The Derived Crystal Packing Model: a Way to Predict Crystal Structures and Structural Phenomena

1
The Derived Crystal Packing Model a Way to
Predict Crystal Structures and Structural
Phenomena

• Claire GERVAIS
• Present Address Department of Chemistry and
  Biochemistry, University of Berne, Switzerland

2
Introduction
3
Introduction
4
Introduction
Polymorphism
Analogy between crystal packings
Concomitant crystallization
Lamellar epitaxy
5
Introduction
Derived Crystal Packing model
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Derived Crystal Packing Model
Mother phase
Step I Analysis of the mother phase and
extraction of periodic fragments (PF)
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Derived Crystal Packing Model
PF1
Daughter phase 1
PF3
PF2
Daughter phase 2
Step II Generation of daughter phase(s) by
adding new symmetry operators to PF
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Consequences of Structural Similarities between
Mother and Daughter Phases ?
9
Expression of the Daughter Phases
Two-step procedure to generate new phases

• Extraction of periodic fragments
• Addition of symmetry operators

Mother phase
Daughter phase
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Expression of the Daughter Phases
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Expression of the Daughter Phases
Similar growth unit
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Expression of the Daughter Phases

• Aminoff and Broomé (Z. Krist., 80, 1931)
• The transition structure is that of a
  possible polymorphic modification of the
  structure or else that of a modification which
  could be plausible for that substance.
• Dauphiné twin of quartz a

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Expression of the Daughter Phases
During crystal growth Continuation of the
lattice
Or formation of twins or epitaxies.
Growth
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Expression of the Daughter Phases
During crystal growth Continuation of the
lattice
Or formation of twins or epitaxies.
Growth
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Expression of the Daughter Phases
Structural relationships between mother and
daughter phases

• Similar lattice energies similar stability
• Same growth unit similar conditions of growth

16
Applications of the DCP Model

• Resolution of racemic mixtures
• Design of polar structures
• Verification of structural purity
• Help in crystal structure prediction

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Resolution of Racemic Mixtures

• The DCP model can generate racemic compounds from
  enantiomer structures and vice versa

If structural relationships close lattice
energies between chiral and racemic structures
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Resolution of Racemic Mixtures
Stable conglomerate
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Resolution of Racemic Mixtures
Stable conglomerate

• Several examples
• 5-ethyl-5-methyl-hydantoin (see poster),
• Hexahelicene,
• a-amino-acids,
• Triazolylketone,
• Ammonium salts

Torbeev et al., J. Phys. Chem. B, 2003, 107,
13523-13531 and references (7)
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Resolution of Racemic Mixtures
Stable racemic compound
R
S
S
R
S
R
S
S
R
S
R
R
S
R
S
S
R
R
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Resolution of Racemic Mixtures
S
S
R
R
S
R
Tailor-made additive R to inhibit nucleation of
R,S and R nuclei but
R
R
S
S
R
R
S
R
R
R
R
S
R
S
S
R
2D nucleation of R,S
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Resolution of Racemic Mixtures

• Already observed experimentally for alanine
• I. Weissbuch et al. Chem. Mater. 1994, 6,
  1258-1268
• See Poster

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Resolution of Racemic Mixtures

• Generation of daughter phases with similar
  lattice energies and structures
• Lamellar epitaxy between two enantiomers hinders
  preferential crystallization
• Epitaxy enantiomer / racemic compound structures
  hinders resolution by tailor-made additives

The DCP model could be of help to predict these
problems
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Design of Polar Structures

• Design of 2D polar layers by crystal engineering

Building block
S. George et al., NJC, 2003 V. Videnova-Adrabinska
et al., J. Mater. Chem., 2000
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Design of Polar Structures

• Generation of polar and non-polar 3D phases by
  the DCP model

2D polar layer
Building block
3D daughter phases
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Design of Polar Structures

• Chances to obtain polar structures driven by the
  stability of the different daughter phases

C. Gervais, submitted to Mol. Cryst. Liq. Cryst.
Poster
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Help in Structure Prediction

• When polymorphism is of importance (drugs,
  pigments)

C. Gervais, G. Coquerel, Acta Cryst B. 2002, 58,
662 Poster
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Help in Structure Prediction

• Complementary tool to ab initio methods

Rank 1 2 3 4
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Conclusion
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Conclusion
Twinning
Polymorphism
71H, TNT, ZNPPA
DCP model
Concomitant crystallization
TNT, ZNPPA
Lamellar epitaxy
12H, a-aminoacids, hexahelicene
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Conclusion
Particular phenomena for chiral and polar
compounds
Twins and epitaxies
Crystal structures
Mother phase
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Conclusion
Particular phenomena for chiral and polar
compounds
Twins and epitaxies
Crystal structures
For the moment, its not automatic !
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Conclusion

• Automation of the model at

Unité de Croissance Cristalline, de
Chromatographie et de Modélisation Moléculaire
(Director Prof. Gérard Coquerel) UPRES EA
2659, IRCOF, University of Rouen, 76821
Mont-Saint-Aignan CEDEX, France
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Conclusion

• Automation of the model
• PBC analysis to extract the most energetic PFs
• Use of Transformation Matrices to generate new 3D
  packings
• Further developments in the field of chirality
  and polarity
• Extension to other types of compounds or phases
  (organometallics, solvates, hydrates)

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Thanks To

• Prof. Gérard Coquerel who proposed me to develop
  this idea during my PhD. thesis
• Prof. Jürg Hulliger who introduced me in the
  field of polarity
• All the authors named in this presentation who
  gave me the opportunity to apply the model to
  nice examples
• All of you !

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For further information and examples, see Poster
Gérard Coquerel and me!
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Help in Structure Prediction
Modafinil crystallises in various polymorphic
forms and solvates
Form I P21/a (Z2) a  14.517Å b 9.710Å c
20.875Å ?  110.14Å
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Help in Structure Prediction

• Form III detected experimentally
• X-ray powder diffraction (XRPD) pattern closely
  similar to that of form I

BUT...
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Help in Structure Prediction
BUT Twinned crystals with dendritic growth
Great difficulty to resolve the structure by
Single Crystal X-ray diffraction
Application of the DCP model
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Help in Structure Prediction
Form I (P21/a, Z2)
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Help in Structure Prediction
Form I (P21/a, Z2)
Hydrophilic PF (one molecule)
Hydrophobic PF (two independent molecules)
The two molecules of the asymmetric unit have
close conformations
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Help in Structure Prediction
Regeneration of an H-bond network
Hydrophobic PF
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Help in Structure Prediction
Hydrophobic PF
Pna21 with Z2
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Help in Structure Prediction
Hydrophilic PF
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Help in Structure Prediction
Suppression of symmetries contained in the PF
Hydrophilic PF
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Help in Structure Prediction
Hydrophilic PF
Pna21 with Z2
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Help in Structure Prediction
Hydrophilic slice (one molecule)
Hydrophobic slice (two molecules)
Regeneration of the H-bond network
Suppression of symmetries
Daughter Phase Pna21 Z2
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Help in Structure Prediction
Daughter Phase
Form III
Good match between the XRPD patterns
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Help in Structure Prediction

• Recently, single crystals of form III have been
  obtained, and the crystal structure resolved.

M. Pauchet, C. Gervais, G. Coquerel et al.,
Cryst. Growth Des. (submitted)