The focus of this book is to use organic chemistry principles and reactions to explain the funda-mentals of biochemistry. The inspiration for this book came from teaching the second semester of organic chemistry with many students who were taking introductory biochemistry at the same time. Many students commented that the things we were discussing in organic chemistry helped explain and better understand the concepts they were discussing or had discussed in biochemistry. On many occasions, topics were discussed in organic chemistry that had been covered previously in the bio-chemistry course. An understanding of the organic chemistry reactions and mechanisms helped the students better understand many of those biochemical principles. It is hoped that understanding the organic chemistry foundations of biochemistry will provide similar assistance to students today. Where feasible, organic chemical reactions such as those found in a typical undergraduate organic chemistry course are included in this book to bring their biological chemistry counterparts into perspective. 

Biochemistry An Organic Chemistry Approach pdf free Michael B. Smith


The first chapter is meant as a review of the fundamentals of an undergraduate organic chem-istry course. For those who have not had a full organic chemistry course, this chapter will not suffice. This chapter is only intended as a supplement for an organic chemistry course and to function as a review for the biochemical principles to follow. The next chapter discusses the importance of water in chemistry and also acid-base chemistry Elimination reactions such as E2 and E1 reactions are introduced here as well. The third chapter discusses nucleophilic sub-stitution and chapter Chapter 4 discusses radicals and radical reactions. Dienes and conjugated systems are discussed in Chapter 5, along with sigmatropic rearrangements. Enols and enolate reactions are discussed in the next chapter, including aldol-type reactions and Claisen condensa-tion type reactions. 

Chapter 7 introduces enzymes, enzyme kinetics and classes of enzymes. Pertinent organic chem-ical reactions are included for each enzyme class for a direct comparison. Chapter 8 discusses carboxylic acids and acid derivatives as well as various lipids. Chapter 9 is devoted to aromatic chemistry, including the SEAr and SEAr reactions. Heterocyclic aromatic compounds are also dis-cussed in this chapter. 

Chapter 10 introduces organometallic compounds, beginning with the well-known Grignard reagents and organolithium reagents. Biologically relevant metals and chelating reagents are dis-cussed in this chapter. Amino acids are introduced in Chapter 11 and the use of amino acids to form peptides and proteins, as well as the importance of those biologically important compounds are discussed in Chapter 12. Carbohydrates are introduced in Chapter 13. The chemistry of carbohy-drate derivatives and glycosides is elaborated in Chapter 14. Chapter 15 concludes the book with a discussion of nucleosides, nucleotides, DNA and RNA. 

I thank all of my former students who inspired this book with the sincere hope that this approach will help those students interested in biochemistry. I also thank editors Hilary Lafoe and Jessica Poile and my publisher, Dr. Fiona McDonald, and all at Taylor & Francis, for their support and their help. This book would not have been possible without them. 

All structures and reactions were drawn using ChemDraw Professional 18.0.0.231. I thank PerkinElmer Informatics, Inc. for a gift of this software. All 3-D drawings and molecular models were prepared using Spartan’18 software, version 1.2.0 (181121). I thank Warren Hehre and Sean Ohlinger of Wavefunction, Inc. for a gift of this software. I thank Ms. Christine Elder (https://chris-tineelder.com), graphics design artist, for her graphic arts expertise to render the drawings in Figures 1.4, 1.9, 1.11, 1.15, 1.16, 1.20, 1.22, 1.29, 1.32, 1.37, 1.44, 1.45, 2.7, and 9.1. 


1 Fundamental Principles of Organic Chemistry


It is likely that this book will be used after, or concurrently with, a course in organic chemistry. This chapter is therefore intended as a review of fundamental principles of organic chemistry. It is not intended as a stand-alone treatment. The intent is to bring the reader “up to speed” with important principles of organic chemistry that are important for understanding the extension of those prin-ciples to biochemistry. 

Arguably, the most fundamental concept in organic chemistry is the nature of the bond between two carbon atoms or between carbon and another atom. Bonding is an important concept in organic chemistry because chemical reactions involve the transfer of electrons with the making and break-ing of chemical bonds. Since the molecules associated with biochemistry processes are organic molecules, the bonding will be similar to those organic molecules commonly discussed in a sopho-more organic chemistry course. For the most part, the bonds between carbon and another atom are covalent, so the initial focus will be on covalent bonds between two carbon atoms or covalent bonds on a different atom to carbon. The definition of covalent bonds and polarized covalent bonds will be reviewed, as well as the concept of functional groups. The concept of isomers, different connectivity within organic molecules, and rules for naming organic molecules will also be reviewed. 


2 The Importance of Water in Biochemical Systems


Without water, life as we know it would not exist. Life arose in an aqueous medium and the content of water in living organisms ranges from about 50–65% in adult humans. The human heart and brain are about 70–75% water whereas the human lungs are about 80–85% water. Water is critically important to the shape and function of biomolecules such as proteins and nucleic acids. Water is the medium by which nutrients are transported and of course blood is about 92% water. The water environment is obviously important, and it has a strong influence on the structure and function of biomolecules. 


3 Nucleophiles and Electrophiles


Aliphatic substitution reactions are early examples of organic chemical reactions in a typical under-graduate organic chemistry course. Such reactions involve the reaction of nucleophilic species with an electrophilic species, and for the most part they follow frst-order or second-order kinetics. There are nucleophiles that are prevalent in biochemical reactions, including alcohols, amines, and thiols. Substitution reactions in a typical organic chemistry course involve reactions at carbon that is con-nected to a heteroatom moiety such as a halogen leaving group. In biochemistry the leaving group is often a phosphonate ester or another biocompatible group. Another type of nucleophilic reaction involves carbonyl compounds, including acyl addition of ketone and aldehyde moieties and acyl substitution reactions of carboxylic acid derivatives. 


Radicals

Radicals are highly reactive intermediates. However, radicals play an important role in many bio-logical processes. There are several methods for generating radicals, and many involve diatomic 

oxygen, •O=O•. Once radicals are generated in a biological environment, they tend to react quickly in a localized environment. This chapter will describe radical reactions in organic chemistry and 

radical reactions in biological systems. 


5 Dienes and Conjugated Carbonyl Compounds in Biochemistry

This chapter primarily discusses dienes and alkene–ketones, alkene–aldehydes, or alkene–esters with a particular emphasis on those molecules that are conjugated. In conjugated molecules, the 

π-bonds are directly connected with no intervening sp3 atoms. Conjugated dienes react similarly to other alkenes, but due to conjugation the carbocation or radical intermediates formed from conju-gated dienes are resonance-stabilized. Therefore, there are two sites of reactivity: the carbonyl as well as the C=C unit and so there are differences in product distribution when compared to simple alkenes. 



6 Enolates and Enolate Anions

Ketones and aldehydes react with nucleophile primarily by acyl addition, whereas acid derivatives proceed by acyl substitution. In these reactions, the carbonyl carbon is an electrophilic center. It is also possible for carbonyl compound to react as nucleophiles. In the presence of a protic solvent, tautomerization leads to an equilibrium concentration of an enol form that can react as a nucleo-phile. In addition, aldehydes, ketones, or esters that have a proton on the carbon directly connected 

to the carbonyl carbon, the α-carbon are weak acids. With a suitable base, these carbonyl com-pounds generate a carbon nucleophile called an enolate anion. This chapter will discuss the forma-

tion and nucleophilic reactions of enols and enolate anions. 


7 Enzymes

A catalyst is defned as a substance added to a reaction is substoichiometric amounts that increases the rate of a chemical reaction but is not consumed by the reaction and is present at the end of the reaction. Acid catalysts such as sulfuric acid or p-toluenesulfonic acid are commonly added to reactions and serve as sources of H+. An example is the acid (H+) catalyzed reaction of an alkene with water, as shown in Figure 7.1. An alkene such as 2-methylbut-2-ene is too weak of a base to react directly with a weak acid such as water, so there is no reaction. However, adding a small amount of a strong mineral acid such as sulfuric acid allows a facile reaction with the alkene to generate a tertiary carbocation intermediate, which reacts quickly with water to give an oxonium ion. Loss of a proton in an acid-base reaction gives the alcohol product, 2-methylbutan-2-ol with loss of the H+ catalyst. 


8 Lipids

Lipids are organic compounds such as fatty acids or natural oils, waxes, and steroids that are insol-uble in water but soluble in organic solvents. Fatty acids are components of triglycerides and the hydrolysis of triglycerides is important for energy conversion in living systems. Lipids are important for the formation of lipid bilayers and the chemistry of esters is important to the discussion of lipids. 


9 Aromatic Compounds and Heterocyclic Compounds


Benzene is a special type of hydrocarbon. Derivatives are known by replacing the hydrogen atoms of benzene with substituents and/or functional groups. There are hydrocarbons related to benzene that have two, three, or more rings fused together (polycyclic compounds). The unifying concept of all these molecules is that they are aromatic, which means that they are especially stable with respect to their bonding and structure. 


10 Carbon–Metal Bonds, Chelating Agents and Coordination Complexes


When a metal is incorporated into a molecule with a metal–carbon bond, the resulting molecule is called an organometallic compound. Inorganic chemistry, organometallic compounds are used most often as nucleophilic reagents, effectively as carbanion surrogates. On general, organome-tallic reagents are reactive species and often used as reagents. In biology, metals are important at cofactors for the effcient activity of enzymes, and their ability to form multivalent compounds leads to the use of metals as chelating agents and their importance for the formation of coordina-tion complexes. 


Amino Acids


There is an important class of difunctional molecule that is critical to an understanding of biological processes. Amino acids comprise the backbone of peptides, and thereby of enzymes. This chapter will discuss the structure, nomenclature, and characteristics of amino acids. 


Peptides and Proteins

Polymeric chains of amino acids are peptides, and proteins are poly(peptides). Proteins are essential to living systems and the critically important proteins called enzymes catalyze processes that are essential to life. This chapter will discuss peptides, their characteristics and how they are formed. In addition, the structure and function of proteins will be discussed. 


Carbohydrates

Another important class of molecules that are critical to an understanding of biological processes are carbohydrates, commonly known as sugars. Carbohydrates are key components of glycosides and cells, and they comprise the backbone of nucleotides, including DNA and RNA. This chapter will introduce the fundamentals of carbohydrate structure and nomenclature. 


Glycosides

Carbohydrates were introduced in Chapter 13. This chapter will focus on carbohydrate derivatives, especially those that are functionalized at the anomeric carbon. A glycoside is a molecule in which a carbohydrate is bonded to another functional group by a glycosidic bond. A glycosidic bond usually refers to the bond of a functional group with the anomeric OH unit, but the IUPAC nomenclature for such compounds is C-glycosyl compounds. Glycosides can be linked by an O- (an O-glycoside), N- (a glycosylamine), S- (a thioglycoside), or C- (a C-glycoside) glycosidic bond. A Haworth projection (Section 1.14) is typically used for the functionalized carbohydrate, such as that used for the ribose unit in DNA and RNA structures. The carbohydrate group in a glycoside is known as the glycone and the non-sugar group as the aglycone or genin part of the glycoside. The glycone can consist of a single carbohydrate or several sugar groups. 


15 Nucleic Acids, Nucleosides and Nucleotides

Carbohydrates are essential to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), especially ribose. Nucleosides and the phosphate ester derivatives called nucleotides are ribose derivatives that have a purine or pyrimidine heterocycle attached to the anomeric carbon. This chapter will describe the formation and characteristics of nucleic acids, the formation of nucleosides and then nucleotides.


16 Answers to Homework Problems


CHAPTER 1 

01-1. This reaction is a SN2 reaction and is characterized by heterolytic bond cleavages. 

CHAPTER 2 

02-1. If two dipeptide units are brought into close proximity, the oxygen of one carbonyl can form a hydrogen bond to the proton on the amide nitrogen of the second dipeptide. For hydrogen bonding to occur, however, one dipeptide must have an anti-orientation. 

 


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