CurlySMILES: a chemical language to customize and annotate encodings of molecular and nanodevice structures.

Abstract

CurlySMILES is a chemical line notation which extends SMILES with annotations for storage, retrieval and modeling of interlinked, coordinated, assembled and adsorbed molecules in supramolecular structures and nanodevices. Annotations are enclosed in curly braces and anchored to an atomic node or at the end of the molecular graph depending on the annotation type. CurlySMILES includes predefined annotations for stereogenicity, electron delocalization charges, extra-molecular interactions and connectivity, surface attachment, solutions, and crystal structures and allows extensions for domain-specific annotations. CurlySMILES provides a shorthand format to encode molecules with repetitive substructural parts or motifs such as monomer units in macromolecules and amino acids in peptide chains. CurlySMILES further accommodates special formats for non-molecular materials that are commonly denoted by composition of atoms or substructures rather than complete atom connectivity.

Full text

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SOFTWAREOpen Access
CurlySMILES: a chemical language to customize
and annotate encodings of molecular and
nanodevice structures
Axel Drefahl
Abstract
CurlySMILES is a chemical line notation which extends SMILES with annotations for storage, retrieval and modeling
of interlinked, coordinated, assembled and adsorbed molecules in supramolecular structures and nanodevices.
Annotations are enclosed in curly braces and anchored to an atomic node or at the end of the molecular graph
depending on the annotation type. CurlySMILES includes predefined annotations for stereogenicity, electron
delocalization charges, extra-molecular interactions and connectivity, surface attachment, solutions, and crystal
structures and allows extensions for domain-specific annotations. CurlySMILES provides a shorthand format to
encode molecules with repetitive substructural parts or motifs such as monomer units in macromolecules and
amino acids in peptide chains. CurlySMILES further accommodates special formats for non-molecular materials that
are commonly denoted by composition of atoms or substructures rather than complete atom connectivity.
Background
CurlySMILES (Curly-braces enhanced Smart Material
Input Line Entry Specification) is introduced as a chemi-
cal language for the specification of chemical materials
and supramolecular structures. The CurlySMILES
approach provides a flexible format to encode patterns
in materials and molecule-based architectures. Curly-
SMILES includes its own set of symbols, descriptors and
rules to denote respective entities and also modifies the
well-established SMILES language.
SMILES is based on a set of rules that allow the repre-
sentation of a molecular structure as a sequence of atom
and bond symbols in a single word or string [1-3].
Unique SMILES strings are suitable as database keys
while storing the structural information within the key
itself [4]. Since SMILES notations are constructable
from molecular principle, namely the molecular graph,
notations can be derived for virtual, not-yet-synthesized
chemical species. The flexibility and portability of
SMILES has been demonstrated by its use in modeling
and property estimation software [5-9] and combinator-
ial libraries [10,11].
SMILES is bridging the opposite ends of human-
friendly molecular drawings, achieved with molecule
editors [12,13], and computer-friendly connection tables
(matrices), both used in representing molecular struc-
tures. Molecular information collapsed into a compact
SMILES string can efficiently be managed by computer
programs and stored in markup language fields, like the
<sSmiles> tag of ThermoML [14].
SMILES comes in various dialects with modifications
or minor extensions of the originally published language.
Implementations of SMILES parsers differ with respect
to the treatment and acceptance of additionally intro-
duced symbols and syntax [2]. SMILES also has been
extended to encode a peptide or peptoid sequence on
monomer level [15] and in template format [16].
Recently, the IUPAC International Chemical Identifier
(InChI) has been designed as a string-based identifier
for chemical substances [17]. Like a SMILES notation,
an InChI string is derived from a molecular structure
representations. However, InChI is intended for
“behind-the scenes” use by computers. It is typically
derived from structure representations by software,
whereas SMILES handily supports molecular communi-
cation between humans and computers.
The user-friendliness and popularity of SMILES
encouraged us to modify this chemical language for
Correspondence: axeleratio@yahoo.com
Axeleratio, 4330 Tuscany Circle, Reno, Nevada 89523, USA
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© 2011 Drefahl; licensee Chemistry Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.

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communication of molecular architectures that can not
adequately be encoded with the current SMILES lan-
guage and its derivatives. CurlySMILES modifies the
SMILES language by including a novel format to encode
molecular details and extra-molecular features such as
non-covalent interactions and attachment to a biomole-
cule as well as the surface of a substrate material or
nanoparticle. CurlySMILES is designed with an open
format to provide users with choices of integrating
shorthands such as aliases or compaction of repetitive
structural units. In the following, formats and rules for
constructing CurlySMILES notations are described.
Applications of CurlySMILES for document annotation
and chemical search are then discussed.
Results
CurlySMILES notation
A CurlySmiles notation is a string of dot-separated com-
ponent notations. A component notation can either be a
plain SMILES, an annotated SMILES, or a special format
notation. A plain notation maintains the grammar and
rules of the known SMILES language. A plain notation
is modified by introducing attributes, such as structural
variations, details and decorations, enclosed in curly
braces. An annotation can be anchored to a particular
atomic node or placed at the end of a SMILES compo-
nent. A special format notation begins with an opening
and ends with a closing curly brace and includes an
alias or a notation for a structure that defies molecular-
graph encoding. A string with exactly one component
notation is referred to as a unary CurlySMILES notation.
A CurlySMILES notation is typically not unique since
the SMILES language allows for alternate notations by
selecting a starting atom arbitrarily. Further, Curly-
SMILES provides flexible annotations formats that
leaves it to a user or application software to add and
granulate details. The clear separation of attributes from
the molecular-graph encoding, however, provides appli-
cations with options to match and screen notations in
large data sets with precedence to attributes, while
deferring molecular-connectivity processing to a later
stage, at which only a selected set of candidates will be
considered.
Here, we focus on the core format of CurlySMILES,
outlining the basic syntax that can be extended into dif-
ferent domains of future interest. Example notations are
supplied for selected molecules and materials, demon-
strating how to represent a targeted structure or a gen-
erically defined class of structures. More examples are
available in Additional file 1 and on the Web [18,19].
Example notations are displayed in monospace font.
Parts of a CurlySMILES notation, which are given in ita-
lics, present descriptive metalanguage text meant to be
replaced by code in CurlySMILES format.
Multiplier
A shorthand format is introduced to encode multiple
occurrences of the same component notation. The mul-
tiplier is an integer greater than one and enclosed in
curly braces. It is appended to a component notation
as illustrated for cobalt(II) nitrate hexahydrate (Co
(NO3)2·6H2O):
[Co+2].[O-]N(=O)=O{2}.O{6}
notation,
[Co+2].[O-]N(=O)=O.[O-]N(=O)=O.O.O.O.
O.O.O
exhaustive notation.
multiplier
A multiplier is not considered an annotation. If anno-
tations occur at the end of a component notation, they
have to precede the multiplier.
Alias
An alias is a short form for a component notation. An
alias is enclosed in curly braces. CurlySMILES distin-
guishes between predefined and customer-defined
aliases.
This distinction is critical for the implementation of a
CurlySMILES parser. Look-up of the replacement nota-
tion for an alias is internal for a predefined alias,
whereas customer-defined aliases require submission of
a look-up dictionary by the customer.
An alias begins with a letter or a dollar sign followed
by zero or more alphanumerical, hyphen, underscore,
plus sign and round bracket characters. For example, we
use commonly applied short notations for cations and
anions of ionic liquids and solids, such as bmim and
NTf2 for 1-butyl-3-methylimidazolium and bis[(trifluor-
omethyl)sulfonyl]imide, respectively. This allows the fol-
lowing shorthand encoding:
{bmim(1+)}.{NTf2(1-)}
dazolium bis[(trifluoromethyl)sulfonyl]imide.
1-butyl-3-methylimi-
A customer-defined alias has to be indicated by a preced-
ing dollar sign, allowing for notations like the following:
{$myCation}.{$myAnion}.{$mySolvate}{4}
aliases-customized notation.
Stoichiometric formula notation
A stoichiometric formula notation (SFN) is defined to
encode materials with known atomic or substructural
stoichiometry, but without a discrete pattern of finite
atom connectivity (molecular structure) that could be
captured in a SMILES notation. SFNs are particularly
useful for encoding a broad range of solids. Further,
many homo- and hetero-polyatomic clusters with
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complex atom connectivity can be encoded as SFNs in a
compact, yet distinctive manner. CurlySMILES applies
an SFN format that resembles the nomenclature typi-
cally used to name compounds by their stoichiometric
composition [20], but eliminates the use of sub- and
superscript markup. Multiple entries of the same atomic
symbol are allowed and the symbols may occur in any
order. A stoichiometric integer directly follows a symbol,
whereas an isotope label precedes a symbol and is
marked with the ^ character; for example ^13C, for13C.
Further, selected atomic symbols may be grouped by
enclosing them within round braces. If a stoichiometric
integer applies to a group, it immediately follows the
closing round brace. Finally, a charge notation (n+) or
(n-), where n≥1, is placed at the end of a SFN nota-
tion for ionic species.
To distinguish an SFN-encoded component from an
alias or a composite notation, an asterisk (*) precedes
the SFN. The general format is {*SFN}. A few exam-
ples illustrate SFN encoding in CurlySMILES:
{*Cr23C6}
{*Bi5(4+)}
{*Cu3(CO3)2(OH)2}
(carbonate mineral)
tricosachromium hexacarbide, Cr23C6
pentabismuth(4+) cation, Bi54+
azurite, Cu3(CO3)2(OH)2
Groups in an SFN notation can be nested to any
depth level:
{*K(AuS(S2))}
rate(1-), K[AuS(S2)]
potassium (disulfido)sulfidoau-
Notice that the SFN format also accommodates struc-
tures with molecular connectivity. It is the user’s choice
to encode such structures as SFN or SMILES notations.
When in doubt about the topological description of a
structure or when isomeric forms should intentionally
be included, SFN is the notation of choice.
An SFN can appear within a special format notation
for a component, within a composite notation to encode
a constituent (see next section) and within a SMILES
annotation.
Composite notation
Composite or hybrid materials are made from constitu-
ents that remain separate and distinct, even on an
above-nanoscale level (mesoscale). The constituents
should not be encoded by dot-separated notations, a
format which should be reserved for compounds in
which the different species interact with each other on a
molecular/ionic level rather than on an interface or
grain-boundary level. CurlySMILES defines a special for-
mat for encoding composites and other materials built
from interface-connected phases:
{/constituent#1/constituent#2/.../constituent#n}
Herein, constituent#i is the constituent notation of the
i-th constituent, which is either an SFN or a SMILES
component notation. The forward slash between two
adjacent constituents, which is typically used in the scien-
tific literature for materials and device structures of this
type, symbolizes a contact through a common interface.
A composite notation is always a unary CurlySMILES
notation. For example, a composite material based on
poly[bis(methoxy-ethoxy-ethoxy)phosphazene] (MEEP)
and zirconium dioxide [21] is encoded as
{/N{-}=P{+n}(OCCOCCOC)(OCCOCCOC)/
{*ZrO2}}
MEEP/ZrO2
The first constituent is presented as an annotated
SMILES notations, using the macromolecule syntax
introduced below, and the second constituent is pre-
sented as SFN.
Plain SMILES notation
A component notation that does not begin with an
opening curly brace is a plain SMILES or an annotated
SMILES notation. A plain SMILES notation is encoded
with the grammar and rules of the SMILES language
[1]. A plain notation contains atomic node code
(ANC) and may contain bond symbols and special
characters to denote branching and ring formation. An
ANC is either a bare atomic symbol or a square
bracket atomic code (SQC) which includes an atomic
symbol and, depending on the targeted structure, addi-
tional characters to denote the number of adjacent
hydrogen atoms, a charge value, and an isotope label.
CurlySMILES includes the symbols *, ~, and $ to
encode an atomic wildcard, an unspecified bond and a
quadruple bond, respectively. Stereodescriptive symbols
such as @, /and \ are not accepted, since CurlySMILES
provides a special annotation syntax to specify and dis-
tinguish stereoisomers.
CurlySMILES requires an atomic wildcard always to be
encoded as a SQC. For example, the notation [*H2]=[*]
encodes a molecule in which one atom with two adjacent
hydrogen atoms is connected by a double bond to another
atom, which has no further neighbor atoms. The symbol ~
was introduced in SMARTS [22] as a wildcard-like any-
bond symbol. Unless the bound atoms are encoded by
wildcards, a bond is predetermined by the element type of
the adjacent atoms and their orbital interactions. Whereas
the atomic wildcard is a placeholder for atomic symbols,
the symbol for an unspecified bond has not primarily the
role of a bond placeholder; rather, it indicates bond-type
ambiguity with respect to the limited classification scheme
of single, double, triple, quadruple and aromatic bonds.
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CurlySMILES treats the character ~ as a bond symbol that
encodes a bond, which cannot adequately be encoded as a
covalent bond with symbols -, =, #, :, and $. The latter
symbol is used to encode a quadruple bond. CurlySMILES
requires all atomic symbols, that encode atoms connected
by a $ or ~ bond, to be encoded in SQC notation. As
described below, CurlySMILES provides an annotation for-
mat that allows encoding of bond details.
Annotated SMILES notation
A plain notation is annotated by inserting one or more
curly-enclosed annotations into the notation. An anno-
tation has to be either anchored at a particular atomic
node or appended to the end. An atom-anchored anno-
tation (AAA) directly follows the ANC. The only char-
acters allowed to occur between an AAA and ANC are
digits that designate ring-closing. A component-
anchored annotation (CAA) follows the last ANC,
including its AAAs, but precedes the multiplier, if any is
present in the component notation. AAA types include
stereodescriptive and structural unit annotations as well
as group environment, molecular detail and operational
annotations. CAA types include state and shape annota-
tions and miscellaneous interest annotations. In the fol-
lowing text we use the term annotation to refer to the
content between the curly braces.
A stereodescriptive annotation consists of one of the
upper-case letters D, E, L, R, S, and Z. There meaning
corresponds to their definition in the chemical nomencla-
ture: R and S mark a stereogenic atom, D and L mark an
atom to relate a chiral molecule to an enantiomer of
glyceraldehyde, and E and Z distinguish cis/trans isomers
by using the E/Z convention. Examples E1 and E2 in
Additional file 1 demonstrate stereodescriptive annotation.
A structural unit annotation defines a boundary of a
structural unit. This boundary is an open or dangling
bond. The annotation consists of a one-character bound-
ary descriptor, which is a CurlySMILES bond symbol (-,
=, #,:, &, or ~). For descriptors:, &, and ~, the anchor
atom always has to be SQC-encoded. For -, =, and #,
SQC-encoding is not required as long as the anchor atom
belongs to the organic set and has no isotope label or
charge contribution. Structural unit annotations apply to
the encoding of formal fragments or groups. Their use is
demonstrated in E3 in Additional file 1.
Stereodescriptive and structural unit annotations consist
of exactly one character, while all other annotation types
require a two-character annotation marker (AM), which is
optionally followed by an annotation dictionary to specify
attributes. The general format for a dictionary-containing
annotation,
{AMk1=v1;k2=v2;...;kn=vn},
employs a semicolon-separated list of dictionary
entries. An entry is a key/value pair, ki/vi. A key is a
short name which starts with a letter or a dollar sign
followed by zero or more letters or underscore charac-
ters. A beginning dollar sign indicates a customized
entry, in which key name and possible values have to be
defined by the user. Otherwise, key names and asso-
ciated values are predefined [23].
A group environment annotation marker (GEAM)
starts with a bond symbol (-, =, #, :, &, ~) or a dot. A
bond symbol followed by Y describes bonding to an
adjacent substructure. Y is to be interpreted generically
as any substructure, but can be specified through dic-
tionary entries. The bond symbol - may alternately be
followed by R or X to indicate an alkyl or halogen
group. Symbols - and ~ can be followed by a vertical
bar to indicate surface attachment. Further, the GEAM.
| indicates ionic interaction with a surface. Examples
are given below and in E4 and E5 in Additional file 1.
A molecular detail annotation starts with an exclama-
tion mark. The second character of a molecular detail
annotation marker (MDAM) is a, p, m, r, H, and I
denoting anchor atom, pair of atoms, multiplet of
atoms, ring, hydrogen-bonding and non-hydrogen-based
interaction, respectively. Examples E6 to E8 in Addi-
tional file 1 illustrate their use.
The first character of an operational annotation mar-
ker (OPAM) is a plus sign. The following character is a
letter. An upper-case letter indicates formal addition or
substitution of a structural part. A lower-case letter indi-
cated formal repetition of an annotated unit. OPAMs
+R, +X, and +Y mean formal substitution of a H-atom
by an alkyl group, halogen atom and “any group”,
respectively. OPAM +L means ligand addition and is
used to encode coordination compounds. OPAMs +n
and +r formally encode linear marcomolecules and
macrocycles, respectively. Examples E9 to E14 in Addi-
tional file 1 provide details on their use.
A state and shape annotation is denoted by a state and
shape annotation marker (SSAM) consisting of two
lower-case letters. SSAM annotations qualitatively
describe the physicochemical state, phase structure and/
or the nano- or mesoscale characteristics of a material
[24]. Examples E15 to E18 in Additional file 1 show
their application.
A miscellaneous interest annotation is denoted by a
two-character miscellaneous annotation marker (MIAM).
Examples E19 and E20 in Additional file 1 illustrate their
employment.
The following two examples demonstrate the combined
use of annotations to encode molecular arrangements.
The imidazolium functionalized SiO2surface [25] in
Figure 1 is encoded in CurlySMILES by applying the
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group environment annotation format. The two O
atoms, which attach the molecular species to the mate-
rial surface, are annotated with the -|marker:
O{-|sfn=SiO2}[Si](O{-|i=-2})(O)
CCCn1ccn{-R}c1{!re=+}
(Figure 1)
The material is SFN-encoded in a dictionary entry
with key sfn. Instead of repeating this entry in the
annotation of the second surface-attached O-atom, that
annotation contains an entry with key i, pointing to the
atomic node with the material-surface description. The
value -2 means that one has to move to the left by two
atomic nodes to locate the relevant node. This notation
further contains annotation {-R} at the N atom of the
imidazolium ring to specify an alkyl substituent. The
delocalization of the ring charge is encoded by annotat-
ing the node at which the ring is formally closed. The
molecular detail annotation, marked with !r, includes
the dictionary entry e=+, which denotes the positive
ring charge.
The functionalized calix[4]arene of the complex
shown in Figure 2 is encoded by combining structural
unit, group environment and operational annotations.
The molecular ring is encoded as a fragment with two
open bonds. The first is encoded as a structural unit
annotation and the second as an operational annotation.
Corresponding atomic nodes and annotations are given
in boldface:
CC(=O)COc1c{-}cc{-R}cc1C{+rn=4}
lized calix[4]arene
functiona-
The +r annotation formally instructs to close the open
single bond at the C atom of the last structural unit with
the open single-bond at the aromatic-ring C atom of the
first structural unit after repeating the unit as a ring con-
stituent four times. The complete Eu3+/cryptand complex
is given by encoding the rare-earth cation in SQC, anno-
tated with the ligand notation:
[Eu+3]{+Lc=CC(=O)COc1c{-}cc{-R}cc1C
{+rn=4}}
(Figure 2)
The dictionary key c expects a CurlySMILES notation.
This example demonstrates that CurlySMILES notation
can be recursive. Occurrence of notations at different
hierarchical levels allow selective and role-specific par-
sing and interpretation of CurlySMILES notations within
application context.
Software
A suite of Python modules have been implemented that
perform parsing and molecular descriptor generation for
CurlySMILES notations. These modules have been
wrapped as software package csmpy-1.0.1.tar.gz,
which is released under the terms of the GNU General
Public License (GPLv3) as published by the Free Soft-
ware Foundation. The package can be downloaded from
http://www.axeleratio.com/csm/py/code/downloads.htm.
Discussion
Comparison of CurlySMILES with other SMILES
modifications
Versions of SMILES use the symbols @ and @@ to distin-
guish an asymmetric atom in a chiral molecule. Cis and
trans isomers are denoted via directional bond symbols
/ and \ around a double bond. In CurlySMILES, corre-
sponding notations for stereoisomers are encoded by
inserting annotations containing R and S (optionally D
and L for certain configurations) and E and Z, depend-
ing on the actual configuration. Stereodescriptor assign-
ment in CurlySMILES follows the rules of chemical
nomenclature. This allows for a direct correspondance
Figure 1 Alkylimidazolium ionic species immobilized on silica
surface.
Figure 2 Eu3+cation coordinated by a cryptand.
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between descriptors in a systematic name and an asso-
ciated CurlySMILES notation.
CurlySMILES introduces a format to mark a fragment
or chemical group by using structural unit annotations.
This allows distinction between a radical and a group.
The SMILES notation [CH3] encodes a methyl radical.
CurlySMILES uses the same notation to encode the
radical, but encodes a methyl group as C{-}.
In a CurlySMILES notation, SMILES code is strictly
separated and distinguishable from other parts in the
notation by using curly braces. CurlySMILES uses
marked annotations to define structures in generic
terms or to construct molecular patterns with a tunable
depth of information granularity. CurlySMILES provides
completely new, extra-molecular patterns, such as [*]
{+Rn=4-16}{-|}, which reads as “branched or
unbranched alkyl group with four to sixteen C-atoms at
any bivalent hydrogen-free atom that is grafted to a
material surface by a single bond.” The possibility of
encoding surface-attached molecules enhances the use
of the SMILES language for encoding and querying
nanostructures and molecular devices, which often con-
sists of molecules attached to the surface of quantum
dots, nanowires, nanotubes and other nano-objects.
Those architectures often include non-molecular solids
such as semiconductors, alloys, and ceramics. The SFN
format of CurlySMILES provides a formalism to encode
these materials on their own. The SFN notation also is
critical in encoding certain composite phases or in spe-
cifying matrix materials or solid interfaces. Combinator-
ial libraries of functionalized surfaces and nanoparticles
can efficiently be generated and/or screened by applying
these versatile encoding options.
CurlySMILES is designed for applications in specialized
domains and for clients with particular tasks, including
repetitive processing of certain structural entities. For
this purpose, CurlySMILES includes various shorthand
approaches, especially the alias format. Domain-specific
abbreviations and codes for structures and materials are
frequently used within chemical communities to replace
long names and complex structural concepts. The alias
format makes it possible to integrate those terms into
notations and replace them when needed.
As a machine-readable code, a CurlySMILES notation
(like SMILES or InChI) is a document-neutral represen-
tation (ASCII string) of a chemical structure that, sup-
ported by the methods in the supplied software package,
can automatically be converted into a document specific
format. Formula-based names of coordination com-
pounds are a case in point.
Data mining and semantic search
A special feature of CurlySMILES is that it integrates
textual parts, acronyms, other encoding schemes and
client-defined aliases. Thus, a CurlySMILES notation can be
used on various levels in search and data mining. CurlyS-
MILES allows formulation of complex search pattern by
using atomic-symbol placeholders and annotations that
denote generic functional groups and compound classes.
The annotation syntax of CurlySMILES makes it possible
to associate a structural part with a specific role such as a
structural repeat unit in a polymer, a substituent, ligand,
cryptand, dopant, adsorbate or dissolved species. By imple-
menting search and matching algorithm that include the
information contained in CurlySMILES annotations, a
plethora of search strategies can be envisioned, including
precise, needle-in-the-hay-stack search and customer-
focused report-and-review style extraction of chemical data.
Conclusions
CurlySMILES is a chemical language for the communi-
cation of chemical information related to molecular
structure and complex nanoscale architectures. This lan-
guage offers a versatile approach in encoding material
composition and structure by supplementing attention
to extra-molecular features. Symbols and grammar of
this language allow users to encode structures and to
formulate context-annotated queries with variable gran-
ularity of molecular or supramolecular details. The open
format makes it easy to extend the current version to
application-specific tasks.
Additional material
Additional file 1: CurlySMILES encoding examples. The encoding
examples illustrate the application of CurlySMILES formats and rules to
derive linear notations for selected structures including stereoisomers,
fragments, ring molecules with delocalized charge, coordination
compounds, macromolecules, nanostructures as well as doped and
surface-functionalized materials.
Abbreviations
AAA: Atom-Anchored Annotation; AM: Annotation Marker; ANC: Atomic
Node Code; CAA: Component-Anchored Annotation; CurlySMILES: Curly-
braces enhanced Smart Material Input Line Entry Specification; GEAM: Group
Environment Annotation Marker; InChI: IUPAC International Chemical
Identifier; MDAM: Molecular Detail Annotation Marker; MIAM: Miscellaneous
Interest Annotation Marker; OPAM: OPerational Annotation Marker; SFN:
Stoichiometric Formula Notation; SMILES: Simplified Molecular Input Line
Entry System; SQC: SQuare bracket atomic Code; SSAM: State and Shape
Annotation Marker
Authors’ contributions
AD designed the CurlySMILES language. AD has implemented software to
parse and test CurlySMILES notation and to use them in CurlySMILES-
annotated archives of chemical property data and bibliographic
collections.
Competing interests
The author declares that they have no competing interests.
Received: 15 September 2010 Accepted: 7 January 2011
Published: 7 January 2011
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References
1. Weininger D: SMILES, a Chemical Language and Information System. 1.
Introduction to Methodology and Encoding Rules. J Chem Inf Comput Sci
1988, 28:31-36.
2.
SMILES line notation. [http://www.eyesopen.com/docs/docs-v1.7.0-2/html/
OEChemTK-python/SMILES.html].
3.
OpenSMILES Specification. [http://www.opensmiles.org/].
4.Weininger D, Weininger A, Weininger JL: SMILES. 2. Algorithm for
Generation of Unique SMILES Notation. J Chem Inf Comput Sci 1989,
29:97-101.
5.Reinhard M, Drefahl A: Handbook for Estimating Physicochemical
Properties of Organic Compounds. New York: Wiley & Sons; 1999.
6.Convard T, Dubost J-P, Le Solleu H, Kummer E: SmilogP: A Program for a
Fast Evaluation of Theoretical Log P from the SMILES Code of a
Molecule. QSAR 1994, 13:34-37.
7.Roy K, Toropov A, Raska I Jr: QSAR Modeling of Peripheral Versus Central
Benzodiazepine Receptor Binding Affinity of 2-Phenylimidazol[1,2-a]
pyridineacetamides using Optimal Descriptors Calculated with SMILES.
QSAR Comb Sci 2007, 26:460-468.
8. Guerra A, Páez JA, Campillo NE: Artificial Neural Networks in ADMET
Modeling: Prediction of Blood-Brain Barrier Permeation. QSAR Comb Sci
2008, 27:586-594.
9. Sykora VJ, Leahy DE: Chemical Descriptors Library (CDL): A Generic, Open
Source Software Library for Chemical Informatics. J Chem Inf Model 2008,
48:1931-1942.
10. Schüller A, Schneider G, Byvatov E: SMILIB: Rapid Assembly of
Combinatorial Libraries in SMILES Notation. QSAR Comb Sci 2003,
22:719-721.
11.Schüller A, Hähnke V, Schneider G: SmiLib v2.0: A Java-Based Tool for
Rapid Combinatorial Library Enumeration. QSAR Comb Sci 2007,
26:407-410.
12.Ertl P: Molecular structure input on the web. J Cheminf 2010, 2:1.
13.Ihlenfeld W-D, Bolton EB, Bryant SH: The PubChem chemical structure
sketcher. J Cheminf 2009, 1:20.
14.Frenkel A, Chirico RD, Diky V, Dong Q, Marsh KN, Dymond JH,
Wakeham WA, Stein SE, Königsberger E, Goodwin ARH: XML-Based IUPAC
Standard for Experimental, Predicted, and Critically Evaluated
Thermodynamic Property Data Storage and Capture (ThermoML). Pure
Appl Chem 2006, 78:541-612.
15.Siani MA, Weininger D, Blaney JM: CHUCKLES: A Method for Representing
and Searching Peptide and Peptoid Sequences on Both Monomer and
Atomic Levels. J Chem Inf Comput Sci 1994, 34:588-593.
16.Siani MA, Weininger D, James CA, Blaney JM: CHORTLES: A Method for
Representing Oligomeric and Template-Based Mixtures. J Chem Inf
Comput Sci 1995, 35:1026-1033.
17.Heller SR, McNaught AD: The IUPAC International Chemical Identifier
(InChI). Chemistry International 2009, 31:7-9.
18.
CurlySMILES encoding examples. [http://www.axeleratio.com/csm/proj/
encoding_examples.pdf].
19.
Encoding examples for CurlySMILES notations. [http://www.axeleratio.
com/csm/proj/examples.htm].
20.Connelly NG, Damhus T, Hartshorn RM, Hutton AT, (Ed): Nomenclature of
Inorganic Chemistry. RSC Publishing, Norfolk (UK); 2005.
21. Guglielmi M, Brustatin G, Facchin G, Gleria M: Poly(organophosphazene)s
and the Sol-gel Technique. Appl Organometal Chem 1999, 13:339-351.
22.
SMARTS - A Language for Describing Molecular Patterns. [http://www.
daylight.com/dayhtml/doc/theory/theory.smarts.html].
23.
CurlySMILES: annotation dictionary keys. [http://www.axeleratio.com/csm/
proj/anndictkeys.htm].
24.
CurlySMILES: state and shape annotation. [http://www.axeleratio.com/
csm/proj/stateshapeann.htm].
25.Gadenne B, Hesemann P, Moreau JJE: Supported ionic liquids: ordered
mesoporous silicas containing covalently linked ionic species. Chem
Commun 2004, 1768-1769.
doi:10.1186/1758-2946-3-1
Cite this article as: Drefahl: CurlySMILES: a chemical language to
customize and annotate encodings of molecular and nanodevice
structures. Journal of Cheminformatics 2011 3:1.
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