BIOVIA® MATERIALS STUDIO®
POLYMORPH PREDICTOR™
DATASHEETBIOVIA Materials Studio Polymorph Predictor allows you topredict potential polymorphs of a given compound directlyfrom the molecular structure. Polymorphism is the ability for acompound to crystallize in more than one chemically identicalbut crystallographically distinct form. Crystalline materials
are prevalent in many industries, including pharmaceuticals,
agrochemicals, pigments, dyes, explosives, and specialty
chemicals. Polymorphs may differ in key properties suchas shelf-life, bioavailability, solubility, morphology, vapor
pressure, density, color, and shock sensitivity. It is therefore
important to know how many polymorphs are possible as well
as how their properties might differ when working in the solidstate.

THE CHALLENGES FACED
Once a particular solid form of a material is chosen for its desired
properties, researchers need to control the crystallization andformulation conditions so that unwanted polymorphs do notappear. In order to do so, they need to fully understand thestructural aspects of each polymorph. This knowledge is also
important for patenting and registration purposes.
The most common method for determining a crystal structure
is to grow quality crystals for single crystal X-ray diffraction.
Growing single crystals of appropriate size, however, is often
difficult or even impossible. Furthermore, one can not becertain that all possible polymorphs have been discovered
experimentally. Thus, methods that help predict potential
stable and metastable crystal packing arrangements from theknowledge of just the contents of the asymmetric unit, would
be extremely valuable.

WHAT DOES BIOVIA MATERIALS STUDIOPOLYMORPH PREDICTOR DO?
BIOVIA Materials Studio Polymorph Predictor explores andranks polymorphs of fairly rigid, non-ionic or ionic molecules(1, 2, 3). The approach is based on the generation of possible
packing arrangements in all reasonable space groups to search
for the lowlying minima in lattice energy.

BIOVIA Materials Studio Polymorph Predictor employs thefollowing procedure:• A fast and reliable Monte Carlo simulated annealing process(MC-SA) searches the lattice energy hypersurface forprobable crystal packing alternatives, typically generating
thousands of possible structures• Optionally, these potential structures are clustered into
unique groups based on packing similarity• The geometry of each unique structure is optimized
with respect to all degrees of freedom or with rigid body
constraints where the relative distance between a group ofatoms are fixed• The optimized structures are clustered again to remove
duplicates• The final structures are ranked according to lattice energy• The resulting low-energy crystal structures are potential
polymorphs. Powder patterns simulated for these structures
can be compared to experimental powder data for verification
using BIOVIA Materials Studio Reflex. Rietveld refinement
can be performed to optimize the agreement with theexperimental powder data. Additionally, polymorphs can bescored based on a statistical analysis of their hydrogen bond
topology with respect to known crystal structures using MSMotif.

THE BIOVIA MATERIALS STUDIO ADVANTAGEBIOVIA Materials Studio Polymorph Predictor is operated
within the BIOVIA Materials Studio® modeling and simulation
suite. BIOVIA Materials Studio’s integrated model building andediting tools enable you to construct, visualize, and manipulatemolecular structures in an asymmetric unit or structures ofcrystalline solids (e.g. drugs, pigments, metal oxides, andzeolites).
Potential crystalline structures suggested by the BIOVIA
Materials Studio Polymorph Predictor can be analyzed using
BIOVIA Materials Studio’s spreadsheetlike table (called astudy table) environment. The study table combines an easy
association of structures and crystalline properties (e.g. spacegroup, cell parameters, density, and energy for each structure)with powerful sorting and plotting functionality. It also provides
a flexible and convenient way to evaluate additional structuralproperties for developing quantitative structure-property
relationship models.

BIOVIA Materials Studio Polymorph Predictor can be utilized
in two ways:
1. When experimental powder data is available, it may be
used to aid the identification of the correct crystal structurefrom the list of generated trial structures using the Powder
Comparison feature and to refine the structural parameters
using the Rietveld method in BIOVIA Materials Studio Reflex.
2. Ab initio prediction of polymorphs when experimental
powder data is not available.

BIOVIA Materials Studio Polymorph Predictor workflow

The potential crystalline structures can further be optimized
using molecular mechanics tools (BIOVIA Materials Studio
Forcite and BIOVIA Materials Studio Compass), or quantum
mechanics tools (BIOVIA Materials Studio DMol3 or BIOVIAMaterials Studio CASTEP).

HOW DOES BIOVIA MATERIALS STUDIOPOLYMORPH PREDICTOR WORK?
The goal of BIOVIA Materials Studio Polymorph Predictor isto search for lowlying minima of a high-dimensional potential
energy surfaces representing all possible packing arrangementsof molecules in a crystalline environment as a function of spacegroups, lattice parameters, and contents of an asymmetric unit.

HOW DOES BIOVIA MATERIALS STUDIOPOLYMORPH PREDICTOR BENEFIT YOU?
Polymorphism has been recognized as a phenomenon thatmany industries are increasingly trying to control and exploit.
The appearance of an undesirable polymorph late in productdevelopment can lead to costly delays. In order to control
polymorphism, researchers need to understand how the crystal
structures of each polymorph differ. Knowledge of polymorphic
forms is also important for patenting and registration purposes.
BIOVIA Materials Studio Polymorph Predictor searches for
all possible packing arrangements of crystalline materials
from their molecular structures. Once the different crystal
structures are known, additional analyses can be performed tohelp explain other characteristics unique to each polymorph,including analysis of surface chemistry for different facets.
Researchers can define parameters for each step with aneasy-touse graphical user interface. The required input is themolecular structures of the contents of an asymmetric unit.
The starting conformations of these molecules can be importedfrom an existing crystal structure or created using 3D Sketcher
tools in Materials Visualizer and conformational analysis.

BIOVIA Materials Studio Polymorph Predictor can be used alone
or as the first step in a sophisticated structural analysis withother modules in BIOVIA Materials Studio. BIOVIA Materials
Studio Visualizer can be used to examine the packing accelrys.
com/materials-studio arrangement and hydrogen bonding foreach structure. In order to control crystal shape and growth,
the surface chemistry can also be analyzed. Furthermore, ifmedium- to high quality experimental powder data is available,
BIOVIA Materials Studio Reflex Plus, better suited to analyze
salts, solvates, and more flexible compounds, can be used todetermine the structure directly from the powder data.

KEY FEATURES• Crystals with more than one molecule in the asymmetric unit
can be considered.
• Geometry Optimizations can be run in parallel• Simulation results for each space group are stored intrajectory files for further analysis.
• Analysis is carried in study tables, displaying various
properties such as space group, energy and cell parameters.
• The Powder Comparison analysis feature allows for theautomated quantitative comparison of experimental powder
data to simulated powder patterns for each generated structure.
• The Crystal Similarity Measure analysis feature allows forthe automated quantitative comparison of experimentally
determined crystal structure to each generated structure.
• The Polymorph Clustering analysis feature allows forautomated quantitative comparison of each generated
structure to all the other structures generated in the same ordifferent space group, and same or different simulation runs.
• A variety of property calculations, including• Powder Comparison and Crystal Similarity measures, canbe carried out on all or a subset of the crystal structures in astudy table.
• You can access Polymorph functionality through theMaterialsScript API. Scripting allows you to automate
repetitive task and customize workflows.

RUNNING JOBS
• All BIOVIA Materials Studio Polymorph Predictor jobs are runin the background freeing up the BIOVIA Materials Studioclient for other research.
• All BIOVIA Materials Studio Polymorph Predictor jobs can besubmitted to remote computer servers.

RESULTS
Simulation results for each space group are stored in trajectory
files for further analysis.

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• Analysis is carried out with the help of spreadsheet-liketables, called study tables.
• Multiple trajectories files (e.g. corresponding to different
space groups) can be imported into a study table to beanalyzed simultaneously.
• When each trajectory file is loaded, various properties such as
space group, energy and cell parameters, are automaticallyentered into the study table as well.
• Each crystal structure is embedded in the study table, which
can be viewed independently and displayed along withvarious properties.
• The Powder Comparison analysis feature allows for theautomated quantitative comparison of experimental powder
data to simulated powder patterns for each generated
structure.
• The Crystal Similarity Measure analysis feature allows forthe automated quantitative comparison of experimentally
determined crystal structure to each generated structure.
• The Polymorph Clustering analysis feature allows forautomated quantitative comparison of each generated
structure to all the other structures generated in the same ordifferent space group, and same or different simulation runs.
• A variety of property calculations, including Powder
Comparison and Crystal Similarity measures, can be carriedout on all or a subset of the crystal structures in a study table.
To learn more about BIOVIA Materials Studio, go toaccelrys.com/materials-studioOur 3DEXPERIENCE Platform powers our brand applications, serving 12 industries, and provides a richportfolio of industry solution experiences.
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