Last week I co-hosted a symposium with Noel O'Boyle and Andrew Lang on "Visual Analysis of Chemical Data" at the American Chemical Society meeting in San Francisco (March 22-23, 2010). The ACS recorded almost every talk in our symposium and I'll provide the link here when available (they tell me mid April).
Liz Dorland kicked off the symposium with a great keynote presentation covering effective visualization in a number of fields and the special challenges faced in chemistry. There were several talks about QSAR and I particularly enjoyed Edmund Chapness who incorporated the visualization of confidence in predictions with an intuitive colored molecule map. Geoff Hutchison gave an informative overview of Avogadro.
Perhaps the biggest revelation was the "iTunes for Cheminformatics" project by NIH researcher Ajit Jadhav (leading the team which includes Rajarshi Guha). The alpha version will be available for testing on April 5, 2010 and many of us are eagerly anticipating being able to give it a spin. From what I understand the system will automatically be able to identify scaffolds (fragments) in a collection of molecules and make it easy to search for and filter assay results.
Carmen Drahl covered in minute by minute detail announcements about new drug candidates on Twitter. Following the FriendFeed feed for the conference flagged a very interesting post about a Cold Fusion Symposium that was being held. In spite of the notorious lack of wireless availability at ACS conferences, attendees seem to be making due with accessing their social networks via their cell phone devices.
Andrew Lang and I spoke about Visualizing Chemistry in Second Life - our slides are here - hopefully I'll be able to post the recordings as well soon.
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Polynucleotides
Biopolymers IV
Polynucleotides
Introduction
Polynucleotides, which are more often called nucleic acids, are polymeric glycosylamines in which the polymer backbone consists of sugars that are linked together by phosphodiester bonds. There are two types of nucleic acids, those in which the polymer backbone is composed of D-ribose units and those in which it is composed of D-2-deoxyribose units. Nucleic acids based on these two sugars are called ribonucleic acids (RNA) and deoxyribonucleic acids (DNA), respectively. Figure 1 identifies the essential structural features of the repeat unit of RNA.
Figure 1
The Repeat Unit of RNA
The D-ribose portion of the structure is shown in red. The blue B represents any of the four heterocyclic bases shown in Figure 2. The phospho diester group that links C3 of one D-ribose unit with C5 of the next is shown in green. The term nucleic acid reflects the fact that phosphoric acid, H3PO4, is a tribasic acid, i.e. it has three acidic OH groups. Two of them are involved in the formation of the phosphodiester bonds that link one sugar to the next. The third is available to act as an acid.
Figure 2
The Heterocyclic Bases in RNA
One of these four heterocyclic bases is attached to the anomeric carbon of each D-ribose unit in the polymer chain. Adenine and guanine are members of a class of heterocyclic bases called purines. Cytosine and uracil belong to the family called pyrimidines.
Exercise 1 Draw the structure of the two dinucleotides that contain adenine and cytosine.
In DNA, the sugar is D-2-deoxyribose. Instead of having uracil as one of the four heterocyclic bases attached to each anomeric carbon of the sugar, DNA has thymine. Figure 3 presents the structure of D-2-deoxyribose and thymine for comparison to Figures 1 and 2.
Figure 3
The Structures of D-2-Deoxyribose and Thymine
Keto-Enol Tautomerization
Each of the 5 heterocyclic bases mentioned above contains an aromatic system of pi electrons, although it is not obvious in guanine, cytosine, uracil, and thymine because these bases exist as keto tautomers. Figure 4 shows the two tautomeric forms of thymine.
Figure 4
Tautomerization in Heterocyclic Bases
The aromatic six pi electron system is more obvious in the enol tautomer of thymine.
Exercise 2 Using water as both an acid and a base, write equations to show how the protons are transferred from the nitrogens to the oxygen atoms in thymine.
Exercise 3 Ultraviolet radiation is known to damage DNA. One UV-induced reaction that has been implicated in such damage involves a 2+2 cycloaddition of a thymine molecule on one sugar with a second thymine on an adjacent sugar. The formation of this "cyclobutylthymine dimer" is thought to cause a local distortion of the shape of the DNA, thereby altering its activity. Draw the structure of the dimer that is formed by the 2+2 cycloaddition of the keto forms of two thymine molecules.
The Primary Structure of Nucleic Acids
The primary structure of nucleic acids describes the sequence of heterocyclic bases attached to the anomeric carbon of each sugar in the polymer backbone. A compact description of the primary sequence is afforded by using the 1-letter abbreviation of each of the heterocyclic bases. For example, AAGCUC describes an oligoribonucleotide in which the heterocylcic bases are adenine, adenine, guanine, cytosine, uracil, and cytosine. Figure 5 shows the structure of the compound.
Figure 5
The Structure of AAGCUC
The 6 letter string is read from the 5' end towards the 3' end of the chain. Note that since uracil occurs in RNA and thymine in DNA, the sequence AAUCGC identifies this nucleic acid chain as a ribonucleic acid.
The Secondary Structure of Nucleic Acids
It is hard to imagine anyone who hasn't heard of the a-helix of DNA. This is the dominant secondary structure of this polynucleotide. But the a-helix of DNA is, in fact, a double helix, i.e. one strand of DNA is wrapped around another. In proteins the association of two polypeptide chains is considered an aspect of quaternary structure, but in nucleic acids, the intertwining of two a-helices is regarded as part of the polymer's secondary structure.
Hydrogen Bonding: Inter-Chain Association
The elucidation of the structure of DNA required the efforts of many people and the interpretation of huge amounts of data. A key part of that data was the observation that the ratio of certain pairs of heterocyclic bases was nearly 1/1 regardless of the source of the DNA. For example, the A/T ratio in DNA obtained from wheat germ was 1.01/1, while that from human liver tissue was 1.00/1. The G/C ratio in DNA from these two species was 1.00/1 and 0.98/1, respectively. These ratios suggested a 1/1 correspondence between adenine bases on one chain of the double helix and thymine bases on the other. Similarly, it seemed reasonable to assume that each cytosine on one chain was associated with a guanine on the other. The "association" assumed was hydrogen bonding. Figure 6 shows idealized representations of the inter-chain H-bonding between A and T and G and C bases.
Figure 6
H-Bonding Between Heterocyclic Bases in DNA
Note that in both cases a purine base is associated with a pyrimidine base. Note, too, that the A/T base pair involves two H-bonding interactions, while the G/C pairing entails three.
If you would like to explore the structures of some DNA molecules, go to Molecules to Explore at USM's Biochemistry web site. There you will find four interactive structures of DNA molecules. For the brave of heart there is also a RasMol tutorial if you are interested in learning how to view all of the structural features of a protein or DNA molecule.
Polypeptides
Biopolymers III
Polypeptides
Introduction
One of the most common reactions of carboxylic acids and related compounds is nucleophilic acyl substitution. Figure 1 depicts this transformation in general terms.
Figure 1
Nucleophilic Acyl Substitution
When Y represents the nitrogen atom of an amine, the transformation converts a carboxylic acid or a derivative of a carboxylic acid into an amide. Equation 1 provides a simple example.
As we have seen, extension of reaction 1 to a bifunctional acid chloride and a bifunctional amine may be used to prepare polyamides such as nylon:
An alternative method of making polyamides is available when an acyl and an amino group are part of the same molecule:
The latter approach is the one involved in the formation of polyamides known as polypeptides or proteins. This topic looks briefly at the chemistry of these biopolymers. Before we consider that chemistry, you should familiarize yourself with the chemistry of the bifunctional molecules from which these polymers are made, amino acids.
Peptides
Peptides are amides formed by the reaction of the a-amino group of one amino acid with the carboxylate group of another amino acid. Peptides which contain two amino acids are called dipeptides. Figure 2 shows the structure of a dipeptide formed from glycine and alanine.
Figure 2
Glycylalanine
Peptides made from three amino acids are called tripeptides, etc. Peptides containing from 2-10 amino acids are arbitrarily called oligopeptides. Compounds containing more amino acids are called polypeptides or proteins.
In order to simplify the representation of peptides, chemists assigned a 3-letter code to each amino acid. By this convention the dipeptide in Figure 6 would be Gly-Ala; the N-terminal amino acid is written first. Bradykinin, a nonapeptide which is involved in regulating blood pressure, has the structure Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg.
Peptide Structure
Peptides are structurally complex. However, two aspects of peptide structure make it easier to understand this complexity.
- The H-N-C=O fragment of each peptide unit is planar.
- The stereochemistry at each chiral a-carbon is the same, i.e. the R group always projects in the same direction.
Exercise 1 According to VSEPR theory, the geometry around the nitrogen atom of an amide should be approximately
trigonal planar pyramidal which means that the hybridization of the nitrogen atom should be approximately
sp2 sp3
Exercise 2 Resonance theory rationalizes the planarity of the amide group by suggesting that the lone pair of electrons on the nitrogen atom interacts with the pi system of the carbonyl group. Use curved arrows to depict this interaction. Draw the structure of the resonance contributor that is produced when the lone pair is fully delocalized onto the oxygen atom of the carbonyl group. Indicate all formal charges. What is it about this resonance contributor that is consistent with a planar fragment?
The structural features of proteins have been broken down into 4 categories, primary, secondary, tertiary, and quaternary structure.
Primary Structure
This is simple. The primary structure of a peptide is the sequence in which the amino acids are connected, starting with the N-terminal amino acid. In the case of bradykinin mentioned above, the primary structure is Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg. A Lewis structure of bradykinin is shown in Figure 3. Bradykinin is a nonapeptide. The 8 peptide bonds that connect the 9 amino acids are shown in red in Figure 3.
Figure 3
Bradykinin: A Nonapeptide
The presence of the substituents attached to the a-carbon can obscure the primary structure of even a simple peptide like bradykinin. Figure 4 shows the "backbone" of a nonapeptide stripped of its Ca substituents.
Figure 4
A Peptide Backbone
There are several features about this representation that are noteworthy. First, it represents an idealized conformation in which all the "backbone" atoms lie in the same plane. (The substituents attached to each a-carbon project in front of and behind that plane.) Second, if you "read" the structure from left-to-right, the carbonyl group of the each amide unit points in the opposite direction of the N-H bond of that unit. This is called the "all-trans" conformation. It's a fantasy. Doesn't happen. Third, since the bond between the carbonyl carbon and the nitrogen atom of each amide unit has significant double bond character, rotation about that bond is restricted. However, "free" rotation about the N-Ca bond as well as the C-Ca bond of the O=C-Ca group is possible.
Rotation around single bonds in alkanes is described in terms of a dihedral angle. In the case of peptides, this parameter is called the torsional angle. There are two torsional angles of interest in peptides. The first, designated F, defines the angle of rotation about the N-Ca bond, while the second, which is labeled Y, is the angle of rotation about the C-Ca bond. Figure 5 defines these angles for an "all-trans" segment of polypeptide.
Figure 5
Torsional Angles
Note that F and Y are the rotational angles around the two main-chain bonds to Ca. Rotation around these bonds gives rise to the secondary structure of proteins.
Secondary Structure
The primary structure of a peptide doesn't convey any information about the 3-dimensional shape of the peptide. The secondary structure does. In talking about secondary structure, we are actually referring to the topology of regions within the peptide. Such localized structure is a reflection of the conformations about a sequence of peptide bonds. These conformations are determined in large part by the nature of the R groups attached to the a carbon. Biochemists have identified three common topologies, helices, pleated sheets, and turns. Figure 7 presents an interactive model of Gly-Gly-Gly-Gly-Gly-Gly-Gly-Gly-Gly which clearly indicates the helical nature of this synthetic nonapeptide.
Tertiary Structure
The tertiary structure of a polypeptide describes the way in which the chain loops and twists and bends. While the primary structure usually depicts the backbone of a polypeptide as an extended chain in which the N-terminal amino acid is far away from the C-terminus, the fact is that the chain is not extended, and it is possible for the 5th amino acid to be spatially quite close to the 45th or the 450th, for example. Figure 6 shows the structure of one polypeptide chain from human insulin. This chain contains 51 amino acids.
Figure 6
Tertiary Strucutre in a Simple Protein
Quaternary Structure
One of the roles that proteins play is that of reaction catalyst. In this role proteins are more commonly referred to as enzymes. Most enzymes are comprised of two or more polypeptide chains that are held together by non-covalent forces. The individual polypeptide chains are called sub-units. Hemoglobin, for example, contains four sub-units, each of which is organized around a central iron atom. Human insulin is a hexamer, i.e. it contains 6 sub-units. (Note-When you click on the Human insulin link, you will open a file. Before viewing the file enter 1 into the text field that asks you how many models you want to display. Click OK. Click OK on the next window that appears. You should now see a wireframe model of human insulin.) The spatial relationship of one sub-unit to another is called the quaternary structure of a protein.
Protein Function
Proteins serve two main functions, structural and catalytic. Structural proteins are generally fibrous in nature. Hair and smooth muscle are examples of structural proteins. Catalytic proteins generally have a globular quaternary structure that is more or less spherical. The catalytic site is buried in the interior of the structure.
Polysaccharides
Biopolymers II
Polysaccharides
Introduction
By far the most important polysaccharides are polymers of D-glucose. These materials are generally divided into two categories depending upon 1. the nature of the glycosidic bond that connects one monomeric unit to the next 2. whether the "backbone" of the polymer is branched or unbranched. In this topic we will focus on the most common polysaccharides, cellulose and starch. We will also look briefly at an interesting class of polysaccharides known as cyclodextrins.
Cellulose
Cellulose is a "straight chain" polymer of D-glucose in which the monomeric units are connected together by b-1,4 linkages. This means that the oxygen at C-4 of one D-glucose is connected to C-1 of another D-glucose, and that the C1-OC4 bond, the glycosidic linkage, occupies an equatorial position in the D-glucopyranose ring. This bond is highlighted in red in Figure 1.
Figure 1
A b 1,4 Linkage
Cellulose is not a single compound, but rather a mixture of polymers of D-glucose in which the chain length varies from one molecule to the next. A typical polymer chain may contain 10,000-15,000 D-glucose units. Because each monomer unit contains several OH groups, inter-chain hydrogen bonding is extensive. Figure 2 illustrates the secondary bonding interactions between polymer chains.
Figure 2
Between the Sheets
The figure shows fragments of four polymer chains, one pair of which lie in the roughly same plane, the second pair lying in a parallel plane. The dashed red lines indicate inter-chain H bonds for those molecules that lie in the same plane. The dashed blue lines suggest inter-chain H bonds between chains in different planes.
Starch
Starch is a mixed polysaccharide consisting of two main components, a-amylose and amylopectin. The primary difference between cellulose and a-amylose is the nature of the glycosidic linkage. In cellulose it is a b-1,4 linkage, while in a-amylose the D-glucose units are joined together by a-1,4 linkages. While this is a seemingly small difference, it has a major impact on the shapes and functions of these two polymers. Unlike cellulose, the polymer strands of a-amylose do not assemble in planar sheets. Rather, as Figure 3 suggests, they adopt a helical structure similar to that found in nucleic acids. Typical chain lengths for a-amylose are approximately 1000 monomer units.
Figure 3
Around the Bend
The second component of starch is amylopectin. Like a-amylose, the D-glucose units in amylopectin are connected by a-1,4 linkages. The major difference between a-amylose and amylopectin is that amylopectin is a branched polymer; at irregular intervals there are branch points where a secondary polysaccharide chain is connected to the main chain by a-1,6 linkages. In amylopectin the branches occur, on average, every 24-30 D-glucose units along the main chain. Starch is the form in which plants store excess D-glucose. In animals it is stored as glycogen, which is similar in structure to amylopectin, except that it is more highly branched. Typically there is an a-1,6 linkage to a side chain every 8-12 D-glucose units along the main chain. Figure 4 offers a generic structure for amylopectin and glycogen. Two side chains are shown in color.
Figure 4
Energy Storage in Plants and Animals
The highest concentrations of glycogen are found in muscle and liver cells.
Exercise 1 Classify the glycosidic linkage highlighted in red an blue in the following polysaccharide fragment:
The bond highlighted in red isa-1,2 b-1,2 a-1,3 b-1,3 a-1,4 b-1,4 a-1,6 b-1,6
The bond highlighted in blue isa-1,2 b-1,2 a-1,3 b-1,3 a-1,4 b-1,4 a-1,6 b-1,6
Cyclodextrins
Linking D-gluocse units together with a-1,4 linkages means that the growth of the polysaccharide follows a helical path. Occassionally, this coiling brings the D-glucose at the end of the growing polymer chain close enough to the one at the beginning that a glycosidic bond can form between them, thereby creating a cyclic polysaccharide. These structures are known as cyclodextrins. Figure 5 presents the structure of one such compound which contains a ring comprised of eight D-glucose units. This compound is known as g-cyclodextrin.
Figure 5
A Cyclodextrin Molecule
Cyclodextrins are natural products formed by the action of enzymes called cycloglucosyltransferases, CGTases, on starch. These enzymes are found in a microorganism called Bacillus macerans. Cyclodextrins participate in host-guest interactions, serving as hosts for a variety of small molecules. The number of monomer units in the macrocyclic ring determines the size of the cavity the host makes available to the guest. The ability of cyclodextrins to "encapsulate" small molecules has led to the development of a number of interesting applications. They have been used to
- enhance the chromatographic separation of chiral drugs
- protect the active ingredients in perfumes
- increase the solubility of antineoplastic drugs for use in chemotherapy
- separate cholesterol from dairy products
In Figure 5 you are looking down on the cavity from above. Figure 6 presents a perspective drawing of the 3-dimensional structure of g-cyclodextrin. Note that the polar OH groups project to the exterior of the structure while the hydrogens attached to the glucose units point into the cavity. Thus the interior is comparatively non-polar. These structural features make the polymer water soluble while still able to transport non-polar materials such as cholesterol.
Figure 6
A Perspective on Cyclodextrins
Condensation Polymers
Polymers and Plastics II
Introduction
One of the characteristic reactions of carboxylic acids is esterification, a process that involves the condensation of a carboxylic acid with an alcohol. This transformation is depicted in general terms in Equation 1. The word condensation refers to the fact that the formation of the ester is accompanied by the formation of a molecule of water. In order to drive equilibrium 1 to the right the water is distilled and the vapors are condensed in a receiving flask. A more general definition of a condensation reaction is one in which the formation of the desired product is accompanied by the formation of another small molecule such as H2O, HCl, or NH3.
Reaction 1proceeds by a mechanism known as nucleophilic acyl substitution. As Equation 2 indicates, the process may be extended to the formation of polymers by the simple expedient of reacting a dicarboxylic acid with a diol.
Polymers that are formed by this pathway are commonly referred to as condensation polymers. In this topic we will examine the formation of two main classes of condensation polymers, polyesters, and polyamides.
Condensation Polymers
Polyesters
One of the most ubiquitous polymers in our society today is poly(ethylene terephthalate), PET. It is used to make fibers for clothing as well as containers for carbonated beverages. When used to make clothing it's known as dacron. Figure 1 shows the repeat unit of this material.
Figure 1
Anyone Care for a Soda?
Exercise 1 Draw the structures of the dicarboxylic acid and the diol from which PET is made.
Carboxylic acids are easily converted into acyl chlorides as shown in Equation 2.
Since acyl chlorides undergo facile nucleophilic acyl substitution reactions, many polyesters are prepared by treatment of a diacyl chloride with a diol. Figure 2 shows the repeat unit of the polycarbonate ester Lexan™ which is formed by the reaction of the diacid chloride of carbonic acid (H2CO3) and a diphenol.
Figure 2
Let's Repeat
Exercise 2 Draw a valid Lewis structure for carbonic acid.
Exercise 3 Draw the structures of the diacid chloride and the diphenol from which Lexan™ is made.
Exercise 4 The diphenol referred to above is prepared by the acid-catalysed reaction of phenol with acetone. What type of reaction is this? Write an equation for it.
Polyurethanes
Isocyanates, R-N=C=O, react with alcohols to form compounds known as urethanes. Equation 3 describes the reaction in general terms.
While this process is not technically a nucleophilic acyl substitution reaction, it is treated as such because isocyanates are derivatives of carbonic acid.
Exercise 5 Using curved arrows to depict the movement of electrons, show how reaction 3 occurs.
If water is used instead of an alcohol, the product, a carbamic acid, spontaneously decomposes into an amine and carbon dioxide as shown in Equation 4.
Extension of the chemistry described in Equation 3 to a diisocyanate and a diol provides a route to polyurethanes as shown in Equation 5.
If a small amount of water is added to the diisocyanate/diol mix, some of the diisocyanate undergoes a reaction analogous to that shown in Equation 4 and the CO2 that is liberated becomes entrapped in the polymer. This is the basis of polyurethane foams that are use as insulating materials.
Spandex™, a stretchable fabric made by DuPont, is an interesting example of a "mixed" polyurethane. As outlined in Figure 3, it is prepared in a 2-stage process, the first stage involving the condensation of two moles of methylene diisocyanate with one mole of poly(butylene oxide). This forms an intermediate known as a prepolymer. Treatment of this material with ethylenediamine yields the final product.
Figure 3
Exercise 6 Draw the structure of the product of the following reaction: 
Polyamides
In the same way that they react with diols to produce polyesters, diacyl chlorides condense with diamines form polyamides. Commercially these compounds are more commonly called nylon. Equation 6 describes the process in general terms, while Figure 3 shows the repeat units of two common forms of nylon.
Figure 3
Commercially Important Nylons
Nylon 6,6 is used to make fibers that are used to make carpets and fabrics. Kevlar is also spun into fibers which are woven into fabrics that are used in bullet-proof vests, as well as the cloth that is used to make high-end canoes, kayaks, and sailboats. It is also found in fishing poles and tennis racquets.
Natural fibers such as hair, silk, and wool are polyamides, too. We will discuss these materials more in the topic Biopolymers.
Biopolymers I
Biopolymers I
Introduction
Many of the most important and most interesting naturally occuring molecules are polymeric. In general these biopolymers belong to one of five classes of materials:
- polyisoprenoids
- polyphenols
- polysaccharides
- polypeptides
- polynucleotides
In this topic we will consider just the first two classes.
Polyisoprenoids
Natural rubber, is a polymeric form of isoprene, 2-methyl-1,3-butadiene. Figure 1 presents the structure of a tetrameric fragment of polyisoprene.
Figure 1
Natural Rubber
The red lines connecting the 4th carbon atom of one isoprene unit with the 1st carbon of the next indicate that latex is an addition polymer that results from the 1,4-addition of one isoprene unit to the next. Note the head-to-tail pattern in which the isoprene units are connected. Note, too, that the stereochemistry is the same at each double bond, namely cis.
The regularity that is evident in the structure of polyisoprene is characteristic of terpenes as well. Terpenes are oligomers of isoprene, typically containing 2, 4, or 6 isoprene units. Whether oligomeric or polymeric, these compounds all arise from a common biosynthetic path.
Exercise 1 Assume that you polymerized a sample of isoprene by treating it with a catalytic amount of sulfuric acid. Use curved arrows to indicate how the polymer fragment shown in Figure 1 would be formed. Draw the structures of the intermediate carbocations and show the resonance interaction between each cation and the double bond that is conjugated to it.
Unnatural Polyisoprenoids
Synthetic Rubber
In 1839 Charles Goodyear discovered, literally by accident, that heating natural rubber with elemental sulfur altered the properties of the polymer, most notably making it tougher and more elastic. Goodyear's discovery led to the development of synthetic rubber, a material that found its most profitable application in the manufacture of automobile tires. Investigation of the structure of synthetic rubber revealed that the sulfur had formed disulfide bonds that linked one polyisoprene chain to the next. As Figure 2 demonstrates, these cross-links serve to restore the polymer to its original shape after it has been deformed by the application of a force.
Figure 2
Bouncing Back
Neoprene
Not surprisingly, the desireable properties of natural as well as synthetic rubber led to investigations of the polymerization of structural analogs of isoprene. One notable success came from the polymerization of 2-chloro-1,3-butadiene, sometimes called chloroprene. Polychloroprene is known commercially as neoprene rubber. It is widely used in the automotive industry for the manufacture of oil-resistant hoses. Neoprene that contains entrapped air has good insulating properties and is used in the production of wet suits.
Exercise 2 Draw a tetrameric fragment of polychlorprene similar to that shown for polyisoprene in Figure 1. Identify the repeat unit.
Polyphenols
Some of the structurally most complex natural polymers are the polyphenols that occur in woody plants. These materials are referred to as lignins. Degradation of lignins has revealed that they are composed of three basic building blocks, p-coumaric acid, ferulic acid, and syringyl alcohol. These structures are shown in Figure 3 along with the structure of gallic acid, the principal phenolic component in tannins.
Figure 3
Lignin Monomers
Figure 4 suggests a possible fragment of a lignin co-polymer based on these three monomers. The point here is simply that lignins are structurally very complex and, therefore, very difficult to characterize completely.
Figure 4
Putting the Pieces Together
Exercise 3 Cellulose is a polysaccharide. As such it contains many alcohol OH groups. While there are many alcohol OH groups in lignins, they also contain phenolic OH groups. The pKa values of alcohols and phenols are 16 and 10, respectively. The paper industry exploits this difference in pKa values to separate cellulose from lignins during the pulping process. Can you explain how?
Unnatural Polyphenols
Bakelite
In the presence of a catalytic quantity of acid, a mixture of phenol, C6H5OH, and formaldehyde, H2C=O, condenses to form a polymeric material known as Bakelite. This was one of the first commercial polymers. It was used for many years in the manufacture of cases for radios and televisions as well as electronic circuit boards. The formation of this co-polymer involves several of the types of reactions we have discussed:
- nucleophilic addition
- nucleophilic aliphatic substitution
- electrophilic aromatic substitution
Figure 5 illustrates how the combination of these reactions leads to the formation of polymeric material.
Figure 5
Shake and Bake(lite)
Exercise 4 Which of the steps labeled in Figure 5 involves nucleophilic addition? 1 2 3 4
Exercise 5 Which of the steps labeled in Figure 5 involves nucleophilic aliphatic substitution? 1 2 3 4
Exercise 6 Which of the steps labeled in Figure 5 involves electrophilic aromatic substitution? 1 2 3 4
Nuclear Magnetic Resonance
Nuclear Magnetic Resonance
INEPT Spectroscopy
Introduction
In our discussion of DEPT spectroscopy we saw how it is possible to alter the populations of specific spin states by irradiating a sample with a radio wave whose energy, i.e. frequency, matches the energy difference between the spin states. In this topic we will consider a related technique called Insensitive Nuclei Enhanced by Polarization Transfer or INEPT. We will begin by presenting several equivalent views of the magnetization of a sample. Then we will look at how the spectrometer is used to manipulate that magnetization and how the magnetization responds to irradiation. Finally, we will see one example of a case in which an INEPT experiment allowed for the differentiation between two structural alternatives.
Magnetization Revisited
In our introduction to NMR spectroscopy we saw that application of a strong magnetic field, Bo, created two spin states of slightly different energies. Those nuclei in the lower energy state, a, have their magnetic moments aligned with Bo, while those in the higher energy state, b, have them aligned against Bo. Furthermore, there is a slight excess of nuclei in the a spin state. In our discussion of DEPT spectroscopy we represented that excess as a population difference, i.e. we set the number of nuclei in the highest energy spin state to zero and then subtracted that number from each of the spin states of lower energy. For the discussion that follows we will focus on the net magnetization, the vector sum of the individual nuclear magnetic moments, which we will represent with an arrow. It is useful to think of the orientation of that arrow in terms of a Cartesian coordinate system. Figure 1 compares these four ways of looking at nuclear magnetization. Note in View 4 that the net magnetization is aligned with the applied field. Also, it is important to understand that while Views 2 and 3 suggest that the b spin state is empty, it is not. There is simply an excess of nuclei in the a spin state.
Figure 1
Four Views of Nuclear Magnetization
To appreciate the fundamental nature of polarization transfer, it is necessary to understand how the net magnetization responds to the application of a second magnetic field, B1. This second magnetic field is generated by an RF coil that is wound around the x-axis, perpendicular to Bo as shown in Figure 2.
Figure 2
Introducing B1
Application of B1 along the x axis tips the net magnetization vector away from the z axis towards the xy plane. The angle of the tip depends upon the length of time that current flows through the coil. This is referred to as the pulse width. By convention, pulse widths are expressed in radians; a pulse width of p/2 tips the magnetization vector by 90 degrees, i.e. from the z axis into the xy plane. A pulse width of p tips the magnetization from the +z to the -z axis. Regardless of the pulse width, once tipped, the magnetization vector precesses around the z axis. Figure 3 animates this motion.
Figure 3
Think Gyroscope
It is important not only to understand that the magnetic moments associated with the nuclei precess around the applied field, but to realize that they precess at different rates. Furthermore, nuclei in the a spin state precess in the opposite direction of those in the b spin state.
Techniques such as DEPT and INEPT involve transferring magnetization from a sensitive nucleus such as hydrogen to a less sensitive nucleus such as carbon. The transfer occurs between nuclei that are spin-spin coupled. Each transfer technique is characterized by a particular pulse sequence. Figure 4 diagrams the INEPT pulse sequence using two alternative conventions. Figure 5 shows the response of the magnetization that pulse sequence induces.
Figure 4
Do You Have a Pulse?
Figure 5
Topsy Turvy
The a and b spin states rotate away from each other at a frequency equal to J/2 Hz. The secret to a successful INEPT experiments lies in setting the delay time, tD, between pulses to appropriate multiples of the value of the coupling constant between the sensitive and insensitive nuclei. For example, after the concurrent 13C and 1H p pulses, a delay time equal to 1/(4J) seconds is required for the a and b magnetization vectors to align along the x-axis. At that point the final 1H (p/2)y pulse completes the inversion of the a and b spin states. Figure 6 outlines the spin state populations and their corresponding NMR signals before and after the pulse sequence.
Figure 6
Population Inversion
Carbohydrates III
Carbohydrates III
Disaccharides
Disaccharides are sugars which contain two monosaccharide units joined together. Figure 1 illustrates the combination of a D-glucose and a D-fructose unit to form the disaccharide sucrose. While this animation indicates that creation of the disaccharide is accompanied by the formation of a water molecule, it is not intended to present an accurate picture of the mechanism of disaccharide formation.
Figure 1
Formation of a Disaccharide
Figure 2 highlights some of the important structural features of polysaccharides in general and of sucrose in particular.
Figure 2
Structural Features of Polysaccharides
Sucrose provides a good example of a non-reducing sugar; there are no aldehyde or hemiacetal groups in this molecule.
In sucrose, the oxygen atom attached to C1 of the D-glucopyranose ring is also bonded to C2' of the D-fructofuranose ring. This is called a 1,2-glycosidic linkage. Since sugars are polyhydroxyaldehydes and ketones, it should not be surprising that other linkages are possible. Maltose and lactose are disaccharides which contain alternative glycosidic linkages. Figure 3 presents the structures of these two sugars.
Figure 3
Maltose and Lactose: Alternative Glycosidic Linkages
Maltose contains two molecules of D-glucose. Lactose is comprised of one molecule of D-glucose and one of D-galactose. In both cases the monosaccharide units are connected by 1,4-glycosidic linkages, i.e. they both contain a C1-O-C4' link. In maltose the C1-O bond is in the a position, while in lactose it is oriented b to the D-galactose ring. Remember that the a and b designations refer to the disposition of the oxygen atom at an anomeric carbon.
Would you expect maltose and/or lactose to be reducing sugars?
Polyaccharides
Cellulose
By far the most common polysaccharide is cellulose. While the structure of cellulose is complex, the "backbone" of this polymer consists of D-glucopyranose rings joined together by C1-O-C4 links. Figure 4 illustrates this bonding mode for 4 D-glucopyranose units.
Figure 4
A Partial Structure of Cellulose
Note how the D-glucopyranose rings alternate their orientation along the "backbone". Apparently this arrangement allows for one cellulose chain to pack close to another, thus maximizing "inter-chain" hydrogen bonding interactions. Note also that all the glycosidic connections are b-1,4 linkages.
Starch
Starch is also a polymeric form of D-glucose. It consists of two components, amylose and amylopectin. Amylose is a linear poly-D-glucose in which the monosaccharides are connected by a-1,4 linkages. The basic repeat unit of amylose is illustrated in Figure 5.
Figure 5
The Repeat Unit of Amylose
Amylopectin is structurally more complex than amylose. It consists of multiple "strands" of amylose "cross-linked" by a-1,6 linkages. Approximately every 20th-25th D-glucose unit of one amylose chain is "cross-linked" to another amylose chain. Figure 6 gives a partial structure for amylopectin.
Figure 6
Partial Structure of Amylopectin
The structure of glycogen, the form in which D-glucose is stored in the liver, is similar to that of amylopectin. However, glycogen is even more highly "cross-linked". Approximately one out of every 10 glucose units in one amylopectin chain is connected to another amylopectin chain by an a-1,6 link. With a molecular weight of over 1,000,000, glycogen contains nearly 3,000 D-glucose units.
Analysis of Polysaccharides
One of the first steps in determining the structure of a polysacchride is acid catalysed hydrolysis of the glycosidic linkages to produce the monomeric components of the polymers. This reaction is the reverse of the nucleophilic addition of alcohols that is typical of aldehydes and ketones. Write a mechanism for the hydrolysis of sucrose.
Glycosylamines and Amino Sugars
Glycosylamines
Sugars in which the OH group at C1 is replaced by an amino group are called glycosylamines. A special category of glycosylamines is known as nucleosides. They are sugars in which C1 is connected to a nitrogen atom of a heterocyclic amine. The most common nucleosides are those found in RNA and DNA. Their structures are presented in Figures 7 and 8, respectively.
Figure 7
The Nucleosides of RNA
The glycosylamines in Figure 7 are also called ribonucleosides because the sugar component is D-ribose. These four molecules are the building blocks of ribonucleic acids, RNA.
Figure 8
The Nucleosides of DNA
The glycosylamines in Figure 8 are also called deoxyribonucleosides because there is no oxygen atom attached to C2 of the sugar. These four molecules are the building blocks of deoxyribonucleic acids, DNA.
The abbreviations RNA and DNA stand for ribonucelic acid and deoxyribonucleic acid, respectively. These molecules are polymeric sugars in which the ribose or 2'-deoxyribose units are linked together by phosphate bonds between hydroxyl group at C-3' of one sugar and the hydroxyl group at C-5' of the next. Figure 9 shows the bonding pattern for four ribose units of RNA .
Figure 9
The Glycosidic Bonds in Nucleic Acids
The polymeric chain is similar to that in cellulose. However, unlike cellulose, the glycosidic bonds do not involve the anomeric carbons. The designations B1, B2, etc. in Figure 9 represent heterocyclic bases that are depicted in Figure 7.
Amino Sugars
Amino sugars are carbohydrates in which a non-anomeric oxygen atom has been replaced by a nitrogen atom. The simplest example is b-D-glucosamine. The structure of this amino sugar and its N-acetyl derivative are given in Figure 10.
Figure 10
Two Amino Sugars
Langganan:
Postingan (Atom)