(1) Chapter title: Organic Chemistry Primer
(a) A list of vocabulary words is found toward the end of this document
(b) Life on Earth is carbon-based. That is, living things are made up, first and foremost, of carbon atoms bound to other carbon atoms, all floating around in a water solvent. Fortunately for life, carbon atoms are extremely versatile in how they bond to one another, as well as to non-carbon atoms. On the down side, this makes understanding the chemistry of "carbon compounds" central to understanding life at a molecular level. Thus, in an introductory biology course one tends to be immediately and relentlessly deluged with descriptions of carbon compounds. Consequently, it is crucial that you have at least a working understanding of organic chemistry. Since many attend their first biology course not necessarily first having been exposed to organic chemistry (e.g., in their inorganic chemistry class), I have assembled below a primer on organic chemistry for introductory biology students. Note that there is quite a bit more to organic chemistry than what is discussed below. However, the review provided here should provide you with more than enough organic chemistry to get you through your first course in biology.
(a) Organic compounds are molecules that, minimally, contain both carbon and hydrogen.
(b) This term is often used to describe compounds both derived from and not-derived from living organisms, but historically the first carbon and hydrogen compounds described were indeed derived from living organisms.
(c) If one is used to the common usage of organic (e.g., natural, unadultorated, not synthetic), then the definition of organic compound used here may be anti-intuitive since it implies that an organic compound may be synthesized in a laboratory and still be called an organic compound. In fact, a compound may be synthesized in a laboratory, be of a type that never, in the history of the earth, has been found associated with an organism, and still be called an organic compound. The common, lay usage of the word organic, though perhaps historically reasonable, is no longer scientifically valid and therefore not useful to your understanding of the concept organic compound, nor to one’s understanding of organic chemistry in general.
(a) Hydrocarbons are the simplest of organic compounds.
(b) Hydrocarbons may be branched or not branched and may or may not include double or even triple bonds between individual carbon atoms. The simplest of hydrocarbons are not-branched and contain only single bonds between carbon atoms.
(c) While many biological molecules have hydrocarbons at their cores, actual hydrocarbons (in this strict sense – molecules containing only hydrogen and carbon) are not very prevalent in biological systems.
(a) One thing that hydrocarbons are particularly adept at is displaying weak intermolecular interactions known as van der Waals interactions. Such interactions are weaker than hydrogen bonding and are very dependent on how well, spatially, hydrocarbons nestle in with one another.
(b) Often van der Waals interactions are the only thing only holding hydrocarbons together, which is why many of the smaller hydrocarbons are so often found as gasses (e.g., methane, butane, ethane, propane, etc.).
(a) The term isomer describes the relation one compound has to a second compound if the two compounds share chemical formulas but not structures (i.e., each represents a different arrangement of the same atoms). A branched and a not branched hydrocarbon, each containing the same types of bonds and the same number of carbon atoms would be examples of isomers.
(b) Since isomerization has so much do with structure, and structure so much to do with biological function, the type of isomers a chemical occurs as is usually of great relevance in biology.
(a) "Any of a group of isomers in which atoms are linked in the same order but differ in their spatial arrangement." (Webster medical dictionary)
(a) When a carbon atom has four different groups attached to it, then the resulting molecule can exist in two different forms together called optical isomers. This concept is a bit difficult to understand without an image to look at so I refer you to the links below.
(b) Two compounds that are true mirror images of each other, and still structurally different are enantiomers.
(b) Rings containing alternating double bonds are referred to as aromatic.
(a) Organic molecules really start getting interesting (and relevant to biological systems) when atoms in addition to hydrogen and carbon are present.
(b) These carbon-hydrogen-plus other elements compounds are called hydrocarbon derivatives (reflecting, of course, that, at least theoretically — i.e., conceptually if not operationally – hydrocarbon derivatives may be derived from hydrocarbons).
(b) Since the addition of these groups often dramatically changes the chemistry of an organic compound, we refer to them as functional groups. That is, their addition often results in the addition of a new chemical function to those associated with the bare hydrocarbon.
(a) A R group is a portion of a molecule other than a given functional group.
(b) We use the concept of R groups to indicate a region that may vary without drastically changing the chemistry of the explicitly described regions of the molecule that we are trying to understand. This idea will make more sense as we explicitly discuss various functional groups below such as alcohols = R-OH.
(a) The orientation of bonds about a carbon atom depends upon the number of bonds about that carbon atom.
(b) By and large, four bonds may be arranged in three dimensions as a tetrahedron, i.e., such that all four bonds are equally spaced about the central carbon atom (with 109.5° angles between them).
(c) By contrast, three atoms will arrange themselves into a plane so long as those are the only electrons present in carbon's outer shell. The angle between those bonds is more or less 120°. Note, however, that for three atoms to arrange themselves around a neutral carbon molecule, at least one of these atoms must be double bonded to carbon. Consequently, strings of hydrocarbons zig-zag, and do so regardless of whether they contain single or double bonds.
(d) A carbon triple bonded to another atom will tend also to be bonded to a second atom, and the two atoms to which it is bonded will be maximally separated with an 180° angle between them. That is, all three atoms are found in a straight line (i.e., H-CºC-H). Note, however, triple-bonded carbons don't play important roles in biological systems.
(e) A fact of life is that it is difficult to represent many of the bond orientations about carbon atoms in two-dimensions. Thus, the structure of hydrocarbons and their derivatives as rendered on paper should always be taken with a grain of salt, especially as those representations are drawn more and more simplistically.
(f) Various bond-geometry links: [index]
(vii) [delta blocks (fun with tetrahedron building blocks) (Hop’s Pages)]
(a) Often it is difficult to represent an organic compound on paper for reasons other than difficulties in correctly representing bond orientations. This is because bonds between carbon atoms, as well as bonds within and between functional groups, often display intermediate values due to the sharing of electrons in complex ways (classically one considers the molecule benzene, an aromatic hydrocarbon, in describing these intermediate values). These intermediate values play havoc with one's ability to infer chemical behavior from simplistic chemical representations of hydrocarbons and their derivatives. We call this tendency resonance (as in to resonate between more than one state).
(b) An important secret to understanding organic chemistry (and doing well in an organic chemistry course) is that odds are always good that the answer to any given difficult question is some sort of resonance that you have not yet noticed.
(c) Because organic compounds are crucial to the existence of life, and resonance is very important to understanding the chemistry of organic compounds, resonance, not surprisingly, plays important roles in biological systems.
(d) Fortunately, it is often good enough to memorize the consequences of resonance rather than routinely deriving chemistries from first principles. Indeed, for organic chemistry at the level it must be understood for an introductory biology course, it is above all most important for you to realize that 2-D representations of molecules are often misleading in part because of the existence of resonance.
(a) To facilitate the naming of hydrocarbon derivatives, carbons in compounds are often sequentally numbered (or named, depending on how long the structure has been known). In general, carbons are numbered starting at the end of carbon chains such that functional groups are bound to carbons having the lowest numbers.
(b) This numbering system has often been co-opted by biochemists to describe the orientation of polymers such as DNA. Also, one frequently comes upon numbers in the naming of the various products and intermediates of metabolism.
(a) An alcohol has attached to one or many of its carbons one or more hydroxyl group (generally no more than one per carbon). Thus, at the very least an alcohol has the structure C-OH (with additional hydrogen or carbon atoms, which are bound to the presented carbon, not shown).
(b) Note that the hydroxyl group does not dissociate from the carbon. However, as with water, the oxygen can take on a partial negative charge. Thus, alcohols can participate, through their hydroxyl group, in hydrogen bonding. Similarly, alcohols , can be hydrophilic, though alcohols with long hydrocarbon chains tend, instead, to dissolve poorly in water.
(c) Typical alcohols are shown below:
H-C-OH = methanol
H-C-C-OH = ethanol
(d) Other important alcohols (and alcohol-like things which have hydroxyl groups such as glycerol and carbohydrates) will be taken up in detail in subsequent lectures.
(a) An ether is an oxygen bridge between two organic compounds. For example: R-O-R'
(b) An alcohol is a special case of an ether, one in which one R is replaced with a hydrogen (for that matter, water could very well be considered to be an ether in which both R groups are replaced with hydrogens, though in this latter case one would no longer be referring to a organic compound).
(c) Conversely, the hydrogen of a hydroxyl group may be replaced with a organic compound. This is actually a fairly common occurrence in biological systems. It occurs when two alcohols join through the loss of a water molecule in a reaction called dehydration synthesis: R-OH + HO-R' à R-O-R' + HOH
(d) Note that the presence of an ether bridge between organic compounds tends to have minimal impact on the hydrophilicity of the molecule (e.g., such molecules will remain hydrophilic). Note also that molecules, especially polymers joined by ether bridges are extremely important in biology.
(18) Phosphodiester bond (phosphodiester link, phosphodiester bridge)
(a) A linkage between two carbons and a phosphate group (Pi) through two oxygens. Phosphodiester are formed through successive dehydration synthesis reactions and form much of the backbone of DNA and RNA.
3HC-OH + HO-CH3 + Pi à C-Pi-C + 2H2O
(a) A nitrogen atom bound to three atoms (through three single bonds) is called an amine. The simplest amine consists of nitrogen bound to two hydrogens and a single R group
(b) However, even when nitrogen is bound to two or more R groups it is still called an amine:
(c) Nitrogen is not as strong an electron acceptor as oxygen. Nevertheless, nitrogen is sufficiently strong an electron acceptor that nitrogen-bound hydrogens are capable of participating in hydrogen bonds. This plays important roles in hydrogen bonding between polymerized amino acids and, especially, between nitrogenous bases in both DNA and RNA. An amino group also is the amino in amino acid.
(d) Amines tend to be ionized at physiological pH, in particular accepting a proton to form, for example, 3HC-NH3+. This tendency to accept protons not only results in amines taking on positive charges, but also their acting as weak bases.
(a) A sulfhydryl goups is an -SH functional group.
(b) Similar to a hydroxyl group in some aspects of their chemistry, sulfhydryl groups are found in the R group of the amino acid cysteine, there forming the basis of chemical reactions within proteins that serve to internally bind together polypeptide chains.
(a) R-S-H is a thiol.
(b) In proteins, the sulfhydryl group of a cysteine (a thiol) link with a second sulfhydryl group belonging to a second cysteine (a second thiol) to form a disulfide bridge: R-S-S-R' which is also known as a cystine residue (i.e., two cysteines bound sulfhydryl to sulfhydryl).
(a) An alcohol represents a degree of oxidation of carbon over that exhibited by a hydrocarbon. In terms of hydrogens, think of the oxygen as being placed between a hydrogen and a carbon. This moves the hydrogen away from the carbon, thus oxidizing it:
H-C-H becomes H-C-O-H
(b) Next, imagine getting rid of the hydrogen attached to the oxygen all together (thus forming a carbonyl group). This would represent an additional level of oxidation of the carbon (the electrons are gone from the molecule). Note, however, that to make up for the loss of the electrons, the carbon and the oxygen must form a double bond between themselves. In order to accomplish this, not only must the hydrogen attached to the oxygen be removed, but a hydrogen attached to the carbon must be lost as well. Consequently one is left with an additional link to the chain that we began with above. This product is called an aldehyde:
H-C-O-H becomes C=O + 2H
(c) Or, more generally:
(d) Formaldehyde (2HC=O) and glutaraldehyde are both aldehydes. Aldehydes are found, often, among biological molecules including the linear forms of some sugars.
(a) A ketone is a generalization of the aldehyde concept. That is, the carbonyl group is found on an other-than-end carbon. Alternatively, one may envisage a ketone as an aldehyde which has the end carbon-bonded hydrogen replaced with an R group. Thus:
(b) Based simply on there being more non-end carbon carbons (in carbon chains) than there are end carbons, one would expect ketones to outnumber aldehydes among biologically relevant organic compounds. While I'm not willing to make such a sweeping generalization, it is true that a number of biologically relevant organic compounds are indeed ketones including glycolysis and Krebs citric acid cycle intermediates (both of which are biochemical pathways employed in the conversion of foods to energy), plus various sugars including fructose. Ketones can also be found among the nitrogenous bases of nucleic acids.
(b) Carboxylic acids represent an additional level of oxidation over that displayed by alcohols or aldehydes. That is, note, in the compound depicted above, that the carbon atom is bound to only a single non-oxygen atom.
(c) Carboxylic acids readily dissociate their hydroxyl-group hydrogen, hence the use of the term acid to describe them (this is driven by resonance as is so much in organic chemistry, i.e., the two oxygens may display an equivalent, energetically favorable, intermediate level of bonding to carbon, two "1.5" bonds, only so long as the hydrogen ion is lost; carboxylic acids do not, however, tend toward complete dissociation across the whole population of molecules and therefore are not strong acids such as HCl).
(d) Ignoring resonance, an ionized carboxylic acids takes on the following form:
R-C=O + H+
(e) Because this dissociation so readily occurs, carboxylic acids tend to be referred to as salts in well-buffered, metal-ion-rich biological solutions, rather than as acids. This ionization, too, results in carboxyl groups displaying significant hydrophilicity and water solubility.
(f) Carboxyl groups are all over the place in biological systems. For example, the acid in amino acid is a carboxyl group as are the acids in citric acid (a.k.a., tricarboxylic acid) and fatty acids (though not the acid in nucleic acids which instead is a phosphate group). Carboxyl groups are also present in the R groups of two amino acids, glutamic acid and aspartic acid.
R-C=O + HO-R' à R-C=O + HOH
(c) Note that the bridge formed between fatty acids (which are carboxylic acids containing a not-branched-hydrocarbon R group) and glycerol (an alcohol) to produce triglycerides (i.e., fats) is an ester.
(a) Carboxylic acids readily dissociate from their proton and these protons are readily replaced with a metal ion thus producing a salt derivative:
(b) Note two things: (i) At normal physiological pHs dissociation is the norm among carboxyl groups. (ii) Given this dissociation, buffered pHs, and the ready availability of metal ions, carboxylic acids are often spoken of in terms of their salts. Thus we say glutamate rather than glutamic acid when referring to this amino acid (or pyruvate or citrate, etc.).
(c) Very often, whether one uses one or the other terms (salt vs. acid) doesn't make a lot of difference when referring to biological systems (even if the two terms really aren't interchangeable, everyone knows what you mean), though it does make a big difference if you are pulling a reagent off of a shelf.
Begin with an amino group:
Replace one H with R’, yielding an amide:
Replace the remaining H with R’’ and it is still an amide:
(b) Amides are found in various amino-acid R groups such as asparagine and glutamine (note the suffix -ine which distinguishes them from the carboxylic acids or salts from which they are derived). Peptide bonds, too, are examples of amides.
(a) As described above in more detail, the degree to which a carbon atom has been oxidized can be discerned from the functional groups bound to it. Thus, in terms of functional groups and in order of increasing degrees of oxidation (indicated, to a degree, as the ratio of hydrogen, H, to carbon, C, atoms in the example molecule), there are:
(b) all hydrogens (e.g., 3HC-H; H/C = 4)
(c) three hydrogens and one hydroxyl group (e.g., 3HC-OH; H/C = 3)
(d) two hydrogens and one carbonyl group (e.g., 2HC=O; H/C = 2)
(e) one hydrogen and one carboxyl group (e.g., HCOOH; H/C = 1)
(f) and, finally, there is the inorganic carbon compound CO2 (H/C = 0) which represents carbon at its most oxidized (note that the carbon to hydrogen ratio has dropped to zero in carbon dioxide).
(e) Amino group
(f) Carbon dioxide
(g) Carbonyl group
(h) Carboxyl group
(i) Carboxylic acids
(n) Functional group
(o) Geometric isomer
(r) Hydroxyl group
(v) Optical isomer
(w) Organic compound
(bb) R group
(dd) Structural isomer
(a) Nebergall, W. H., Holtzclaw, H. F., Jr., Robinson, W. R. (1980). General chemistry. 6th edition. D. C. Heath and Co. Lexington, MA. pp. 662-683.
(b) Morrison, R. T. and Boyd, R. N. (1973). Organic chemistry. 3rd edition. Allyn and Bacon, Inc. Boston. various pages.