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IUPAC Chemical Reaction Representation
Version 4.1
November 18, 2013
IUPAC REPRESENTATION STANDARDS FOR CHEMICAL REACTIONS
Background and Goals
Although chemical structures and chemical reaction diagrams have been called “the language of chemistry”
[1], few documents have attempted to provide any sort of guidelines for the production of chemical
structure diagrams [XXX] or for the production of chemical reaction diagrams [XXX].
The task group that produced this document (with some changes of membership) has previously published
recommendations on the graphical representation of stereochemical configuration [XXX], and on graphical
representation standards for chemical structure diagrams (IUPAC Recommendations 2008) [XXX]. Although
some existing IUPAC nomenclature recommendations already discuss some aspects of chemical reaction
diagrams, they do so only tangentially. Even if they were to be collected in one location, these existing
IUPAC recommendations on chemical reaction diagrams are incomplete, and do not discuss many basic
issues.
This IUPAC project began informally with a “scoping exercise” in which some members of the chemistry
community were invited to discuss those aspects of creating chemical reaction diagrams that are amenable
to standardization through IUPAC recommendations. The participants in the scoping exercise also identified
several areas that are likely to be contentious or otherwise were incompletely specified; those areas will
receive specific attention during the course of the project and are likely to be postponed to a later phase.
Initial stages of this project have researched and examined existing guidelines and utilized these accepted
protocols as the framework on which to build more precise reaction descriptor and representation elements.
With the ever-increasing importance of electronic publication, this project has focused on issues related to
the production of chemical reaction diagrams both in printed and in electronic media. Where possible, every
effort has been made to ensure identical recommendations in all media. At some point in the near future,
recognition and interpretation of printed reactions into database-useful information will be a major outcome
of this project.
There are at least two distinct goals for establishing reaction representation guidelines.
1. Provide a system of representation that is universally recognized and adopted as standard in the
chemical community. The general considerations for this representation are:
 Chemical structures, arrows, conditions, yields and other data convey the same meaning to
all readers.
 Reaction modes are unambiguous.
 Representation is visually pleasing.
2. Drive software development toward the use of standardized formats and symbols that have
universal “electronic meaning”. This application distinguishes the product of this effort from the
graphic design nature of the first goal. Software developers can adopt these guidelines to provide:
 Tools for authors
 Tools for publishers
 Tools for database production:
 create chemical reactions
 search for chemical reactions
 capability for “OCR” of reactions
Contents
0. Introduction
1. Definitions
a. Chemical Reactions
b. Chemical Equations
c. Transformations
d. Chemical Equations
e. Chemical Schemes
f. Reagents and Reactants
g. Products
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h. Reaction Mechanism
i. Side Products
j. By-Products
k. Chemical Equilibrium
l. Solvents
m. Chemical Synthesis
n. Retrosynthesis
o. Metabolic Pathways
p. Catalysis and Catalysts
q. Enzymes
r. Other Biological Catalysts
s. Solvents
2. Use of Arrows in Chemical Equations and Schemes
A. Straight Arrows
A-1. Solid Arrows
A-2. Open Arrows
A-3. Double Arrows
A-4. Double Headed Arrows
A-5. Dashed Arrows
A-6. Broken Arrows
B. Curved Arrows
B-1. Curved Full-headed Arrows
B-2. Curved Half-headed Arrows
B-3. Looped Arrows
3. Placement of Reactants, Reagents, and Products in Depictions of Chemical Reactions and Transformations
A. Orientation of Reactants
B. Orientation of Products
C. Reaction Conditions and Representation
D. Product Results and Yields
4. Racemates and Enantiomers
5. Appearance
6. Further Considerations
SECTION 0. Introduction
The task group that produced this document (with some changes of membership) has also published
recommendations on the graphical representation of stereochemical configuration [XXX], and on graphical
representation standards for chemical structure diagrams (IUPAC Recommendations 2008) [XXX]. Although
some existing IUPAC nomenclature recommendations already discuss some aspects of chemical reaction
diagrams, they do so only tangentially. Even if they were to be collected in one location, these existing
IUPAC recommendations on chemical reaction diagrams are incomplete, and do not discuss many basic
issues.
Many organizations have formulated their own guidelines for creating chemical reaction diagrams. However,
none of those guidelines is comprehensive. Basic protocols for representing reactions can be found in
chemical textbooks, authors’ guides for chemical publications (such as Wiley-VCH and Elsevier), professional
society publications [such as American Chemical Society (ACS) and the Royal Society of Chemistry (RSC)],
and online. In the 430-page ACS Style Guide, the chapter on “Chemical Structures” occupies only XXXX
pages that include discussions of several topics in addition to simple representation [XXX]. Provision of a
single, comprehensive set of guidelines for creating chemical reaction diagrams will be a significant benefit
to the chemistry community. And yet chemists have strong feelings for how chemical reaction diagrams
should look, even in the absence of formal guidelines. Show most chemists a series of diagrams representing
something as simple as benzene, and there will be near-unanimity about which ones are “good” diagrams
and which ones are “bad”.
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Production of good chemical reaction diagrams will likely always remain something of an art form. There are
only a few cases where it can be said that a specific representation is “right” and that all others are “wrong”.
These guidelines do not try to do that. Rather, they try to codify the sorts of general rules that most
chemists understand intuitively but that have never been collected in a single printed document. Adherence
to these guidelines should help produce drawings that are likely to be interpreted the same way by most
chemists and, as importantly, that most chemists feel are “good-looking” diagrams. The most important
advice in any style guide is to know your audience. In the context of these recommendations, it follows that
the more specific the audience for a chemical reaction diagram, the less important it is for that diagram to
honor the guidelines discussed here. A chemical reaction diagram drawn on the back of a table napkin will
not be drawn with the same accuracy or precision as one that appears in a printed journal. There is nothing
wrong with that. A napkin drawing has an audience of one—your colleague on the next stool—while a
printed journal has a much broader audience.
The opposite, however, is not true. Chemical reaction diagrams drawn for a general audience can be
understood without problems by a more specific one. Your colleague on the next stool can surely understand
a nicely printed diagram if he or she can also understand your scribble-on-a-napkin. Accordingly, these
guidelines encourage those styles that are most likely to be understood by everyone and discourage the use
of unusual, archaic, and ambiguous drawing styles.
Throughout these guidelines, you will see two recurring themes: reduction of ambiguity and proper use of
context. With no context, a simple line might represent a single bond, half of a double bond, a free valence,
an iodine atom, or a negative charge. On occasion, it might even represent nothing more than a simple line
itself. Context is critical. The end of one bond should not touch the end of another unless they truly are both
bonded to the same atom. Text should not be placed near the end of a bond unless it is intended to be an
atom label, or is so visually different from other labels (in font, size, style, color, or some combination of
those) that it could not possibly be mistaken for an atom label. If you create diagrams that are difficult to
interpret, you should not be surprised if people have problems interpreting them.
In this digital age, more importantly, the same is true when creating reaction diagrams that need to be
interpreted by computer. In many ways, computers today are much more demanding than human chemists.
Few programs will interpret a block of text as being an atom label, no matter how close it is to the end of a
bond—unless the software is told, specifically, “That’s an atom label”. Fortunately, most software makes it
easy to do so. On the other hand, software programs may let you assign specific meanings to objects that
otherwise look identical, so that the symbol could be made to mean 17 connected carbon atoms without any
ambiguity at all. Whatever your audience, keep it in mind as you create your reaction diagrams.
The recommendations in this publication are presented approximately in the order that they should be
considered by an author who is creating a chemical reaction diagram. First, it is necessary to define the
terms that are used within the chemistry community to describe chemical processes. Then, it is necessary to
decide on basic drawing styles, including general issues such as depicted bond lengths, colors and font types
for both atom labels and conditions. Drawing styles specific to chemical structure diagrams also need to be
considered, primarily those related to the depiction of bonds and labeled atoms. Other common features,
including formal charges and un-paired electrons as well as delocalization have special needs that are
considered separately, while the depiction of salts and related ionic forms requires the relative positioning of
several fragments that have been depicted individually. Once the basic styles have been chosen, the reaction
diagram itself can be produced, starting with the overall orientation of the diagram and continuing until all
elements have been positioned. Various other issues are discussed in the remainder of the publication.
Throughout this publication are numerous examples of chemical reaction diagrams drawn in styles that are
labeled as “preferred”, “acceptable”, “not acceptable”, or occasionally “wrong”. Due to space constraints in
this document, only a few diagrams are shown for each case, with the intention that those examples are
representative of the topic being discussed. The presence of one diagram labeled as “preferred” does not
preclude the possibility of other “preferred” diagrams, including those with slight differences from the
depicted structure in terms of structure orientation, bond length, line thickness, localization of double bonds
in aromatic systems, or other minor details. Beyond that, it is worthwhile to clarify further the meaning of
those terms as they are used here.
A chemical reaction diagram is most commonly used simply as a means of describing a transformation, a
way to answer the implied question, “What is the chemical reaction of X and Y?”, or “How is X transformed
to Z?”. The styles labeled as “preferred” show how the reaction should best be depicted in such cases,
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where there are no other overriding concerns.
Sometimes, however, overriding concerns are present. The generation of an aesthetic diagram of the whole
reaction pathway might require that individual portions are depicted in ways that would not be ideal if that
portion were viewed in isolation. The diagrams labeled as “acceptable” indicate additional depiction styles
that could be considered if the preferred style is inappropriate for some well-considered reason. Many of the
reaction depictions included in this document are provided as counter-examples, offering clarification of how
chemical reactions should not be shown. Those depictions are labeled as “not acceptable”, indicating that
they should be strongly avoided in normal usage. Where possible, they have been accompanied by further
description of why they are not acceptable, and why the alternative depictions are preferred or more
acceptable.
Finally, a small number of examples are labeled as simply “wrong”. Those show representations that should
be avoided in all cases, generally because they depict something that is either self-contradictory or because
they accurately represent a reaction other than the one intended. For the sake of readability within this
paper, angular measurements of diagrams are listed with exact numerical values, such as 180°. Unless
otherwise specified, all such measurements should be considered to be approximate, and specifying a range
within roughly 10° of the listed value. The same applies to textual descriptions of angles, so the term
“collinear” should be interpreted as “forming an angle between 170° and 190°”. In other words, two bonds
that look nearly collinear should be treated as exactly collinear, even if that is not exactly true for their
actual geometric relationship. Similarly, any mention of bonds being “adjacent” or atoms being “connected
to” refers to their appearance in the two-dimensional representation. Any of the four bonds of an atom with
a physical (three-dimensional) tetrahedral configuration is physically adjacent to every other bond, but in a
two-dimensional representation it is depicted as adjacent to only two others, and “opposite” to the third. In
cyclohexane, each carbon atom is truly “connected to” four atoms: its two neighboring carbon atoms in the
ring, and two external hydrogen atoms. In most diagrams, however, cyclohexane will be depicted as a
regular hexagon with the hydrogen atoms implicit and not shown within the diagram. It is useful to describe
those carbon atoms as being connected to only two other atoms, the two neighboring carbon atoms that are
explicitly depicted. These conventions will be used throughout this publication.
The recommendations in this publication are intended for use in chemical reaction diagrams drawn in the
“standard” two-dimensional format where single bonds are represented with one line segment connecting a
pair of atoms, double bonds are represented with two parallel line segments connecting a pair of atoms,
atoms are labeled with atomic symbols (or not shown at all in the case of carbon atoms and the hydrogen
atoms bonded to them), and so on. There are other valid ways to represent structures including Newman
projections, ball-and-stick models, and many others. These recommendations should not be overgeneralized as applying to anything beyond the “standard” two-dimensional chemical reaction diagrams.
SECTION 1. Definitions
Chemical Reactions
A process that results in the interconversion by transformation or chemical change of chemical species.
Chemical reactions may be single step reactions or stepwise reactions (It should be noted that this definition
includes experimentally observable interconversions of conformers.) Detectable chemical reactions normally
involve sets of molecular entities as indicated by this definition, but it is often conceptually convenient to use
the term also for changes involving single molecular entities (i.e. 'microscopic chemical events'). (IUPAC Gold
Book)
A chemical reaction is a process that leads to the transformation of one set of chemical substances to
another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the
forming and breaking of chemical bonds between atoms, with no change to the nuclei (no change to the
elements present), and can often be described by a chemical equation.
The substances (or substance) initially involved in a chemical reaction are called reactants or reagents.
Chemical reactions are usually characterized by a transformation or chemical change, and they yield one or
more products, which usually have properties different from the reactants. Reactions often consist of a
sequence of individual sub-steps, the so-called elementary reactions, and the information on the precise
course of action is part of the reaction mechanism. Chemical reactions are described with chemical
equations, which graphically present the starting materials, end products, and sometimes intermediate
products and reaction conditions.
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Chemical reactions happen at a characteristic reaction rate at a given temperature and reactant
concentration. Spontaneous reactions are those that release free energy and move to a thermodynamically
stable energy state, although they may need activation by adding energy in the form of heat or light. Nonspontaneous reactions generally do not proceed in the forward direction, but rather in the revers
Different chemical reactions are used in combinations during chemical synthesis in order to form a desired
product. In biochemistry, a similar series of chemical reactions may be described as metabolic pathways.
These reactions are often catalyzed by enzymes. Such enzymes increase the rates of biochemical reactions
by lowering activation energies, so that metabolic syntheses and decompositions impossible under ordinary
conditions may be performed at the temperatures and concentrations present within a cell.
Transformations or Chemical Changes
Chemists more commonly use chemical transformations to show the conversion of a substrate into a
particular product, irrespective of reagents or mechanisms involved rather than chemical reactions. For
example, the transformation of aniline (C 6H5NH2) into N-phenylacetamide (C6H5NHCOCH3) may be
effected by use of acetyl chloride or acetic anhydride or ketene. A transformation is distinct from a reaction,
the full description of which would state or imply all the reactants and all the products. (IUPAC Gold Book)
Chemical changes occur when one substance reacts with another to form a new substance, called synthesis
or, alternatively, decomposes into two or more different substances. These processes are called chemical
reactions and, in general, are not reversible except by other chemical reactions. Some reactions produce
heat and are called exothermic reactions and others may require heat to enable the reaction to occur and
are called endothermic reactions. Understanding chemical changes is a major part of the science of
chemistry.
When chemical reactions occur, http://en.wikipedia.org/wiki/Atom chemical bonds rearrange and the reaction is
accompanied by an energy change as products are formed. An example of a chemical change is the reaction
between sodium and water to produce sodium hydroxide and hydrogen. So much energy is released that the
hydrogen gas released spontaneously burns in the air. This is an example of a chemical change because the
end products are chemically different from the substances before the reaction.
Chemical Equations
Symbolic representation of a chemical reaction where the reactant entities are shown on the left hand side
and the product entities on the right hand side separated by a directional arrow(s) wherein all reactants,
products are fully accounted for stoichiometry. The coefficients next to the symbols and formulae of entities
are the absolute values of the stoichiometric numbers. Different symbols are used to connect the reactants
and products with the following meanings: for a stoichiometric relation; for a net forward reaction; for a
reaction in both directions; for equilibrium. (IUPAC Gold Book)
A chemical equation is the symbolic representation of a chemical reaction where the reactant entities are
given on the left hand side and the product entities on the right hand side of a directional arrow. The
coefficients next to the symbols and formulas of entities are the absolute values of the stoichiometric
numbers. The first chemical equation was diagrammed by Jean Beguin in 1615.
A chemical equation consists of the chemical (or structural) formulas of the reactants (the starting
substances) and the chemical (or structural) formula of the products (substances formed in the chemical
reaction). The two are separated by an arrow symbol (
, usually read as "yields") and each individual
substance's chemical formula (either as starting material or product) is separated from others by a plus sign.
As an example, the equation for the reaction of hydrogen chloride with sodium can be denoted:
2HCl + 2Na
2NaCl + H2
This equation would be read as "two HCl plus two Na yields two NaCl and H two." But for equations involving
complex chemicals, rather than reading the letter and its subscript, the chemical formulas are read using
IUPAC nomenclature. Using IUPAC nomenclature, this equation would be read as "hydrochloric acid plus
sodium yields sodium chloride and hydrogen (gas)."
This equation indicates that sodium and hydrogen chloride react to form sodium chloride and hydrogen. It
also indicates that two sodium atoms are required for every two hydrochloric acid molecules and the
reaction will form two sodium chloride molecules and one diatomic molecule of hydrogen gas for every two
hydrochloric acid and two sodium molecules that react. The stoichiometric coefficients (the numbers in front
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of the chemical formulas) result from the law of conservation of mass and the law of conservation of charge
Chemical Schemes
A chemical scheme is most commonly used to represent chemical transformations wherein the reaction
components and products are not balanced (and thus differs from a chemical equation). Use of chemical
schemes simplifies the reaction representation to focus on the transformation of interest.
A chemical scheme is the symbolic representation of a chemical transformation where the reactant entities
are given on the left hand side and the product entities on the right hand side of a directional arrow.
A chemical scheme consists of the chemical (or structural) formulas of the reactants (the starting
substances) and the chemical (or structural) formula of the products (substances formed in the chemical
reaction). The two are separated by an arrow symbol (
, usually read as "yields") and each individual
substance's chemical formula (either as starting material or product) is separated from others by a plus sign.
Reagents and Reactants
A reactant is a substance that is consumed in the course of a chemical reaction. It is sometimes known,
especially in the older literature, as a reagent, but this term is better used in a more specialized sense as a
material that is added to a system in order to bring about a reaction on a reactant or to see whether a
reaction occurs (e.g. an analytical reagent). (IUPAC Gold Book)
A reagent is a "substance or compound that is added to a system in order to bring about a chemical
reaction, or added to see if a reaction occurs." Although the terms reactant and reagent are often used
interchangeably, a reactant is more specifically a "substance that is consumed in the course of a chemical
reaction" caused by a reagent. Solvents, although they are involved in the reaction, are usually not referred
to as reactants. Similarly, catalysts are not consumed by the reaction, so are not described as reactants.
In organic chemistry, reagents are compounds or mixtures, usually composed of inorganic or small organic
molecules that are used to effect a transformation on an organic substrate. Examples of organic reagents
include the Collins reagent, Fenton's reagent, Grignard reagent, etc.
Products
Substances that are formed during a chemical reaction. (IUPAC Gold Book)
Product(s) are formed during chemical reactions as reactants and reagents are consumed. The reactions
may require energy for their promotion or emit energy. The required energy may be in the from of heat,
light, microwave or others to promote changes in chemical bonds between atoms in reactants and reagent
molecules. Energy may be given off in the form of heat or light. Products are formed as the chemical
reaction progresses and reactants and reagents are consumed.
Depending on the relative amounts of the reagents and the equilibrium of the reaction, the terms "reactant"
and "product" may overlap.
But in the end, the product is the result of a chemical reaction.
Reaction Mechanism
A reaction mechanism depicts in detail what is believed to take place at each stage of an overall chemical
reaction (transformation). It depicts reactive intermediates, activated complexes, and transition states, and
which bonds break and which bonds form. “Electron pushing” usually is used as a method to explain a
reaction mechanism. A reaction mechanism should account for the order in which molecules react. Usually,
but not always, the depicted “steps” are not proven but are predicted from known chemical reactions.
Mechanisms show presumed reaction intermediates, often unstable and short-lived, which are not reactants
or products of the overall chemical reaction, but are temporary products or reactants. Reaction
intermediates are often free radicals or ions. Transition states can be unstable intermediate molecular states
even in the elementary reactions. Transition states are commonly molecular entities involving an unstable
number of bonds and/or unstable geometry. They correspond to maxima on the reaction coordinate, and to
saddle points on the potential energy surface for the reaction.
Catalysts lower energy requirements of transition states to promote the reaction.
Side products
A side product is the product of a side reaction resulting from alternative reaction pathways or by
subsequent degradation of the desired product. At times, side-products can be useful and marketable in
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their own right.
By-products
A by-product is a secondary (usually undesired) product derived from a chemical reaction. These are
frequently not shown in a reaction scheme, but are constituted of spent reagents, catalysts, and ligands. A
by-product is usually considered waste, By-product profiles can be used as ‘fingerprints’ to determine the
synthetic route that was used to synthesize the product. By-products, if they are not removed, can also lead
to undesired properties of the product, for example toxicity in a drug formulation.
Chemical Equilibrium
In a chemical reaction, chemical equilibrium is the state in which both reactants and products are present at
concentrations that have no further tendency to change with time. Usually, this state results when the
forward reaction proceeds at the same rate as the reverse reaction. The reaction rates of the forward and
backward reactions are generally not zero, but equal. Thus, there are no net changes in the concentrations
of the reactant(s) and product(s).
Chemical Synthesis
In chemistry, chemical synthesis is a purposeful execution of a chemical reaction(s) to obtain a product, or
several products, usually through several steps. This happens by physical and/or chemical manipulations
usually involving one or more reactions. In modern laboratory usage, this tends to imply that the process is
reproducible, reliable, and established to work in multiple laboratories.
A chemical synthesis begins by selection of compounds that are known as reagents or reactants. Various
reaction types can be applied to these to synthesize the product, or an intermediate product. This requires
mixing the compounds in a reaction vessel such as a chemical reactor or a simple round-bottom flask. Many
reactions require some form of work-up procedure to isolate and purify the product. The amount of product
in a chemical synthesis is the reaction yield. Typically, chemical yields are expressed as a weight in grams or
as a percentage of the total theoretical quantity of product that could be produced. A side reaction is an
unwanted chemical reaction taking place and that produces one or more by-products and diminishes the
yield of the desired product.
Retrosynthesis
Retrosynthetic analysis is a tool used to plan a (expected) multistep sequence of chemical reactions to
product a target chemical. It is a technique used for the planning of organic syntheses with the goal of
simplifying the target molecules in a backward synthetic progression. This is accomplished by breaking a
target molecule into simpler precursor structures using known chemical steps and without assumptions
regarding starting materials. Each precursor material is examined using the same method. This procedure is
repeated until simple or commercially available structures are reached.
Metabolic pathways
In biochemistry, metabolic pathways are series of chemical reactions occurring within a biological system. In
each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these
reactions, and often require dietary minerals, vitamins, and other cofactors in order to function properly.
Because of the many chemicals (a.k.a. "metabolites") that may be involved, metabolic pathways can be
quite elaborate. In addition, numerous distinct pathways co-exist. This collection of pathways is called the
metabolic network. Pathways are important to the maintenance of homeostasis within an organism.
Catabolic (break-down) and Anabolic (synthesis) pathways often work interdependently to create new
biomolecules as the final end-products.
A metabolic pathway involves the step-by-step modification of an initial molecule to form another product.
The resulting product can be used in one of three ways:
 To be used immediately,
 To initiate another metabolic pathway, called a flux generating step
 To be stored by the cell
A molecule called a substrate enters a metabolic pathway depending on the needs of the cell and the
availability of the substrate. An increase in concentration of anabolic and catabolic intermediates and/or endproducts may influence the metabolic rate for that particular pathway.
A chemical species or reactant, the reaction of which with some other chemical reagent or enzyme is under
observation (e.g. a compound that is transformed under the influence of a catalyst). The term should be
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used with care. Either the context or a specific statement should always make it clear which chemical
species in a reaction is regarded as the substrate. (IUPAC Gold Book).
In biochemistry, a substrate is a reactant molecule upon which an enzyme acts. Enzymes catalyze chemical
reactions involving the substrate(s). In the case of a single substrate, the substrate binds with the enzyme’s
active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or more
products that are then released from the active site. The active site is now free to accept another substrate
molecule. In the case of more than one substrate, these may bind in a particular order to the active site,
before reacting together to produce products.
For examples, curd formation (rennet coagulation) is a reaction that occurs when the enzyme rennin is
added to milk. In this reaction, the substrate is a milk protein (e.g., casein) and the enzyme is rennin. The
products are two polypeptides that have been formed by the cleavage of the larger peptide substrate.
Another example is the chemical decomposition of hydrogen peroxide carried out by the enzyme catalase. As
enzymes are catalysts, they are not changed by the reactions they carry out. The substrate(s), however,
is/are converted to product(s). Here, hydrogen peroxide is converted to water and oxygen gas.
E+S
ES
EP
E+P
where E = enzyme, S = substrate(s), P = product(s). While the first (binding) and third (unbinding) steps
are, in general, reversible, the middle step may be irreversible (as in the rennin and catalase reactions just
mentioned) or reversible (e.g., many reactions in the glycolysis metabolic pathway).
By increasing the substrate concentration, the rate of reaction will increase due to the likelihood that the
number of enzyme-substrate complexes will increase; this occurs until the enzyme concentration becomes
the limiting factor.
Catalysis and Catalysts
A substance that increases the rate of a reaction without modifying the overall standard Gibbs energy
change in the reaction; the process is called catalysis. The catalyst is both a reactant and product of the
reaction. The words catalyst and catalysis should not be used when the added substance reduces the rate of
reaction (see inhibitor). Catalysis can be classified as homogeneous catalysis, in which only one phase is
involved, and heterogeneous catalysis, in which the reaction occurs at or near an interface between phases.
Catalysis brought about by one of the products of a reaction is called autocatalysis. Catalysis brought about
by a group on a reactant molecule itself is called intramolecular catalysis. The term catalysis is also often
used when the substance is consumed in the reaction (for example: base-catalysed hydrolysis of esters).
Strictly, such a substance should be called an activator. (IUPAC Gold Book)
Catalysis is the increase in rate of a chemical reaction due to the participation of a substance called a
catalyst. Unlike other reagents in the chemical reaction, a catalyst is not consumed. A catalyst may
participate in multiple chemical transformations. The effect of a catalyst may vary due to the presence of
other substances known as inhibitors or poisons (which reduce the catalytic activity) or promoters (which
increase the activity). An enzyme is a type of catalyst.
Catalyzed reactions have a lower activation energy (rate-limiting free energy of activation) than the
corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature. However,
the mechanistic explanation of catalysis is complex. Catalysts may affect the reaction environment favorably,
or bind to the reagents to polarize bonds, e.g. acid catalysts for reactions of carbonyl compounds, or form
specific intermediates that are not produced naturally, such as osmate esters in osmium tetroxide-catalyzed
dihydroxylation of alkenes, or cause dissociation of reagents to reactive forms, such as chemisorbed
hydrogen in catalytic hydrogenation.
Kinetically, catalytic reactions are typical chemical reactions; i.e. the reaction rate depends on the frequency
of contact of the reactants in the rate-determining step. Usually, the catalyst participates in this slowest
step, and rates are limited by amount of catalyst and its activity. In heterogeneous catalysis, the diffusion of
reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterialbased catalyst is an example of a heterogeneous catalyst. Analogous events associated with substrate
binding and product dissociation apply to homogeneous catalysts.
Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, or destroyed
by secondary processes. In heterogeneous catalysis, typical secondary processes include coking where the
catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into
the solution in a solid–liquid system or evaporate in a solid–gas system.
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Enzymes
Macromolecules, mostly of protein nature, that function as (bio)catalysts by increasing the reaction rates. In
general, an enzyme catalyses only one reaction type (reaction specificity) and operates on only one type of
substrate (substrate specificity). Substrate molecules are attacked at the same site (regiospecificity) and only
one or preferentially one of the enantiomers of chiral substrates or of racemic mixtures is attacked
(stereospecificity). (IUPAC Gold Book)
Enzymes are catalytic proteins and are large biological molecules responsible for the thousands of chemical
interconversions that sustain life. Each enzyme is highly selective for a specific conversion. They are highly
selective catalysts, greatly accelerating both the rate and specificity of specific metabolic reactions, from the
digestion of food to the synthesis of DNA. Most enzymes are proteins that adopt a specific three-dimensional
structure, and may employ organic (e.g. biotin) and inorganic (e.g. magnesium ion) cofactors to assist in
catalysis.
In enzymatic reactions, the molecules at the beginning of the process (substrates) are converted into
different molecules called products. Almost all chemical reactions in a biological cell need enzymes in order
to occur at rates sufficient for life. Since enzymes are selective for their substrates and speed up only a few
reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic
pathways occur in that cell.
Enzyme activity can be affected by other molecules. Inhibitors are molecules that decrease enzyme activity;
activators are molecules that increase activity.
While enzymes catalyze natural processes, they have been used for a number of laboratory processes such
as kinetic resolutions to produce enantiomerically pure chemicals, among others.
Other Biological Catalysts
Besides the natural catalytic protein enzymes, there are other natural catalysts. Catalytic antibodies
(abzymes) are monoclonal antibodies that have catalytic activity. While some occur naturally, most abzymes
are artificially produced as a unique type of enzyme to effect a specific reaction by stabilizing an unstable
intermediate.
Ribozymes are RNA molecules capable of catalyzing specific biochemical reactions. Their catalytic activity
was identified in the early 1990s. Many natural ribozymes catalyze either the hydrolysis of one of their own
phosphodiester bonds, or the hydrolysis of bonds in other RNAs, as well as to catalyze the aminotransferase
activity of ribosomes. Since their discovery, modifications have been made for a variety of diagnostic and
therapeutic uses.
Deoxyribozymes are DNA molecules that have catalytic activity. In contrast to the RNA ribozymes, which
have many catalytic capabilities, in nature DNA is only associated with gene replication and nothing else. For
the most part, these molecules are limited to use for laboratory reactions.
Solvents
A liquid or solid phase containing more than one substance, when for convenience one (or more) substance,
which is called the solvent, is treated differently from the other substances, which are called solutes. When,
as is often but not necessarily the case, the sum of the mole fractions of solutes is small compared with
unity, the solution is called a dilute solution. A superscript attached to the
symbol for a property of a
solution denotes the property in the limit of infinite dilution. (IUPAC Gold Book)
A solvent (from the Latin solvō, "I loosen, untie, I solve") is a substance that dissolves a solute (a chemically
different liquid, solid or gas), resulting in a solution. A solvent is usually a liquid but can also be a solid or a
gas. The maximum quantity of solute that can dissolve in a specific volume of solvent varies with
temperature. Common uses for organic solvents are in dry cleaning (e.g., tetrachloroethylene), as paint
thinners (e.g., toluene, turpentine), as nail polish removers and glue solvents (acetone, methyl acetate, ethyl
acetate), in spot removers (e.g., hexane, petrol ether), in detergents (citrus terpenes), in perfumes
(ethanol), nail polish and in chemical synthesis. The use of inorganic solvents (other than water) is typically
limited to research chemistry and some technological processes.
Section 2. Arrows used in Chemical Equations and Schemes
A. Straight Arrows
A-1. Straight Arrows denote a forward chemical reaction or transformation. (
)
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CO2H
+
COCl2
A-2. Open Arrows denote a retrosynthetic reaction (or analysis). (
O
O2N
catalyst
O2 N
A-3. Double Arrows denote equilibrium or tautomerism (
)
or
)
preferred
These arrows denote a reversible reaction where, under normal conditions, both the starting material and
product coexist and/or interconvert. The position of an equilibrium may be denoted by one of the arrows
being longer than the other, showing that the equilibrium favors either the starting material or product.
NMe
NHMe
Equilibrium Favoring Products: (
)
Equilibrium Favoring Reactants: (
)
A-4. Double Headed Arrows denote resonance equivalence wherein no reaction is occurring but rather there
is electronic equivalence (
)
A-5. Dashed Arrows represent a theoretical reactions that are proposed (
)
or
A-6. Broken Arrows represent failed reactions (no reaction) (
)
B. Curved Arrows
B-1. Curved Full-headed Arrows denote:
a. electron-pair transfer to denote a mechanistic step of a chemical reaction
+
O
O
H
b. approach or elimination of reagents, fragments, etc. denoted in a mechanism of reaction
–Cl
H2O
H
Pd
Cl
H2 O
LnPd(0)
O
Cl
R
D
2 CuCl2
O
D
Cl
Pd
2 CuCl
R
O2 + 2 HCl
OH2
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B-2. Curved Half-headed Arrows denote mechanistic single electron processes, especially useful in describing
free radical chemistry.
H
H• + H•
H
B-3. Arrows containing closed loops denote rearrangement reactions
+
CH2NMe3 X–
CH3
CH2NMe2
NaNH2
Where does this go, if anywhere?
c. Curved Arrows for assignment of stereogenic descriptors
Cl
Me
H
F
Section 3. Placement of Reactants, Reagents, and Products in Depictions of Chemical Reactions
and Transformations
Organic Chemistry
An organic chemical reaction in which substrates are treated with reagents, catalysts, and/or additives under
defined conditions to give products is typically represented as a transformation in a chemical scheme. The
substrates are placed on the right side of the arrow, which points left to right. Multiple substrates, or
reactants, are separated by a plus sign. The products are placed at the head end of the arrow. Multiple
products are separated by a plus sign. Typically the yield is placed in parentheses near the product, or under
the arrow.
Chemical Scheme
Br
H2N
CO2H
+
H
N
CuCl (20 mol %), aq TBAH
CO2H
(41%)
MeCN, reflux, 24 h
The example shown includes a catalyst (CuCl), and an additive (TBAH). These are "reagents", and are
written over the arrow. Stoichiometric amounts of the reagents are written either before the reagent, or in
parentheses behind the reagent.
The solvent (MeCN in this example) is not typically a reagent.
The temperature and time are variables that every reaction is subject to. That is to say, there is always a
temperature and a time associated with a given reaction, even if it is instantaneous. Some adopt the
convention of putting the solvent, temperature, and time under the arrow.
Other data that may be included in a reaction are ratios of stereoisomers (geometric, optical), generally
written as er (enantiomer ratio), dr (diastereomer ratio), ( R)/(S), (E)/(Z), etc. The placement of this data is
usually under the structure.
Inorganic Chemistry
The conventions for representing an inorganic reaction are similar. More often, the chemical reactions are
balanced and thus depicted as chemical equations.
Chemical Equation
Cu
+
2NO3–
+
4H+
2NO2
+
Cu2+
+
2H2O
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In this example, there are no reagents shown and it appears the reaction proceeds spontaneously. Thus
there is no information either above or below the arrow.
Orientation of Reactants
Orientation of Products
Reaction Conditions and Representation
Product Results and Yields
Section 4. Racemates and Enantiomers
Section 5. Appearance
Presentation media
For the most part, these guidelines are written as in the context of a “perfect” presentation medium, where
nothing will detract from the chemical reaction diagrams themselves. Practical reality will rarely be that
simple. Some styles that have been recommended for various printed publications are shown and contrasted
in Table I, demonstrating the wide range of well-considered styles that are possible even within a single
medium but become significant across media. For example, when preparing diagrams for a low-resolution
format such as the World Wide Web, it might be appropriate to make diagrams slightly larger or use a larger
font than in printed journals, so that the diagrams can be read more easily on the computer screen.
Presentations in printed journals have an absolute maximum width physically determined by the page size of
that journal, and structures have to be sized and positioned accordingly. It is certainly reasonable (and
altogether proper) to consider how the structures will eventually be presented and processed. There is no
problem in deviating from these guidelines whenever necessary.
The prevalence of computers in chemical research provides some special problems. Compared to the
number of human chemists, there are very few computer applications designed to process (display, store,
search, analyze, etc.) chemical reaction diagrams. Chemical reactions that are likely to be interpreted by
computer must be considered as having an extremely specific audience, and a fairly stupid one at that. Even
the best computer programs available today are quite sensitive to the way that reactions are drawn. These
programs will surely become more intelligent over time, but they will not rival human intelligence in the near
future. In addition to being easily interpretable by humans, structures drawn in the recommended styles are
much more likely to be interpreted correctly by computers.
In some cases, no computer software currently available will be able to interpret a depiction that is
otherwise completely reasonable, even preferred. We have tried to indicate those cases clearly, in sections
of this document labeled with the phrase “SOFTWARE CAUTION:”, and we hope and expect that software
will evolve over time. If chemical reaction diagrams are required that must be interpreted by computers
now—for example, for entry in a chemical laboratory notebook—it is particularly important to understand the
strengths and limitations of the software you are currently using. Again, structure drawings that follow these
guidelines are more likely to be interpreted correctly than those that do not.
Text
Any roman font is acceptable, but plainer fonts are preferred. Times, Times New Roman, Helvetica, and Arial
are the most commonly seen serif and sans serif fonts, but that list is not exclusive. Normally, the fonts used
in a chemical reaction diagram should match those used in any associated text, or be different from them in
a clearly visible way (such as serif vs. sans serif). Text should be scaled to a size that is comfortable for
reading. In printed materials, that is usually in the range of 8–14 points. In other media, different sizes
might be appropriate; in posters or projections, for example, a much larger size might be required. When
increasing the size of text, it will usually also be necessary to increase the length of the bonds in the
structure diagram somewhat proportionally. Text that is smaller than six points in size is too small for most
people to read comfortably, and is therefore not acceptable. Formatting of text, including bold, italic, and
underlined styles, should follow standard (non-chemical) style guidelines. For the most part, that means that
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the majority of text should be unformatted. Formatted text could be reasonably used to draw emphasis to a
portion of a diagram; if emphasis is required, bold formatting is preferred over the use of italics or
underlining because it provides a greater visual difference.
Within the realm of biochemical reaction diagrams only, the capital P symbol has different meanings
depending on whether it is roman (a phosphorus atom) or italic (an abbreviation that represents a
hydroxyphosphoryl or dihydroxyphosphoryl moiety in a phosphate group [XXX]). Due to the long history of
usage, both the roman and italic forms of the capital P must remain acceptable; however, authors should
consider that the italicized version may be unfamiliar to readers who are not familiar with biochemical
nomenclature. Also, from the perspective of computer interpretation, such different meanings will likely
cause error. For the broadest understanding, it is preferable to depict the phosphorus-containing fragments
fully with explicit atoms and bonds. It is not acceptable to create new abbreviations whose meaning is
changed by the presence or absence of text formatting. The formatting for text should be used consistently
throughout the diagram, whatever specific fonts, font sizes, and font styles are chosen. It is not acceptable
to use multiple fonts and styles within a single diagram, again with intentional emphasis being an exception.
Within those general guidelines, many publications have specific preferences regarding the use of text.
When producing diagrams that are to be used by someone else, it is always recommended that authors
check if there are any additional preferences that need to be followed.
Lines
Lines are most commonly used in chemical reaction diagrams to represent bonds, but may also be used in a
strictly graphical sense, for example, to divide a larger space or as the shaft of an arrow. Most lines should
be drawn at a width that is consistent with the remainder of the drawing, usually close to the width of the
strokes of any accompanying text. Lines that are thinner than 0.5 points should be avoided. Thicker lines
should be reserved for places where emphasis is required or (when drawn as bonds) to emphasize
perspective. Within those general guidelines, many publications have specific preferences regarding line
widths just as they often do for text. When producing diagrams that are to be used by someone else, it is
always recommended that authors check if there are any additional preferences that need to be followed.
Colors
Except when emphasis is desired, use of color should be avoided, and chemical structures should be
displayed in the same color as any associated material. Most commonly, that means that the structures
should be displayed in black on a white background, although some circumstances prefer alternative coloring
schemes (projected transparencies are often displayed as white or yellow on a dark blue or black
background).
When emphasis is desired, colors may be used to provide that emphasis. Any colors used in a document
should be clear and visually distinct. Most commonly, red would be used as the primary color for emphasis.
A dark blue or dark gray color is likely a very poor choice for emphasis in a diagram that is mostly black, and
similar choices of low-contrast color combinations should be avoided. Authors are encouraged to remember
that roughly 10% of men are color blind [XXX]. The combined use of red and green as contrasting colors in
one diagram is strongly discouraged.
Size of diagrams
For the most part, the overall size of a chemical structure diagram will be determined by the size chosen as
the length of a standard bond and by the recommended angles between bonds in various circumstances as
described in the remainder of this document. Although computers can store diagrams of any size, there are
many other situations that impose restrictions on the space available for each chemical reaction diagram. In
printed journals, for example, there is an absolute restriction that every structure must fit on the physical
page, and the structures will often need to fit within specific column widths as well. Similarly, low-resolution
media, such as the World Wide Web, may require a larger diagram overall in order to maintain legibility of
fine details. For very large, rigid molecules, there is little option but to shrink the diagram uniformly as much
as necessary as to fit within the space available. When diagrams are resized, they should always be resized
uniformly in both dimensions at the same time, and any associated text (such as atom labels) should be
resized by the same amount.
As discussed, it is not acceptable to reduce the size of a diagram if doing so would produce atom labels that
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are illegibly small. If a portion of a structure diagram is normally depicted in a standard orientation, that
portion should remain fixed and only the other portion should be rotated.
Section 6. Further Considerations