Application of CurlySMILES to the encoding of polymer systems

Application of CurlySMILES to the
encoding of polymer systems
Presented on August 16, 2015, at the ACS 250th
National
Meeting in Boston
Division: Computers in Chemistry
Session: Accelerated Discovery of Chemical Compounds:
Design New Polymers & Inorganic Materials from
Integration of Polymer Science, Materials Science &
Informatics
Axel Drefahl
axeleratio@gmail.com
Axeleratio, Reno, Nevada
www.axeleratio.com/axel/acs/boston2015/CurlySMILESpolymers.pdf

Copyright © 2015 Axel Drefahl
What is CurlySMILES?
CurlySMILES is:
● a chemical language to capture, process and share,
nanostructures, based on molecular constitution,
connectivity and arrangement;
● a line notation system integrating SMILES with atom-
and molecule-anchored annotations, inserted via
curly braces: {…};
● custamizable by annotation: encoding of polymers,
complexes, multi-phase systems, ...;
● available as a suite of Python 3 modules, including a
notation parser and unique notation generator.

Overview
● Current state of polymer informatics
● Brief introduction to CurlySMILES
● Encoding of Structural Repeat Units (SRUs)
● Encoding of single-strand polymers
● Encoding of multi-strand polymers
● Encoding of copolymers and miscellaneous
polymer systems
● CurlySMILES software/task-specific integration
● Perspective: virtual polymer chemistry

Cheminformatics (sub)domains
Established informatics
● “Small molecules”
● Crystalline solids
● Peptides, DNAs, ...
Capturing & processing
● Molecular graph
● Unit cell, space group
● Fragment sequence
Capturing & processing
● Struct. repeat unit (SRU)
● Nano-object (sphere,rod,...)
● Variable groups: R,X,Y,Z,...
● Metalevel components
Evolving informatics
●
Polymer systems
● Nanomaterials
● Material classes
● Composites & design

Polymer informatics: approaches
and tools
● IUPAC nomenclature & seniority rules (head-tail selection)
● S-group (superatom): SRU with crossing bonds and
brackets (common representation, MDL, MarvinSketch),
● ThermoML with polymer block to specify compounds,
● Polymer Markup Language (PML),
● Polymer Informatics Knowledge System (PIKS) - PolyInfo
database | “walled gardens” of polymer information,
● InChI polymer project (awaits implementation),
● CurlySMILES project, actively designs a human-machine
interface for nanoarchitectures, including polymers, and
develops open-source Python code.

From SMILES to CurlySMILES
SMILES: Simplified Molecular Input Line Entry
System
Published by David Weininger in 1988
doi: 10.1021/ci00057a005
CurlySMILES: Curly-braces enhanced Smart
Material Input Line Entry Specification
Published by Axel Drefahl in 2011
doi: 10.1186/1758-2946-3-1

CurlySMILES Motivation
● Chemical nomenclature and encoding languages typically
employ idealized representations, while minor structural
irregularities and impurities are ignored. CurlySMILES
encoding enables their insertion via annotation, if desired.
● A molecular-graph-derived notation is often taken to represent
molecule and substance interchangeably. CurlySMILES
employs molecule multipliers and allows for phase distinction,
for example, by using state and shape annotations such as lq,
tf, am, cr, np, ...
● Variability of detail: stoichiometric formula notation (SFN)
● Encoding of molecular arrangements: hydrogen-bonded
molecules, complexes, macromolecules and other
nanoassemblies.

Format of curly-enclosed
annotations in CurlySMILES
{AMk1=v1;...;kn=vn}
AM is a one-char or two-char annotation marker; a two-char
AM may by followed by an annotation dictionary, a
semicolon-separated list of key/value (ki/vi) pairs. Keys
are predefined, but extensible by customization ($ prefix).
Example: n-octanethiol functionalized gold nanoparticle
dispersed in toluene (●_
SCH2
(CH2
)6
CH3
in toluene)
S{-|c=[Au]{np}}CCCCCCCC{dpc=Cc1ccccc1}
AMs: -| for surface-attached, dp for dispersed, np for
nanoparticle.

Annotated Molecular Graph
Example: (Z)-but-1-ene-1,4-diyl substructure
CurlySMILES: C{-}=C{Z}CC{-}
Atom-anchored annotations:
Structural unit annotation (pendent single bond): {-}
Stereodescriptive annotation: {Z}

Poly[(Z)-but-1-ene-1,4-diyl]
CurlySMILES: C{-}=C{Z}CC{+n}
Atom-anchored annotations:
Structural unit annotation: {-} at head node
Stereodescriptive annotation: {Z}
Operational notation:{+n} at tail node

Does CurlySMILES encode
macromolecules or polymers?
Answer: both (user choice). CurlySMILES comes with a rich
annotation dictionary to encode chain length variation and phases.
A macromolecule is a single molecule. The term “polymer” can
mean “macromolecule” or a “substance” composed thereof,
typically with a “degree of polymerization” (DOP) range.
An oligomer or a macromolecule of a specific length is encoded
based on the chain graph, i.e. the SRU graph, using annotation
dictionary key n: {+nn=10} for ten-time-occurrence of SRU.
A polymer is encoded by leaving out n (generic polymer). The key
dpr may specify a DOP range: {+ndpr=gt250}. AMs such as am
(amorphous) or cr (crystalline) indicate a particular polymer phase.
A polymer system is encoded by additional annotations specifying,
for example, impurities, additives and solvents.

Tail node annotations to formally
construct polymers
{+n} anchored at tail node of divalent SRU to build single-
strand polymer via head-tail single-bond connection.
{+r} anchored at tail node of SRU to build single-strand
macrocycle (last tail node connects first head node).
{+m} anchored at tail node of non-single-bond or multivalent
SRU to build multibond/multi-strand polymer via
specified head-tail connection using key ich to
provide index of corresponding head node.
{+s} anchored at tail node of the last (right-most) SRU in a
copolymer sequence to provide copolymer details;
for example, a copolymer qualifier via key cpq to
specify an alternating, block or random sequence.

CurlySMILES notations of some
common single-strand homopolymers
Structure-Based Name Structural Formula CurlySMILES Notation
Poly(oxymethylene) -[OCH2
]-n O{-}C{+n}
Poly(iminoethylene) -[NHCH2
CH2
]-n N{-}CC{+n}
Poly(1-hydroxyethylene) -[CH(OH)CH2
]-n OC{-}C{+n}
Poly(1-cyanoethylene) -[CH(CN)CH2
]-n N#CC{-}C{+n}
Poly(1,1-difluoroethylene) -[CF2
CH2
]-n FC{-}(F)C{+n}
Poly(1-phenylethylene) -[CH(Ph)CH2
]-n C{-}(c1ccccc1)C{+n}
Poly(oxy-1,4-phenylene) -[O-paraPh]-n O{-}c1ccc{+n}cc1
Poly(methylene) -[CH2
]-n C{-}{+n}
Poly(difluoromethylene) -[CF2
]-n FC{-}{+n}F

Polydispersity characterization
With the exception of the dimensionless pdi, units are kg/mol.
Example: {+npMn=89.2} to encode a single-strand
polymer with a number-average molar mass of 89.2 kg/mol
Key Symbol Meaning ThermoML tag name
pMn Mn Number-average molar mass nNumberAvgMolWt
pMm Mm Mass-average molar mass nWeightAvgMolWt
pMz Mz z-Average molar mass nZAvgMolWt
pMv Mv Viscosity-average molar mass nViscosityAvgMolWt
pMp Mp Peak molar mass nPeakAvgMolWt (?)
pdi Mm
/Mn
Polydispersity index nPolydispersityIndex

Anionic homopolymer with
monoatomic cations
Example: poly(sodium 1-carboxylatoethylene)
CurlySMILES: O=C([O-]{+Cc=[Na+]})C{-}C{+n}
The operational annotation marker +C is used to
include [Na+] as counterion to [O-]. [Na+]is part
of the repeat unit.

Homopolymer with terminating
groups at head and tail
Example: poly(ethylene terephthalate) by
esterification of terephthalic acid with ethylene glycol
[H]O{-}CCOC(=O)c1ccc(cc1)C{+ninc=2-15;ich=2}
(=O)OCCO
Nodes 2 to 15 are parts of SRU. Node 1 makes the head
terminus and nodes 16-20 belong to tail end group.

Cyclic polymers or oligomers
Example: cyclic poly(silaether)
[Si]{-}(C)(C)[Si](C)(C)O{+rn=24}
Shortcut for a long SMILES notation:
[Si]1(C)(C)[Si](C)(C)O...[Si](C)(C)[Si](C)(C)O1
Such cyclic poly(silaether) are obtained, for example, as by-products
while making their linear homologs by ring-opening polymerization of
octamethyl-1,4-dioxatetrasilacyclohexane [10.1021/ma00086a048].

Surface-grafted functional oligomer
Example: polyacrylamid brush grown on
silicon
N{-|c=[Si]}C(=O)c1ccc(cc1)CCC{-}
C{+ninc=12-16;ich=12}C(=O)N
Group environment annotion -| for bond to substrate
Growth of such polyacrylamide brushes on a silicon wafer is studied
to understand how to reduce or prevent microbial adhesion on
surfaces by chemical surface modification [doi: 10.1021/la063531v].

Regular double-strand polymers:
chain of formally fused cycloalkane rings
Example: poly(butane-1,4:3,2-tetrayl)
CurlySMILES notation:
C{-}C{+mich=1}C{+mich=4}C{-}
two head nodes: C{-}, two tail nodes C{+m}
For IUPAC nomenclature of this polymer see
A Brief Guide to Polymer Nomenclature.

Regular double-strand polymers:
chain of formally fused heterocycles
Example: poly(2,4-dimethyl-1,3,5-trioxa-2,4-disilapentane-
1,5:4,2-tetrayl)
O{-}[Si]{+mich=1}(C)O[Si]{+mich=7}(C)O{-}
two head nodes: O{-}, two tail nodes [Si]{+m}
For IUPAC nomenclature of this polymer see page 1573 in
http://old.iupac.org/publications/pac/1993/pdf/6507x1561.pdf.

Double bond between head and tail
Example: poly(piperidine-3,5-diylideneethanediylidene)
CurlySMILES notations:
A: C1{=}CNCC(C1)=CC{+mich=1;b==}
B: C{-}C1CNCC(C1)=C{+n}
Both notations encode correct atom connectivity. In the
IUPAC-compliant notation A, key b specifies = as bond between
tail and head.
For IUPAC nomenclature of this polymer see page 1941 in
Nomenclature of Regular Single-Strand Organic Polymers.

Encoding with copolymer qualifiers
Copolymer Qualifiers Example:
poly(styrene-co-isoprene)
CurlySMILES notation of above example:
C{-}C{+ninc=1-8;ich=1}(c1ccccc1)
C{-}C=C(C)C{+ninc=9-13;ich=9}{+scpq=c}
cpq Qualifier Meaning
a alt alternating
b block block
c co generic
g graft graft
p per periodic
r ran random
s stat statistical

Encoding of a terpolymer
Example: poly[methyl-N-(3,4-dimethylphenyl)-N-(4-biphenyl)-N-(4-
phenyloxy)siloxane-co-phenylmethylsiloxane-co-
methylhydrosiloxane]
c1ccccc1[Si]{-}(C)O{+ninc=1-9;ich=7}[SiH]{-}
(C)O{+ninc=10-12;ich=10}[Si]{-}(C)
(Oc2ccc(cc2)N(c3cc(C)c(C)cc3)c4ccc(cc4)-
c5ccccc5)O{+ninc=13-43;ich=13}{+scpq=c}
For more about this terpolymer see 10.1021/ma202041u.

Nesting of SRUs
Example: unsaturated polyester with α,ω-alkanediyl
bridges
C{-}(=O)OC{-}{+ninc=4;ich=4;n=5-9}
OC(=O)C(C)=CCC{+ninc=1-13;ich=1}C

Encoding of polymer blends
Example: polystyrene/poly(methyl methacrylate) blend
C{-}C{+n}c1ccccc1.C{-}C{+n}(C)C(=O)OC{mx}
Annotation {mx} indicates a compatible or incompatible mixture.
CurlySMILES encoding as a two-phase system (composite):
{/C{-}C{+n}c1ccccc1/C{-}C{+n}(C)C(=O)OC}

Encoding of polymer solutions
Example: poly(1-cyanoethylene) dissolved in
dihydrofuran-2(3H)-one (γ-butyrolactone)
C{-}(C#N)C{+n}{dsc=O=C1OCCC1}
Annotation marker ds for dissolved
Key c for CurlySMILES notation with assigned value O=C1OCCC1

Encoding of doped polymers
Example: poly(1,4-phenylene sulfide) doped with
arsenic pentafluoride
c1{-}ccc(cc1)S{+n}{IMc=F[As](F)(F)(F)F}
Annotation marker IM for impurity
Key c specifying dopant F[As](F)(F)(F)F

Encoding of polymer sets
Example: poly[(alkylimino)methyleneimino-1,3-
phenylene] with specified alkyl groups
N{-}{+Rcc=C{-},CC{-},CCC{-},CC{-}C,CC{-}
(C)C}CNc1cccc{+n}c1
Annotation marker +R for alkyl group insertion
Key cc for list of comma-separated CurlySMILES notations; here,
encoding the specified alkyl groups methyl, ethyl, n-propyl, iso-
propyl and tert-butyl

CurlySMILES in Python 3
Current iteratively tested implementations
● Modules to parse and analyze molecular-graph-based notations
and their annotations
● CANGEN-based methods for input-to-unique conversion of
notations (regular single-strands)
● Substructure and descriptor generation methods
● Programs to maintain and screen Axeleratio's in-house
bibliography of CurlySMILES-tagged literature, including nano-
device and polymer publications.

Transformation of a CurlySMILES
notation based on node ranks
Example: poly[(2-propyl-1,3-dioxane-4,6-
diyl)methylene]
Entered: C1{-}OC(CCC)OC(C1)C{+n}
Unique: C1{-}CC(OC(CCC)O1)C{+n}
The CH2 ring node ranks lower than the left O node; the CH2 tail node
ranks higher than the right O node.

Uniqueness depending on selection
of head/tail (H/T) pair
O{-}CC{+n} C{-}OC{+n} C{-}CO{+n}
poly(oxyethylene)
Nomenclature-conform selection of head and tail
nodes is recommended in polymer encoding.
[see examples of unique notations for regular single-strand polymers]

Task-specific integration of
CurlySMILES modules
● Interfacing polymer structure (input/output)
Form-to-notation editors
Notation-to-sketch and notation-to-query software
● Pipelining polymer data (data administration)
Automatic ranking and comparison of structure/data pairs
Screening of structured lists and repositories
● Generating virtual libraries
Automatically building lists of polymer notations for QSPR
analysis and identification of optimal-design candidates

Application to polymer data mining:
“nurturing the mine sites”
SRU-based CurlySMILES notations in unique form are
identifiers of macromolecules and polymer systems that
can be employed to
• function as search keys in database applications,
• tag factsheets, notes and bibliographic entries,
• populate spreadsheet cells and XML text nodes,
• index and abstract the polymer literature & patents,
• create ontologies that organize polymer information,
..which can be shared via Semantic Web technologies.

Application to polymer data mining:
search and data extraction
The CurlySMILES language has a rich and extensible
dictionary to encode polymers in diverse contexts and at
various levels of detail.
Notations work both ways as precise data annotations
and as query formulations for “needle-in-the-haystick”
requests.
Today's polymer knowledge systems are not marked up by
CurlySMILES. But client-server mediation can be
achieved, behind-the-scenes, via CurlySMILES code to
• compact polymer input provided through entry forms,
• expand notations into query language formats.

Application to polymer modeling
CurlySMILES representations of polymer systems contain
detailed structural information to derive macromolecular
descriptors and substructures (groups) as entry points
for property prediction and model development:
• Structure property relationships (QSPRs, GCMs)
• SRU similarity (kNN and pattern recognition methods)
• MC & MD simulations (flexibility, solution behavior)
• Backbone modeling (polymer stability & degradation)
• Kinetic & ab initio methods (controlled polymerization)

Application to polymer design
Specialty polymers must meet multifaceted
requirements (multi-dimensional property windows).
The virtual design of polymers by permutationally
building (co)polymers (or blends) based on systematically
varied monomer structures often results into large
libraries of structurally related polymers with predictable
properties.
The automatic generation of the polymer structures of
such libraries as compact CurlySMILES notation and the
implementation of predictive methods for the desired
properties will allow virtual high-throughput screening
to initialize the synthesis of potential candidates.

Summary & Outlook
Done
● SRU annotations to encode
polymers
● Polymer description grammar
● Python implementation
To Do
● Stereochemical descriptions
● Unique notations for nested
polymers
● Conquering polymer space
Topics to be addressed for CurlySMILES applications
● Representation and iterative development of models for
structure/property estimation
● Extension to advanced architectures: dendrimers, 3D polymers
and nanostructure designs combining polymers with carbon
nanotubes and fullerene-based bowls and cages

Application of CurlySMILES to the encoding of polymer systems

Recomendados

Recomendados

Más contenido relacionado

La actualidad más candente

La actualidad más candente (7)

Destacado

Destacado (20)

Similar a Application of CurlySMILES to the encoding of polymer systems

Similar a Application of CurlySMILES to the encoding of polymer systems (10)

Último

Último (20)

Application of CurlySMILES to the encoding of polymer systems