Chemical Structures - ACS Publications - American Chemical Society

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CHAPTER 17

Chemical Structures Antony Williams

T

he communication of chemical structures is inherently visual, so the language of both chemistry and biochemistry would be sparse without the ability to accurately represent chemistry in a graphical format. Scientific manuscripts today benefit from the visually appealing output of software used to generate structure representations conveying the details of molecular connectivity as well as the details associated with chemical structures, reactions, and schemes. This chapter discusses the use of chemical structures; the related reactions, charts, and schemes, in a scientific manuscript; and methods of preparing and submitting structures for publication. The chapter presents general guidelines; authors should consult with their publishers for specific instructions.

When To Use Structures A chemical structure is a pictorial representation of the bonding of atoms in a molecule. Chemical structures appear within text at the point at which they are discussed. Structures are numbered sequentially with either arabic or roman numerals; consult the publisher’s guidelines to determine if one is preferred over the other. Generally, there is no need to provide graphical representations of structures for materials that can be accurately represented on one line or in the form of text. For scientific publications, structures should be included for clarity of communication only. For example, papers describing previously unreported syntheses or reaction sequences, structure–activity relationships, or newly discovered chemical compounds make good use of chemical structure images. Simple chemical strucCopyright 2006 American Chemical Society In The ACS Style Guide; Coghill, A., et al.; The ACS Style Guide; American Chemical Society: Washington, DC, 2006.

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➤ The ACS Style Guide O O

O

O

OH

OH H

O

HN

HO O

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O

O

O O

O

Figure 17-1. Example of a chemical structure.

tures can often be represented by a line formula, such as C6H5COOH or 1,2,4Br3C6H3, or by the systematic name of the compound, such as benzoic acid or 1,2,4-tribromobenzene, but complex chemical structures depend on structural representations exhibiting the atom–atom connectivity, including the order and stereochemistry of the bonds. Even though a systematic name can accurately describe the chemical structure of paclitaxel, specifically, (2aR,4S,4aS,6R,9S, 11S,12S,12aR,12bS)-6,12b-diacetoxy-9-{[(2R,3S)-3-(benzoylamino)-2-hydroxy3-phenylpropanoyl]oxy}-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a, 5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2b]oxet-12-yl benzoate), most chemists would prefer to visualize the structure (shown in Figure 17-1).

✐ Reminder: Simple chemical structures can often be represented by a line

formula or by the systematic name of the compound, but complex chemical structures depend on structural representations exhibiting the atom–atom connectivity, including the order and stereochemistry of the bonds.

A chemical reaction is a pictorial representation of a change or process. Reactions can be represented with either line formulas or structures; they are placed in text and numbered much like mathematical equations. See pp 272–274 of Chapter 13 for information on how to format chemical reactions. Groups of structures are called charts. Charts contain representations of multiple structures to facilitate discussion of them. Groups of reactions are called schemes; as shown in Figure 17-2, several reactions can be presented together to show, for example, a step-by-step process. Schemes show action; charts do not.

How To Cite Structures ➤ Structures are identified in text with boldface numerals (either arabic or

roman), boldface alphabet letters (capital or lowercase), or a combination of

In The ACS Style Guide; Coghill, A., et al.; The ACS Style Guide; American Chemical Society: Washington, DC, 2006.

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Scheme 1 Sn (Closed form)

1 ms)

Ph

Ph O EEZ (48 µs) Major isomer

Figure 17-2. Example of a scheme representing a group of reactions. Representing work reported by Kodama, Y.; Nakabayashi, T.; Segawa, K.; Hattori, E.; Sakuragi, M.; Nishi, N.; Sakuragi, H. J. Phys. Chem. A 2000, 104, 11478.

these. (These numbers should also appear as labels on the structures themselves.) For several structures or for a series of structures, use a consistent sequence of labels. Typical series may include the following: 1, 2, 3 I, II, III A, B, C

a, b, c 1a, 1b, 1c Ia, Ib, Ic

1A, 1B, 1C IA, IB, IC

If a compound is mentioned several times within the text, refer to it only by its label (e.g., “as shown by the reaction with 9”). Do not include or label structures that are not discussed in the text. ➤ Chemical reactions set as equations should be labeled with lightface roman

letters, numerals, or combinations in parentheses in the right margin (see Chapter 13). Depending on the text, it may be appropriate to use one set of labels for both chemical reactions and mathematical equations, or two separate and distinct numbering sequences (for instance, eqs 1, 2, 3, … and reactions I, II, III, …). The numbering sequences for structures and for reactions should always remain separate.

✐ Reminder: If a compound is mentioned several times within the text, refer to it only by its label.

➤ Charts are numbered consecutively as Chart 1, Chart 2, and so on, with either

arabic or roman numerals. Charts should be labeled with “Chart” and a number; they also may have brief titles and footnotes.

In The ACS Style Guide; Coghill, A., et al.; The ACS Style Guide; American Chemical Society: Washington, DC, 2006.

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➤ Schemes are numbered consecutively as Scheme 1, Scheme 2, and so on, with

either arabic or roman numerals. Schemes should be labeled with “Scheme” and a number; they also may have brief titles and footnotes.

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How To Prepare Structures The quality and size requirements for structures (and, by extension, reactions, schemes, and charts) are similar to those for other illustrations (see Chapter 15). The requirements associated with the representation of structures are supported by most of the software programs for drawing chemical structures (described in Box 17-1). The following guidelines should be used when creating the graphics for chemical structures. ➤ Arrange structures in horizontal rows within the width of a column. ➤ Make the size of the rings and the size of the type proportional. The published size of six-membered rings should be approximately ¼ in. (6.35 mm) in diameter; the published size of five-membered rings should be slightly smaller. The type size should be 5–8 points. ➤ Keep oddly shaped rings and the shapes of bicyclic structures consistent

throughout a manuscript. In multiring structures such as steroids, use partial structures that show only the pertinent points. ➤ In three-dimensional drawings, use dashed lines for lines in the background

that are crossed by lines in the foreground to give a greater three-dimensional effect. Make lines in the foreground heavier, as shown below.

➤ Center the compound labels (either numbers or letters) just below the structures. If a series of related compounds are being discussed, draw only one parent structure, use a general designation (e.g., R or Ar) at the position(s) where the substituents differ, and specify modifications below the structure.

✐ Reminder: Take care that the structure graphic inserted into your text

file is of sufficient resolution, that is, 300 ppi minimum, with 600 or 1200 ppi even better.

➤ For structures mentioned in tables, provide labeled structures as separate art-

work (in text or charts), and use only their labels in the table.

In The ACS Style Guide; Coghill, A., et al.; The ACS Style Guide; American Chemical Society: Washington, DC, 2006.

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➤ Center the reaction arrows vertically on the midline of the structure height

and align the centers of all structures. The midline for all structures is the center of the “tallest” structure on the same line.

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An example of a correctly drawn reaction is represented below. As shown, the arrow and the one-line structure are centered, top to bottom, in the height of the full structure. The reaction arrow and the plus sign have an equal amount of space on both sides. O R4

O

N

OH + H N 2

R'

R4

O

N R' N H

➤ Do not waste space, either vertical or horizontal. Use the full column width

before starting a new line. A compact presentation is most effective. Avoid using vertical arrows unless it is necessary to portray a cyclic or “square” reaction scheme. Schemes generally read from left to right. As long as the proper sequence is maintained, it does not matter on which line any given structure appears. If a reaction continues to the next line, keep the arrow or other operator on the top line. Refrain from the use of double-column-width charts or schemes unless absolutely necessary because these charts and schemes consume a significant amount of space. ➤ Do not place circles around plus or minus signs. ➤ For most chemical structure drawing programs, it works best to use the

copy-and-paste feature to insert the structure drawing into a Microsoft Word document. However, you should take care that the structure graphic inserted into your text file is of sufficient resolution, that is, 300 ppi minimum, with 600 or 1200 ppi even better. The author bears the responsibility to ensure the appropriate insertion.

Software for Creating Chemical Structures A number of chemical structure drawing and rendering programs are available to create structure images of excellent quality and accuracy for inclusion in scientific publications. The most popular commercial structure-drawing packages today include ISIS/Draw, ChemDraw, and ChemSketch (see Box 17-1). Other commercial packages include ChemWindow (now known as DrawIt) and Chemistry 4-D Draw. At this time, Web-based applets do not support the production of graphical output of sufficient quality for most books and journals; other software, such as JMol, should be considered as structure-rendering engines only. Box 17-2 contains parameter settings for ACS publications.

In The ACS Style Guide; Coghill, A., et al.; The ACS Style Guide; American Chemical Society: Washington, DC, 2006.

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Box 17-1. Software for Drawing Chemical Structures

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The following is a selection of commercially available software for drawing chemical structures suitable for publication. ChemDraw: Cambridgesoft, 100 CambridgePark Drive, Cambridge, MA 02140. Commercial: http://www.chemdraw.com. Chemistry 4-D Draw: Cheminnovation, 7966 Arjons Dr, #A-201, San Diego, CA 92126. Commercial: http://www.cheminnovation.com/products/ chem4d.asp. ChemSketch: Advanced Chemistry Development, 110 Yonge Street, 14th Floor, Toronto, Ontario M5C 1T4, Canada. Commercial: http:// www.acdlabs.com/products/chem_dsn_lab/chemsketch/. Freeware: http://www.freechemsketch.com. DrawIt (formerly ChemWindow): Bio-Rad, Informatics, Sadtler Group, 3316 Spring Garden Street, Philadelphia, PA 19104-2596. Commercial: http://www.knowitall.com/. ISIS/Draw: Elsevier MDL, 14600 Catalina Street, San Leandro, CA 94577. Commercial: http://www.mdli.com/products/framework/isis_draw/index.jsp. Freeware: http://www.mdli.com/downloads/downloadable/index.jsp. MDL will ultimately discontinue ISIS/Draw and replace it with Mol Draw.

The cost of these software packages can vary considerably based on academic or industrial usage. Fortunately, the cost should not be a barrier to the inclusion of appropriate renderings of chemical structures because several freeware structure-drawing packages are now available for download from the World Wide Web. These include freeware versions of both ISIS/Draw and ChemSketch. A detailed comparison of capabilities for both the freeware and commercial versions of the packages has been made by Tamas Gunda (http://dragon.klte. hu/~gundat/rajzprogramok/dprog.html). This review is an objective comparison, updated on an almost annual basis, of the capabilities of five popular drawing packages [ISIS/Draw, ChemDraw, DrawIt (ChemWindow), ChemSketch, and Chemistry 4-D Draw].

✐ Reminder:

The cost should not be a barrier to the inclusion of appropriate renderings of chemical structures because several freeware structuredrawing packages are now available for download.

It is preferable to use one of the drawing packages that offer journal-based templates containing the appropriate bond widths, bond lengths, fonts, and

In The ACS Style Guide; Coghill, A., et al.; The ACS Style Guide; American Chemical Society: Washington, DC, 2006.

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Box 17-2. Parameter Settings for ACS Publications At present, ACS journals request that chemical structures be prepared according to the guidelines below. (The guidelines are also available at https://paragon.acs.org/paragon/index.jsp. Click on “Read Author Information”, and then select the appropriate journal for specific information.) The parameters below are specifically for ChemDraw, using the ACS 1996 document settings; authors using other drawing packages should adapt these parameters to their systems. Most commercial and freeware packages allow these settings to be reproduced either by manual settings or by some sort of journal template feature. Drawing Settings

Text Settings

Preferences

chain angle

120 degrees

bond spacing

18% of width

fixed length

14.4 pt (0.2 in.)

bold width

2.0 pt (0.0278 in.)

line width

0.6 pt (0.0083 in.)

margin width

1.6 pt (0.0222 in.)

hash spacing

2.5 pt (0.0345 in.)

page setup

US/Letter/Paper

scale

100%

font

Helvetica (Mac), Arial (PC)

size

10 pt

units

points

tolerances

3 pixels

other settings recommended by a particular journal. Using these templates aids in the production of a chemical structure drawing acceptable to the publishers.

How To Submit Chemical Structures Many common graphical formats can be generated using structure-drawing packages, including TIFF, GIF, and BMP; follow the guidelines for submitting figures presented in Chapter 15. Also, because file formats continue to develop and the preferences of a given publisher can change, authors should check with the publisher’s or journal’s author guidelines for acceptable software and file formats. Box 17-3 shows guidelines for submitting structures to ACS journals.

In The ACS Style Guide; Coghill, A., et al.; The ACS Style Guide; American Chemical Society: Washington, DC, 2006.

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Box 17-3. Guidelines for Submitting Chemical Structures to ACS Journals •

In manuscripts submitted to ACS journals through Paragon, structures should be embedded in text documents. In manuscripts submitted through the Paragon Plus environment, structures can be embedded in the text or supplied separately.

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Submit graphical images of chemical structures to ACS journals as embedded TIFF files, using a resolution of 300 pixels per inch (ppi) for color and 1200 ppi for black-and-white images.

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ACS journals accept application files (native formats) for several common software programs, including .skc files from ISIS/Draw and .cdx files from ChemDraw.

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Information on submitting chemical structure connection tables is available at https://paragon.acs.org/paragon/application? pageid=content&mid=preferredsoftware.html&parentid= authorchecklist&headername=Preferred%20Software.

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CML is accepted by the ACS Paragon System for submission of supporting information.

The visual appeal of a structure or reaction can differ from one software package to another, so authors may wish to interchange data between programs to obtain the best graphical display required for publication. Such an interchange is normally performed using a specific format of the atom– atom connection table known as a molfile. (Information on the MDL molfile format is available at http://www.mdl.com/downloads/public/ctfile/ctfile.pdf.) Such collections may, for example, describe molecules, molecular fragments, substructures, substituent groups, polymers, alloys, formulations and mixtures, and unconnected atoms. Most chemical structure drawing software packages available today allow both import and export of a molfile. An alternative generic file format is CML, the chemical markup language, which takes advantage of the strength of Web-based technologies and is discussed in Chapter 8.

The Future of Representing Chemical Structures Despite the vast array of tools available today for structure drawing and representation, each tool is lacking in some way for the representation of complete structure space. Small organic molecules have been well supported, but the needs

In The ACS Style Guide; Coghill, A., et al.; The ACS Style Guide; American Chemical Society: Washington, DC, 2006.

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of the inorganic, organometallic, and polymer chemist have commonly lagged behind. Chemical structure drawing programs will continue to develop version by version as software vendors deliver an ongoing array of functionality for their customers. The need to introduce additional flexibility for structure representation will be ongoing, specifically as standards are set for preferred drawing styles by organizations such as IUPAC. A scoping exercise initiated by the IUPAC commission has defined the preferred drawing styles for structure representation to ensure accurate communication of chemical structures. (See http://www.iupac. org/projects/2003/2003-045-3-800.html. The stereo part of this project is now available as provisional recommendations at http://www.iupac.org/reports/ provisional/abstract05/brecher_310705.html.) It is likely that publishers will embrace the opportunity to standardize the structure representations within their publications to try to achieve greater homogeneity. Whereas chemical structures will always be the primary vehicle for visual communication, it is possible that journal articles will be reporting a unique label representing a chemical structure in the near future, especially because this label will already allow the searching of chemical structures contained in publications indexed using Web-based search engines. For more on this, see Appendix 8-1.

In The ACS Style Guide; Coghill, A., et al.; The ACS Style Guide; American Chemical Society: Washington, DC, 2006.