Organic and Bio-Molecular Chemistry - … Chapters/C06/E6-101.pdfOrganic and Bio-Molecular chemistry...

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ORGANIC AND BIOMOLECULAR CHEMISRTY – Organic and Bio-Molecular Chemistry - Francesco Nicotra

ORGANIC AND BIO-MOLECULAR CHEMISTRY Francesco Nicotra Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy Keywords: Organic compounds, Carbon atom, Chemical structures, Alkanes, Alkenes, Alkynes, Aromatic hydrocarbons, Haloalkanes, Alcohols, Thiols, Ethers, Amines, Aldehydes, Ketones, Carboxylic acids, Chemical reactivity, Carbohydrates, Amino acids, Nucleic acids, Lipids, Fats , Oils, Waxes, Dyes, Medicinal drugs, Nutraceutics, Polymers, Chemical separation, Structure determination, Chromatography Contents 1. Introduction 2. The Carbon atom 3. Structure of organic compounds 4. Classification of organic compounds, the functional groups 5. Attractive interactions and molecular recognition 6. Reactivity of organic compounds 7. Molecules of life 8. Organic compounds in the market 9. Isolation, purification and analysis of organic compounds 10. Conclusions Glossary Bibliography Biographical Sketch To cite this chapter Summary Organic and Bio-Molecular chemistry is the discipline that studies the molecules of life, which are made by carbon atoms, and includes also all the synthetic compounds the skeletons of which contain carbon atoms. Living organisms are “built up and organized” exploiting compounds the skeleton of which is mainly made up of carbon atoms. The study of these compounds, defined Natural Compounds, as far as structure, properties and biological role is concerned, is the subject matter of Organic and Bio-Molecular Chemistry. Chemists have been able to synthesize a great variety of new compounds with a skeleton mainly based on carbon atoms; these new molecules also belong to the class of Organic Compounds. The carbon skeleton of organic compounds represent the stable scaffold, in which the presence of multiple bonds and heteroatoms, mainly oxygen, nitrogen, sulfur, and phosphor, eventually allow the organic molecule to perform “functions” such as molecular interactions and reactivity. For this reason these groups are defined as functional groups and give rise to the most common classification of organic compounds. Organic chemistry studies the structure, nomenclature, physico-chemical properties and reactivity of each single class of organic compounds. Particular attention is devoted to organic compounds of living organisms, such as carbohydrates, amino acids and proteins, nucleic acids, lipids; they perform all structural and/or

©Encyclopedia of Life Support Systems (EOLSS)

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functional roles that allow an organism to live and reproduce. Organic compounds have also an important role in the market, and the chemical industries strongly contribute to the economy of industrialized countries. Many organic compounds such as polymers, dyes, compounds for health care such as medicinal drugs and cosmetics, compounds for food industry such as sweeteners, nutraceutics, preserving agents, emulsifiers and stabilizers, are widely used and contribute to our quality of life. The extensive production and use of synthetic organic compounds has generated some environmental problems, therefore particular attention is devoted to environmentally safe production processes and biodegradable organic polymers. Organic and Bio-Molecular chemistry also studies how to isolate organic compounds from a mixture, how to determine the chemical structure and how to detect purity. A variety of instrumental techniques have been developed for these purposes; it is now possible to detect the presence of organic compounds, even in traces, and to determine their chemical structure. 1. Introduction Chemistry is the discipline that studies the structure, properties, and methods of manipulation and transformation of all materials around us, from simple gases present in the air, nitrogen and oxygen, to the strangest and most complex compounds produced by microorganisms. Organic and Bio-Molecular Chemistry concerns in particular, as indicated by the name, the wide variety of compounds that constitute the living organisms; it includes however also structurally related compounds that have been mass-produced in laboratories and by industry in the 20th century. The origin of modern Organic Chemistry can be dated at the beginning of the 19th century, when scientists such as Gay-Lussac (1810) and Berzelius (1814) developed methods of analysis of the compounds derived from living organisms, allowing a systematic study which put into evidence the common characteristics of these compounds, that have been classified as “organic compounds”. For a long time it was believed that organic compounds were generated in Nature by a sort of magic “vital force”, despite the fact that in 1828 Wölher was able to demonstrate that the urea produced in the laboratory by heating ammonium cyanate, an inorganic compound, was identical to the urea of natural origin. Looking for a common characteristic of organic compounds, it was very soon clear that there is a relevant difference in chemical composition between them and inorganic compounds. Rocks are mainly made up of Oxygen (O) and Silicon (Si) atoms (see Table 1), whereas the structure of compounds of living organisms is mainly made with Carbon (C) atoms. Table 1 describes the percentage of the different elements present in the inanimate earth with respect to the human body. Considering that one of the most abundant compounds in the human body is water (H2O), it is clear from the Table that the most abundant element in the structure of organic compounds is Carbon.

Earth Human body Element % Element %O 47 H 63Si 28 O 25.5Al 7.9 C 9.5


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Fe 4.5 N 1.4Ca 3.5 Ca 0.31Na 2.5 P 0.22K 2.5 Cl 0.08Mg 2,2 K 0.06Ti 0.46 S 0.05H 0.22 Na 0.03C 0.19 Mg 0.01

Table 1: Percentage of the different elements present in the inanimate earth with respect

to the human body Organic Chemistry is therefore the chemistry of carbon-containing compounds, no matter if they are natural or synthetic. The evolution of Organic Chemistry has been impressive, there are practically no limits as to what can be synthesized in a laboratory; apart for very complex natural compounds, a large number of new compounds have been synthesized for different purposes. Organic compounds have a place in our everyday life; they constitute many useful materials such as plastic or fibers; they are present in food and beverages (which by the way are by definition organic compounds) as sweeteners, vitamins, flavors, coloring agents, emulsifiers, preservatives; they are used for health care, as medicinal drugs or cosmetics. Starting from petrol, which is presently the cheapest and most abundant reserve of organic compounds, a potentially infinite number of different molecules can be synthesized, by exploiting the great variety of chemical reactions that have been developed since the 21st Century, and progress in the techniques of purification and structural determination. On the other hand, the molecular mechanisms of life, all involving organic compounds, from complex proteins to very small neurotransmitters such as acetylcholine or noradrenaline, have been largely elucidated. Proteins, carbohydrates, nucleic acids, lipids, products of the secondary metabolism, and more in general organic compounds of the biological systems, are specifically defined “bio-molecules” and the branch of organic chemistry that studies the nature of these bio-molecules and their behavior in the organism, is defined “bio-molecular chemistry” 2. The Carbon Atom The Carbon atom is the main constituent of organic molecules, as shown in Table 1, whereas the Silicon atom is the main component of rocks. Why? Why are rocks mainly built-up of Silicon and Oxygen atoms whereas Nature has selected the Carbon atom for living organisms? Silicon and Carbon have a common feature: they are “tetravalent”, in other words they are like scaffolds that can be elongated in four directions. Silicon and Carbon atoms can establish four molecular bonds, represented with a line in Figure 1, each of which links a different atom. Four linkages with different atoms is the highest possibility for the most abundant elements present in the earth; hydrogen and chlorine are monovalent, they can establish only one linkage; oxygen is bivalent, it establishes two linkages; nitrogen, boron and aluminum are trivalent, they can establish three


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linkages with different atoms. Therefore silicon and carbon, the two abundant tetravalent elements, are the most efficient scaffolds to build up tridimensional molecular structures. There is however an important difference between silicon and carbon: the energy of C-C linkage is around 80-90 kcal/mol, whereas the Si-Si linkage is much weaker, 53 kcal/mol, which makes it very unstable. On the other hand, the Si-O bond is very strong (108 kcal/mol), therefore very stable molecular architectures can be generated intercalating Si and O atoms as shown in Figure 1 for silicates. This kind of structure is so stable, let us say “static”, to be inadequate for living organisms which require more “dynamic” compounds. Living organisms generate fructose, an organic compound with a six carbon atom chain, from carbon dioxide and water, in a process defined as photosynthesis which exploits the energy of the sun. Fructose undergoes metabolic transformations to generate other organic compounds. It is clear therefore that organic molecules must be “dynamic”, as they must be generated (biosynthesized) and transformed (metabolized) by cleavage of some bonds and formation of new ones. The carbon atom is much more suitable for this purpose, 80-90 kcal/mole of the C-C bond is the strength of choice, not too strong and not too weak; therefore it has been selected in Evolution to generate organic compounds. Palmitic acid, in Figure 1, present in palm tree oil, is an interesting example of an organic compound in which sixteen carbon atoms are linked together generating a long chain.

Figure 1: Silicon and carbon atoms are scaffolds that can elongate in four different directions generating four linkages, the two examples refer to the general structure of

silicates (the oxygen atoms can be linked to other silicon atoms, for further elongation, or hydrogen atoms)

2.1. The Carbon Atom Building Blocks: Hybridizations The carbon atom is tetravalent and, as stated before, is a building block that can give rise to four different bonds. These four bonds are oriented in the space at 109.5°, as shown in the first example of Figure 2. However the carbon atom is a very ductile and dynamic building block; it can assume different “hybridizations” that make bonds in


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different directions in space. In the so called sp3 hybridization (first example in Figure 2) the carbon atom generates linkages in four directions at 109.5° exploiting the so defined “orbitals” (spaces that can be occupied by electrons and therefore can generate molecular bonds). Alternatively, in the so called sp2 hybridization (second example in Figure 2), the carbon atom generates linkages in three directions at 120°. Finally, in the so called sp hybridization (third example in Figure 2), the carbon atom generates linkages in two directions at 180°. It is interesting to note that 109.5°, 120° and 180° are the angles that allow respectively four, three and two linkages to be at the highest reciprocal distance.

Figure 2: The different hybridization of carbon atom allows it to generate bonds in

different directions in space. 2.2. Single and Multiple Bonds

Figure 3: Ethane has two carbon atoms with sp3 hybridization, which generate four σ-bonds each. Ethylene has two carbon atoms with sp2 hybridization, generating each

three σ-bonds and one π-bond. Acetylene has two carbon atoms with sp hybridization,


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generating each two σ-bonds and two π-bond. 1,2-Butadiene has one carbon atom hybridized sp, generating one σ-bonds and one π-bond with each of the two carbon

atoms linked to it. The linkages so far described, that join the atoms like a line starting from the centre of each atom, are defined sigma (σ) bonds. Without entering into details on the nature of the orbitals that generate the molecular bonds, in the sp2 hybridization the carbon atom will generate also a second bond, defined pi-Greek (π) bond, with one of the three atoms with which it is linked; in other words a double bond is generated (see ethylene in Figure 3). The carbon atom with an sp hybridization will create two more bonds (π bonds) with one of the two atoms linked to him, therefore generating a triple bond (see acetylene in Figure 3). Alternatively, the sp hybridized carbon atom can generate two double bond (see 1,2-butadiene in Figure 3). In each case the carbon atom generates in total four bonds. The hybridization of the carbon atoms is a dynamic feature, which means that in a chemical reaction a single carbon atom can change the hybridization, and consequently the geometry of the linkages and the type of bounds. 3. Structure of Organic Compounds Once we know the geometry of the three carbon atom building blocks, we can start to build and represent the organic molecules emphasizing their size and geometry. In order to do that we need a conventional method to draw the three-dimensional structures in two dimensions on a sheet of paper. 3.1. Graphical Representation of the Structures of Organic Compounds Historically, the first way to represent the structure of organic compounds was simply to draw the four linkages established by a carbon atom with four lines at 90°, linking the neighboring atoms, as in Figure 1 for palmitic acid. This representation is still used, although it does not respect the correct angles of the tetrahedral sp3 carbon atom (109.5°). However, it is also time consuming for large molecules such as palmitic acid. The evolution of the methods of graphical representation of organic molecules has followed two different requirements, that of simplicity and the need to give information on the real geometry of the molecule, if required. Therefore, different conventional representations find application depending on what we want to highlight. In order to simplify the representation of an organic compound, the lines representing the bonds can be omitted, like in Figure 4B for a simpler representation of palmitic acid. A further simplification allows us to represent a sequence (chain) of CH2 with just one CH2 in brackets, with a subscript number indicating the amount of CH2 in the chain (Figure 4C). Another way to represent organic molecules, which simplifies the drawing as much as possible, and is therefore useful and often indispensable to represent molecules with very complex structures, omits the symbols of carbon and hydrogen atoms. The molecule is represented with a sequence of lines, as reported in Figure 4D for palmitic acid, each angle and extremity represent a carbon atom linked to the hydrogen needed to complete the structure.


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Figure 4: Conventional representations of organic compounds. In A all the bonds and atoms are represented, but the real geometry of the bonds is not respected. In B the

bonds are omitted for simplicity; in C the representation of the carbon chain is simplified, in D the symbols of the atoms in the carbon chain are omitted for simplicity. This last representation can be adopted to show the real geometry of the bonds of a sp3 hybridized carbon atom, two of which are represented by the two lines on the plane, drawn at about 109.5°. The other two bonds, one of which is directed towards the observer and the other to the back of the plane, can be represented respectively with a wedge and a hatched line (Figure 5). Another representation of a sp3 hybridized carbon atom, which describes the geometry of the bonds, is the historical conventional method invented by Emil Fisher and still used for amino acids and sugars. In the Fisher representation the four bonds are drawn like a cross, with the carbon atom in the centre. The horizontal lines are conventionally oriented towards the observer (out from the plane), whereas the vertical lines are conventionally oriented back to the plane, opposite to the observer (Figure 5, right).

Figure 5: Conventional representations of the sp3 hybridized carbon atom, describing the real geometry of the molecule.


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3.2. Different Shapes that a Molecule can assume: Conformations In Figure 4 palmitic acid has been represented as a long bar. Is this true? Is it a rigid molecule or it is flexible like a string? The study of the shape of a molecule, in other words, the orientation of the atoms in the space, requires further information. The rotation around single (σ) bonds is generally allowed, therefore a molecule such as palmitic acid, in which each C-C bond is a single bond, is like a piece of string that can be turned as we like and assume an almost infinite series of orientations in the space. To be more precise, let us study the case of a simple molecule with four carbon atoms like butane (Figure 6), the rotation around the single bond will generate all possible angles between the two CH3 at the extremity of the chain, which correspond to different sizes of the molecule, defined “conformations”. Some conformations however are more stable than others. In the conformation described at the left in Figure 6, which is defined “anti conformation”, the two CH3 are at 180° (as far as possible), whereas in the conformation represented at the right, which is defined “gauche conformation”, the two CH3 are at 60° (much closer). The anti conformation is the most stable among all the possible conformations because the repulsive interaction between the CH3 (or any other group in the case of a different molecule) is minimized at 180°.

Figure 6: Rotation around the σ-bond allows the molecule to assume an infinite number of conformations, a couple of which are reported for butane.

The presence of a double bond in a molecule generates a conformational rigidity: the rotation around a π-bond is not allowed. Nature takes advantage of the decreased flexibility of compounds presenting a double bond. To make an example of the macroscopic difference that the presence or absence of a double bond can generate, oil and butter have essentially the same chemical structure (triglycerides, see Section 7.4.1) with the only difference that oil contains a substantial amount of double bond in its long chain components (fatty acids such as oleic acid, Figure 7), which prevent the ordered aggregation of the linear carbon chains that determine the solid state of butter. Figure 7 shows the most stable conformation of palmitic acid, which is linear and generates ordered aggregates with molecules of the same type, and oleic acid in which the double bond prevents a linear conformation and therefore an ordered aggregation.


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Figure 7: Palmitic acid and oleic acid. The double bond of oleic acid prevents a totally

linear conformation. 3.3. Asymmetry of some Organic Molecules: Chirality and Stereoisomers A carbon atom linking four different elements or groups, such as that represented by the cross in Figure 5, is asymmetric (stereogenic, see Stereochemistry), and the molecule to which it belongs is defined “chiral”. A different molecule can be generated by changing the reciprocal position of two substituents. Figure 8 represents at the left the same molecule represented in Figure 5, and on the right different, non super-imposable, molecules which differ only by the orientation of the group in space. Compounds with these reciprocal structural characteristics are defined stereoisomers (stereo refers to space, and isomer refers to a structural similarity, same number of atoms, differently positioned). The two different orientations of the elements and groups at the stereogenic carbon atom are defined configurations.

Figure 8: Two stereoisomers, molecules that differ only in the orientation of atoms or groups in the space. The two compounds represented are mirror images.


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The two compounds represented in Figure 8 have opposite configurations, they are stereoisomers. In particular, the molecules of the two compounds in Figure 8 are mirror images, a geometrical property that make them identical in their chemical and physical properties, and only an asymmetric “instrument” can discriminate between them, they are defined enantiomers. The example of the hands is pertinent; the two hands, left and right are non super-imposable and are mirror images. Only an asymmetric glove (the left is different from the right) allows us to discriminate between them, it fits only one of the two hands. Molecular asymmetry is widely spread in Nature. Amino acids that constitute the proteins (proteogenic) are all chiral except glycine. The configuration of proteogenic amino acids is constantly “L”, a conformational descriptor that, according to the Fisher projection formulas, is given to the amino acid that in the representation shown in Figure 9 presents the nitrogen atom on the left. More in detail, the Fischer projection formula requires that the carbon chain is drawn in vertical with the most oxidized carbon atom at the top. The chiral carbon atom is then represented with a cross, and if the “main” group is on the left, the conformational descriptor is L, if it is at the right, the descriptor is D. This convention is still used for amino acids and sugars, but for all the other organic compounds, a newer convention is used, the conformation descriptors being R and S. For a detailed description see Stereochemistry. It is interesting to mention that bacteria contain D-alanine, which they use to generate their cell wall. D-Alanine is therefore an important target for medicinal chemistry, indispensable for bacteria and absent in our organism. Penicillins, which mimic two molecules of D-alanine linked together, are able to inhibit the biosynthesis of the bacterial cell walls, without interfering with the human metabolism.

Figure 9: L-Alanine and D-Alanine, the first is the proteogenic amino acid whereas the

second is present in the bacterial cell wall. A dramatic example of the different behavior of two enantiomers (mirror images), comes from the drug Taledomide that was used in Europe and Canada in the 1960s for the treatment of nausea in pregnant women. The drug was administered as a mixture of the two mirror image stereoisomers, although only one of the two was responsible for the anti-nausea activity, because separation was difficult and it was believed that the inactive stereoisomer was safe. Unfortunately it was mutagenic and anti-abortive, and


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was responsible for the birth of deformed infants with underdeveloped limbs. This event led to new restrictions in the commercialization of drugs, and in fact stereochemical purity is now required. 4. Classification of Organic Compounds, the Functional Groups The structure of organic compounds, as shown in the case of palmitic acid, is made by a skeleton of carbon atoms, to which hydrogen atoms are linked to complete the structure (the carbon tertavalence). Palmitic acid however presents at one extremity a different structural situation: the carbon atom links two oxygen atoms, one with a double bond and the other with a single bond; this latter oxygen atom completes the bivalence linking a hydrogen atom. This arrangement of atoms is responsible for some “functions” of palmitic acid, such as the acidity, the possibility to link other molecules or the formation of micelles in alkaline aqueous solution; therefore this arrangement of atoms and bonds is a “functional group”. In general, the skeleton of organic compounds is mainly made up of carbon atom chains or cycles, whereas the functions are mainly due to groups that present atoms different to carbon and hydrogen (defined heteroatoms), and/or by multiple bonds. These groups are therefore defined functional groups. Organic compounds are generally classified according to the functional groups present in their structure. The name alcohol, for example, is well known; it refers to an organic compound in which the carbon atom is linked to an oxygen atom, which in turn links a hydrogen atom. The alcohol present in beverages, ethanol, is made by a chain of two carbon atoms, one of which links an oxygen atom bearing a hydrogen atom: CH3CH2-O-H. A carbon chain can be represented more in general with the letter R, therefore the general structure of alcohols is R-O-H. The main classes of organic compounds are reported with their names in Table 2.

Alkanes

C

R

R

R R

R can be H

Amines

NR

RR

one or two R can be H

Alkenes

CR

RC

R

R R can be H

Aldehydes

CR

HO

R can be H Alkines

CR C R R can be H

Ketones

CR

RO

Alkyl halides

C

R

R

R Cl

R can be H, Cl can be Br, I

Carboxylic acid

CROH

O

R can be H


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Alcohols

C

R

R

R OH

R can be H

Carboxylic esters

CRO

O

R' R can be H

Ethers

C

R

R

R O C

R

R

R

R can be H

Amides

CRN

O

R'R' R and R’ can be H

Thiols

C

R

R

R SH

R can be H

Nitriles

CR N

Thioethers

C

R

R

R S C

R

R

R

R can be H

Table 2: Main classes of organic compounds

4.1. Alkanes Compounds made up exclusively of carbon and hydrogen atoms, and presenting only single bonds, are defined alkanes. Methane (CH4), propane (CH3CH2CH3) and butane (CH3CH2CH2CH3), used at home for heating or cooking, are examples of alkanes. Polyethylene is a polymer formed by a chain of –CH2-, and therefore belongs to the class of alkanes. Alkanes can be linear, branched, cyclic an even polycyclic. The main source of alkane is petroleum, or crude oil, a fossil fuel formed over many thousands of prehistoric plants. Commercial products obtained by the fractional distillation of crude oil contain alkanes with a different number of carbon atoms. Gasoline for example, the motor fuel, is a mixture of alkanes with 5-12 carbon atoms, whereas Diesel contains alkanes with 15-20 carbon atoms. Lubricant oils are made with a mixture of alkanes containing 20-30 carbon atoms, and asphalt used as road surface material contains alkanes with more than 40 carbon atoms. 4.2. Alkenes Compounds presenting one or more carbon-carbon double bonds are defined alkenes. The simplest alkene is ethylene, CH2=CH2, which is very important as a starting material for the production of polyethylene and in ripening of fruit. Some plants generate small quantities of ethylene during the ripening of their fruits; therefore this alkene is used to ripen fruit, which has been picked green to be transported intact to destination. A great variety of natural products contain carbon-carbon double bonds. We


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have already seen the example of oleic acid (Figure 7) in which the presence of a double bond alters the linear geometry of the molecule. A great number of fragrant substances extracted from plants such as limonene or γ-terpinene (Figure 10), respectively components of the essential oil of lemon and coriander, belong to the class of alkenes. β-Carotene, the pigment responsible for the orange color of carrots, is another interesting example of a naturally occurring alkene; it contains 11 carbon-carbon double bonds (Figure 10).

Figure 10: Examples of alkenes of natural origin. It is interesting to mention that, in the light of the fact that the rotation around a double bond is not allowed, two different molecules (once more defined stereoisomers, see Section 3.3) can be generated depending on the geometry of the double bond. In oleic acid (Figure 7) the two chains are located on the same side of the double bond, a geometry that is defined with the letter Z (from the German term zusammen: together). The other stereoisomer, in which the substituents at the double bonds are located on the opposite side, is not present in olive oil; the geometry of its double bond is defined E (from the German word entgegen: opposite). 4.3. Alkynes Compounds presenting carbon-carbon triple bonds are defined alkynes. The best known example of alkyne is acetylene, which has been used as a combustible for lamps. Alkynes are relatively rare in living organisms, and often present physiologically relevant activities. Ichtyotherol (Figure 11), which contains three C-C triple bonds, is the active principle in the plant extract used by natives in the Amazon region to poison their arrowheads.


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Figure 11: The structure of ichtyotherol, active principle of the plant extract used by

natives in Amazon to poison their arrowheads. The example in Figure 11 put into evidence the limit of the classification of organic compounds according to the functional group they present. Ichtyotherol has not only three carbon-carbon triple bonds, but also a carbon-carbon double bond, and a carbon linked to an –O-H; therefore it is not only an alkyne, but also an alkene and an alcohol. The classification of organic compounds according to the functional group is however very useful to study the properties and the behavior of each functional group in a molecule. 4.4. Aromatic Hydrocarbons Alkanes, alkenes and alkynes, which possess only carbon and hydrogen atoms, are also called hydrocarbons (from hydrogen-carbon).

Figure 12: A) Benzene, naphtalene and anthracene, examples of aromatic hydrocarbons; B) pyridine, purine, pyrrole, furan, thiophene, imidazole, indole and purine, examples of

heteroaromatic compounds


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Benzene (Figure 12) presents only carbon and hydrogen atoms, and therefore is a hydrocarbon. Benzene however has a different chemical behavior (reactivity) due to a peculiar stability of planar cyclic compounds with an alternation of double and single bonds and with a well defined (4n+2), 0,1, 2,3,n = … number of electrons in the π-orbitals. These compounds are defined aromatic compounds (an exhaustive definition of aromatic compounds is not possible at this level). Naphtalene and anthracene are other examples of aromatic hydrocarbons. A wide variety of aromatic compounds contain also heteroatoms in the cycles that characterize and determine their aromacitity. These compounds are defined heteroaromatic compounds; the most important are reported in Figure 12 B. Pyridine and purine are six member cyclic compounds respectively with one or two nitrogen atoms instead of the carbon atom of benzene. Pyrrole, furan and thiophene are cycles containing five atoms, one of which is, respectively, nitrogen, oxygen and sulfur, whereas imidazole contains two nitrogen atoms (Figure 12B). Indole and purine are bicyclic compounds, the first with just one nitrogen atom in one cycle, whereas the second contains four nitrogen atoms (Figure 12 B). From these examples it is clear how big is the structural variance in aromatic compounds. Nature exploits this variance for many functions: some derivatives of purine and pyrimidine are constituents of nucleic acids (see below); indole and imidazole are present in the structure of two amino acids that constitute the proteins, the structure of pyridine is part of NAD, an important enzymatic cofactor that allow to establish the biological oxidation and reduction. 4.5. Haloalkanes Haloalkanes are a class of organic compounds containing the carbon-halogen bond. These compounds are rare in Nature because their high reactivity (except for fluorides) makes them dangerous for living organisms. Iodomethane, CH3I, for example is carcinogenic. On the contrary, when the halogen is linked to an aromatic skeleton, the compound is very stable, often so stable that it cannot be biodegraded. A relevant example of this behavior is DDT (Figure 13) which was widely used in the past as a pesticide, but caused serious environmental problems due to its stability and toxicity. Another example of a stable and very dangerous halogenated compound is dioxin (Figure 13).

Figure 13: The structures of DDT and dioxin, two environmentally dangerous

halogenated compounds. Haloalkanes are used as solvents and in the production of polymers such as PVC (polyvinyl chloride) and Teflon (Figure 14)


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Figure 14: The structure and PVC and Teflon, two halogenated polymers

Fluoroalkanes have a different behavior: they are not reactive like the other haloalkanes, furthermore they are not toxic or flammables. Chlorofluoroalkanes (CFC or Freon) are the most known, widely used as fluids for refrigeration and in aerosols. However in 1974 it was demonstrated that these compounds are responsible for the destruction of ozone in the atmosphere. As a consequence of these scientific results, in 1987 the protocol of Montreal was approved by the United Nations that strongly limits the use of these compounds. 4.6. Alcohols Alcohols are a class of organic compounds containing the -O-H (hydroxyl) functional group.

Figure 15: Sucrose contains eight hydroxyl groups, glycerin three hydroxyl groups.


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The alcoholic function is one of the most widely present in natural compounds. Sugars for example contain numerous hydroxyl groups, as shown in Figure 15 for sucrose, the table sugar, which contains 8 hydroxyl groups. Another widely used alcohol is glycerin (or glycerol) which is the main component of the cosmetic creams. Cholesterol also contains an alcoholic function (Figure 15). The hydroxyl function of alcohols is like a hook that can be used to link a different molecule, exploiting the reactivity of the hydroxyl group with other functional groups, such as a carboxylic acid or an aldehyde. The hydroxyl group of cholesterol for example is the hook to link a fatty acid (like palmitic acid) or a sugar, in order to tone its hydrophilicity. The hydroxyl group is also one of the functional groups of choice for the reactivity; it can be oxidized, it can be eliminated as a molecule of water generation a double bond, it can be substituted. In other words it is a “first actor” in the metabolic processes and in synthetic chemistry. When the hydroxyl group is linked to the aromatic ring of benzene, the alcohol is defined phenol. Phenols are important components of natural products, such as salicylic acid, or morphine (ring A), or estradiol (Figure 16).

Figure 16: Phenol and some natural products containing the phenol entity. 4.7. Thiols When a sulfur atom replaces the oxygen of alcohols, the compounds are named thiol. The main characteristic of most thiols is the bad smell. Ethanthiol (HS-CH2CH2-SH) for example is added in traces to methane in order to warn in case of accidental emission of this gas, which is odorless. The thiol group has a strong tendency to generate a sulfur-sulfur linkage: R-S-S-R with another thiol. This process is particularly important in proteins, in which two units of cysteine, an amino acid containing the thiol group, can link together and generate a disulfide bridge which turns the protein chain (Figure 17) and therefore contribute to the folding of proteins. This process does not occur with alcohols because the oxygen-oxygen bond, present for example in hydrogen peroxide H-O-O-H, is very unstable and generates radicals.


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Figure 17: In a protein chain the linkage of two thiol units, coming from cysteine,

induce a turn of the protein chain. 4.8. Ethers Ethers, R-O-R, are formally generated by two alcohols by loss of a molecule of water. More generally, when two equal or different alkyl groups R are linked through an oxygen atom, an ether is generated. Among the ethers, diethyl ether CH3CH2-O-CH2CH3, generally called simply ether, is a well known anaesthetic and highly flammable compound. Ethers are particularly stable molecules in which the oxygen atom contributes to increase the polarity, useful for their use as solvents, and the capacity to bind metal cations. The system of transport of sodium, potassium and calcium cations across the cell membranes is based on this type of binding. 4.9. Thioethers, Disulfides and Trisulfides

Figure 18: Thioethers, disulfides and trisulfides responsible for the flavor of garlic and onions.


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Thioethers, R-S-R are the analogues of ethers in which a sulfur atom substitutes the oxygen. The stability of the sulfur-sulfur linkages allows the existence of disulfides R-S-S-R, trisulfides R-S-S-S-R, and so on (Figure 18). These sorts of compounds are present in essential oils of garlic, onion and cabbages, and are responsible for their flavor (Figure 18). 4.10. Amines Organic compounds formally derived from ammonia NH3 by substitution of one, two or three hydrogen atoms with carbon atoms are defined amines. R-NH2, is defined as a primary amine; R2NH, is a secondary amine, and R3N is a tertiary amine. Amines are basic compounds, they are able to capture a proton (H+) giving rise to the corresponding ammonium salts (RNH2 + H+ → RNH3

+). This is a most useful behavior of amines that is exploited both in metabolic processes and in synthetic chemistry as soft bases. Besides that, the primary or secondary amino group, like the hydroxyl group, is an important hook through which a second molecule can be connected. Aldehydes, ketones and carboxylic acids are functional groups connectable with primary and secondary amines. The presence of a hydrophobic R group makes amines insoluble in water, whereas their conversion in ammonium salts converts them into hydrophilic species due to the positive charge on the nitrogen atom. This behavior allowed the easy isolation of natural occurring amines with physiological properties from herbs extracts. Treatment of the pulp obtained from herbs with an acidic aqueous solution permits the isolation of water soluble natural components, among which the ammonium salts. Then, treatment of the aqueous extract with an alkaline (basic) solution results in the precipitation of the amines, which is insoluble in water. Historically, the natural compounds isolated following this procedure have been defined alkaloids. A great variety of alkaloids have shown significant physiological activities; examples are nicotine, atropine, cocaine, serotonin (Figure 19) or morphine (Figure 16).

Figure 19: Examples of alkaloids, compounds of natural origin containing an amino

group.


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4.11. Aldehydes and Ketones The carbon-oxygen double bond (C=O) is defined carbonyl group. The carbonyl group is present in different classes of organic compounds, which vary depending on what is linked to the C=O. As a matter of fact, the reactivity of compounds containing a carbonyl group changes if it links only with hydrogen or carbon atoms, or if it links with a heteroatom. If the carbonyl group links two hydrogen atoms or one hydrogen atom and one carbon atom, the functional group is defined aldehyde. If the substituents are two carbon atoms, the functional group is defined ketone. Aldehydes and ketones present a very similar chemical behavior. Aldehydes however are generally less stable and can be easily oxidized to carboxylic acids, whereas ketones are not. Among the aldehydes, formaldehyde, the first member of the class, with only one carbon atom, is used as disinfectant. Benzaldehyde is responsible for the flavor of almonds, and retinal is involved in the mechanism of vision (Figure 20). Vanillin, the flavor isolated from the vanilla bean, contains three functional groups, an aldehyde, e phenol, and an ether (Figure 20).

Figure 20: Examples of aldehydes

The most known ketone is probably acetone, which is used as solvent. Much more complex ketones are widely present in Nature, such as muscone, the main component of the fragrance of musk, and steroidal hormones such as testosterone and progesterone (Figure 21)

Figure 21: Examples of ketones


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As reported before, aldehydes and ketones are able to link alcohols and primary and secondary amines. 4.12. Carboxylic Acids, Esters and Amides Carboxylic acids are organic compounds containing the –COOH functional group, in which the carbon atom links one oxygen with a double bond, and the other oxygen with a single bond, see palmitic acid in Figure 1. The best known example of carboxylic acid is probably acetic acid, CH3COOH, the component of vinegar obtained by microbial (acetobacter) oxidation of ethanol in wine. As indicated by the name, carboxylic acids have acidic properties, by treatment with a base they generate the corresponding salt (RCOOH + NaOH → RCOO- Na+ + H2O). Salts of carboxylic acids are soluble in water, even tough R is a long chain. In this case they form micelles, that are very small aggregates in the internal part of which the hydrophobic long chains find place whereas the ionic COO- extremity constitute the external hydrophilic part. These micelles are soluble in water and at the same time can dissolve lipophilic compounds, such as fats and oils, in the internal lipophilic part. Treatment of fats with NaOH, or other alkali, is a process known since ancient times as saponification, which generates soaps, salts of fatty acids (such as palmitic acid, Figure 1), which constitute fats and oils.

Figure 22: Triglyceride (a fat) and the constituent molecules, glycerol and three fatty acids.


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The most relevant behavior of carboxylic acids is their ability to link other functional groups, such as alcohols or primary and secondary amines, to generate respectively esters or amides. This behavior is widely exploited by Nature, for example in the production of fats or proteins. In the first case three long chain carboxylic acids with an even number of carbon atoms (fatty acids) link the three hydroxyl groups of glycerol generating a triglyceride (a fat) (Figure 22). In the second case many amino acids, natural compounds containing an amino group and a carboxylic acid in the same molecule, generate a chain by sequential linkages of the two complementary functional groups, the carboxylic acid and the amino group (Figure 23).

Figure 23: Amino acids are the monomers that constitute proteins.

Nylon, a fiber the commercial name of which derives by combining New York-NY and London LON, NYLON the two places of the ICI company where the substance was first synthesized, is made approximately in the same way. In Nylon-66 a dicarboxylic acid and a diamine, both containing six carbon atoms, are linked together in a reiterative way to form the polymer which takes the general name of polyamide (Figure 24).


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Figure 24: Nyon-66 and its components, a dicarboxylic acid and a diamine.

Aspirin (Figure 25) is an example of organic compound containing a carboxylic acid and an ester; it derives from salicylic acid (Figure 16) by esterification of the hydroxyl group with acetic acid.

Figure 25: Aspirin contains a carboxylic acid and an ester group.

5. Attractive Interactions and Molecular Recognition Organic molecules interact with themselves, with other organic molecules, with water, with inorganic compounds, depending on their structure. These interactions, that can be attractive or repulsive, are responsible for the properties of organic compounds, such as their physical state (solid, liquid or gaseous), their solubility, the possibility to generate aggregates, the folding properties, the molecular recognition phenomena. The attractive interactions are due to the following weak bonds:

1) ionic interactions, occurring when the compounds present opposite charges 2) dipole-dipole interactions, occurring when the molecules present a dipole

moment, generated by elements of different electronegativity. In organic compounds, the carbon-heteroatom bonds generate a dipole moment.

3) Hydrogen bonds, occurring between a hydrogen atom bonded to an electronegative element (such as halides, oxygen, nitrogen) and an electronegative element of another (or even the same) molecule.


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4) London forces. Compounds which do not present dipole moments perform very weak attractive interactions; this is due to the motion of electrons that generate temporary dipole moments.

In general, the polar part of a molecule interacts attractively with polar compounds, such as water (hydrophilic interaction). On the contrary the hydrophobic part of a molecule interacts attractively with hydrophobic compounds, such as hydrocarbons (hydrophobic interaction). The example of soap well exemplifies this concept. The long hydrophobic chains of fatty acid salts perform hydrophobic interactions with themselves inside the micelle, whereas the polar carboxylic group at the surface of the micelle interacts with water. Molecular interactions are at the basis of Life. Any message in our organism, such as cell adhesion or physiological responses, any mechanism of living organisms, such as the transmission of genetic information or enzymatic processes, occur via molecular recognition phenomena. 6. Reactivity of Organic Compounds Organic compounds undergo transformations in the organisms (the metabolism), and can be modified in laboratory experiments, in other words they can react. These reactions occur according to defined roles, in a certain period of time, and when the required amount of energy is provided. The roles that define how and why organic compounds react, depending on the functional groups present in the molecule, are defined as “mechanism of the reaction”. The parameters of time for a chemical reaction are defined “kinetic of the reaction”. The energy required to perform a reaction concerns the “thermodynamics of the reaction”. Understanding of the mechanisms, the kinetic and the thermodynamic aspects of the different organic reactions allowed the development of synthetic chemistry, which is our capacity to transform molecules, joining them, cleaving them in smaller fragments, changing the nature of their functional groups, to produce whatever organic compound we want. In each reaction there is an intermediate situation in which a bond starts to break in order to allow the formation of a new one. This situation, defined transition state of the reaction, corresponds to the higher level of energy that the system must overcome in order to react. Only the fraction of molecules that possess an amount of energy equal or higher than this barrier, defined activation energy, can overcome the barrier and generate the product. An increase in temperature stimulates the kinetic energy of the molecules and therefore the fraction of them that can react; therefore any reaction is faster at higher temperatures. Living organisms however cannot increase the temperature when and where they need to perform a chemical reaction; they use a different strategy, exploit some “machineries” that are able to stabilize the transition state of the reaction, therefore lowering the activation energy. This phenomenon is termed as catalysis, and the machineries that allow stabilization of the transition state, and consequent reduction of the activation energy, are defined catalysts. The biological catalysts are called enzymes. Living organisms perform their metabolic reactions using


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enzymes, which accommodate the organic compound in a sort of mould, called active site. The active site has a particular affinity for the transition state of the reaction, which therefore is stabilized; this stabilization results in a lowering of the activation energy. Catalysis is widely used in laboratory and industrial processes, in order to accelerate the reactions, save energy and perform reactions that otherwise are not practicable. Most industrial reactions exploit catalysts, which very often contain metal derivatives. Chiral catalysts allow us to produce only one stereoisomer when a stereogenic carbon is generated in the reaction. In this way living organisms are able to generate chiral molecules, such as L-amino acids. Enzymes are by definition chiral catalysts, performing stereoselective reactions, in other words reaction in which only one (or mainly one) stereoisomer is generated. Stereoselective catalysts are very important in laboratory and in industrial processes as well. The example of Taledomide shown before (Section 3.3) clearly indicates how important it is to produce only (or mainly) one stereoisomer.

Figure 26: Sulfonamides mimic p-aminobenzoic acid, one of the biosynthetic precursors of folic acid, the carboxylic acid being substituted by a similar, but ineffective

functional group.


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The understanding of reaction mechanisms occurring in biological processes, allows us to design inhibitors of such processes. This is one of the strategies adopted in drug research. To give an example, sulfonamides are able to inhibit the biosynthesis of folic acid, vitamin B9, which is indispensable for living organisms. Mammalians assume this molecule in the diet, whereas bacteria produce it through a biosynthetic pathway which utilizes p-aminobenzoic acid (Figure 26). The structure of sulfonamides mimics that of p-aminobenzoic acid, the carboxylic acid being substituted by a very similar, but ineffective functional group (the sulfonamide). 7. Molecules of Life . Living organisms generate and contain an enormous variety of organic compounds, some of them are particularly relevant as structural and functional components, whereas others are present in very small quantities and act as regulators, messengers, or defense compounds. It is not easy to classify natural compounds depending on their role. Carbohydrates, for example, perform structural roles like cellulose in plants or chitin in the insect exoskeleton, roles of energy reserve like in starch, roles of cellular recognition in cell wall glycoproteins and glycolipids. It is easier therefore to classify natural compounds depending on their structure. The main classes of natural compounds are: carbohydrates (glycides), amino acids and proteins (protides), nucleic acids (nuclides) and lipids. 7.1. Carbohydrates Carbohydrates are a wide and important class of organic compounds, the most abundant in Nature. It is well known that plants are able to generate glucose from water and carbon dioxide in a process called photosynthesis which exploits the energy of the sun. This is an example of generation of organic compounds from inorganic starting materials. On the other hand, it is known that living organisms produce the energy they need via the opposite process: glucose is converted into carbon dioxide and water with liberation of energy. The two processes are very complex and their description requires the knowledge of the reaction mechanisms, therefore they will not be discussed at this level. Carbohydrates are organic compounds characterized by the presence of a carbonyl group (generally aldehyde or ketone) and multiple hydroxyl groups. Figure 27 shows how many different sugars can exist depending on the number of carbon atoms and the stereochemistry of each stereogenic centre. The sugars shown in Figure 27 are aldoses (contain an aldehyde) with three, four, five and six carbon atoms— and all present the last hydroxyl group to the right (D-series by definition). The mirror images of the sugar shown in Figure 27 maintain the same name, but with the prefix L (L-series by definition) instead of D.


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Figure 27: Aldoses with three, four, five and six carbon atoms, all presenting the last hydroxyl group to the right (D-series)

The most relevant behavior of carbohydrates is their ability to generate a cycle by reaction of the carbonyl group with a hydroxyl group of the same molecule, and the capacity of the same carbon atom, called “anomeric centre”, to link another hydroxyl group of a different molecule (Figure 28). This different molecule can be any type of alcohol or some amino groups. Of particular interest is the case in which the alcohol


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belongs to another molecule of sugar; in this way oligosaccharides and polysaccharides are formed. The process with which a sugar links another molecule, exploiting the anomeric centre and the alcoholic function of the other molecule, is defined glycosylation. In glycosylation two different stereoisomers can be generated the α-anomer and the β-anomer (see Figure 28). The stereochemistry of this linkage is very important and influences very much the properties of the two different compounds: cellulose and starch differ only for the stereochemistry of the glycosidic linkage (Figure 29).

Figure 28: Glucose generates a cyclic structure by reaction of the carbonyl group with one of the hydroxyl group of the same molecule. This cyclic compound can link the

hydroxyl group of a second molecule ROH.

Figure 29: Cellulose and starch differ only for the stereochemistry of the glycosidic

linkage


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Carbohydrate chains, linked to proteins (glycoproteins) or lipids (glycolipids) decorate the cell walls and participate in cellular recognition phenomena responsible for cell adhesion, development, differentiation, morphogenesis, fertilization, immune response, signaling and other cellular events including cancer metastasis. To give an example, blood groups determinants A, B and H are constituted by a sugar sequence. In blood group determinant H an L-fucose links with an α-anomeric configuration the hydroxyl group in position two of D-galactose, which in turn links, with a β-anomeric configuration, a molecule of N-acetyl-D-glucosamine. In the determinant of blood group A, a further sugar, N-acetyl-D-galactosamine links position three of the D-galactose unit of the trisaccharide of group H. In the determinant of blood group for group B, D-galactose links position three of the D-galactose unit of the trisaccharide of group H. Carbohydrates have primary importance in food. Sucrose (Figure 15), the table sugar, is the main sweetener used in nutrition; this disaccharide is converted by the enzymes present in saliva into glucose and fructose, also used as sweeteners. The disadvantage of these sugars as sweeteners consists in the fact that they are caloric and favor dental caries by microbial oxidation of the aldehydes which generate the corresponding carboxylic acid. In order to avoid this problem, other sweet sugars lacking the aldehyde group have been used in the food industry: mannitol, sorbitol and xylitol are examples of widely used non carcinogenic sweeteners (Figure 30).

Figure 30: Monnitol, sorbitol and xylitol, three sugars used in the food industry as sweeteners

Less caloric sweeteners such as saccharin, which is 300 times as sweet as sucrose, and aspartame which is 200 times more sweet than sucrose, does not belong to the class of sugars (Figure 31).


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Figure 31: Non caloric sweeteners.

Starch, ubiquitous in our diet (bread, rice, pasta, pizza, …) is also degraded enzymatically into units of glucose which are used by the organism in glycolysis to get energy. 7.2. Amino Acids, Peptides and Proteins Proteins are polymers constituted by the 20 different amino acids shown in Figure 32. The amino acids are molecules that contain in the same structure an acid (the carboxylic acid) and a base (the amino group), therefore they exist as internal salts (zwitterions). All proteogenic (that generate proteins) amino acids are α-aminoacids, which means that the amino group is on the carbon atom adjacent (in position α) with respect to the carboxylic acid. Furthermore they are all chiral, except glycine, and the stereochemistry is L according to the Fisher descriptor (see Section 3.3). Depending on the nature of the side chain, amino acids are divided into not polar, polar and charged. The nature of the side chain is very important; as a matter of fact in proteins the carboxylic and the amino groups are involved in the linkage that generates the chain, whereas the side chains are responsible for the properties and functions. Structural proteins such as collagen are poorly functionalized; they are made mainly from glycine, which has no side chain. Functional proteins, such as enzymes, generate globular structures containing cavities (the active site of the enzyme). Depending on the size of the cavity, and the presence of non polar, polar or charged side chains in the active site of the enzyme, specific molecules (the substrates of the enzyme) can accommodate generating adequate attractive interactions, and undergoing the reaction that the enzyme catalyses.


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Figure 32: The 20 amino acids that constitute the proteins In living organisms amino acids are present not only in proteins; they also constitute peptides that play relevant physiological roles. An example, is angiotensine II, an octapeptide with potent vasoconstrictor activity.


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Amino acids are exploited by living organisms as starting materials to generate a variety of other metabolites. For example, adrenaline, the “fight or fly” hormone, is generated from the amino acid tyrosine (Figure 33).

Figure 33: The hormone adrenaline is generated from the amino acid tyrosine. There is currently great interest in aminoacids as nutraceutics (in sports and health care), and therefore industrial methods to synthesize them stereoselectively present industrial interest. 7.3. Nucleic Acids Nucleic acids, RNA and DNA, are the organic compounds responsible for the transmission of genetic information. They are polymers made by the sequence of monomeric entities formed by three different parts: a sugar, a “base” and a phosphate. The backbone of nucleic acids is essentially formed by the sugar, ribose in RNA and 2-deoxyribose in DNA, linked to each other through a phosphate bridge (see Figure 34). Each sugar links, at the anomeric centre, a so called “base”, that is an aromatic compound containing some nitrogen atoms (therefore termed as heteroaromatic compounds). Two bases, adenine (A) and guanine (G), contain two heteroaromatic fused cycles derived from a so called purine skeleton; these bases are also called purine bases. Two other bases, cytosine (C) and thymine (T) (uracil, U, in RNA) present a structure containing only one heteroaromatic cycle, derived from the skeleton of pyrimidine, which are therefore called pyrimidine bases. The chemical structure of the bases is made so that a couple of them, a purine and a pyrimidine, are “complementary”. Adenine is complementary to uracil in RNA or to thymine in DNA (A-U or A-T), whereas guanine is complementary to cytosine (G-C). This complementarity is due to the hydrogen bonds that can be generated between the two complementary bases (Figure 35) and allows the generation of a complementary filament of nucleic acid that is at the basis of the transmission of the genetic information. The two complementary filaments of DNA generate a double helix structure


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Figure 34: Nucleic acids, RNA and DNA

Figure 35: The complementarity of nucleic acid bases.


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The process by which DNA replicate themselves in the nucleus of cells is termed as replication. Replication of DNA begins by partial unwinding of the double helix, and the generation of a complementary chain. In each molecule of DNA therefore one chain comes from the original filament whereas the other is enzymatically synthesized choosing the complementary bases. RNA has a different role, it takes the information from DNA and utilizes this information for the synthesis of proteins. This is a complex process, in which three types of RNA are utilized, the messenger RNA ( m-RNA) that carries the genetic information from DNA to the ribosomes, where the proteins are synthesized; the ribosomial RNA (r-RNA) which generates ribosomes in combination with proteins; and the transfer RNA (t-RNA) which is able to transport specific amino acids to ribosomes, where they are joined together to generate proteins. Each of the 20 proteogenic amino acids has at least one t-RNA molecule that carries it to the ribosomes.

Figure 36: Adenine and phophorylated derivatives

The monomers constitute nucleic acids— the base linked to ribose that is called nucleoside (agenosine, guanosine, cytosine, uridine). The nucleoside phosphorylated in position 5 is defined nucleoside phosphate (or nucleotide) (Figure 36).


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Figure 37: The enzymatic glycosylation process is an example of utilization of

nucleoside diphosphate derivatives, in the specific case reported in figure, UDP-glucose.

Nucleosides and nucleoside phosphates are widely used in living organisms for roles other than the formation of nucleic acids. ATP (adenosyl triphosphate) for example is a molecule that furnishes energy in a good number of enzymatic processes. Nature exploits nucleotide triphosphates taking advantage of the high reactivity of the triphosphate group. One example of this utilization is the glycosylation process in which a sugar links at the anomeric position the hydroxyl group of another sugar (or a different


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molecule such as serine in glycoprotein synthesis). Glucose, for example, reacts with uridine triphosphate (UTP), to generate UDP-glucose and inorganic phosphate (Figure 37). UDP-Glucose reacts with the alcoholic function of another molecule with formation of the glycoside and liberation of UDP. 7.4. Lipids Lipids are hydrophobic biomolecules soluble in organic solvents and insoluble in water, displaying a wide range of biological functions in the cell. Lipids include a broad range of natural products, like fatty acids and their derivatives, carotenoids, terpenoids, steroids, bile acids. A most common type of lipid present in Nature is fatty acids. These are long chain carboxylic acids, with an even number of carbon atoms, as shown in Figure 7 for palmitic and oleic acid, Fatty acids are linked to glycerol, or to other alcohols such as cholesterol via an ester linkage, or to sphingoid bases via an amide bond. In addition they may contain alkyl moieties other than fatty acids, phosphoric acids, organic bases, carbohydrates and other components. Even if lipids cannot be grouped in terms of functional groups, they can be divided into two main categories: hydrolysable lipids such as waxes, triglycerides, phospholipids and glycolipids, and non-hydrolysable lipids such as terpenoids, steroids and some vitamins. Hydrolysable lipids are cleaved, by treatment with alkali, such as sodium hydroxide, into two components, one of which is invariably the salt of a fatty acid, a carboxylic acid with a long chain with an even number of carbon atoms. These salts constitute the soaps, and the process, which is known from the old times, is defined saponification. 7.4.1. Fats, Oils and Waxes Triglycerides constitute the common fats and oils, and play the main role of energetic reserves; they are formed by three fatty acids which esterify glycerine; an example is represented in Figure 20. Besides triglycerides, a variety of diacylglycerols are present in living organisms, the third hydroxyl group of which links a polar residue such as phosphatidyl choline (in phospholipids) or a sugar (in glycolipids) (Figure 38). Waxes are esters of fatty acids and long chain alcohols. 7.4.2. Phospholipids and Glycolipids Phospholipids and glycolipids are assembled in a double layer, so that the hydrophobic chain aggregates in the internal part, whereas the polar part is at the surfaces and interacts with the aqueous medium inside and outside the cell. The lipophilic internal part of the cell wall membrane plays a very important physiological role: polar compounds, including ions, cannot penetrate into the cell indiscriminately, but require specific mechanisms of transport.


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Figure 38; Hydrolysable lipids 7.4.3. Terpenoids Terpenoids are a wide variety of organic compounds formed by repeating five-carbon units called isoprene units (Figure 39). They can be linear, or cyclic, and can have heteroatoms, especially oxygen, included in their structure (Figure 40). Many essential oils isolated from plant sources by distillation, such as citral or cedral shown in Figure 40, are terpenoids.

Figure 39: The isoprene unit


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Figure 40: Terpenoids 7.4.4. Fat-soluble Vitamins

Figure 41: Fat-soluble vitamins Vitamins are organic compounds required in small quantities for normal metabolism, and usually cannot be synthesized by our body and must be taken up with the diet. Vitamins A, D, E and K are fat-soluble vitamins found in fruits and vegetables (Figure 41) Vitamin A is synthesized from β-carotene; in the organism it is oxidized to 11-cis-retinal (the corresponding aldehyde), the light sensitive compound responsible for


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vision in all vertebrates. It is also needed for healthy mucous membranes. A deficiency of vitamin A causes night blindness, as well as dry eyes and skin. Vitamin D3 is the most abundant of D vitamins; it can be synthesized by the body from cholesterol. Vitamin D is involved in calcium and phosphorus metabolism. Deficiency of vitamin D causes rickets, spinal curvature, and other deformities. The term vitamin E refers to a family of structurally similar compounds, the most biologically active being α-tocopherol (Figure 41). Vitamin E acts as antioxidant; a deficiency of vitamin E causes numerous neurological problems. Vitamin K (phyllokinone) regulates the synthesis of proteins needed for blood clotting. A deficiency of vitamin K leads to excessive and sometimes fatal bleeding. 7.4.5. Steroids Steroids are a class of organic compounds containing a common skeleton with four condensed cycles.

Figure 42: Steroids

Cholesterol, the most abundant steroid in animal tissue, has an important role in membranes and in lipid metabolism. Elevated cholesterol levels are associated with the pathogenesis of the cardiovascular system. Many other important steroids are hormones secreted by the endocrine glands, such as sex hormones (Figure 42). Estradiol and estrone are estrogens synthesized in the ovaries; they control the development of secondary sex characteristics in females and regulate the menstrual cycle. Testosterone and androsterone are androgens synthesized in the testes; they control the development


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of secondary sex characteristics in males. Progesterone (pregnancy hormone) is responsible for the preparation of the uterus for implantation of a fertilized egg. 8. Organic compounds in the market The market of organic compounds has reached an impressive level; it ranges from petroleum, currently the most abundant and economic source of starting materials for the chemical industry, to structurally complex and expensive medicinal drugs. The variety of organic compounds that find application and use explains the flourishing state of the chemical industry in developed countries, which strongly contributes to their economical growth. With regard to fossil reserves, we are now faced with the paradoxical situation that while crude oil (petroleum) is being consumed faster than ever, the “proven oil reserves” have remained at about the same level of thirty years ago as a consequence of new oil findings. Nevertheless, these “proven oil reserves” are located in increasingly difficult to reach places. Therefore, the cost of extracting crude oil rises continuously, as reflected in increasing oil prices. Agricultural by-products such as straw are 10 times less expensive than petroleum. The ability to use renewable materials is of utmost importance and has significant growth perspectives. It can be speculated that 5 billion tons of renewable materials could be used for the synthesis of approximately 1 billion tons of organic products, fully meeting our need for chemicals. We can divide the chemical market into two main categories, that of bulky-chemicals, low added value compounds produced in thousands of tons, and that of fine-chemicals, high added value compounds in some cases produced in kilos or even in grams scale (such as some vaccines for example). The methods of production, equipment and environmental impact of a chemical factory are quite different depending on which category of organic compounds it produces; developed countries tend to invest in the production of fine-chemicals. 8.1. Dyes The origin of the chemical industry goes back to the beginning of the XX century in Germany, when factories for the production of dyes from aniline were created. At that time dyes were obtained from natural sources and some of them, like carminic acid (Figure 43), the red pigment obtained from coccid insects, were very expensive.

Figure 43: Carminic acid.


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The reaction of aniline derivatives with sodium nitrite and hydrochloric acid affords a reactive compound, defined diazonium salt, which is able to react with aromatic compounds to generate a class of dies such as the “para red”, a cotton dye, or the butter yellow that was used as food coloring for margarine before being considered carcinogenic (Figure 44).

Figure 44: Synthetic dyes derived from aniline.

In general, dyes are compounds with an extensive presence of double bonds alternated with single bonds a characteristic, called conjugation that allows the absorption of light at the wavelength of the visible light (400-750 nm). The presence of heteroatoms such as oxygen, sulfur or nitrogen, modulates the color. Dyes are classified as natural dyes and synthetic dyes. As far as the structure concerns, synthetic dies are generally made from aromatic compounds, in order to take advantage of the extensive conjugation of double bonds present in aromatic compounds, and are divided into a) dyes derived from aniline, b) dyes derived from phenols, c) dyes derived from heteroaromatic compounds. It is interesting to mention that from the dye industry, an important class of antibacterial agents, the sulfonamides, was discovered. In 1913 it was serendipitously observed that one dye derived from aniline, crisoidine (Figure 44), showed antibacterial activity. Following this observation in 1927 at Farbenindustrie in Germany, a systematic study was made on the antibacterial activity of this class of dyes, and in 1932 prontosyl rubrum (Figure 44) a new dye with strong in vivo antibacterial activity was discovered. However, prontosyl rubrum did not show any activity in vitro. Subsequent studies indicated that the active molecule was the sulfonamide prontosyl album (Figure 45) produced in the organism by degradation of prontosyl rubrum. Prontosyl rubrum is therefore a pro-drug (a molecule that will generate a drug), whereas the real drug is prontosyl album. This example is an interesting case in which a discovery starts from an observation and proceeds with a clever and deliberate research. From this discovery a pharmaceutical industry had originated.


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Figure 45: Prontosyl album, a sulfonamide.

Figure 46: Some dyes approved by the FDA for use in food.

The pharmacological properties revealed by same dyes suggest that some of them could be dangerous for our health. Some dyes revealed in fact carcinogenic properties. The nature and chemical properties of the dye of choice depend on what must be colored: tissues, walls, plastics, paper and even food and beverages. Particular attention is actually devoted to the safety of dyes, in particular if they are used as additives in food and beverages or for food packaging. Some safe dyes, approved by the Food and Drug Administration (FDA) for use in food and ingested drugs, are shown in Figure 46. An interesting example of a safe dye of natural origin is astaxanthin, a pink pigment with a terpenoid structure that is used, inter alia, to feed sea-farm raised salmon to obtain the beautiful pink salmon meat. Wild salmons get the pigment from their natural diet.


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8.2. Compounds for Health Care The main classes of organic compounds used for health care are medicinal drugs, nutraceutics and cosmetics. The market of these compounds is very florid, and the added value in their production is particularly high. Medicinal drugs are the most important compounds for health care. From the use of herb extracts as medicaments, and the isolation of their active principles, medicinal chemistry has grown as a mature science that is able to understand the molecular mechanisms of many pathological phenomena and to design in a rational way new medicinal drugs. On the other hand, the cost of pharmaceutical research, from the design and synthesis of a new drug to the approval for medicinal use, is becoming more and more expensive, due to the increasing costs of the pharmacological studies required to certify the safety of the new compound. Antibiotics and their intermediates are among the most important fine chemicals, with a world market value of about 20 billion euro. Most antibiotics, such as penicillin, cephalosporin and tetracycline are products of the secondary metabolism of microorganisms, and therefore they are almost exclusively made by fermentation processes .The structural complexity of most antibiotics, such as tetracycline or streptomycin (Figure 47), is so great that chemical synthesis is problematic. Only in the case of so-called semi-synthetic antibiotics, the building blocks are obtained by fermentation, and subsequently chemically modifications generate new antibiotic derivatives with improved effectiveness. This is the case of penicillin (Figure 47), penicillin G is obtained by fermentation, whereas amoxicillin is a semi-synthetic drug.

Figure 47: Structure of some antibacterial agents.


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There are also examples of totally synthetic drugs, such as sulfonamides, as seen before, or benzodiazepines such as Valium (Figure 48), a widely used tranquillizer, obtained by systematic screening made on a wide variety of synthetic organic compounds.

Figure 48: Structure of Valium (Diazepam), a benzodiazepine

The theme of medicinal chemistry is described in Chemistry of Nutraceutics, Flavors, Dyes and Additives. Humanity has taken great advantage from the discoveries of medicinal chemistries, and many diseases have been defeated. Nutraceutics refers to compounds, such as vitamins, amino acids and other tonics and energizing substances that contribute to our health. The use of nutraceutics, as additives in food and beverages, or in pills for use in sports, is increasing mainly in developed countries not only among athletes but also in the public at large. Amino acids are increasingly used as supplements in human food and animal feed. The world-wide production of L-glutamic acid, for example, is over 1 million tons a year. It is one of the most important fermentation products with a tonnage comparable to many petrochemical products. Glutamic acid is used in the form of monosodium glutamate as a taste enhancer in many foods. L-lysine (350,000 t/year) is another large-scale produced amino acid, mainly used in animal feed. L-Phenylalanine is yet another amino acid, taking part in the synthesis of L-aspartame. L-Carnitin (Figure 49) is a vitamin-like natural component in animal tissues that stimulates lipid metabolism. Initially, L-carnitine was produced via chemical synthesis, but is now entirely made through a fermentation process, starting from renewable raw materials. The L-carnitine obtained in this way is very pure and is increasingly used as a food supplement for humans and animals since it stimulates their fat metabolism (more energy, reduced fat synthesis and increased growth).


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Figure 49: Carnitine, essential cofactor for fatty acid metabolism

Vitamins are important fine chemicals that are produced in relatively large quantities. Whereas a number of vitamins can be prepared only via biotechnology such as vitamin B12, other more simple vitamins can be produced by either a chemical route or a biotechnological route and quite often by a combination of both. The synthesis of vitamin B2 (riboflavin, 4,000 t/year) is a good example of this. The conventional process consisted in the synthesis of the building block D-ribose by fermentation with Bacillus bacteria, followed by a sequence of chemical reactions to obtain riboflavin. 8.3. Compounds for Food Industry Sweeteners, flavors, colorants, emulsifiers and preservatives are the main class of organic compounds that have found application in the food industry. The most important sweetener is sucrose, a sugar (disaccharide) known as table sugar. The limits of sucrose lie in its caloric content and induction of dental caries. Some sugar alcohols, such as sorbitol, xyliton and mannitol (Figure 50) are used in food industries as sweeteners that do not contribute to the formation of caries. Dietetic sweeteners are those compounds that, being some order of magnitude sweeter than sucrose, are used in quite small amounts. Moreover, some of them cannot be metabolized and therefore are not caloric. Aspartame (Figure 50) is an artificial sweetener 200 times sweeter than sugar. It is used in many foodstuffs, such as “light” beverages. Worldwide, around 15,000 tons of aspartame are produced each year at an approximate world market price of 35 €/kg. Saccharin (Figure 50) is 300 times sweeter than sucrose; it does not contribute energy or calories. Saccharin has been the centre of controversy for many years because of its alleged relationship with cancer; however, research studies have been unable to find direct associations. Cyclamate is 30 times sweeter than sucrose; is heat stable, and so can be used in hot and cold foods.


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Figure 50: Some common sweeteners

Flavors are more or less volatile substances produced by fruit or vegetables during different stages of ripening or during manipulation. In particular ripening is the main process through which fruit flavors are produced, while manipulation (like cutting or chewing) is the main cause of vegetable flavor generation. Natural flavors are generally due to a mixture of volatile organic compounds, and the difficult task is to mix them in an appropriate manner. Vanillin, the fragrance of vanilla; cinnamyl aldehyde, the fragrance of cinnamon; 4-Decalactone, a peach aroma; α-ionone, responsible for the flavor of violet, are just some examples of fragrances that find industrial application (Figure 51).

Figure 51: Some common flavors


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Food manufacturers add preservatives to the food preparation, which prevent spoilage. Preservatives serve as either antimicrobials or antioxidants or both. As antimicrobials, they prevent the growth of molds, yeasts and bacteria. As antioxidants, they keep foods from becoming rancid, browning, or developing black spots. Antioxidants suppress the reaction that occurs when foods combine with oxygen in the presence of light, heat, and some metals. Antioxidants also minimize the damage to some essential amino acids, the building blocks of proteins, and the loss of some vitamins. Antioxidant can be classified in two main classes according to their specific action: primary and secondary antioxidants. Primary antioxidants are compounds that interrupt the free-radical chain of oxidative reactions, themselves forming stable free radicals which do not initiate or propagate further oxidation of lipids. Some primary antioxidants are substituted phenols obtained by synthesis, such as butylated hydroxyanisole (BHA) or alkyl gallates, or of natural origin, such as tocopherols (Figure 52).

Figure 52: Examples of primary antioxidants Secondary antioxidants can also retard rancidity by different mechanisms. They can be reducing agents or "oxygen scavengers" or chelating agents. Ascorbic acid, citric acid, and ethylenediaminetetraacetic (EDTA) belong to this second class (Figure 53). Ascorbic acid functions as an oxygen scavenger, making it particularly useful in canned or bottled products with a headspace of air.


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Figure 53: Examples of secondary antioxidants Antimicrobial preservatives prevent the growth of molds, yeasts and bacteria. Among the most diffused antimicrobial agents there are benzoic acid and its esters, esters of p-hydroxybenzoic acid, sorbates, sulfur dioxide, nitrites and nitrates (Figure 54).

Figure 54: Examples of antimicrobial preservatives. Many food systems are composed of two incompatible substances: water (hydrophilic, polar) and oil (lipophilic, non-polar). Since oil and water are unmixable, they require mechanical agitation for dispersion. However, the contact between fat and water is energetically unfavorable, such dispersions are thermodynamically unstable. It is therefore necessary to incorporate emulsifiers and stabilizers in food emulsions to extend shelf life. Some common food emulsions are cream, butter, margarine, mayonnaise, salad dressing, sausage, ice cream, chocolate, milk, egg yolk and many others.


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Emulsifiers can be divided into two categories: small molecules such as mono- and diglycerides, sucrose esters, sorbitan esters (SPAN), polysorbates (TWEEN), stearoyl lactylates, lecithin and derivatives (Figure 55), and macromolecules such as proteins like bovine serum albumin, beta-lactoglobulin, lysozyme, and ovalbumin

Figure 55: Some common small molecular weight emulsifiers. An emulsion system can be stabilized by increasing the viscosity of the continuous phase. Gelatin and gums are not surface active at the interface; however, they are useful in stabilizing oil/water emulsions because of their effect on the viscosity of the aqueous phase. 8.4. Polymers Polymers (from the Greek words “poly” = many, and “meroi” = units) are long-chain molecules constituted by numerous repeating units of monomers linked together. Polymers can be either natural, like cellulose, DNA, proteins, or synthetic, like polystyrene. Both classes are relevant in our life and strongly contribute to our commodities. Fibers, such as cotton, silk, polyester fibers; plastic materials made by polyethylene, polystyrene; gums and resins have daily application.


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A large group of polymers behave as plastic materials. Every year around 100 billion tons of diverse plastics are currently produced in the world. The reasons for this commercial success are the low cost of precursors and simple processing, combined with good properties, such as low density, resistance to corrosion and mechanical strength. Several commodities for different applications are currently made of plastics such as any sort of packaging, shoppers, bottles for soft drinks, synthetic fibers, toys, car components, and furniture components and so on. Polymers are used also for advanced applications, such as biodegradable and biocompatible materials for surgery or for tissue regeneration, or techno-polymers with improved thermal and mechanical resistance for the aerospace industry and for any other advanced application, including sport. The largest use of plastics is in packaging, which account for about 30 percent of the annual plastics production. About 15 percent of plastics are used for heavy-duty building materials, and another 14 percent for consumer products. Other plastics are used in transportation products, furniture, agriculture, and various biomedical applications. Almost all plastics are made from oil or natural gas, which are presently the cheapest starting material. These sources however are non-renewable, and although plastics only account for six to eight percent of the total oil and gas consumption, this fraction looks significant in view of environmental considerations. Despite the size and efficiency of the world’s oil industry makes it the cheapest starting material for the production of organic compounds, research efforts are made in order to generate plastics from renewable sources. The production of plastics from renewable sources can be achieved by identifying sources of abundant polymers in Nature, or by producing monomers through bacterial fermentation or chemical modification of natural compounds, in particular carbohydrates. Typical polyesters that can be made from renewable resources are poly(glycolic acid) (PGA) and poly(lactic acid) (PLA), whose monomers are produced by fermentation. PLA is a rigid material which finds applications for thermoformed products such as containers, drink cups and so on. Most plastics have been engineered for being durable, despite most people use them once or a few times and then throw away. Durable plastics are persistent in the environment; therefore improperly disposed plastic materials are a significant source of environmental pollution. Recycling of conventional plastics is in principle a way of reducing the problems associated with plastic waste. De-polymerization technologies have also been developed that can return the plastics to their starting reagents. Incineration has the advantage that the plastics have high caloric values, but gas emissions must be taken under control to ensure that no toxic gases are released. Biodegradable plastics are particularly welcome for the production of disposable materials. Traditional candidates for biodegradable polymers are represented by polysaccharides, as for instance starch and cellulose grafted and blended to improve processability and physical properties. Poly(glycolic acid) (PGA) and poly(lactic acid) (PLA) are biodegradable and, as mentioned before, the monomers are produced by fermentation.


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Some biodegradable polymers can be generated by bacterial species from simple metabolic intermediates. This is the case of some polymeric materials collectively known as poly-hydroxyalkanoates (PHA). Naturally produced biodegradable polyesters are represented by poly-hydroxybutyrate-co-polyhydroxyhexanoates (PHBHs) copolymers, completely biodegradable under aerobic as well as anaerobic conditions, and are digestible in hot water under alkaline conditions. 9. Isolation, Purification and Analysis of Organic Compounds At the origin of organic chemistry the isolation, purification and determination of the structure of natural organic compounds fascinated numerous scientists, and required experimental ability, intelligence and fantasy. At that time the methods for the isolation of a single compound from a complex mixture were few and relatively naïf: extraction and partition between two immiscible solvents, usually water and chloroform or ethyl ether, and crystallization. Exploiting these procedures, and in particular taking advantage from the ionizable functional groups, carboxylic acids and amino groups, a variety of natural compounds have been isolated. The term alkaloids, for example, refers to a class of lipophilic natural compounds containing an amino group. These compounds can be isolated from the natural sources by extraction of all the lipophilic molecules with an organic solvent, then acidification, in order to convert the amino group of alkaloids into the corresponding ammonium salt, and extraction of the organic phase with water, in which the ammonium salt is soluble. Subsequent treatment of the aqueous phase with a base converts the ammonium salt into the corresponding amine, which is no more soluble is water and separates as solid precipitate or alternatively can be extracted with an organic solvent. A great variety of bioactive organic compounds, belonging to the class of alkaloids, such as cocaine, nicotine, adrenaline, morphine, stricnine, have been isolated from plant extracts exploiting this procedure. At the beginning of the XX century a new powerful separation technique was discovered: chromatography. In a paper published in 1906 Mikhail Tswett reported the separation of pigments of vegetal origin, among which chlorophyll, by filtration of the extract in petroleum ether on a column containing calcium carbonate. These results stimulated subsequent studies, that allowed us to develop different and very sophisticated chromatographic methodologies, which are all based on the “competition” between a stationary phase (in the first example sodium carbonate), and a mobile phase (in the first example petroleum ether) in the attractive interaction with the different compounds in the mixture. Compounds with higher affinity with the mobile phase will be transported faster through the stationary phase and vice versa. A great variety of different stationary and mobile phases, based on different type of interactions (adsorption, repartition, ionic, affinity, ..) have been developed, and nowadays chromatography is the most powerful method for separation and analysis of organic compounds. Once a single compound has been isolated, it is important to determine its structure. Chemists have two possibilities for structure determination: comparison with known compounds or ex novo determination. If the compound is already known, the comparison with an authentic sample could be enough. As with the finger print, this comparison is based on the identity of an adequate number of physico-chemical


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properties, such as boiling or melting points, chromatographic behavior and the spectra of adsorption of Infra Red light. With new instrumental techniques there is also the possibility of gaining structural information. Mass spectroscopy (MS) permits us to know the molecular weight of the compound and other structural information based on the usual and classified fragmentation patterns of organic compounds in the experimental conditions adopted. Nuclear Magnetic Resonances (NMR) affords precise information on the arrangement of hydrogen, carbon, nitrogen and phosphorous atoms in the organic molecule, that allow us to get the structure. X-rays provide a sort of “photo” that shows the arrangement of atoms in the molecule. Presently, the structure of even very complex organic molecules, such as some proteins, can be determined exploiting sophisticated instrumental analysis, and the presence of even small traces of undesired organic compounds in air, food and beverages can be detected. Accurate chemical analysis of the components allows us also to certify the origin of food and beverages, and detect adulterations, in other words furnish a robust contribution to the safety of our environment and alimentation. 10. Conclusions Organic and Bio-Molecular Chemistry contributes in so many ways to our healthy life and to our commodities, that in this short chapter it has been possible to mention just some of them. Most of the tools we use every day, such as the wheel of our car or the small bags in which the greengrocer put our fruit, comes from the polymerization technology that exploits organic compounds. The soap, the creams, the cosmetics, and much more important the medicinal drugs that we use for our health care, are all results of the organic chemistry research. There results have been obtained thanks to the results of the studies on the structure, the reactivity, the isolation and structural determination techniques that have been developed by the Organic Chemists since the 19th century. The progresses in this field will continue with the finding of new drugs, new materials, and new commodities. In this Encyclopedia the theme of Organic and Bio-Molecular Chemistry has been divided in 13 topics: 1) Organic Substances and Structures, Nomenclature of Organic Compounds, 2) Stereochemistry, 3) Organic Chemical Reactions, 4) Synthetic Organic Chemistry, 5) Organic Chemistry and Biological Systems –Biochemistry, 6) Chemistry of Natural Compounds, 7) Medicinal Chemistry, 8) Chemistry of Nutraceutics, Flavors, Dyes and Additives, 9) Computational Organic Chemistry, 10) Photochemistry, 11) Organo-metallic Chemistry, 12) Polymer Chemistry and Environmentally Degradable Polymers, 13) Organic Spectroscopy. The idea is to start with the structural aspects, then move to the reactivity and the synthesis, describe the relevant categories of organic compounds that find application, and finally discuss some methods of analysis. This choice of course is personal and certainly not exhaustive, but allow us to understand what Organic Chemistry is and what the potentialities of this science are. Glossary Activation energy:

the minimum amount of energy required for a molecule to perform a specific reaction


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Alkaloids: naturally occurring amines of vegetal origin Amino acids: organic compounds containing an amino and a carboxylic group,

20 of them constitute the proteins Aromatic compounds:

organic compounds presenting a special stability due to the circular delocalization of defined number of electrons.

Carbohydrates: defined also sugars or glycides, are a wide class of compounds present in living organisms.

Catalysis: is a phenomenon that accelerates a reaction. Catalyst: is a chemical species responsible for the catalysis, therefore

accelerating a reaction. Chirality: is a geometrical property that prevents us to superimpose an object

to its mirror image. Chromatography: is an important method for separation of organic compounds based

on the competition of the attractive interaction of the compounds to be separated between a stationary and a mobile phase.

Conformations: Different possible spatial arrangement of the atoms of a molecule. Dipole moment: a measure of the charge separation in a molecule Double bond: a covalent bond formed by the shearing of two couple of electrons

between adjacent atoms; is made by a σ-bond and a π-bond Electronegativity: The intrinsic ability of a chemical element to attract electrons. Enzyme: A protein that act as catalyst in the organism Emulsifier: refers to an organic compound used as additive in food to maintain

an emulsion and therefore preventing the separation of hydrophobic compounds from the aqueous phase.

Esterification: a chemical reaction that allow to link a carboxylic acid and an alcohol generating an ester.

Fatty acids: a class of natural compounds made by carboxylic acids with a linear chain with an even number of carbon atoms.

Fisher projection formulas:

a conventional method invented by Emil Fisher to describe the stereochemistry of chiral molecules, in particular sugars and amino acids.

Functional group: the group of atoms and the associated bonds that define the chemical behavior of a family of organic compounds.

Heteroaromatic compounds:

aromatic compounds presenting one or more heteroatoms in the cyclic structure responsible for the aromaticity.

Heteroatoms: in organic chemistry refers to all atoms except carbon and hydrogen.

Hybridisation: the different combination of atomic orbitals obtained by mathematical combination of the ground state atomic orbitals.

Hydrocarbons: organic compounds containing only carbon and hydrogen atoms. Hydrogen bond: the bond between a hydrogen atom linked to an heteroatom and a

second heteroatom. Hydrophilic: a term given to compounds that perform attractive interactions

with water, and therefore are water soluble. Hydrophobic: a term given to compounds that perform repulsive interactions

with water, and therefore are not water soluble. Inhibitor: a compound that inactivate a catalyst, such as an enzyme,

therefore lowering the reaction rate.


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Kinetic of the reaction:

studies the parameters that determine the speed of a chemical reaction.

Lipids: a class of natural compounds with the common feature to be hydrophobic.

London forces: instantaneous molecular dipole moments due to a induced asymmetric distribution of electrons in a molecule.

Monovalent: that can establish only one linkage. Nucleic acids: biomolecules formed by the sequence of nucleosides, a

phosphorylated sugar (ribose in RNA and deoxyribore in DNA) bonded to the purine or pyrimidine base, the sequence is generated via a phosphate bridge that links a sugar to the subsequent one.

Nucleoside: the portion of a nucleic acid that contains the sugar (ribose or deoxyribose), bonded to the purine or pyrimidine base.

Nucleotide: the portion of a nucleic acid that contains the phosphorylated sugar (ribose or deoxyribose), bonded to the purine or pyrimidine base.

Nutraceutics: compounds that find application in alimentation for health care, such as vitamins, amino acids, etc.

Polymers: high molecular weight compounds made of repeating units of small molecules, defined monomers.

Protein: natural occurring polymers made by a sequence of amino acids. Proteogenic amino acid:

refers to the 20 amino acids that constitute the proteins.

Purine bases: heteroaromatic bicyclic compounds, namely adenine and guanine, present in nucleic acids.

Pyrimidine bases: heteroaromatic compounds, namely cytosine, thymine and uracil, present in nucleic acids.

Saponification: the hydrolysis of esters in basic conditions, which generates salts of carboxylic acids (soaps in the case of long chain carboxylic acids)

Single bond: a covalent bond formed by the shearing of one couple of electrons between adjacent atoms; is made by a σ-bond

Stereogenic: refers to an atom bearing a number of different substituents (4 for the carbon atom) so that the interchange of two of them generate a different (non super-imposable) molecule.

Stereoisomers: refers to molecules that differ only for the arrangement of the atoms or groups in the space.

Steroids: a class of natural compounds containing a common skeleton with four condensed cycles, that perform important biological activities.

Terpenes: a class of natural compounds that originate biosynthetically by junction of isoprene units, a chemical entity with 5 carbon atoms.

Tetravalent: refers to an element that establishes four bonds, this is the case of the carbon atom.

Thermodynamic of a reaction:

studies the energy parameters associated to a chemical reaction.

Transition state: The point of maximum energy between reactants and products in a reaction.


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Triglycerides: a class of natural compounds, belonging to the so defined fats, that are made by three units of fatty acid linked to a molecule of glycerine.

Triple bond: a covalent bond formed by the shearing of three couple of electrons between adjacent atoms; is made by a σ-bond and two π-bond

Vitamins: organic compounds required in small quantities for normal metabolism, and usually cannot be synthesised by our body and must be taken up with the diet.

Zwitterion: a molecule presenting a positive and a negative charge. Bibliography The bibliography on Organic Chemistry is extremely wide, and most of the textbook are clear and exhaustive. Some books with different characteristics are reported as examples.

Gorzynski Smith J. (2006) Organic Chemistry, McGraw-Hill International edition, New York [a modern textbook that put into evidence the applications of organic compounds]

Schmid G. H. (1996) Organic Chemistry, Mosby-Year Book, Inc, St. Louis [an exhaustive didactic textbook of organic chemistry]

Bruice P. Y., (2004) Organic Chemistry 4th Edition, Pearson Education, Inc. [an exhaustive didactic textbook of organic chemistry]

Atkins R. C., Carey F. A. (2002) Organic Chemistry, a brief course, third edition, McGraw-Hill. New York. [a concise didactic textbook of Organic Chemistry]

Solomons T. W. G., (2005) Organic Chemistry 8th Edition Custom with Student Study Guide 8th, Wiley, New York [a widely appreciated textbook of Organic Chemistry]

Brown W. H. (1999) Introduction to Organic Chemistry: 2nd Edition. Wiley, New York [this introductory book emphasizes the interrelation between organic chemistry and the biological and health]

Clayden J., Greeves N., Warren S., Wothers P. (2001) Organic Chemistry. Oxford University Press [a concise introductory textbook of organic chemistry]

Biographical Sketch Francesco Nicotra was born in Catania in 1950. He graduated in Chemistry at the University of Catania in 1973; then he moved to the University of Milano where he became permanent researcher in 1981 and associated professor in 1987. In 1985 he spent a post-doc period at the University of Orleans, under the supervision of Pierre Sinay. Actually he is full professor of organic chemistry at the University of Milano Bicocca and Director of the Department of Biotechnology and Biosciences. He is member of the IUPAC Committee of Organic and Biomolecular Chemistry and chairman of the subcommittee of Biotechnology. He is also the Italian representative in the International Carbohydrate Organisation. The research interests ranges across the synthesis of various biologically active compounds, in particular carbohydrates and structural analogs, the development of new synthetic methods and the use of biocatalysis. To cite this chapter Francesco Nicotra, (2003), ORGANIC AND BIO-MOLECULAR CHEMISTRY, in Organic and Biomolecular Chemistry, [Ed. Francesco Nicotra], in Encyclopedia of Life Support Systems (EOLSS), Developed under the Auspices of the UNESCO, Eolss Publishers, Oxford ,UK, [http://www.eolss.net]


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