Author royalties from this book are being donated to the Cystic Fibrosis Foundation
Author royalties from this book are being donated to the Cystic Fibrosis Foundation. 39144_ FM_i-xxiv.indd xxiv 8/26/09 10:48:56 AM
Structure and Bonding A model of the enzyme which reductas step in the body's synthe. sis of cholesterol. CONTENTS A scientific a revolution that will give us safer and 1.3 Atomic Structure:Electron and improve the quality of Confgurations ure a ely21 000ge he an Development of Chemical e enabling s Bonding Theory ular ade the revor be 1.5 The Nature of Chemical n pos nd tha ofthe rem rkable sto drive it.Anyon who want Bonds:Valence Bond Theory cine and the biologi 16 As an ovamnle of how nic and biological chemistry to affecting modern medicine.look at coronary heart disease the buildup of of Methane s on the walls of arteries in the heart.leading sp3Hybrid Orbitals to restricted blood flow the leading cause of death for both men and women older than age 20.and 1.8 it's estimated that up to one-third of women and one-half of men will develop the disease at some point in their lives. of Ethylene The onset of coronary heart disease is directly correlated with blood cho- 1.9 pHybrid Orbitals lesterol levels,and the first step in disease prevention is to lower those levels. and the Structure It turns out that only about 25%of our blood cholesterol comes from what we of Acetylene eat;the remaining 75%(about 1000 mg each day)is made,or biosynthesized. 1.10 Hybridization of Nitroger by our bodies from dietary fats and carbohydrates.Thus,any effective plan for lowering our cholesterol level means limiting the amount that our bodies bio- 9hospious synthesize,which in turn means understanding and controlling the chemical 1.11 reactions that make up the metabolic pathway for cholesterol biosyr ong it will make perfectly good sense 112 Drawing Chemical Structures atar ine A MC-CoA is the biological of a compound Online homewor for this hapter can be asined in Orpanie OWL.one
1 Online homework for this chapter can be assigned in Organic OWL, an online homework assessment tool. 1 Structure and Bonding contents 1.1 Atomic Structure: The Nucleus 1.2 Atomic Structure: Orbitals 1.3 Atomic Structure: Electron Confi gurations 1.4 Development of Chemical Bonding Theory 1.5 The Nature of Chemical Bonds: Valence Bond Theory 1.6 sp3 Hybrid Orbitals and the Structure of Methane 1.7 sp3 Hybrid Orbitals and the Structure of Ethane 1.8 sp2 Hybrid Orbitals and the Structure of Ethylene 1.9 sp Hybrid Orbitals and the Structure of Acetylene 1.10 Hybridization of Nitrogen, Oxygen, Phosphorus, and Sulfur 1.11 The Nature of Chemical Bonds: Molecular Orbital Theory 1.12 Drawing Chemical Structures Lagniappe—Chemicals, Toxicity, and Risk A scientific revolution is now taking place—a revolution that will give us safer and more effective medicines, cure our genetic diseases, increase our life spans, and improve the quality of our lives. The revolution is based in understanding the structure and function of the approximately 21,000 genes in the human body, but it relies on organic chemistry as the enabling science. It is our fundamental chemical understanding of biological processes at the molecular level that has made the revolution possible and that continues to drive it. Anyone who wants to understand or be a part of the remarkable advances now occurring in medicine and the biological sciences must first understand organic chemistry. As an example of how organic and biological chemistry together are affecting modern medicine, look at coronary heart disease—the buildup of cholesterol-containing plaques on the walls of arteries in the heart, leading to restricted blood flow and eventual heart attack. Coronary heart disease is the leading cause of death for both men and women older than age 20, and it’s estimated that up to one-third of women and one-half of men will develop the disease at some point in their lives. The onset of coronary heart disease is directly correlated with blood cholesterol levels, and the first step in disease prevention is to lower those levels. It turns out that only about 25% of our blood cholesterol comes from what we eat; the remaining 75% (about 1000 mg each day) is made, or biosynthesized, by our bodies from dietary fats and carbohydrates. Thus, any effective plan for lowering our cholesterol level means limiting the amount that our bodies biosynthesize, which in turn means understanding and controlling the chemical reactions that make up the metabolic pathway for cholesterol biosynthesis. Now look at Figure 1.1. Although the figure may seem unintelligible at this point, don’t worry; before long it will make perfectly good sense. What’s shown in Figure 1.1 is the biological conversion of a compound called 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate, a crucial A model of the enzyme HMG-CoA reductase, which catalyzes a crucial step in the body’s synthesis of cholesterol. 39144_01_0001-0032.indd 1 7/27/09 1:28:30 PM
CHAPTER 1 STRUCTURE AND BONDING step in the pathway by which our bodies synthesize cholesterol.Also shown in the figure is an X-ray crystal structure of the active site in the HMG-CoA reductase enzyme that catalyzes the reaction.along with a molecule of the drug atorvastatin(sold under the trade name Lipitor)that binds to theenzyme's active site and stops it from functioning.With the enzyme thus inactivated cholesterol biosynthesis is prevented. FIGURE 1.1 Th of-hdr H3C OH H3C OH pin th ath cholesterol.An x-ray crystal 02C ctas 3-Hydroxy-3-methyl with a molecule of atorvastatin (Lipitor)that is bound in the ive site an sis is prevented. Atorvastatin (Lipitor) Atorvastatin is one of a widely prescribed class of drugs called stat. coronary he se by lowering oles od Tal the stat vasta r).i atin(C ith 4.6 billion st wal sa The statins s function by the HMG.CoA reduc and eby lim ing the ody's biosynthesis of cholesterol.As a result,blood chole esterol levels dro and coronary heart disease becomes less likely.It sounds simple,but it would be impossible without a detailed knowledge of the steps in the pathway for cholesterol biosynthesis,the enzymes that catalyze those steps,and how pre cisely shaped organic molecules can be designed to block those steps.Orga chemistry is what makes it all happen. Historically.the term organic chemistry was used to mean the chemistry of compounds found in living organisms.At that time,in the late 1700s,little was known about chemistry.and the behavior of the"organic"substances iso- lated from plants and animals seemed different from that of the"inorganic
2 chapter 1 structure and bonding step in the pathway by which our bodies synthesize cholesterol. Also shown in the figure is an X-ray crystal structure of the active site in the HMG-CoA reductase enzyme that catalyzes the reaction, along with a molecule of the drug atorvastatin (sold under the trade name Lipitor) that binds to the enzyme’s active site and stops it from functioning. With the enzyme thus inactivated, cholesterol biosynthesis is prevented. HO H H CH3 CH3 CO2 – H H Cholesterol Atorvastatin (Lipitor) 3-Hydroxy-3-methyl- Mevalonate glutaryl coenzyme A (HMG-CoA) H H3C OH OH –O2C H3C OH O SCoA C CH3 CH3 O F 3.0 3.2 3.0 2.7 2.7 L4 S4 K735 L967 L853 V683 S684 R590 D690 K691 K692 A850 R508 D586 L562 R556 H752 L1 L6 L10 2.5 2.9 2.8 2.8 2.9 N N H CO2 – OH HO H Atorvastatin is one of a widely prescribed class of drugs called statins, which reduce a person’s risk of coronary heart disease by lowering the level of cholesterol in their blood. Taken together, the statins—atorvastatin (Lipitor), simvastatin (Zocor), rosuvastatin (Crestor), pravastatin (Pravachol), lovastatin (Mevacor), and several others—are the most widely prescribed drugs in the world, with an estimated $14.6 billion in annual sales. The statins function by blocking the HMG-CoA reductase enzyme and preventing it from converting HMG-CoA to mevalonate, thereby limiting the body’s biosynthesis of cholesterol. As a result, blood cholesterol levels drop and coronary heart disease becomes less likely. It sounds simple, but it would be impossible without a detailed knowledge of the steps in the pathway for cholesterol biosynthesis, the enzymes that catalyze those steps, and how precisely shaped organic molecules can be designed to block those steps. Organic chemistry is what makes it all happen. Historically, the term organic chemistry was used to mean the chemistry of compounds found in living organisms. At that time, in the late 1700s, little was known about chemistry, and the behavior of the “organic” substances isolated from plants and animals seemed different from that of the “inorganic” FIGURE 1.1 The metabolic conversion of 3-hydroxy- 3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate is a crucial step in the body’s pathway for biosynthesizing cholesterol. An X-ray crystal structure of the active site in the HMG-CoA reductase enzyme that catalyzes the reaction is shown, along with a molecule of atorvastatin (Lipitor) that is bound in the active site and stops the enzyme from functioning. With the enzyme thus inactivated, cholesterol biosynthesis is prevented. FIGURE 1.1 The metabolic conversion of 3-hydroxy- 3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate is a crucial step in the body’s pathway for biosynthesizing cholesterol. An X-ray crystal structure of the active site in the HMG-CoA reductase enzyme that catalyzes the reaction is shown, along with a molecule of atorvastatin (Lipitor) that is bound in the active site and stops the enzyme from functioning. With the enzyme thus inactivated, cholesterol biosynthesis is prevented. 39144_01_0001-0032.indd 2 7/27/09 1:28:33 PM
1.1 ATOMIC STRUCTURE:THE NUCLEUS 3 alymoeaimpoundswe hancesoundinminerals.Og ow-mel re usu hat the vas no fund compounds. By the d1800 was clea th be veen orga organic com e princip f all is that all contain theele ishing chara erist But why is carbon special?Why.of the more than 37 million p ds dome re than 99%of ther contain c arbon?The auestions come from carbon's electronic structure and its con ent position in the periodic table(Figu e 1 21 As a or up 4A elemen carbon can share four valence electrons and form four strong covalent bonds Furthermore carbon atoms can bond to one another forming long chains and rings.Carbon,alone of all elements,is able to form an immense diversity of compounds,from the simple to the staggeringly complex-from methane.with one carbon atom,to DNA,which can have more than 100 million carbons. FIGURE 1.2 Carbon,hydro gen,and other elements H 2A 3A 4A 5A 6A 7A He commonly found in organi Be B C N o Ne sent them. Na Mg Si K Ca Sc Mn Fe Co Ni Cu Zn Ge As Se Br Rb Sr Zr Nb Mo Te Ru Rh Pd Ag Cd In Sn Te e Cs Ba Hf Ta w Re Os Ir Pt Au Hg T Po At Rn Fr Ra Ac Not all carbor have developed ns of years c gn anc synthe y sophis organi mp touches the everyone:itsstudy canb in.co ganic mistry ing un tak WHY THIS CHAPTER? cular geometry that y may recall from you general chemistry course.Much of the material in this chapter and the next is likely to be familiar to you,but it's nevertheless a good idea to make sure you understand it before going on. 11 Atomic Structure:The Nucleus neral chemistry ounded at a relatively la dis
substances found in minerals. Organic compounds were generally low-melting solids and were usually more difficult to isolate, purify, and work with than high-melting inorganic compounds. By the mid-1800s, however, it was clear that there was no fundamental difference between organic and inorganic compounds. The same principles explain the behaviors of all substances, regardless of origin or complexity. The only distinguishing characteristic of organic chemicals is that all contain the element carbon. But why is carbon special? Why, of the more than 37 million presently known chemical compounds, do more than 99% of them contain carbon? The answers to these questions come from carbon’s electronic structure and its consequent position in the periodic table (Figure 1.2). As a group 4A element, carbon can share four valence electrons and form four strong covalent bonds. Furthermore, carbon atoms can bond to one another, forming long chains and rings. Carbon, alone of all elements, is able to form an immense diversity of compounds, from the simple to the staggeringly complex—from methane, with one carbon atom, to DNA, which can have more than 100 million carbons. Li O Group 1A H Na K Rb Cs Fr Be 2A Mg Ca Sr Ba Ra B Al Ga In Tl Si P C N Ge Sn Pb As Sb Bi S Se Te Po F Cl Br I At Ne Ar He 3A 4A 5A 7A 6A 8A Kr Xe Rn Sc Y La Ti Zr Hf V Nb Ta Cr Mo W Mn Tc Re Fe Ru Os Co Rh Ir Ni Pd Pt Cu Ag Au Zn Cd Hg Ac Not all carbon compounds are derived from living organisms of course, and over the years chemists have developed a remarkably sophisticated ability to design and synthesize new organic compounds in the laboratory—medicines, dyes, polymers, and a host of other substances. Organic chemistry touches the lives of everyone; its study can be a fascinating undertaking. why this chapter? We’ll ease into the study of organic chemistry by first reviewing some ideas about atoms, bonds, and molecular geometry that you may recall from your general chemistry course. Much of the material in this chapter and the next is likely to be familiar to you, but it’s nevertheless a good idea to make sure you understand it before going on. 1.1 Atomic Structure: The Nucleus As you probably know from your general chemistry course, an atom consists of a dense, positively charged nucleus surrounded at a relatively large distance by negatively charged electrons (Figure 1.3). The nucleus consists of FIGURE 1.2 Carbon, hydrogen, and other elements commonly found in organic compounds are shown in the colors typically used to represent them. FIGURE 1.2 Carbon, hydrogen, and other elements commonly found in organic compounds are shown in the colors typically used to represent them. 1.1 atomic structure: the nucleus 3 39144_01_0001-0032.indd 3 7/27/09 1:28:34 PM
4 CHAPTER 1 STRUCTURE AND BONDING subatomic particles called neutrons,which are electrically neutral,and pro- tons,which are positively charged.Because an atom is neutral overall,the number of positive protons in the nucleus and the number of negative elec- trons surrounding the nucleus are the same Although extremely small-about 10-14 to 10-15 meter(m)in diameter- the nucleus nevertheless contains essentially all the mass of the atom.Elec- ph mtabaut 2 X 10m,or 200 picometers (pm),where 1 pm 10 2 m.To give you an idea of how small this is,a thin pencil line is about 3 million carbon aton wide.Many organic chemists and biochemists still use the unit angstrom(A) 100 pm 10 m,but we'll stay FIGURE1.3 A schematic view of Nucleus (protons neutrons) ato Ih ,positiveh s c rounded by egatively charged electrons.The thr -dimensional ces steadily toward the nucleus and A specific atom is described by its atomic number(Z),which gives the number of protons (and electrons)it contains,and its mass number(A) han at the gray which gives the total number of protons plus neutrons in its nucleus.All the mesh surface atoms of a given element have the same atomic number-1 for hydrogen 6 for carbon.15 for phosphorus,and so on-but they can have different mass numbers depending on how many neutrons they contain.Atoms with the same atomic number but different mass numbers are called isotopes.The weighted average mass in atomic mass units(amu)of an element's naturally occurring isotopes is called the element's atomic mass(or atomic weight)- 1.008 amu for hydrogen,12.011 amu for carbon,30.974 amu for phosphorus, and so on. 12 Atomic Structure:Orbitals the elec model,the vior of sp can t ed by a mathe sion c calle afluid.The solu tion toa the Greek letto mation is called a wave func ion,or orbital,and is denoted plottin are of the wave function 2 in three-dimens nal und a nucleus that an elec tron is most likely to occupy.You might therefore think of an orbital as look. ing like a photograph of the electron taken at a slow shutter speed.In such a u the lu doesn't have a sharp boundary,but for practical purposes we can set the limits
4 chapter 1 structure and bonding subatomic particles called neutrons, which are electrically neutral, and protons, which are positively charged. Because an atom is neutral overall, the number of positive protons in the nucleus and the number of negative electrons surrounding the nucleus are the same. Although extremely small—about 1014 to 1015 meter (m) in diameter— the nucleus nevertheless contains essentially all the mass of the atom. Electrons have negligible mass and circulate around the nucleus at a distance of approximately 1010 m. Thus, the diameter of a typical atom is about 2 1010 m, or 200 picometers (pm), where 1 pm 1012 m. To give you an idea of how small this is, a thin pencil line is about 3 million carbon atoms wide. Many organic chemists and biochemists still use the unit angstrom (Å) to express atomic distances, where 1 Å 100 pm 1010 m, but we’ll stay with the SI unit picometer in this book. Nucleus (protons + neutrons) Volume around nucleus occupied by orbiting electrons A specific atom is described by its atomic number (Z), which gives the number of protons (and electrons) it contains, and its mass number (A), which gives the total number of protons plus neutrons in its nucleus. All the atoms of a given element have the same atomic number—1 for hydrogen, 6 for carbon, 15 for phosphorus, and so on—but they can have different mass numbers depending on how many neutrons they contain. Atoms with the same atomic number but different mass numbers are called isotopes. The weighted average mass in atomic mass units (amu) of an element’s naturally occurring isotopes is called the element’s atomic mass (or atomic weight)— 1.008 amu for hydrogen, 12.011 amu for carbon, 30.974 amu for phosphorus, and so on. 1.2 Atomic Structure: Orbitals How are the electrons distributed in an atom? According to the quantum mechanical model, the behavior of a specific electron in an atom can be described by a mathematical expression called a wave equation—the same sort of expression used to describe the motion of waves in a fluid. The solution to a wave equation is called a wave function, or orbital, and is denoted by the Greek letter psi, . By plotting the square of the wave function, 2, in three-dimensional space, the orbital describes the volume of space around a nucleus that an electron is most likely to occupy. You might therefore think of an orbital as looking like a photograph of the electron taken at a slow shutter speed. In such a photo, the orbital would appear as a blurry cloud indicating the region of space around the nucleus where the electron has been. This electron cloud doesn’t have a sharp boundary, but for practical purposes we can set the limits FIGURE 1.3 A schematic view of an atom. The dense, positively charged nucleus contains most of the atom’s mass and is surrounded by negatively charged electrons. The three-dimensional view on the right shows calculated electron-density surfaces. Electron density increases steadily toward the nucleus and is 40 times greater at the blue solid surface than at the gray mesh surface. FIGURE 1.3 A schematic view of an atom. The dense, positively charged nucleus contains most of the atom’s mass and is surrounded by negatively charged electrons. The three-dimensional view on the right shows calculated electron-density surfaces. Electron density increases steadily toward the nucleus and is 40 times greater at the blue solid surface than at the gray mesh surface. 39144_01_0001-0032.indd 4 7/27/09 1:28:34 PM