary for beginners to benefit from further study. Subsequent discussion of organic reactions and mechanisms will be more meaningful for students already familiar with organic chemistry basics. Chapter 2 describes acid-base chemistry, elimination reactions, and the importance of water in chemistry. Chapter 3 discusses nucleophilic substitution; chapter 4 explains free radical reactions. Subsequent chapters discuss, respectively, dienes, conjugated systems, sigmatropic rearrangements, enols and enolate reactions, enzymes, enzyme kinetics, carboxylic acid and derivatives, lipids, aromatic chemistry, heteroaromatic chemistry, organometallic compounds, biologically relevant metals, chelating reagents, amino acids, peptides, proteins, carbohydrates and derivatives, glycosides, nucleosides, nucleotides, DNA, and RNA. Each chapter concludes with homework questions; finally, chapter 16 includes the answers to the questions. Common abbreviations are listed at the beginning of the book, and several compounds and functional groups also have line formulas or partial structures shown. The book can be used by teachers and students of chemistry, and will be useful for all chemists as a review.--R. E. Buntrock, independent scholarSumming Up: Recommended. Lower- and upper-division undergraduates. Graduate students, faculty, and professionals.