Introduction to Organic Chemistry and Alkanes 1. What is Organic Chemistry? The chemistry of Carbon and its compounds. There are over 18 million known.

Introduction to Organic Chemistry and Alkanes 1

What is Organic Chemistry? The chemistry of Carbon and its compounds. There are over 18 million known compounds. Over 95% of all known molecules are organic – Why? Carbon can form stable covalent bonds with other carbons and other atoms, since it is intermediate in electronegativity. 2

The Periodic Table 3

Ionic Bonds Ionic bonds: an attraction between atoms with opposite charges. Examples? NaCl Why is Na positive? Why is Cl negative? Look at the periodic table. 4

The Periodic Table 5

The Octet Rule Atoms can gain stability if they have a filled outer shell of electrons. Na: 1s 2 2s 2 2p 6 3s 1 Cl: 1s 2 2s 2 2p 6 3s 2 3p 5 If Na gives up its 3s electron to become Na +, its outer shell has 8 electrons – Na + : 1s 2 2s 2 2p 6 If Cl gains an electron to become Cl -, its outer shell has 8 electrons – Cl - : 1s 2 2s 2 2p 6 3s 2 3p 6 Hydrogen’s filled outer shell has only 2 electrons – why? 6

Covalent Bonds A covalent bond is the sharing of one or more pairs of electrons between two atoms. A simple example is H 2, molecular hydrogen. The shared pair of electrons can be shown as a pair of dots between the two atoms, or as a line between the two atoms. 7

Examples of Covalent Molecules CO 2 C shares 4 pairs of electrons: why? O shares 2 pairs of electrons: why? HCN N shares 3 pairs of electrons: why? H only makes 1 bond: why? 8

Drawing Structures of Covalent Molecules from Formulas: C 2 H 6 Carbon has 4 valence electrons, (C: 1s 2 2s 2 2p 2 ), and Hydrogen has 1. Therefore, we have 14 electrons to account for. How do we bond the atoms together? Answer 9

Organization of Organic Compounds When you look at an animal, you can often classify it as some type on the basis of certain characteristics, even if you can’t define them well. 12

Functional Groups Organic compounds are classified on the basis of their functional groups. A functional group is a group of atoms in a molecule that imparts a characteristic chemical reactivity. See table 12.1 on page 329 of your book, or the functional group handout. 13

Functional Groups Containing only C and H Alkane C and H with only single bonds Specific example is ethane Alkene One or more C=C. Specific example is ethene or ethylene 14

Functional Groups Containing only C and H Alkyne One or more CΞC. Specific example is ethyne or acetylene Aromatic Ring Generally, a six- membered ring with alternating C=C and C-C. Specific example is benzene 15

Functional Groups Containing C-O single bonds Alcohol One or more C-OH. Specific example is ethanol or ethyl alcohol. Ether Contains C-O-C. Specific example is diethyl ether. 16

Functional Groups Containing C-Other atom Single Bonds Amine One or more C-N. Specific example is ethanamine. Alkyl Halide Contains C-X (X = F, Cl, Br, or I). Specific example is chloroethane or ethyl chloride. 17

Functional Groups Containing C=O Double Bonds Aldehyde Contains Specific example is benzaldehyde (cherry odor). Ketone Contains Specific example is acetone (nail polish remover). 18

Functional Groups Containing C=O Double Bonds Carboxylic Acid Contains Specific example is ethanoic acid or acetic acid. Anhydride Contains Specific example is acetic anhydride. 19

Functional Groups Containing C=O Double Bonds Ester Contains Specific example is ethyl acetate (nail-polish remover). Amide Contains Specific example is acetaminophen. 20

Note the Differences Alcohol Ether Amine Carboxylic Acid Ester Amide 21

Find the Functional Groups 22

Naming Organic Compounds When organic compounds were discovered, often the people who discovered them named them randomly. Morphine, was named after Morpheus, the Greek god of sleep. Acetic acid was named after “Acetum”, which is Latin for vinegar. When people began to figure out the structures, they started naming compounds systematically, so that the name would tell others what the structure of the compound was. This is now overseen by the International Union of Pure and Applied Chemistry (IUPAC). 23

IUPAC Naming Prefix-Parent-Suffix Suffix: tells the highest priority functional group. Parent: tells the longest continuous chain of carbons. Prefix: tells what other stuff is attached to the longest carbon chain. There may be more than one prefix. 24

Naming Alkanes Alkanes: Contain only C and H, and only have single bonds. Suffix is “ane” Parent part 1 = meth 2 = eth 3 = prop 4 = but The parents for 1-4 carbons were “grandfathered in” from older naming systems. 5 = pent 6 = hex 7 = hept 8 = oct 9 = non 10 = dec 25

Naming Examples CH 4 The longest carbon chain is one, so parent is? Meth Suffix is? ane So the name is? Methane CH 3 -CH 2 -CH 2 -CH 3 Parent is? But Name is? Butane 26

Another Example What about this? The longest chain is? Seven So the name is? Heptane This structure could also be written as: CH 3 -CH 2 -CH 2 -CH 2 -CH 2 -CH 2 -CH 3 This is a condensed structure. Or even as the following, which is a line drawing: Each corner is a CH 2, and the ends are CH 3 ’s. 27

A More Complex Example The longest continuous carbon chain is? Eight, which is? Octane I circled the longest chain There is a one-carbon group attached to the octane To name a carbon group, you add “yl” to the parent, so the group is? Methyl You number from the end closest to the group, so the methyl is at carbon 3 3-methyloctane 28 1 2 3

Another Alkane Example The longest continuous chain is? The group is? The group is located where? The name is? 29 Answer

More than One of a Group If there is more than one of a type of group, a prefix is put in front of the group name to tell how many there are. 2 = di 3 = tri 4 = tetra 5 = penta Each group has to have its own number, even is the groups are on the same carbon. Numbers are separated from each other by a comma. Numbers are separated from words with a dash. 30

An Example The longest carbon chain is? Six, which is? Hexane The groups are? Methyls How many methyls are there? Two, which is? Di, so we have a dimethylhexane. Where are the methyls? 3, so the name is? 3,3-dimethylhexane 31

Another Substituted Alkane The longest continuous chain is? The groups are? How many? The groups are located where? The name is? 32 Answer

Naming Cyclic Alkanes Cyclic alkanes have the prefix “cyclo” before the alkane name. If a molecule has a ring and a chain, the ring has priority if it has ≥ the number of carbons as in the chain. This is cyclopentane This is cyclononane 33

More Cyclic Examples Where are the most C’s: the chain or the ring? What is the group? What is the name? Where are the most C’s: the chain or the ring? What is the group? What is the name? 34 Answers

More than One Type of Group If there is more than one type of group, the group prefixes are arranged alphabetically before the parent. The group closest to the end of the chain gets the lowest number. Longest Chain? Groups? Numbers? Name? 35 Answer

More than One Type of Group on a Ring When numbering a ring, start at the carbon that has a group, and number toward the closest group. The goal is to get the lowest numbers. If we start at the smiley- face, the numbers are? If we start at the arrow, the numbers are? If we start at the star, the numbers are? Name? 36 Answer

Ring #2 Problem Sometimes, you can get the same numbers. When you do, put the lowest number closest to the front of the name. If you start at the star, what numbers do you get? If you start at the arrow, what numbers do you get? Name? 37 Answer

Naming Alkyl Halides Halogens (F, Cl, Br, I) are always named as groups. Drop the “ine” from the halogen name and add “o”. How do you name CHCl 3, otherwise called chloroform? How do you name the above structure? 38 Answer

39 Chapter 13: Alkenes, Alkynes and Aromatic Compounds

40 Introduction Alkenes contain C=C. Alkynes contain C  C. Aromatic compounds (ex. Benzene, above) All of these are considered unsaturated, because each carbon is not bonded to four other atoms. Alkanes are saturated, since each carbon is bonded to four other atoms

41 Naming Alkenes The suffix ending for an alkene is “ene”. Number from the end of the longest chain containing the C=C, to give the C=C the lowest number. Name any groups, and number them accordingly.

42 Naming Example #1 CH 3 -CH=CH-CH 2 -CH 2 -CH 2 -CH 3 The longest chain is? Where is the C=C? So the name is? Answer

43 Naming Example #2 What is the longest chain? What group is attached, and where? The name is? Answer

44 Naming Example #3 What is the longest chain? Where is the C=C? What groups are attached, and where? The name is? Answer

45 Naming Example #4 What is the longest chain? Where is the C=C? What groups are attached, and where? The name is? Answer

46 Alkynes Alkynes are named just like alkenes, except the suffix is “yne”. I will not give you a molecule with both an alkene and an alkyne. CH 3 -CH 2 -C  C-CH 3 is named as? 2-pentyne

Cis-Trans Isomers of Alkenes The C=C is rigid, and does not rotate. The second bond of the double bond is very different from the single bond of an alkane, so the bond can’t rotate. Because the C=C doesn’t rotate, you can have isomers that differ in how groups are arranged around the C=C. Example: CH 3 -CH=CH-CH 3, 2-butene 47

Isomers of 2-Butene The 2 H’s are on the same side of the C=C. When this happens, the configuration is called cis. cis-2-butene The 2 H’s are on the opposite side of the C=C. When this happens, the configuration is called trans. trans-2-butene 48

Reactions of Alkenes The general reaction of an alkene is: One bond of the C=C breaks, and the X-Y bond breaks. The X adds to one C, and the Y to the other. 49

Hydrogenation: Addition of H 2 If two hydrogens add to the C=C, an alkene is reduced to an alkane. This reaction requires a catalyst, such as Pd (palladium), to happen quickly. 50

Hydrogenation Examples 51 Answers

Partial Hydrogenation Plant lipids, or oils, are sometimes hydrogenated to change their properties. Oils have lots of C=C’s and are liquids. If you reduce all of the C=C’s, you have a brittle solid. If you reduce some of the C=C’s, you have? 52

Partial Hydrogenation of an Oil 53

Bromination & Chlorination: Adding a Pair of Halogens If you add Br 2 or Cl 2 to an alkene, you make the dibromo- or dichloroalkane. This reaction doesn’t require a catalyst. This reaction can be used to test for an alkene, since the red color of Br 2 goes away as it reacts with the C=C. 54

Halogenation Problems 55 Answers

Addition of H-Br or H-Cl H-Cl and H-Br can add to a C=C, to make a chloro- or bromoalkane. Sometimes, more than one haloalkane product can form. 56

H-X Addition Examples 57 Answers

Predicting the Major Product: Markovnikov’s Rule In the 1860’s, a Russian chemist named Markovnikov studied the addition of HX to alkenes. He discovered a general rule, that the H of the HX ends up bonded to the carbon of the C=C that is bonded to the most H’s, and the X ends up bonded to the C of the C=C bonded to the least H’s. This is called Markovnikov’s Rule. 58

Predicting the Major Product: Markovnikov’s Rule Which is the major product? Why? 59

Markovnikov’s Rule Problems 60 Answers

The Mechanism of a Reaction When reactions occur, bonds are broken and formed in predictable ways, based on the reactivity of the organic compounds and reagents involved. Chemists study reactions in detail to determine how they occur. The series of bond-breaking and bond-making steps involved in the reaction is called the mechanism of the reaction. Chemists use curved arrows to show how electrons “move” to make and break bonds. 61

The Mechanism of Addition of H- Cl to a C=C H-Cl is polar, because Cl is higher in electronegativity than H. To show the polarity of the bond, we write δ +, meaning slightly positive, next to the H, and δ -, slightly negative, next to the Cl. This reminds us that the Cl is tugging the electrons in the single bond closer to itself, and the H would be attracted to a source of electrons. A double bond can be a source of electrons. 62

The Mechanism of Addition of H-Cl to a C=C: Step 1 The double bond electrons are attracted to the δ + H of H-Cl. We use a curved arrow to show how the electrons in the C=C move toward the H. This forms a new bond from the CH 2 to the H, but H can’t form two bonds: why? We break the H-Cl bond, and give the electrons to the Cl, by drawing an arrow from the bond to the Cl. 63

The Mechanism of Addition of H-Cl to a C=C: Step 1 Our electron movements made a C-H bond and broke the H-Cl bond, but this isn’t quite correct yet: why? The Cl gained electrons, so it is… The middle carbon lost electrons, so it is… 64

The Mechanism of Addition of H-Cl to a C=C: Step 2 To finish the mechanism, we need to make the C-Cl bond. To do this, we draw an arrow from the source of electrons to where they end up. Which atom is the source of electrons? 65

Acid-Catalyzed Addition of Water to a C=C Water, in the presence of acid (H + ) catalyst, can add to a C=C. We will see this reaction later when we study the Krebs cycle and fatty acid biosynthesis. It follows Markovnikov’s Rule. 66

Acid-Catalyzed Addition of Water to a C=C Problems 67 Answers

Polymerization of Alkenes Suppose you have 1 million molecules of methylpropene (commonly called isobutylene), and you add 1 H + X -. What will happen? Initially, the H + will attract an electron pair from the C=C and form a carbocation, just like we did above. Now the carbocation is looking for electrons. The most likely source of electrons is the C=C of another molecule of isobutylene, so it attacks the carbocation. This is shown below. 68

Polymerization Mechanism 69 This could repeat over and over again until all of the isobutylene is used up. Finally, the anion (X - ) could attack the cation, and we would have the following.

Polymerization Finished We now have a very large molecule! Very large molecules formed from smaller repeating units are called polymers. Since we polymerized isobutylene above, the polymer we made is called polyisobutylene. 70

Polymer Examples A more general way to write the structure of the polymer is shown below: “n” represents a very large number. Some other monomers and polymers are shown below. 71 MonomerPolymerUses “Styrene” Polystyrene Plastics, Styrofoam containers chloroethene or “vinyl chloride” polyvinyl chloride (PVC) Rubber substitutes, electrical wire- and cable- coverings, pliable thin sheeting, raincoats, tubing, gaskets, shoe soles.

Reactions of Alkynes (C≡C) Anything that adds to a C=C once will add to a C≡C twice, since there are two bonds that can be broken. Markovnikov’s rule applies to alkynes as well. 72

Alkyne Reactions 73 Answers

Aromatic Compounds, such as Benzene Benzene was the first aromatic compound discovered. It can be drawn as a six-membered ring, with alternating single and double bonds. Benzene does not react like an alkene, however. I will not require you to know the reactions of benzene. 74

Ways to Draw Benzene All of the above are benzene. The last one emphasizes that the C=C’s are not in fixed positions on the benzene ring. The above two structures are really the same, since the C=C’s aren’t in fixed positions on benzene. Don’t be fooled! 75

Differences in the Reactions of Cyclohexene and Benzene 76

Naming Alkyl- and Halogen- Substituted Benzenes The ring is benzene. The group is ? The name is ? The ring is benzene. The group is ? The name is ? 77

Naming Alkyl- and Halogen- Substituted Benzenes, 2 The ring is benzene. The group is? Where are the groups? The name is? When two groups are across on the benzene ring, it is sometimes called para. “para-dichlorobenzene” is in mothballs. 78

Benzene Naming Trivia Two groups in a 1,2 relationship are “ortho”. Two groups in a 1,3 relationship are “meta”. The common name for methylbenzene is toluene, which is a solvent in paint and other things. You can ignore the other common names in Table 13.2 for now. 79

Alkenes or Alkynes That Have Benzene Rings as well. IUPAC gives functional groups priorities in naming. Alkenes and alkynes have higher priorities than benzene. Therefore, if an alkene or alkyne also has a benzene, the benzene is names as a group, called phenyl (from “pheno”, an old name for benzene). 80

Final Naming Example 1 The highest priority group is? The longest chain is? Where is the highest priority group? What else is attached? Where is it? What is the name? 81 Answer

Final Naming Example 2 The highest priority group is? The longest chain is? Where is the highest priority group? What else is attached? Where are they? What is the name? 82 Answer

Chapter 14: Alcohols, Ethers, Thiols and Halides CH234 Bruce A. Hathaway 83

Introduction All of these functional groups contain a carbon bonded to a more electronegative atom. Alcohol: C-OH Ether: C-O-C Thiol: C-SH Halide: C-X (I, Br, Cl, or F) The polar bond and the electronegative atom changes the reactivity of these functional groups. 84

IUPAC Names of Alcohols In general, drop the last “e” from the hydrocarbon name, and add “ol”. Number the longest chain so that the alcohol gets the lowest number: the alcohol has priority over alkenes, alkynes, benzene, or alkanes. CH 3 -CH 2 -CH 2 -CH 2 -OH would be named as? 1-butanol 85

More Naming Examples Longest Chain? Where is the OH? What are the groups? What is the name Longest chain? What and where are the groups? What is the name? Answer 86

Another Naming Example This compound has an alkene and an alcohol. Longest chain? If it didn’t have an alcohol, it would be an? Since it is an alcohol, it is an? Where is the alcohol? Where is the alkene? Cis of trans? Name? Answer 87

Yet Another Example I used this compound in my research some years ago. What is its name? Longest chain containing the alcohol? How do we say a 4- carbon alcohol with an alkyne? Answer Where are the alcohol and alkyne? What else do we need? 88

Alcohols Bonded to the Benzene Ring If an OH is bonded to a benzene ring, it is called phenol. It is a special name. What else is bonded to the benzene ring on the right? Where are they What is the name? The common name is thymol. It is found in “Vicks Vap-o-Rub” Answer 89

More Than One Alcohol HOCH 2 CH 2 OH is found in antifreeze, and its common name is “ethylene glycol”. The IUPAC name is 1,2-ethanediol. Why is this the name? Notice the “e” from the hydrocarbon name was retained, probably so you would give the “a” the long ā sound when pronouncing the name. 90

Water-Solubility of Alcohols Alcohols are much more water-soluble than similar-size alkanes. For example… Pentane (CH 3 CH 2 CH 2 CH 2 CH 3 ), MW = 72: 0.036 g dissolves in 100 mL of water 1-butanol (CH 3 CH 2 CH 2 CH 2 OH), MW = 74: 7 g dissolves in 100 mL of water Why is there such a difference? 91

The Polarity of Water Water is polar, because H and O are quite different in electronegativity: O =3.5 and H = 2.1. The O is pulling electrons in the O-H bonds toward itself. Therefore, the O is partially negative and the H’s are partially positive. 92

Insolubility of Alkanes in H 2 O Alkanes only contain Carbon and Hydrogen. C and H are similar in electronegativity. C = 2.5 and H = 2.1 Therefore, C-C and C-H covalent bonds are not polar. The whole molecule is essentially non-polar. There is little attraction of a non-polar molecule to water, so it is essentially insoluble. 93

Solubility of 1-Butanol in Water 1-butanol has an O-H group with is polar. The O-H group is attracted to water, as shown below. 94

Solubility of 1-Butanol in Water The attraction of a partially positive H for an electronegative atom (N, O, F) is called a “Hydrogen-bond”. It is much weaker than a covalent bond, but stabilizes pairs of molecules. Why doesn’t water hydrogen-bond to the butyl group? 95

Effect of Size on Water-Solubility Ethanol (CH 3 CH 2 OH) is miscible with water: soluble in all proportions: Why? Cholesterol, below, contains an OH, but is essentially insoluble in water: Why? 96

Boiling Points of Alcohols Alcohols have higher boiling points than similar-sized alkanes. For example… Pentane (CH 3 CH 2 CH 2 CH 2 CH 3 ), BP = 36 °C 1-butanol (CH 3 CH 2 CH 2 CH 2 OH), BP = 117 °C Why is there such a difference? Boiling involves overcoming forces of attraction molecules of a substance have for one another. 97

Attractive Forces Between Alkane Molecules Since alkanes are non-polar, there are no polar forces to attract molecules to each other. Alkanes only have London Dispersion Forces attracting them (nuclei in one molecule attracting electrons in another molecule: see Sec. 8.11 in book). These are very weak, so it takes less energy to separate molecules from each other. Less energy → Low boiling point All molecules have London Dispersion Forces attracting them to others. 98

Attractive Forces Between Alcohol Molecules Alcohols have a polar O-H group, which can attract other alcohols by hydrogen bonding. Hydrogen bonds are stronger than London Dispersion Forces Since alcohols have both types of forces, it takes more energy to separate alcohols from each other. More energy → Higher boiling point 99

Effect of Size on Boiling Point 1-butanol (CH 3 CH 2 CH 2 CH 2 OH), BP = 117 °C Ethanol (CH 3 CH 2 OH), BP = 78 °C Why is there a difference? 100

Acidity Review An acid is something that can ionize to produce H + ions. Water can ionize to a small extent. K a (the acidity constant) is a measure of how strong an acid is. 101

Acidity Review K a (H 2 O) = 2.0 x 10 -16 This is a very small number, so water is a very weak acid. K a (acetic acid) = 2.0 x 10 -5 Acetic acid is 10 11 (100,000,000,000) as strong an acid as water, but it is still a weak acid. K a (H-Cl) = 10 7, so it is a very strong acid. 102

Acidity of Alcohols K a (CH 3 CH 2 OH) = 10 -16 Ethanol is also a very weak acid. K a (Phenol) = 10 -10 Phenol is a stronger acid than an alcohol, but weaker than a carboxylic acid. 103

Types of Alcohols Primary (1°): OH is bonded to a carbon that is bonded to only one other carbon. Secondary (2°): OH is bonded to a carbon that is bonded to two other carbons. Tertiary (3°): OH is bonded to a carbon that is bonded to three other carbons. 104

Reactions of Alcohols: Dehydration In the presence of a catalytic amount of strong acid (H 2 SO 4 ), alcohols lose water (the OH and an adjacent H) to form alkenes. This is the reverse reaction to acid-catalyzed addition of water to an alkene. 105

Predict the Products 106 Answer

More Dehydration Examples Sometimes, when an alcohol is dehydrated, more than one alkene product can form. The major product is the one that has the most carbons directly bonded to the C=C. 107

Predict the Products & the Major One 108 Answer

Oxidation Review Oxidation: Loss of electrons from an atom. This is often hard to see in organic molecules. In organic molecules, it usually involves adding an O or removing 2 H’s. Generic symbol for an oxidizing agent is [O]. Real oxidizing agents include CrO 3 (chromium trioxide), KMnO 4 (potassium permanganate), NaOCl (bleach) and H 2 O 2 (hydrogen peroxide). 109

Oxidation of Alcohols Oxidation of an alcohol usually involves removing the H from the OH and an H from an adjacent carbon. Both H’s must be removed! 110

Oxidation Demo When CrO 3 (red) oxidizes an alcohol, it is reduced to Cr 2 O 3 (green or blue-green). Was ethanol oxidized? Was 2-propanol oxidized? Was 2-methyl-2-propanol oxidized? What products formed? 111

Oxidation Products 112

Why Didn’t the Tertiary Alcohol Oxidize? While there is an H on the O, there is no H on the adjacent C. We need to lose both H’s to oxidize an alcohol. 113

Ethers Contain a C-O-C Naming Example: CH 3 CH 2 CH 2 CH 2 -O-CH 3 is named 1-methoxybutane: why? Longest chain is 4, so it is butane. O-CH 3 group is named methoxy: ethers are always named as groups on a longest chain. The “1” tells where the methoxy group is on the longest chain. 114

Other Ether Naming Examples A benzene ring with an OH is called… What group and where? The name is? Longest chain? Groups and where? Name? 115 Answer

Properties of Ethers Do not react readily with bases, dilute acids, or most oxidizing agents. Good general solvents. Not very water-soluble, although water can hydrogen-bond with the ether. Boiling points similar to alkanes: they cannot form hydrogen-bonds with other ethers. 116

Thiols Sulfur analogs of alcohols: contain C-S-H. Named as thiols: CH 3 SH is methanethiol. When you smell natural gas, you are actually smelling methanethiol, which is added to natural gas at the part per million (ppm) level: natural gas is odorless. The name of the following compound, found in skunks, is: 117

Naming Priorities Functional Group Alcohol Thiol Alkene Alkyne Benzene Alkane Substituent Name Hydroxy Mercapto “en” in name “yn” in name Phenyl Alkyl 118 Ethers are always groups: alkoxy Halogens are always groups:halo

Thiols as Groups on Alcohols Longest chain containing the alcohol? What groups are there, and where? Name? 119 This is “British Anti-Lewisite”, a war gas antidote. Answer

Oxidation of Thiols When thiols are treated with mild oxidizing agents, such as H 2 O 2, they are oxidized to disulfides. This is a different oxidation reaction than for alcohols. 120

Thiol Oxidations 121 Answer

Chapter 15: Amines CH234 Bruce A. Hathaway 122

Introduction to Amines Amines contain the C-N functional group. Amines are widely found in nature. Many drugs that interact with the central nervous system are amines, such as ephedrine (left) and morphine (right), shown below. 123

Types of Amines Primary (1°): have one C bonded to the N. Secondary (2°): have 2 C’s bonded to the N. Tertiary (3°): have 3 C’s bonded to the N. 124

IUPAC Names of Amines Amines are named like alcohols, except the ending is “amine”. The structure of 2-heptanamine would be? The structure of cyclohexanamine would be? 125 Answers

More Amine Naming Longest chain w/ amine? Groups and where? Name? Longest chain w/ amine? Groups and where? Name? 126 Answers

Priority in Naming Alcohol Thiol Amine (Amino as a group) Alkene Alkyne Benzene Alkane Ethers and halogens are always groups Highest priority thing and longest chain? Groups and where? Name? 127 Answer

Amines on Benzene Benzene with an NH 2 is called aniline. This is a special name, like phenol and toluene. What groups are on the aniline, and where? Name? 128 Answers

Common Names of Amines For simple amines, common names are often used. CH 3 CH 2 CH 2 CH 2 NH 2 has the common name of butylamine CH 3 NHCH 3 has the common name of dimethylamine. Common names are only useful if the groups attached to the N are easily named. 129

Boiling Points of Amines Pentane (CH 3 CH 2 CH 2 CH 2 CH 3 ) BP = 36 °C 1-butanol (CH 3 CH 2 CH 2 CH 2 OH) BP = 117 °C Ethoxyethane (CH 3 CH 2 OCH 2 CH 3 ) BP = 35 °C 1-butanamine (CH 3 CH 2 CH 2 CH 2 NH 2 ) BP = 78 °C 130

Boiling Point Review Ethers and alkanes have low boiling points, because they can’t hydrogen-bond to other molecules of themselves. Alcohols have high boiling points because they CAN hydrogen-bond to other molecules of themselves. Can amines hydrogen-bond to other molecules of themselves? 131

Boiling Points of Amines Explained Yes, for primary and secondary amines. They have N-H bonds, which have a partially negative N and a partially positive H. Electronegativity of N is 3.0, and H is 2.1. So why do amines have lower boiling points than alcohols? 132

Boiling Points of Amines Explained An N-H bond is less polar than an O-H bond, because O is more electronegative than N. Therefore, the partial negative charge on N is smaller than the partial negative charge on O, and the partial + charge on the N-H is smaller than the partial + charge on the O-H. If the charges are smaller, the attraction between molecules is less, so the boiling point is lower. Magnet example. 133

Water-Solubility of Amines Amines are about as water-soluble as the corresponding alcohols: why? Amines can hydrogen-bond to water, just like alcohols can. 134

Amines as Bases Base: Accepts H + (from an acid). Amines, like ammonia (NH 3 ) are bases. They are not as strong as sodium hydroxide (NaOH) as bases. They still react readily with acids to form salts. 135 Ammonia Hydrogen chloride Ammonium Chloride

Reactions of Amines with Acids 136 Answers

Water-Solubilities of Amine Salts This is pseudoephedrine (“Sudafed”). Why are amine salts more soluble in water than the amines? 137

Reaction of Amine Salts with Bases What is the base? What acid will the base react with? 138 What products will be formed? Answer

One More… 139 Answer

Quaternary Ammonium Salts A nitrogen bonded to four carbon groups is called a quaternary ammonium salt. 140

Preparation of Quat. Salts Reactions of tertiary amines with primary alkyl halides gives a quaternary salt. Why does this work? 141 Answer

Heterocyclic Amines Compounds with atoms other than carbon in the ring are called “heterocycles”. Several heterocyclic amines are found in different biological molecules. 142

Find the Heterocyclic Amines 143 Adenine Nicotine Tryptophan

Chapter 16: Aldehydes and Ketones CH234 Bruce A. Hathaway 144

Introduction Aldehydes and Ketones are the first functional groups we will discuss with a C=O (“carbonyl”). The C=O is polar, because O is more electronegative than C. This influences the reactions that C=O’s undergo. Many aldehydes and ketones have distinctive odors, and are used in fragrances of various kinds. 145

Naming Aldehydes and ketones are named like alcohols, except that they have different endings. Aldehyde: “al” Ketone: “one” Both are higher in priority than alcohols. As a group, an OH is called hydroxy. 146

Naming Examples 1 This is an aldehyde with 5 carbons, so it is pentanal. No number is needed for the location of the C=O, since it has to be at the end of the chain for an aldehyde. This is benzaldehyde, a special name. If there are other groups on the benzene ring, the carbon attached to the aldehyde is numbered 1. 147

“Citronellal”: What’s the IUPAC Name? Longest chain? How do you say alkene and aldehyde? Where is the alkene? What and where are the groups? What’s the complete name? Answer 148

“Vanillin”: What’s the IUPAC Name? Special name? Groups and positions? Name? Answer 149

Naming Examples 2 Longest chain? Where is the ketone? Rest of name? Longest Chain? Group? Name? 150 Answers

Naming Examples 3 Longest chain with C=O? Groups and where? Name? Longest chain with C=O? Groups and where? Name Answers 151

Boiling Points 1-Butanol (CH 3 CH 2 CH 2 CH 2 OH) BP = 117 °C Ethoxyethane (CH 3 CH 2 OCH 2 CH 3 ) BP = 35 °C Butanal (CH 3 CH 2 CH 2 CH=O) BP = 76 °C Why is butanal in between? 152

Boiling Points Can butanal hydrogen-bond with other molecules of itself? No, but because O is more electronegative than C, the carbonyls of two butanals are attracted to one another. This is a weaker attractive force than a hydrogen-bond, but it is stronger than London dispersion forces alone. 153

Water-Solubility 1-Butanol (CH 3 CH 2 CH 2 CH 2 OH) 7.4 g/100 mL of water Ethoxyethane (CH 3 CH 2 OCH 2 CH 3 ) 7 g/100 mL of water Butanal (CH 3 CH 2 CH 2 CH=O) 7 g/100 mL of water Why are they all about the same? 154

Water-Solubility Alcohols, ethers, aldehydes and ketones all have O’s that can hydrogen-bond with water! Since they all are attracted to water, they all have similar water-solubilities. 155

Reductions of Aldehydes and Ketones Reduction, symbolized by [H], is the opposite of oxidation. In general, it involves an atom gaining electrons. In organic chemistry, it usually involves gaining a pair of H’s, or losing an O. 156

A Real Reducing Agent: NaBH 4, Sodium Borohydride NaBH 4 in water is a common reducing agent in organic chemistry. It reduces aldehydes and ketones quickly. It does NOT reduce a C=C. The H’s of NaBH 4 are somewhat negative, and react with the C of the C=O. The H’s of water are somewhat positive, and react with the O of the C=O. 157

How Reduction with NaBH 4 Works 158

Reduction Examples Answers 159

NADH: A Biological Reducing Agent NADH (Nicotinamide Adenine Dinucleotide Hydride) is a biological reducing agent. It functions like NaBH 4 in reductions of aldehydes and ketones. We will see this during the Krebs Cycle later in the course. 160

Nicotinamide Adenine Dinucleotide Hydride 161

How NADH Works NADH works just like NABH 4 ! 162

Reactions with Alcohols Aldehydes and Ketones react with one equivalent of an alcohol to form a hemiacetal. This reaction is reversible, and usually requires an acid catalyst. 163

Hemiacetal Examples 164 Answers

Acetal Formation If the aldehyde or ketone is reacted with two equivalents of an alcohol, an acetal and water are formed as the products. A hemiacetal forms first, then the acetal. Hemiacetals also react with an alcohol to form acetals as well. 165

Acetal Examples 166 Answers

Oxidation of Aldehydes Aldehydes can be oxidized to carboxylic acids by the same oxidizing agents that oxidize 1° or 2° alcohols, such as Jones Reagent, which is CrO 3 /H 2 SO 4 /H 2 O. Tollens’ Reagent, which is Ag(NH 3 ) 2 + X - in water, is selective for oxidizing aldehydes: it does not oxidize alcohols. Tollens’ Reagent produces a silver mirror as a byproduct, since Ag + is reduced to Ag metal. 167

How Oxidation of Aldehydes Works Water adds to the C=O to form a hydrate, just like an alcohol added to form a hemiacetal. The oxidizing agent removes 2 H’s from the hydrate to form the carboxylic acid. 168

Oxidation Demos 169 Answers

Chapter 17: Carboxylic Acids, Anhydrides, Esters & Amides CH234 Bruce A. Hathaway 170

Introduction to Carboxylic Acids and Their Derivatives Carboxylic Acid Ester Anhydride Amide 171

Introduction to Carboxylic Acids Carboxylic acids are commonly found in nature. We will discuss amino-acids, the building blocks for proteins, and fatty acids, the building blocks for lipids, later in Biochemistry. Acetic acid, in vinegar, and acetylsalicylic acid, aspirin, are everyday life examples. 172

Naming Carboxylic Acids The ending is “oic acid”. Otherwise, they are named just like aldehydes. Sometimes the acid group is written as COOH or CO 2 H, rather than showing the C=O like below. CH 3 CH 2 CH 2 CH 2 COOH is named as: Pentanoic acid 173

Naming Priorities See the Carboxylic Acid Naming handout. Carboxylic acids are higher in priority than any previous functional group. I will not give you something to name that has a carboxylic acid and an ester or an amide. 174

Naming Examples See the Carboxylic Acid Naming handout. A lot of common names are used, especially for fatty acids: we will cover those later. Two common names to know: – CH 3 COOH is “acetic acid”: found in vinegar. – HCOOH is “formic acid”: found in some ants. 175

Physical Properties CompoundMolecular Weight Boiling Point Water-Solubility (g/100 mL H 2 O) CH 3 CH 2 COOH Propanoic acid 74141Miscible CH 3 CH 2 CH 2 CH 2 OH 1-butanol 741177.4 CH 3 CH 2 CH 2 CH 2 CH 3 Pentane 72360.036 176

Boiling Point Carboxylic acids can hydrogen-bond to other carboxylic acids twice. Therefore, the attraction between molecules is greater, so acids have a higher boiling point. 177

Water-Solubility Acids can hydrogen- bond to water with both O’s, as well as with the O-H. More attractions to water → more water-soluble than alcohols 178

Acidity Terminology pH is a measure of the concentration of acid [H + ] of a solution. pH = -log[H + ] K a is the ionization constant of an acid K a tells us how strong an acid is, by how ionized the acid is. pK a = -logK a pK a (HCl) = -7 179

Acidity of Carboxylic Acids CompoundKaKa pK a = -log 10 (K a ) H-Cl10 7 -7 CH 3 CH 2 COOH Propanoic acid 2 × 10 -5 4.7 CH 3 CH 2 CH 2 CH 2 OH 1-Butanol 10 -16 16 CH 3 CH 2 CH 2 CH 2 CH 3 Pentane ≈ 10 -40 ≈ 40 Phenol10 -10 10 180

Reactions with Bases Because they are acids, carboxylic acids react with bases to form salts. If a hydroxide base is used, water is the byproduct. 181

Reactions of Carboxylic Acids The main reactions of carboxylic acids are those which convert them into the other carboxylic acid derivatives: anhydrides, esters and amides. Most of these reactions involve reacting the acid with a reagent to form the derivative, with water produced as a byproduct. 182

Preparation of Esters Heating a carboxylic acid together with an alcohol, in the presence of an acid catalyst, produces an ester, with water as a byproduct. Usually, an excess of either alcohol or carboxylic acid is used to drive the reaction to completion. 183

Why Esterification Works The partially negative O of the alcohol is attracted to the partially positive C of the C=O. The partially positive H of the alcohol is attracted to the partially negative O of the OH. 184

Predict the Ester Products #1 Answers 185

Predict the Ester Products #2 Answers 186

Making a Polyester 187

Making a Polyester, continued 188 Polyethylene terephthalate (PET), or Dacron

Preparation of Amides Many amides can be prepared by heating a carboxylic acid with an amine at a high temperature (100-200 °C). Water is formed as a byproduct. 189

What Happens in Amide Formation The amine reacts with the acid to form a salt, as we discussed in chapter 15. The salt loses water upon heating to make the amide. 190

Amide Formation Examples Answers 191

Anhydrides Anhydrides are very reactive, and are not often found in nature. They react readily with water, alcohols, and amines to make carboxylic acids, esters and amides, respectively. 192

Preparation of Anhydrides If two molecules of a carboxylic acid are heated at a very high temperature, water is lost, and an anhydride forms. Acetic anhydride is produced in huge quantities this way. 193

Reactions of Anhydrides Anhydrides react with alcohols to produce esters, and with amines to produce amides. A molecule of carboxylic acid is produced as the byproduct. These reactions are much faster than the corresponding reactions of carboxylic acids with alcohols and amines. The anhydride reactions are significantly exothermic! 194

Demo Reaction #1 195 Answer

Demo Reaction #2 196 Answer

Other Anhydrides Other types of acids, such as phosphoric acid, can make molecules similar to anhydrides. These are called diphosphates and triphosphates, depending on how many molecules of phosphoric acid are involved. These are related to “high energy” molecules we will see in biochemistry, such as Adenosine Triphosphate (ATP). 197

Di- and Triphosphates 198 2 Phosphoric Acids Diphosphate Triphosphate

Adenosine Triphosphate (ATP) 199

Esters Esters are commonly found in nature. Some are fragrances and flavorings. Some are lipids and waxes. Sometimes, esters are written as R 1 COOR 2 to save space. 200

Naming Esters Esters are named as two words. The first word is the group attached to the single bonded oxygen. In this case: Methyl The second word has the ester ending “oate” replacing the acid ending, “oic acid”. Second word is: pentanoate The complete name is: Methyl pentanoate. Nothing connects the two words! 201

Ester Naming Examples First Word? Second Word? Name? First Word? Second Word? Name? 202 Answers

Oil of Wintergreen The compound that gives the “Wintergreen” odor is named methyl 2-hydroxybenzoate. What is its structure? 203 Answer

Reactions of Esters Esters can react with water in a process called “Hydrolysis”. Hydrolysis cleaves the ester C-O bond, and forms the carboxylic acid and the alcohol. It is the reverse of the ester forming reaction, and usually requires some acid. 204

Why Hydrolysis Works The partially negative O in water is attracted to the partially positive C in the ester. The partially positive H in water is attracted to the partially negative O in the ester. 205

Hydrolysis Examples 206 Answers

Basic Hydrolysis (“Saponification”) Hydrolysis using NaOH, a base, produces the salt of the carboxylic acid, plus the alcohol. This is because the carboxylic acid formed during hydrolysis reacts with more NaOH to form the salt. See slide 12. Saponification comes from a word meaning “Soap- making”. This reaction is used to make soap. 207

Base Hydrolysis Examples 208 Answers

Reactions of Esters with Amines Esters react with amines to form amides. The reaction is similar to hydrolysis of esters. 209

Esters + Amines #1 210 Answers

Esters + Amines #2 211

Esters + Amines #2 212 One form of Nylon, a polyamide polymer

Amides As we have already seen, amides can be prepared from carboxylic acids, anhydrides, and esters. Amides are found in proteins. Many pharmaceuticals also contain amides, such as acetaminophen. 213

Amide Naming The ending is “amide”: drop the “oic acid” of the acid name and add “amide”. The longest carbon chain for naming purposes is the chain connected to the C=O. Groups on the longest chain are located with numbers. Groups on the N are located as “N-” groups. 214

Amide Naming Examples Longest Chain? Group and where? Name? Longest Chain? Groups and where? Name? 215 Answers

Hydrolysis of Amides Like esters, amides undergo hydrolysis reactions to form amines and carboxylic acids, in general. Amides are less reactive than esters, so the reactions are usually run with concentrated acid or base at reflux. Your book presents hydrolysis on p. 531 as occurring as shown above: why is this wrong? 216

Hydrolysis of Amides Carboxylic acids are acids, and amines are bases, so they will react to form a salt. The book draws amino-acids are charged structures in chapter 18, so we might as well draw them this way to get in practice. 217

Amide Hydrolysis Examples 218 Answers

Chapter 18: Aminoacids CH234 Bruce A. Hathaway 219

Introduction to Biochemistry The principal classes of biomolecules are proteins, carbohydrates, lipids, and nucleic acids. Some biomolecules are small and have only a few functional groups, others are huge and their biochemistry is governed by the interactions of large numbers of functional groups. Despite the huge size of some biomolecules and the complexity of their interactions, their functional groups and chemical reactions are no different than those of simpler organic molecules. All principles of chemistry introduced thus far apply to biochemistry. 220

Introduction to Amino-Acids Most amino-acids in the body have the above general structure. They differ in what the group “G” is. They are referred to as α-amino-acids, since the carbon next to a C=O is generically called the α- carbon. There are about 20 common α-amino-acids that occur in proteins: see Table 18.3, p. 547. 221

Amino-Acids, Cont. I want you to know 5 amino-acids. Valine (Val): G = CH(CH 3 ) 2 or, isopropyl. This is an example of an amino-acid with a neutral, non-polar group. Serine (Ser): G = CH 2 OH Cysteine (Cys): G = CH 2 SH These are examples of neutral, polar groups. 222

Amino-Acids, Cont. Glutamic acid (Glu): G = CH 2 CH 2 COOH This is an example of an acidic group. Lysine (Lys): G = CH 2 CH 2 CH 2 CH 2 NH 2 This is an example of a basic group. You need to know the three-letter abbreviations as well. 223

Acid-Base Properties of Amino-Acids Although we draw amino-acids as shown above left, they probably really don’t look like that at neutral pH: why? Amines are bases, and carboxylic acids are acids. The amine pulls off the carboxylic acid H to form a salt, called a zwitterion (German: zwitter = hybrid). 224

Acid-Base Properties of Amino-Acids If an amino-acid is put into a very acid pH (for example, pH = 2), the negative end will attract an H + to form the carboxylic acid. If the G-group is neutral, the amino acid will be positively charged. Form at a neutral pH Form at a very acidic pH 225

Acid-Base Properties of Amino-Acids If an amino-acid is put into a very basic pH (for example, pH = 12), the base will remove a hydrogen from the NH 3 + group. If the G-group is neutral, the amino acid will be negatively charged. Form at a neutral pH Form at a very basic pH 226

Acid-Base Question What will serine look like at a very acidic pH? How do we approach this? 1.What does serine look like at a neutral pH? 2.What happens when you add acid (H + )? Answer 227

Properties of Amino-Acids Because they are zwitterions at neutral pH, amino acids have many of the physical properties we associate with salts: – can form crystals – have high melting points – are soluble in water – not soluble in hydrocarbon solvents 228

Reactions of Amino-Acids Because amino-acids contain carboxylic acid and amine groups, they undergo the same reactions we studied of carboxylic acids and of amines. The amine reactions we studied are acid-base reactions in chapter 15, and reactions with carboxylic acids and esters in chapter 17. We made esters and amides from carboxylic acids in chapter 17. 229

Reaction of a Carboxylic Acid with an Amine. Carboxylic acids reacted with amines to form salts. When heated, the salts formed amides. 230

What Happens Here? Suppose we react two Valines together: what happens? Water is lost to form an? Amide Val-Val 231

The Dipeptide Val-Val Two amino-acids bonded together is called a dipeptide. The amino end is the N-terminal amino-acid. The carboxyl end is the C-terminal amino-acid. 232

What Happens In This Case? 233

Random Peptide Formation If you make a dipeptide from two different amino-acids randomly, you can get two different dipeptides. If you had three different amino-acids Glu, Ser and Val), how many different tripeptides could you make? 234 Answer

Amino-Acid Stereochemistry See the “Amino-Acid Stereochemistry” handout. If a bond is a wedge (  ), the atom or group is coming at you. If a bond is a dashed line (Ξ), the atom or group is going away from you. 235

Real Peptide Formation We don’t make peptides randomly. DNA codes for the formation of RNA The two types used in protein synthesis are messenger RNA (m-RNA) and transfer RNA (t-RNA). The messenger RNA determines the amino acid sequence. Each transfer RNA has a specific amino ester bonded to it as an ester. 236

M-RNA binds to the ribosome. T-RNA’s bind to the two sites. 237

238 The amine group of one t-RNA reacts with the ester of the other to make the peptide bond. This removes the amino acid from the first t-RNA

The first t-RNA leaves, and the ribosome moves to the right down the m-RNA. 239

A new t-RNA bonds to the new codon, and the amide forming reaction repeats. There are special “stop-codons”, which end the process. 240

Acid-Base Question Answer What will serine look like at a very acidic pH? How do we approach this? 1.What does serine look like at a neutral pH? 2.What happens when you add acid (H + )? Return 241

Random Peptide Formation Answer If you make a dipeptide from two different amino-acids randomly, you can get two different dipeptides. If you had three different amino-acids Glu, Ser and Val), how many different tripeptides could you make? Glu-Ser-Val, Glu-Val-Ser, Ser-Glu-Val, Ser-Val-Glu, Val-Glu-Ser, and Val-Ser-Glu. 242 Return

243 Chapter 18: Proteins Bruce A. Hathaway CH234

Introduction to Proteins At the most basic level, proteins are chains of amino-acids bonded together. This is referred to the the Primary Structure. There is much more to protein structure than the fundamental order of amino-acids. Glu-Ser-Val means? 244

Glu-Ser-Val 245

246 Protein Primary Structure The sequence of amino acids, such as for insulin.

247 Attractive Forces in Proteins: Hydrogen-bonding Hydrogen-bonding between the amide N-H’s and C=O’s in the amino-acid backbone. This gives rise to the alpha helix and beta sheet structures.

248 Attractive Forces in Proteins: Hydrogen-bonding Hydrogen-bonding between polar groups, such as the CH 2 OH groups of two serines.

249 Attractive Forces in Proteins: Salt Bridges Attraction between oppositely charged amino-acid side chains, such as a glutamate and a lysine.

250 Attractive Forces in Proteins: Hydrophobic Attraction Attraction between non-polar groups. The two benzene rings are “pi-stacked”, due to attractions between the p- orbitals in the double bonds. There is some evidence that non-polar groups are really just trying to avoid water on the outside of the protein, so the protein folds to put them on the inside, away from the water. This is a weak attractive force at best.

251 Attractive Forces in Proteins: Disulfide Bonds If two cysteines are located close to each other in the protein chain, they can be oxidized to form a disulfide bond.

252 Levels of Proteins Structure Taken from Lehninger, Principles of Biochemistry, 3 rd Edition

253 Secondary Structure in Proteins: the Alpha-Helix The N-H’s and the C=O’s of the peptide backbone can hydrogen-bond with each other to form a helix. This drawing is taken from Biochemistry, by Stryer, 4 th edition.

254 Secondary Structure in Proteins: the Beta-Sheet The N-H’s and the C=O’s of the peptide backbone can hydrogen-bond with each other to form a sheet. This drawing is taken from http://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/protalbeta.htm.

255 Secondary Structure in Proteins: the Beta-Sheet (another view) The N-H’s and the C=O’s of the peptide backbone can hydrogen-bond with each other to form a sheet. This drawing is taken from http://www.people.virginia.edu/~rjh9u/bsheet.html

256 Tertiary Structure in Proteins Due to the various attractive forces between amino acid side chains, the protein can fold on itself. Taken from Lehninger, Principles of Biochemistry, 3rd Edition

Prentice Hall © 2007 Chapter Eighteen 257 Myoglobin, drawn four ways. (a) tube representing the helical portions. (b) ribbon model shows the helical portions. (c) A ball- and-stick molecular model. (d) A space- filling model, with hydrophobic residues (blue) and hydrophilic residues (purple).

258 Quaternary Structure in Proteins: Hemoglobin Different proteins strands can be attracted to one another by hydrogen bonding and other forces. This drawing is taken from http://pollen.utulsa.edu/Cell- Biology/Proteins/sld040.htm

260 Insulin Tutorial on the Web http://c4.cabrillo.edu/projects/insulin_tutorial/index.html This requires Netscape Navigator and the Chime plug-in, both of which are available as free downloads.

Chemistry of “Perming” Keratin, the main protein in hair, contains lots of disulfide bonds. The disulfide bonds are largely responsible for maintaining hair’s shape. 261

Step 1: Reducing the Disulfide Bonds. Adding a reducing agent reduces the disulfides to thiols. Some of these reducing agents contain thiols, so they stink! 262

Step 2: Realigning the hair molecules Since the proteins are no longer bonded together, the molecules can realigned physically. Different thiols are now next to each other. 263

Step 3: Reoxidizing the thiols Adding an oxidizing agent reforms disulfides between different carbon atoms. The hair now has a new shape! 264

Chapter 19: Acetylcholinesterase Inhibitors Bruce A. Hathaway CH234 265

Types of Enzyme Inhibitors Competitive Reversible Inhibitors Irreversible Inhibitors Non-Competitive Inhibitors 266

Competitive Inhibitors Bind to the active site of the enzyme. Exhibit concentration-dependent inhibition: the more inhibitor, the greater the inhibition of the enzyme. Inhibition can be reversed by adding more substrate. Usually resemble the substrate in chemical structure. 267

ACHE Competitive Inhibitors: Edrophonium Has a quaternary ammonium group like acetylcholine. O-H group can hydrogen bond to the serine O-H group. 268

ACHE Competitive Inhibitors: Edrophonium 269

ACHE Competitive Inhibitors: Neostigmine Has a quaternary ammonium group like acetylcholine. Carbamate is similar to ester of ACH, but is harder to hydrolyze. Carbamate group 270

ACHE Competitive Inhibitors: Neostigmine 271

Neostigmine reacts with the ACHE active site the same way as ACH does initially. 272

The serine OH has now been carbamylated. Edrophonium drifts away, and water comes into the active site. 273

The serine now has a carbamate group. 274

The water cleaves the carbamate group more slowly than an ester group. Therefore, the ACHE cannot be regenerated as quickly. 275

Irreversible Inhibitors Bind to the active site of the enzyme. Exhibit concentration-dependent inhibition: the more inhibitor, the greater the inhibition of the enzyme. Inhibition cannot be reversed by adding more substrate. Usually resemble the substrate in chemical structure somewhat. 276

ACHE Irreversible Inhibitors: Sarin and Diisopropylfluorophosphate (DFP) Have phosphate ester groups. Serine O(-) displaces the fluorine rather than an alcohol group. Sarin DFP 277

Sarin reacts with the Serine in the ACHE active site. 278

Water cannot hydrolyze the phosphate ester bond, so ACHE is inactivated. 279

An Antidote for Sarin and DFP inhibition of ACHE: 2-PAM Has a positive N, like a quaternary salt. Oxime OH is more basic than water, so it can react faster with a phosphate ester. Oxime 280

2-PAM cleaves the phosphate ester bond to the serine, which reactivates the enzyme. 281

2-PAM is now bonded to the Sarin, and the enzyme active site is now back in action. 282

Non-Competitive Inhibitors Do not bind to the active site. Bind to another site (the allosteric site), which changes the enzyme shape, or blocks access to the active site. This makes it harder for the substrate to bind to the active site. Inhibition cannot be reversed by adding more substrate. Often do not look like the substrate. 283

Non-Competitive Inhibition of ACHE: A Schematic of the Enzyme 284

A Non-Competitive Inhibitor of ACHE: Propidium Iodide Propidium iodide is too big to get through the channel to the active site, and binds to the allosteric site. Propidium iodide blocks ACH and nerve gases from getting to the active site. 285

286 Chapter 19 Acetylcholinesterase: A Model of an Enzyme Mechanism Bruce A. Hathaway CH234

287 Introduction Acetylcholineesterase (ACHE) is an enzyme which catalyzes the hydrolysis of the ester group of acetylcholine (ACH). The reaction that occurs is the following: Acetylcholine (ACH) Acetic acidCholine

288 What ACHE Does Acetylcholine (ACH) is a neurotransmitter. When an electrical impulse reaches the end of a nerve cell, ACH is released. The ACH flows across the gap between the nerve cells (the synapse) and binds to a protein on the surface of the next nerve cell (the receptor). This produces some changes in the cell membrane of that nerve cell, which creates an electrical impulse in that nerve cell. The ACH then diffuses away, and can be broken down by ACHE, which is in the synapse. This keeps the ACH from continually producing electrical impulses in the next nerve cell. This is illustrated on the next slide.

289 What ACHE Does

290 What ACHE Does Each electrical impulse releases about 3 million molecules of ACH. A nerve cell has electrical impulses going through it very often, about one every 1 ‑ 5 milliseconds (about 200 ‑ 1000 times per second). There is enough ACHE in the synapse to break down 270 million ACH molecules per millisecond. Under normal conditions, this keeps the nervous system functioning properly.

291 What ACHE Does The ACHE molecule is perfectly designed to break down a molecule of ACH. The key part of the enzyme is the so ‑ called “Active Site" ‑ the place on the enzyme molecule where the reaction with ACH actually takes place. There are four groups that are all necessary for the enzyme to do its job, and they all have to be located in exactly the right places to work. See the next slide.

292 What ACHE Does: the Active Site

293 What ACHE Does The first step in the reaction involves getting the ACH molecule to the active site. That's the job of the glutamic acid R ‑ group. Since it's negatively charged at pH 7, it attracts the positively charged nitrogen on acetylcholine, and pulls the ACH molecule into the active site. This attraction between the (+) and ( ‑ ) charges holds the ACH molecule in place so that the other groups can do their things. Notice that the carbonyl carbon of ACH is very close to the serine's OH group. This is very important.

294 ACH binds to the active site.

295 The base pulls the H off of the serine OH group.

296 The serine O (-) attacks the C=O, and cleaves the ACH ester bond.

297 The choline O (-) pulls the H off of the acidic group in the active site.

298 ACHE changes shape, choline diffuses out of the active site, and is replaced by a water.

299 The Serine OH group has been esterified. To restore enzyme activity, the ester must be hydrolyzed.

300 The negative acid group pulls an H off of the water molecule to form OH (-).

301 OH (-) attacks the ester, and cleaves it to form the serine O (-).

302 The serine O (-) pulls the H of the positive basic group, to regenerate the active site in its original form.

303 After the acetic acid floats away, the active site is ready to react with another ACH.

304 Chapter 21: The Generation of Biochemical Energy Bruce A. Hathaway CH234, Organic and Biological Chemistry, Southeast Missouri State University

305 Sources of Energy

306 Specific Requirements for Energy Energy must be released from food gradually. Energy must be stored in readily available form. The release of energy from storage must be finely controlled so that it is available when and where it is needed. Just enough energy must be released as heat to maintain constant body temperature. Energy must be available to drive chemical reactions that aren’t favorable at body temperature.

307 Free Energy (G) Chemical reactions either release energy or require energy. Reactions that release energy are called Exergonic, and have a negative change in G (  G<0). Reactions that require energy are called Endergonic, and have a positive change in G (  G>0). C 6 H 12 O 6 (glucose) + 6 O 2  6 CO 2 + 6 H 2 O  G = -686 kcal/mole 6 CO 2 + 6 H 2 O  C 6 H 12 O 6 (glucose) + 6 O 2  G = +686 kcal/mole

308 Energy Diagrams Exergonic Reaction Endergonic Reaction

309 Overview of Metabolism And Energy Production (Figure 21.5)

310 Acetyl Coenzyme A (CoAAc)

311 ATP and Energy Transfer ATP + HOH  ADP + Phosphate  G = -7.3 kcal/mole

312 ATP and Energy Transfer

313 ATP and Energy Transfer Reaction  G (kcal/mole) Glucose + phosphate  glucose-6-phosphate + HOH + 3.3 ATP + HOH  ADP + phosphate - 7.3 Overall: Glucose + ATP  ADP + glucose-6-phosphate - 4.0

314 “High-Energy” Phosphate Bonds

315 Oxidized and Reduced Coenzymes Oxidation: Loss of 2 H’s, addition of Oxygen, or loss of electrons. Reduction: Addition of 2 H’s, loss of Oxygen, or gain of electrons. If something is oxidized, something else is also reduced. The coenzymes function as oxidizing and reducing agents in enzymatic reactions.

316 NAD + and NADH, and NADP + and NADPH NAD + or NADP + NADH or NADPH

317 FAD and FADH 2, and FMN and FMNH 2 FAD or FMN FADH 2 or FMNH 2

318 Citric Acid Cycle (Krebs Cycle) Acetyl Coenzyme A is converted to Coenzyme A and 2 CO 2. The “high-energy” molecule ATP, as well as the reduced coenzymes, NADH and FADH 2, are produced.

319 The Citric Acid Cycle

320 The Citric Acid Cycle, Step 1: An Aldol Condensation + An Ester Hydrolysis.  G = -7.5 kcal/mole

321 The Citric Acid Cycle, Step 2: A Dehydration, Then Addition of Water.

322 The Citric Acid Cycle, Step 3: An Oxidation, Then Loss of CO 2.

323 The Citric Acid Cycle, Step 4: Addition of Coenzyme A, then Loss of CO 2

324 The Citric Acid Cycle, Step 5: Hydrolysis of a Thioester.

325 The Citric Acid Cycle, Step 6: Loss of 2 H’s to Form a C=C.

326 The Citric Acid Cycle, Step 7: Addition of Water to a C=C. Notice that only one stereoisomer of malate is produced by this enzyme catalyzed reaction.

327 The Citric Acid Cycle, Step 8: Oxidation of a Secondary Alcohol.

328 Net Result of the Citric Acid Cycle Acetyl CoA + 3 NAD + + FAD + ADP + Phosphate + HOH  CoASH + 3 NADH + 3 H + + FADH 2 + ATP + 2 CO 2 The NADHs and the FADH 2 are used to produce ATP in the Electron Transport Chain.

329 The Electron Transport Chain The Electron Transport Chain (ETC) is a group of enzymes and coenzymes in the inner mitochondrial membrane. NADH and FADH 2 donate protons and electrons to the enzymes and coenzymes, which causes H + ions to cross the membrane. The electrons are passed down the enzymes and coenzymes in the ETC, in a series of reduction and oxidation reactions, that goes downhill in energy (-  G). H + ions pass through ATP synthetase, which provides the energy needed for making ATP from ADP and phosphate.

330 The Electron Transport Chain

331 Energy Produced from One Acetyl Coenzyme A. In the ETC, 1 NADH produces 2.5 ATP. In the ETC, 1 FADH 2 produces 1.5 ATP. One ATP is produced in the citric acid cycle. Total ATPs produced from one acetyl CoA = 3 NADH  2.5 ATP/NADH + 1.5 ATP/FADH 2 + 1 GTP/ATP = 10 ATPs. We’ll see how acetyl CoA is produced from glucose in Chapter 23, and look at the overall energy produced from glucose then.

Chapter Twenty Two Carbohydrates James E. Mayhugh Oklahoma City University  2007 Prentice Hall, Inc. Modified by Bruce A. Hathaway, 2009 Fundamentals of General, Organic, and Biological Chemistry 5th Edition

Prentice Hall © 2007Chapter Twenty Two333 Outline 22.1 An Introduction to Carbohydrates 22.2 Handedness of Carbohydrates 22.3 The D and L Families of Sugars: Drawing Sugar Molecules 22.4 Structure of Glucose and Other Monosaccharides 22.5 Some Important Monosaccharides 22.6 Reactions of Monosaccharides 22.7 Disaccharides 22.8 Ignore this section Variations on the Carbohydrate Theme 22.9 Some Important Polysaccharides

Prentice Hall © 2007Chapter Twenty Two334 22.1 An Introduction to Carbohydrates Carbohydrate: A member of a large class of naturally occurring polyhydroxy ketones and aldehydes. The general formula of a carbohydrate is C x (H 2 O) y Monosaccharide (simple sugar): A carbohydrate with 3–7 carbon atoms. Disaccharide: A carbohydrate composed of two monosaccharides. Polysaccharide (complex carbohydrate): A carbohydrate that is a polymer of monosaccharides.

Prentice Hall © 2007Chapter Twenty Two335 The family-name ending -ose indicates a carbohydrate. Aldose: A monosaccharide that contains an aldehyde carbonyl group. Ketose: A monosaccharide that contains a ketone carbonyl group.

Prentice Hall © 2007Chapter Twenty Two336 Simple sugars are known by common names like glucose, ribose, and fructose, not systematic names. The number of C atoms in an aldose or ketose is given by the prefixes tri-, tetr-, pent-, hex-, or hept-. Most naturally occurring simple sugars are aldehydes with either five or six carbons. Their functional groups also allow reactions with alcohols and with lipids and proteins to form biomolecules with specialized functions. Monosaccharides are chiral molecules. Monosaccharides exist mainly in cyclic forms rather than the straight-chain forms written above.

Prentice Hall © 2007Chapter Twenty Two337 Glucose is an aldohexose (aldo- = aldehyde, - hex = six carbons; -ose = sugar); fructose is a ketohexose (a six-carbon ketone sugar); and ribose is an aldopentose (a five-carbon aldehyde sugar).

Prentice Hall © 2007Chapter Twenty Two338 22.2 Handedness of Carbohydrates Because carbohydrates contain carbon atoms bonded to four different groups, they are chiral (that is, not superimposible on their mirror images). Glyceraldehyde, the three-carbon monosaccharide that is the simplest naturally occurring carbohydrate, has four different groups bonded to the number 2 carbon atom, making it a chiral molecule.

Prentice Hall © 2007Chapter Twenty Two339 Chiral compounds like glyceraldehyde lack a plane of symmetry and exist as a pair of non- superimposable mirror images, enantiomers, a “right-handed” D form and a “left-handed” L form.

Prentice Hall © 2007Chapter Twenty Two340 Solutions of chiral chemical compounds change the plane in which the light is polarized. Each enantiomer of a pair rotates the plane of the light by the same amount, but the directions of rotation are opposite. If one enantiomer rotates the plane of the light to the left, the other rotates it to the right.

Prentice Hall © 2007Chapter Twenty Two341 In general, a compound with n chiral carbon atoms has a maximum of 2 n possible stereoisomers and half that many pairs of enantiomers. The aldotetroses, for example, have n = 2 so that 2 n = 2 2 = 4, meaning that four stereoisomers are possible. These four aldotetrose stereoisomers consist of two mirror-image pairs of enantiomers, one pair named threose and one pair named erythrose. Because erythrose and threose are stereoisomers but not mirror images of each other, they are described as diastereomers.

Prentice Hall © 2007Chapter Twenty Two343 22.3 The D and L Families of Sugars: Drawing Sugar Molecules A standard method of representation called a Fischer projection has been adopted for drawing stereoisomers on a flat page so that we can tell one from another. Bonds that point up and out of the page are shown as horizontal lines, and bonds that point behind the page are shown as vertical lines.

Prentice Hall © 2007Chapter Twenty Two344 In a Fischer projection, the aldehyde or ketone carbonyl group of a monosaccharide is always placed at the top. The result is that -H and -OH groups projecting above the page are on the left and right of the chiral carbons, and groups projecting behind the page are above and below the chiral carbons.

Prentice Hall © 2007Chapter Twenty Two346 Monosaccharides are divided into two families—the D sugars and the L sugars. D Sugar: Monosaccharide with the -OH group on the chiral carbon atom farthest from the carbonyl group pointing to the right in a Fischer projection. L Sugar: Monosaccharide with the -OH group on the chiral carbon atom farthest from the carbonyl group pointing to the left in a Fischer projection. Consistently writing monosaccharide formulas as Fischer projections allows us to identify the D and L forms at a glance.

Prentice Hall © 2007Chapter Twenty Two349 D and L stand for dextro and levo, respectively. The D and L relate only to the position of the - OH group on the chiral carbon furthest from the carbonyl group in a Fischer projection. The D and L isomers do rotate plane-polarized light in opposite directions, but the direction of rotation cannot be predicted. There are D isomers that rotate polarized light to the left and L isomers that rotate it to the right.

Prentice Hall © 2007Chapter Twenty Two350 22.4 Structure of Glucose and Other Monosaccharides You have seen that aldehydes and ketones react reversibly with alcohols to yield hemiacetals. Since simple sugars have hydroxyl groups and a carbonyl group in the same molecule, internal hemiacetal formation is possible.

Prentice Hall © 2007Chapter Twenty Two351 D-Glucose, also called dextrose or blood sugar, is the most widely occurring of all monosaccharides and has the most important function. In nearly all living organisms, D-glucose serves as a source of energy to fuel biochemical reactions. Although they can be written with the carbon atoms in a straight chain, monosaccharides with five or six carbon atoms exist primarily in their cyclic forms. The -OH on C-5 of D-glucose can bond to either side of the planar carbonyl group to make two different six-membered cyclic hemiacetals possible.

Prentice Hall © 2007Chapter Twenty Two353 The hemiacetal carbon is chiral and the two stereoisomers formed are called anomers. Anomer: Cyclic sugars that differ only in positions of substituents at the hemiacetal carbon (the anomeric carbon); the  form has the -OH on the opposite side from the -CH 2 OH the  form has the -OH on the same side as the -CH 2 OH. Anomeric carbon atom: The hemiacetal C atom in a cyclic sugar; the C atom bonded to an -OH group and an O in the ring.

Prentice Hall © 2007Chapter Twenty Two354 Mutarotation: Change in rotation of plane- polarized light resulting from the equilibrium between cyclic anomers and the open-chain form of a sugar. Ordinary crystalline glucose is in the cyclic  form. Once dissolved in water, equilibrium is established among the open-chain form and the two anomers.

Prentice Hall © 2007Chapter Twenty Two355 D and L distinguish enantiomers with different locations for the -OH group furthest from the carbonyl.  and  distinguish anomers with different locations of the -OH on the hemiacetal carbon. When cyclic structures are drawn from the side view they are called Haworth projections. The -CH 2 OH group in D sugars is always above the plane of the ring in Haworth projections.

Prentice Hall © 2007Chapter Twenty Two356 22.5 Some Important Monosaccharides The monosaccharides are generally high- melting, white, crystalline solids that are soluble in water and insoluble in nonpolar solvents. Most monosaccharides and disaccharides are sweet-tasting, digestible, and nontoxic. Except for glyceraldehyde (an aldotriose) and fructose (a ketohexose), the carbohydrates of interest in human biochemistry are all aldohexoses or aldopentoses. Most are in the D family.

Prentice Hall © 2007Chapter Twenty Two358 22.6 Reactions of Monosaccharides Reducing sugar: A carbohydrate that reacts in basic solution with a mild oxidizing agent. Aldehydes can be oxidized to carboxylic acids, a reaction that applies to the open-chain form of aldoses.

Prentice Hall © 2007Chapter Twenty Two359 In basic solution, ketoses are also reducing sugars. A ketone that has an H atom on the C adjacent to the carbonyl C undergoes a rearrangement. This H moves over to the carbonyl O. The product is an enediol, “ene” for the double bond and “diol” for the two hydroxyl groups. The enediol rearranges to give an aldose, which is susceptible to oxidation.

Prentice Hall © 2007Chapter Twenty Two360 Hemiacetals react with alcohols with the loss of water to yield acetals, compounds with two -OR groups bonded to the same carbon. Glucose and other monosaccharides are cyclic hemiacetals, they react with alcohols to form acetals, which are called glycosides.

Prentice Hall © 2007Chapter Twenty Two361 Glycoside: A cyclic acetal formed by reaction of a monosaccharide with an alcohol, accompanied by loss of H 2 O. Glycosidic bond: Bond between the anomeric carbon atom of a monosaccharide and an –OR group.

Prentice Hall © 2007Chapter Twenty Two362 Glycosides that do not contain hemiacetal groups that establish equilibria with open- chain forms are not reducing sugars. A disaccharide forms by reaction of the anomeric carbon of one monosaccharide with an –OH group of a second monosaccharide.

Prentice Hall © 2007Chapter Twenty Two363 The –OH groups of sugars can add phosphate groups to form phosphate esters. Phosphate esters of monosaccharides appear as reactants and products throughout the metabolism of carbohydrates. ATP phosphorylates glucose to start glycolysis.

Prentice Hall © 2007Chapter Twenty Two364 22.7 Disaccharides Maltose, often called malt sugar, is present in fermenting grains and can be prepared by enzyme-catalyzed degradation of starch. It is used in prepared foods as a sweetener. In the body, it is produced during starch digestion by  -amylase in the small intestine and then hydrolyzed to glucose by a second enzyme. Two  -D-glucose molecules are joined in maltose by an  -1,4 link, a glycosidic link between the hemiacetal hydroxyl group at C1 of one sugar and the hydroxyl group at C4 of another sugar.

Prentice Hall © 2007Chapter Twenty Two365 The acetal ring on the left does not open and close spontaneously and cannot react with an oxidizing agent. The hemiacetal group on the right equilibrates with the aldehyde, making maltose a reducing sugar.

Prentice Hall © 2007Chapter Twenty Two366 Lactose (milk sugar) is a disaccharide composed of  -D-galactose and  -D-glucose. The two monosaccharides are connected by a  -1,4 link. Lactose is a reducing sugar because the glucose ring on the right is a hemiacetal at C1.

Prentice Hall © 2007Chapter Twenty Two367 Hydrolysis of sucrose yields one molecule of D-glucose and one molecule of D-fructose. The 50:50 mixture of glucose and fructose that results, often referred to as invert sugar, is commonly used as a food additive because it is sweeter than sucrose. ► Sucrose has no hemiacetal group because a 1,2 link joins both anomeric carbon atoms. The absence of a hemiacetal group means that sucrose is not a reducing sugar.

Prentice Hall © 2007Chapter Twenty Two368 22.9 Some Important Polysaccharides Polysaccharides are polymers of tens, hundreds, or even many thousands of monosaccharides linked together through glycosidic bonds. Three of the most important polysaccharides are cellulose, starch, and glycogen.

Prentice Hall © 2007Chapter Twenty Two369 Cellulose is the fibrous substance that provides structure in plants. Each huge cellulose molecule consists entirely of several thousand  -D-glucose units joined in a long straight chain by  -1,4 links. The H bonds within chains and between chains contribute to the toughness of cellulose fibers.

Prentice Hall © 2007Chapter Twenty Two370 Starch, like cellulose, is a polymer of glucose. In starch, individual glucose units are joined by  -1,4 links rather than by the  -1,4 links of cellulose. Starch is present only in plant material; our major sources are beans, wheat, rice, and potatoes.

Prentice Hall © 2007Chapter Twenty Two371 Starch is fully digestible and is an essential part of the human diet. Only termites, moths, cows, and other grazing animals are able to digest cellulose. Microorganisms in their digestive tracts produce enzymes that hydrolyze its  glycosidic bonds. ► Amylose accounts for about 20% of starch and consists of up to 1000  -D-glucose units connected by  -1,4 links. Instead of lying side by side and flat as in cellulose, amylose tends to coil into helices.

Prentice Hall © 2007Chapter Twenty Two372 Amylopectin, which accounts for about 80% of starch, is similar to amylose but has much larger molecules (up to 100,000 glucose units per molecule) and has  -1,6 branches approximately every 25 units along its chain.

Prentice Hall © 2007Chapter Twenty Two373 Glycogen (animal starch) is similar to amylopectin in being a long polymer of  -D- glucose with the same type of branch points in its chain. Glycogen has many more branches than amylopectin and is larger, with up to 1 million glucose units per molecule.

Prentice Hall © 2007Chapter Twenty Two374 Chapter Summary Monosaccharides are compounds with 3-7 C’s, an aldehyde group on C-1 (an aldose) or a ketone group on C-2 (a ketose), and -OH groups on all other C’s. Disaccharides consist of two monosaccharides; polysaccharides are polymers composed of up to thousands of monosaccharides. Monosaccharides can contain several chiral C atoms, each bonded to –H, –OH, and 2 other C atoms in the chain. A monosaccharide with n chiral C atoms may have 2 n stereoisomers and half that number of pairs of enantiomers.

Prentice Hall © 2007Chapter Twenty Two375 Chapter Summary Cont. Fischer projections represent the open-chain structures of monosaccharides. Enantiomers can have the -OH on the chiral C farthest from the carbonyl group on the right ( D isomer) or the left ( L isomer). Open-chain monosaccharides equilibrate with cyclic hemiacetals. The hemiacetal C is referred to as the anomeric C, and is chiral. Two anomers are possible because the –OH on the anomeric C may lie above or below the plane of the ring. Ketoses, as well as aldoses, are reducing sugars because the ketose is in equilibrium with an aldose form (via an enediol) that can be oxidized.

Prentice Hall © 2007Chapter Twenty Two376 Chapter Summary Cont. Reaction of a hemiacetal with an alcohol produces an acetal and converts the –OH group on the anomeric carbon to an –OR group. The bond to the group, known as a glycosidic bond, is  or  to the ring as was the –OH group. Disaccharides result from glycosidic bond formation between two monosaccharides. In maltose, 2 D-glucose molecules are joined by an  -1,4 link. In lactose, D-galactose and D- glucose are joined by a  -1,4 link. In sucrose, D-fructose and D-glucose are joined by a glycosidic bond between the two anomeric carbons, a 1,2 link. Sucrose is not a reducing sugar because it has no hemiacetal that can establish equilibrium with an aldehyde.

Prentice Hall © 2007Chapter Twenty Two377 Chapter Summary Cont. Cellulose is a straight-chain polymer of  -D- glucose with  -1,4 links. Starch is a polymer of  -D-glucose connected by  -1,4 links in straight-chain (amylose) and branched (amylopectin) forms. Glycogen is similar to amylopectin, but is more highly branched.

379 Glycolysis: Chapter 23 Bruce A. Hathaway, CH234, Organic and Biological Chemistry Southeast Missouri State University

381 Overview of Glucose Metabolism

382 Glucose Metabolism - Step 1: Making Glucose-6-Phosphate

383 Glucose Metabolism - Step 2: Isomerization of Glucose-6-P to Fructose-6-P

384 Glucose Metabolism - Step 3: Preparation of Fructose-1,6-bisphosphate

385 Glucose Metabolism - Step 4: Fragmentation of Fructose-1,6-bisphosphate (the Reverse of the Aldol Reaction)

386 Glucose Metabolism - Step 4: Fragmentation of Fructose-1,6-bisphosphate (the Reverse of the Aldol Reaction) This step breaks down a 6-carbon compound into two 3-carbon compounds. We have used up 2 ATP’s so far. Every time we make an ATP from now on, we really make TWO, since we have TWO 3- carbon compounds.

387 Glucose Metabolism - Step 5: Isomerization of Dihydroxyacetone-P to Glyceraldehyde-3-P Dihydroxyacetone phosphate Glyceraldehyde-3-phosphate

388 Glucose Metabolism - Step 6: Oxidative Phosphorylation of Glyceraldehyde-3-P Glyceraldehyde-3-phosphate 1,3-bisphosphoglycerate

389 Glucose Metabolism - Step 7: Hydrolysis of 1,3-Bisphosphoglycerate to Form ATP

390 Glucose Metabolism - Step 8: Isomerization of Glyceraldehyde-3-Phosphate

391 Glucose Metabolism - Step 9: Loss of Water from Glyceraldehyde-3-Phosphate

392 Glucose Metabolism - Step 10: Hydrolysis of Phosphoenolpyruvate to Form ATP

393 Overall Reactions Steps 1-4: Glucose + 2 ATP → 2 Glyceraldehyde-3- phosphate + 2 ADP Steps 5-10: 2-Glyceraldehyde-3-phosphate + 2 phosphate + 2 NAD + + 4 ADP → 2 NADH + 2 pyruvate + 4 ATP + 2H + Net reaction: Glucose + 2 ADP + 2 NAD + + 2 phosphate → 2 pyruvate + 2 NADH + 2 ATP + 2 H +

394 The Fate of Pyruvate Under Aerobic Conditions Pyruvate is converted to acetyl CoA + CO 2. NADH is formed, since C-2 of pyruvate is oxidized.

395 Energy Output From Complete Aerobic Catabolism of Glucose Glycolysis: Glucose + 2 ADP + 2 NAD + + 2 phosphate → 2 pyruvate + 2 NADH + 2 ATP + 2 H + Pyruvate Oxidation: 2 pyruvate + 2 NAD + + 2 CoASH → 2 Acetyl CoA + 2 NADH + 2 H + Citric Acid Cycle: 2 Acetyl CoA + 6 NAD + + 2 FAD + 2 ADP + 2 Phosphate + 2 HOH  2 CoASH + 6 NADH + 6 H + + 2 FADH 2 + 2 ATP + 2 CO 2

396 Energy Output From Complete Aerobic Catabolism of Glucose Glucose + 10 NAD + + 2 FAD + 2 H 2 O + 4 ADP + 4 phosphate → 6 CO 2 + 10 NADH + 10 H + + 2 FADH 2 + 4 ATP. Potentially, in the ETC, each NADH produces 2.5 ATP’s, and each FADH 2 produces 1.5 ATP’s. So the 10 NADH’s produce 25 ATP’s and the 2 FADH 2 ’s produce 3 ATP’s.

397 ATP Production From Complete Aerobic Catabolism of Glucose One Glucose can potentially produce 32 ATP’s.

398 Reduction of Pyruvate to Lactate Under Anaerobic Conditions Pyruvate is reduced to Lactate. NADH is oxidized to NAD +, so that Glycolysis and the Electron Transport Chain can continue to make ATP.

399 Energy Output From Complete Anaerobic Catabolism of Glucose Glucose + 2 ADP + 2 phosphate → 2 ATP + 2 lactate + 2 H 2 O. Much less energy is formed from glucose under anaerobic conditions, but at least this allows glycolysis to continue.

400 Lipids Chapter 24:1-7, 9 Bruce A. Hathaway CH234, Organic and Biological Chemistry Southeast Missouri State University

401 Structure and Classification of Lipids Lipids are naturally occurring molecules from plants or animals that generally are soluble in nonpolar organic solvents. A lipid molecule contains a large hydrocarbon portion and a smaller polar functional group portion, which accounts for its solubility behavior.

402 Classification of Lipids Lipids that are esters or amides of fatty acids: Waxes – are carboxylic acid esters where both carbon groups are long hydrocarbon chains. They perform external protective functions. Triacylglycerols – are carboxylic acid triesters of glycerol. They are a major source of biochemical energy.

403 Glycerophopholipids - triesters of glycerol that contain charged phosphate diesters. They help to control the flow of molecules into and out of cells. Sphingomyelins – amides derived from sphingosine, an amino alcohol, which also contain charged phosphate diester groups. They are essential to the structure of cell membranes. Glycolipids – amides derived from sphingosine, which also contain polar carbohydrate groups. On the cell surface, they function as receptors and interact with intracellular messengers.

404 Lipids That Are Not Esters or Amides Steroids – They performs various functions, such as hormones, and contribute to the structure of cell membranes. Eicosanoids – They are carboxylic acids that are a special type of intracellular chemical messengers.

405 Properties of Fats and Oils Oils: A mixture of triacylglycerols that is liquid, because it contains a high proportion of unsaturated fatty acids. Fats: A mixture of triacylglycerols that is solid, because it contains a high proportion of saturated fatty acids.

406 Approximate Composition of Some Fats and Oils Saturated Fatty Acids (%)Unsaturated Fatty Acids (%) SourceC 12 Lauric C 14 Myristic C 16 Palmitic C 18 Stearic C 18 Oleic C 18 Linoleic Lard-12515506 Butter2112910275 Corn Oil -1844642 Olive Oil -155837 The %’s don’t add up to 100%, due to other fatty acids present.

407 An “Omega-3” fatty acid!

Fatty Acids to Know Palmitic Acid C 16 Stearic Acid C 18 Oleic Acid C 18 -Δ 9 Linoleic Acid C 18 -Δ 9,12 408

409 Chemical Reactions of Triacylglycerols Hydrogenation: The carbon-carbon double bonds in unsaturated fatty acids can be hydrogenated by reacting with hydrogen to produce saturated fatty acids.

410 Hydrogenation of an Oil

411 Hydrolysis of Triacylglycerols: Triacylglycerols, like any other esters, react with water to form their carboxylic acid and alcohol – a process known as hydrolysis. In the body, this hydrolysis is catalyzed by the enzyme hydrolase, and is the first step in the digestion of dietary fats and oils.

412 Hydrolysis of an Oil

413 Saponification: Production of Soap In the laboratory and commercial production of soap, hydrolysis of fats and oils is usually carried out by strong aqueous bases, such as NaOH and KOH, and is called saponification. This produces the salts of the carboxylic acids, which are soap.

414 Saponification of an Oil

415 Cell Membrane Lipids: Phospholipids and Glycolipids Cell membranes establish a hydrophobic barrier between the watery environment in the cell and outside the cell. Lipids are ideal for this function. The three major kinds of cell membrane lipids in animals are phospholipids, glycolipids, and cholesterol.

416 Fig 24.4 Membrane lipids

417 Phospholipids contain an ester link between a phosphoric acid and an alcohol. The alcohol is either a glycerol, to give a glycerophopholipid, or a sphingosine, to give sphingomyelins. Glycolipids: Glycolipids are derived from sphingosine. They differ from sphingomyelins by having a carbohydrate group at C-1, instead of a phosphate bonded to a choline.

418 Cell Membrane Lipids: Cholesterol Animal cell membranes contain significant amount of cholesterol.

419 Cholesterol Cholesterol is a steroid, a member of the class of lipids that all contain the same four ring system. Cholesterol serves two important purposes: as a component of cell membranes and as a starting materials for the synthesis of all other steroids.

420 Structure of Cell Membranes The basic structural unit of cell membrane is lipid bilayer which is composed of two parallel sheets of membrane lipid molecules arranged tail to tail. Bilayers are highly ordered and stable, but still flexible.

421 Fig 24.7 The Cell Membrane

422 Liposomes When phospholipids are shaken vigorously with water, they spontaneously form a liposome – small spherical vesicle with lipid bilayer surrounding an aqueous center. Water soluble substances can be trapped in the center of the liposome, and lipid-soluble substances can be incorporated into the bilayer. Liposomes are being used to carry drugs to areas of the body the drugs can’t get to.

423 Eicosanoids: Prostaglandins and Leukotrienes The eicosanoids are a group of compounds derived from 20-carbon unsaturated fatty acids and synthesized throughout the body. Eicosanoids function as short lived chemical messengers that act near their points of synthesis.

424 Leukotrienes The release of leukotrienes has been found to trigger the asthmatic response, severe allergic reactions, and inflammation.

425 Prostaglandins Prostaglandins have a five-membered ring that leukotrienes lack. Prostaglandin E 2 is shown below.

426 Prostaglandins: Biological Effects Prostaglandins have a wide range of biological effects. They can lower blood pressure, influence platelet aggregation during blood clotting, stimulate uterine contractions, and lower the extent of gastric secretions. They are also responsible for some of the pain and swelling involved in inflammation. Aspirin relieves inflammation by inhibiting the synthesis of prostaglandins.

Chapter 25: Fatty Acid Biosynthesis CH234 Bruce A. Hathaway 427

Acetyl Coenzyme A Acetyl Coenzyme A is the starting material for fatty acid biosynthesis. It is derived from metabolism of carbohydrates, fats and some amino acids. The two-carbon piece provides the carbons for the new fatty acid. Acetyl Coenzyme A 428

429 Acetyl Coenzyme A (AcCoA)

Overview of Metabolism And Energy Production 430

Step 1: Preparation of Malonyl CoA Acetyl CoA reacts with bicarbonate to form Malonyl CoA. This is energy-requiring, so hydrolysis of an ATP is used to drive the reaction. Malonyl CoA is more reactive than Acetyl CoA. 431

Step 2: Transthioesterifaction Both Acetyl CoA and Malonyl CoA are connected to Acetyl Carrier Protein (ACP), which is another thiol. One thiol replaces another to make a different thioester. ACP shuttles the molecules to the different enzymes needed to do the following reactions. 432

Step 3: C-C Bond Formation Malonyl ACP loses CO 2 to make a carbon anion. An acetyl ACP reacts with the carbon anion to give a four-carbon β-ketoester. 433

Step 4: Reduction of the Ketone The ketone is reduced to an alcohol. Only one stereoisomer is produced: why? NADPH functions similar to NaBH 4 in this reaction. 434

NADPH NADPH is similar to NADH. It has an extra phosphate, while NADH has an H. Metabolism uses NADH. Biosynthesis uses NADPH. 435

Reduction of the Ketone with NADPH NADPH donates a hydride H - to reduce the ketone: the H + comes from water, ultimately. Only one enantiomer is formed. 436

Step 5: Dehydration of the Alcohol The alcohol is specifically dehydrated to the trans alkene. Again, only one isomer is formed. 437

Step 6: Reduction of the Alkene NADPH + H + reduces the C=C to an alkane. We have now made a four-carbon “fatty acid”. 438

Elongation of Fatty Acids The Butyroyl-ACP replaces the Acetyl-ACP in Step 3, to make a 6-carbon ketoacid. 439

Elongation of Fatty Acids The 6-carbon keto-acid is reduced, dehydrated, and reduced again (steps 4-6), to make the six-carbon fatty acid. This can react with more malonyl-ACP… 440

Elongation of Fatty Acids The cycle of steps 3-6 is repeated five more times until the 16-carbon fatty acid is made. For some reason, this enzyme complex only makes palmitic acid. Longer fatty acids and unsaturated fatty acids are synthesized in other locations. 441

Energy Requirements To add two carbons to Acetyl CoA, it requires 1 ATP (to make a malonyl CoA) and 2 NADPH’s. Each NADPH is the equivalent to 2.5 ATP’s. Therefore, it takes the equivalent of 6 ATP’s to add two carbons to Acetyl CoA. To make a 12-carbon fatty acid, lauric acid, requires five cycles, or 30 ATP’s. This compares to the 20 ATP’s we get from metabolizing lauric acid to Acetyl CoA. 442

Chapter 25: Fatty Acid Metabolism CH234 Bruce A. Hathaway 443

Introduction The fatty acids in Fats and Oils are broken down to Acetyl Coenzyme A (AcCoA). AcCoA feeds into the Citric Acid Cycle, and the products of that feed into the Electron- Transport System, where ATP is synthesized. We will cover this in Chapter 21. We will use the results from chapter 21 to determine how much energy we obtain from metabolism of fatty acids. 445

446 Acetyl Coenzyme A (AcCoA)

Getting Started The triacylglycerol is hydrolyzed to the fatty acids and glycerol. Glycerol is metabolized in glycolysis, but provides very little energy, compared to the fatty acids 447

Fatty Acid Activation The fatty acids are thioesterified to Coenzyme A, in process that requires ATP to be hydrolyzed to AMP and 2 phosphates. This essentially costs the equivalent of 2 ATPs, since two high-energy phosphoric anhydride bonds are being broken. 448

449 ATP and Energy Transfer ATP + HOH  ADP + Phosphate  G = -7.3 kcal/mole

Transfer to the Mitochondria The fatty acid CoA’s are transferred to the mitochondria. The enzymes needed to break down the fatty acid CoA’s are all in the mitochondria, although they are not an enzyme complex, as in fatty acid biosynthesis. 450

Step 1: Oxidation In a reaction we can’t do well in organic lab, one hydrogen is removed from each of the alpha and beta carbons to form a double bond. FAD (a cofactor) is reduced to FADH 2 in the process. The double bond is trans! 451

452 FAD and FADH 2 FAD FADH 2

Step 2: Addition of Water Water is added to the C=C to form an alcohol. Only one enantiomer is formed. It is the opposite enantiomer to that formed in biosynthesis. 453

Step 3: Oxidation of the Alcohol The Alcohol is oxidized to a Ketone. NAD + accepts an H (-) to become NADH. The other H becomes H +. 454

455 NAD + and NADH NAD + NADH

Step 4: Breaking off Acetyl CoA Coenzyme A reacts with the ketone group to break the C-C bond, and form acetyl CoA, and a new thioester. This is not are reaction we covered, but is similar to a reaction that is covered in the chemistry major’s organic class. 456

Continuing the Cycle The new thioester is two carbons less than the original thioester. The new thioester can undergo the same four reactions (oxidation, addition of water, oxidation of the alcohol, and addition of CoASH) to form a new thioester with two fewer carbons. 457

458 The four steps of the  -oxidation pathway:

Metabolism of Lauric Acid (C 12 ) Activation of the acid costs 2 ATPs (essentially). Each cycle makes an FADH 2, an NADH, and an AcCoA. 459

Metabolism of Lauric Acid (C 12 ) It takes 5 cycles to completely oxidize a 12- carbon acid. We made: 5 FADH 2 ’s, 5 NADH’s, and 6 AcCoA’s. 460

461 Energy from Fatty Acid Oxidation The total energy output from fatty acid catabolism is measured by the total number of ATPs produced. Current best estimates are that 2.5 ATPs result from each NADH and 1.5 ATPs from each FADH 2. The  -oxidation pathway produces 1 NADH and 1 FADH 2 or 4 ATPs per cycle. This compares to 6 ATP’s per cycle of biosynthesis. Each acetyl-SCoA produces 3 NADH, 1 FADH 2 and 1 ATP or 10 ATPs per acetyl-SCoA in the citric acid cycle.

462 Lauric acid, CH 3 (CH 2 ) 10 COOH, has 12 carbons. After initial activation (-2 ATP), five  -oxidations (5x4 ATP = +20 ATP) will change lauric acid into 6 acetyl- SCoA molecules (6x10 ATP = + 60 ATP). The total energy yield is 78 ATP per lauric acid. 1 mole (200g) lauric acid yields 78 moles ATP. 1 mole (180g) glucose yields 30-32 moles ATP. We can get much more energy by metabolizing a fat than from metabolizing a sugar.

Introduction to Organic Chemistry and Alkanes 1. What is Organic Chemistry? The chemistry of Carbon and its compounds. There are over 18 million known.

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Introduction to Organic Chemistry and Alkanes 1. What is Organic Chemistry? The chemistry of Carbon and its compounds. There are over 18 million known.

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Presentation on theme: "Introduction to Organic Chemistry and Alkanes 1. What is Organic Chemistry? The chemistry of Carbon and its compounds. There are over 18 million known."— Presentation transcript:

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