Systematic naming software tools for exchange

Molecules 1999, 4, 255-263

molecules
ISSN 1420-3049
http://www.mdpi.org

The Need for Systematic Naming Software Tools for Exchange
of Chemical Information
Antony Williams1* and Andrey Yerin2
1
Advanced Chemistry Development Inc., 133 Richmond Street West, Suite 605, Toronto, Ontario,
M5H 2L3 Canada
Tel.: 416-368-3435, Freefone: 1-800-304-3988, Fax: 416-368-5596, E-mail: tony@acdlabs.com,
http://www.acdlabs.com
2
ACD, Inc., ul. Akademika Bakuleva, 6, str. 1, Moscow 117513 Russia
E-mail: erin@acdlabs.com

*Author to whom correspondence should be addressed.

Received: 20 June 1999 / Accepted: 31 June 1999 / Published: 1 September 1999

Abstract: The availability of systematic names can enable the simple textual exchange of
chemical structure information. The exchange of molecular structures in graphical format or
connection tables has become well established in the field of cheminformatics and many
structure drawing tools exist to enable this exchange. However, even with the availability of
systematic naming rules, software tools to allow the generation of names from structures,
and hopefully the reversal of these systematic names back to the original chemical structure,
have been sorely lacking in capability and quality. Here we review the need for systematic
naming as well as some of the tools and approaches being taken today in this area.

Keywords: Systematic Naming, IUPAC Naming, CAS Index Naming, IUPAC rules,
Naming Software.

Introduction

“Well honey, I couldn’t convince the doctor that I needed 5-{2-ethoxy-5-[(4-methyl-1-

© 1999 by the authors. Reproduction of this article, by any means, is permitted for noncommercial
purposes.

Molecules 1999, 4 256

piperazinyl)sulfonyl]phenyl}-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one to
help my high (3S,9S,14S,17R)-17-(1,5-dimethylhexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,
16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol levels. Sorry.”

Results and Discussion

It’s truly unlikely that this type of conversation between a man and his wife, after his visit to the
doctor, will ever happen in any household in the near future. As well as the sheer effort of
remembering the details of a particular chemical name, the subtleties of pronunciation alone are more
than enough to warrant the use of more general names when discussing pharmaceutical drugs for
example. So, we can assume that the need for generic names will remain for the foreseeable future.
From a skilled chemists point of view most of us will know that aspirin is in fact 2-(acetyloxy)benzoic
acid. However, how many of us would know that 2-(acetyloxy)benzoic acid is also the chemical for
the drugs with generic names of acenterine, aceticyl, acetophen, acetosal, acetosalin, acetylin, aspro,
caprin, claradin, duromax, ecotrin, helicon, levius, rhodine, xaxa and over 35 other variants! An
exhaustive list can be found inside the electronic chemical dictionaries available today. An example
screen shot is shown below for the ACD/Dictionary. This dictionary, like many others, is integrated to
a structure drawing package for defining the chemical structure of interest by which to search the
dictionary.

Figure 1.


So, with such possible variations in generic names, but all applicable to a single chemical structure,
we can acknowledge that the chosen manner for communication would be the molecular structure
itself. Herein lies a problem. How can I orally or even in a written format communicate a structure
when a molecular structure exists as a 2D or 3D rendering? As an example, cholesterol is a pretty
demanding structure to draw, never mind communicate between colleagues. Surely we all
acknowledge the medical effects of high levels of the bad type and low levels of the good type of
cholesterol but only as chemists are we concerned with exchanging actual structural detail. The two-
dimensional structure of cholesterol is shown below:

H3C CH3

CH3
H
CH3

H3C H

H H

HO

Figure 2. Cholesterol.

Note that the structure is carrying the stereochemical center descriptions in the bond orientations
within the figure. Today, in the days of electronic exchange, via email attachments, FAX or simple
global networks, there would have no problem in communicating issues around cholesterol since we
would just send an image of the structure (as above captured as a word processor image), or an actual
structure in some standard file format, such as Molfile, which all structure drawing packages should be
able to exchange easily. Alternatively, for this structure I could just mention the word Cholesterol and
most of us would immediately acknowledge the structure to be a steroid core and the detailed structure
could easily be found in a high school chemistry text or at the library, however time demanding and
frustrating that process would turn out to be.
Returning to the issue in question however is oral or written, not graphical communication of a
chemical structure. Patent attorneys, pharmacists and benchtop chemists do not all work in a
consistent exchange format of molecular structure information. Thus the need exists for simple
exchange between the multiple formats of graphical structures and text. We have already explained
lookup dictionaries to deal with generic names but the gap which remains is a systematic nomenclature
system whereby a chemical structure can be named according to agreed upon systematic rules. Such
systems do exist but herein lies yet another problem.
There are actually two widely adopted nomenclature rule bases. These are those of the International
Union of Pure and Applied Chemistry (IUPAC) and the Chemical Abstracts Service (CAS). These
different sets of rules are similar but different in some very distinct ways. The rules were developed
over the years and are continually in some state of flux to deal with new components of molecular


diversity and possible conflicts or confusions that have been identified with the rules that exist today.
The application of rules to deal with all of historical structural space has actually been well
achieved. The results are rules which can be applied to complex structures in order to generate a text
string which is a direct representation of these rules, and, if the rules are applied correctly by separate
parties, the same systematic name will result. Rather than require human intervention at this stage
however, it would only make sense to allow software to assume the generation of a systematic name
directly from a chemical structure since any rules based system can be translated into an electronic
conversion engine, in this case from structure to name. Such software must be correct to the largest
extent possible and should encompass as many of the systematic rules available today to cover as
much of electronic structure space as possible. There have been a number of attempts to deal with
electronic generation of systematic names. These have included programs such as Beilstein Autonom,
Cheminnovation Nomenclator and the most complete of these packages, Advanced Chemistry
Development’s IUPAC Name and Index Name programs which cover both the IUPAC and CAS-rules
based system.
In each case these software packages have delivered to the marketplace a structure drawing
interface which is used as the input screen for the chemical structures [1]. Also, each of the
applications has also been integrated with other well known structure drawing packages available in
the marketplace such as MDL/Isis and Chemdraw [2]. As a result, there are no shortages of interfaces
to input a molecular structure requiring systematic naming. The accuracy of the resulting names
generated is by far the most exacting test of the software but the ease of use and the richness and
flexibility of the interface are also crucial points. A comparison of the capabilities of each of the
naming software packages mentioned above is available [3]. Here we will review the issues of accurate
naming only using ACD/Name as the test module.
In an ideal world the systematic naming rules developed by either of the two bodies would result in
a unique name. In this way, a single name is a unique descriptor which, like the molecular structure
itself is a direct and non-confusing representation of the molecular detail. Unfortunately, this is not the
case. A single molecular structure can result in a series of different names due to the application of the
naming rules.
H3C O
S S
CH3

Figure 3.
1-(methylsulfanyl)-4-(methylsulfinyl)benzene*
methyl 4-(methylsulfanyl)phenyl sulfoxide
1-(methylsulfinyl)-4-(methylthio)benzene**
methyl 4-(methylthio)phenyl sulfoxide
bis(methylthio)benzene monooxide

For example these five names could be considered as IUPAC names and the first (*) is the most


preferred according to current recommendations, and the name labelled with ** is the CAS name.
In order to offer the user the ability to use the different variations of naming options supported by
the different bodies (or local conventions, for example, a corporate practice to use previously
recommended thio and mercapto nomenclature instead of the current sulfanyl, or alternatively the
forward locant position instead of internal locant ), certain options may need to be supported. These
include some of the options listed below. So, in the case of cholesterol, there are a number of names
that can be generated based on settings. In the latter case the option to support naming according to
IUPAC and CAS Index rules for steroids, alkaloids and terpenes was selected. Some of the options
available for naming are illustrated below.

Figure 4.


H3C 22 24 CH3
21 20 23 25 26
CH3
12 18 H
17 CH3
11 13 27
CH3 H 16
1 19 9 14
15
2 10 8
H H
3 5 7
HO 4 6

Figure 5.

1. Using the IUPAC Naming system: (3S,9S,14S,17R)-17-(1,5-dimethylhexyl)-10,13-dimethyl -
2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol
2. Using IUPAC Rules system and option for steroids naming: (3β)-cholest-5-en-3-ol
3. [4] Using CAS Index Rules system: cholest-5-en-3-ol, (3β)-
Notice that in the example above the details regarding stereochemistry is available in the
stereochemical designations for each of the centers. However, when the option to name according to
approved steroidal cores is selected, the naming produces solely the unique aspects of the cholest-5-en-
3-ol molecule which is the 3β-stereochemistry. Using the steroidal molecular core as the basis for
naming, substitution of the molecule will result in a IUPAC name containing the (3β)-cholest-5-en-3-
ol name component as well as all of the substitution detail (see below):

Figure 6.


Systematic generation of names would be insufficient without allowing the user to access the details
of the rules that have been applied. As a result of this need the IUPAC rules have been made available
as a part of the suite and the appropriate selection can be made from the connecting links listed above
to the appropriate IUPAC rule. The IUPAC rules in this searchable format are also available for
download from www.acdlabs.com.

Figure 7.

It should be added that there is another form of nomenclature that can be applied to molecular
structures and this is the SMILES string. A SMILES string is simply a string of characters that carries
within its code the details of the elements and their connectivies. Once again, this can be converted
from its string format back through a connectivity table into the form of a 2D molecular display using
the appropriate SMILES to structure converter. For cholesterol a valid SMILES string is::

SMILES:

CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]
3CC[C@]12C

There are as many valid SMILES strings for cholesterol as there are ways to correctly order the


atoms and this can be. There are numerous SMILES converters available but the general application is
to use SMILES strings as the textual input describing a structure and convert the string to an actual
connection table in order to provide the structure in a form that can be used as input to a prediction or
search engine. Therefore the reverse process of SMILES to structure conversion is a necessary
component of any SMILES parser. The SMILES definition has certain limitations in regard to
completeness but for general organics is a simple and widely used “ nomenclature” .
So far we have seen that the rigorous application of systematic naming rules according to specified
conventions is necessary in order to generate an appropriate name for a chemical compound. These
rules need to be applied faithfully and correctly with an ideal of zero errors in naming. However,
flexibility in the different preferences available for naming can immediately lead to confusion.
The reverse process of taking a chemical name and generating the chemical structure, a process
espoused to be of more general application to benchtop chemists, is also of general utility. There are
three software packages available today that can perform this name to structure conversion. These are
ChemInnovation’s NamExpert, a module within Cambridgesoft’s ChemDraw Ultra and also a module
from Advanced Chemistry Development presently under beta-test. It is to be expected that the critical
application of rules for reverse generation of a structure from a name will need to be as definitively
stipulated as those required to generate a name from a structure. A recent presentation [5] emphasized
that the actual generation of structures from names is a simpler task than the application of systematic
rules to name a structure. However, we remain extremely cautious when it comes to accuracy, even in
the reverse direction of name to structure, as some of the resulting errors generated by software are
extremely noteworthy [3].
It is generally obvious that software for the generation of systematic names either in a structure to
name or reverse mode can be an extremely useful tool for the benchtop synthetic chemist looking for a
manner by which to transfer chemical information in a textual format. Care must be taken in the
decisions used to generate such names including accuracy of the software tool applied, the preference
settings during the naming process and appropriate representation of the structure prior to naming
since stereochemical details are captured within the naming procedures. It is possible to test the
naming process and accuracy online at no charge using the ACD/Interactive Lab at
www.acdlabs.com/ilab using the integrated structure drawing and online prediction service should you
wish.
While it is unlikely that the conversation “Well honey, I couldn’t convince the doctor that I needed
5-{2-ethoxy-5-[(4-methyl-1-piperazinyl)sulfonyl]phenyl}-1-methyl-3-propyl-1,6-dihydro-7H-
pyrazolo[4,3-d]pyrimidin-7-one to help my (3S,9S,14S,17R)-17-(1,5-dimethylhexyl)-10,13-dimethyl-
2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol levels. Sorry.”
will ever occur. Who knows whether the converse, with appropriate trivial names in place, will also
ever happen? “Well honey, I couldn’t convince the doctor that I needed Viagra to help my cholesterol
levels".


References and Notes

1. Advanced Chemistry Development provides their structure drawing software, ACD/Chemsketch
at no charge from their website at www.acdlabs.com/download. The package includes 2D
drawing, 3D optimization, tautomer identifier, 3D viewer with different graphic modes. Over
20,000 copies have been downloaded at the time of writing (June 15th 1999).
2. Free modules integrating to both Cambridgesoft ChemDraw and MDL/ISIS are available from
www.acdlabs.com/download. For ChemDraw these are certain physical property prediction
modules and for MDL/ISIS this is the integrated 3D structure display module.
3. Review of different naming products including Beilstein Autonom, Cheminnovation
Nomenclator, and Advanced Chemistry Development’s ACD/Name (IUPAC rules) and
ACD/Index Name (CAS-based rules) - www.acdlabs.com/products/name
4. The correct CAS Index name is generated if the preference for steroid naming is selected. The
possibility to disable natural product names is included according to the CAS practice to add
additional systematic names for some natural products. However, the main name is based on the
steroid. It is possible to generate a more complete CAS Name by switching off the natural product
preference.
5. Jonathan Brecher, Cambridgesoft, ACS Spring Meeting 1999.

© 1999 by the authors. Reproduction of this article, by any means, is permitted for noncommercial
purposes.

Systematic naming software tools for exchange

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