the derived crystal packing model: a way to predict crystal structures and structural phenomena...

The Derived Crystal Packing Model: The Derived Crystal Packing Model: a Way to Predict Crystal Structures a Way to Predict Crystal Structures

and Structural Phenomenaand Structural Phenomena

Claire GERVAISClaire GERVAIS

Present Address: Department of Chemistry and Biochemistry, Present Address: Department of Chemistry and Biochemistry, University of Berne, SwitzerlandUniversity of Berne, Switzerland

IntroductionIntroduction

N O2

NO 2

O 2N

Molecule Crystal structure

Expected physical properties

Real crystals

Real physical properties


Twinning

Concomitant crystallization

Polymorphism

?Lamellar epitaxy


Analogy between crystal packings


Polymorphism

Lamellar epitaxy

Twinning


Analysis and prediction of structural phenomena

Crystal structure prediction

Derived Crystal Packing model

Derived Crystal Packing ModelDerived Crystal Packing Model

Mother phase Ribbon (PF1)

Ribbon (PF2)

Slice (PF3)

Step I : AStep I : Analysis of the mother phase and nalysis of the mother phase and extraction of extraction of periodic fragments (PF)periodic fragments (PF)

Derived Crystal Packing ModelDerived Crystal Packing Model

PF3PF2

PF1

Daughter phase 1

Daughter phase 2Daughter phase 3

Daughter phase 4

Daughter phase 5

Step II: Generation of daughter phase(s) by adding new Step II: Generation of daughter phase(s) by adding new symmetry operators to PFsymmetry operators to PF

Consequences of Structural Consequences of Structural Similarities between Mother and Similarities between Mother and

Daughter Phases ?Daughter Phases ?

Expression of the Daughter PhasesExpression of the Daughter Phases

Two-step procedure to generate new phases:• Extraction of periodic fragments• Addition of symmetry operators

Mother phase Daughter phase


Lattice energy difference determined by interactions

between PFs

Similar lattice energies

Provided a PF with strong intermolecular interactions,


Similar growth unit



• 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

IndividualQuartz Trigonal

IndividualQuartz Trigonal

Twin zone

hexagonal

Quartz


Twinning of MP

During crystal growth: Continuation of the lattice…

…Or formation of twins or epitaxies.

Growth

Underlying expression of DP at

the twin zone


During crystal growth: Continuation of the lattice…

…Or formation of twins or epitaxies.

Epitaxy of DP on MP

Growth


Structural relationships between mother and daughter phases :

(Concomitant)

Polymorphism

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

Twinning, Epitaxy

Applications of the DCP ModelApplications of the DCP Model

Resolution of racemic mixturesResolution of racemic mixturesDesign of polar structuresDesign of polar structures

Verification of structural purityVerification of structural purityHelp in crystal structure predictionHelp in crystal structure prediction

Chiral PF

Chiral mother phase

+ Symmetry of second kind

Racemic daughter phase

Resolution of Racemic MixturesResolution 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 …


R R R R R R R R RR

SS

SSSS

RRRR

RRRRRR RR

RRRR

RR

SSSSSS

SS

SS

SS

2D nucleation of S2D nucleation of S

SS

R R R R R R R R RRR R R R R R R R RRS S S S S S S S SS

SSRRRRRR

RRRR

SS

SS SS

Diffusion rate is too low

Growth rate is too high

Growth of R

RRSS

R R R R R R R R RRR R R R R R R R RR

SS

RRRR

RRRR

SSSS

SSSS SSSS

SSThe local supersaturation of S enantiomer is too high

Stable conglomerate


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

Stable conglomerate

Torbeev et al., J. Phys. Chem. B, 2003, 107, 13523-13531 and references (7)

Existence or generation of competitive racemic compounds


S

SS

RR

RRR R

RR

R

SSS

S

S

SRRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

R R R R R R R R RR

Stable racemic compound

S S S S S S S S SS

Growth of R,S


R R R R R R RR R R R R R R RR

RRRR

S

S S

RR

RR R

RR

R

R

SSS

SS

SRRR

R

S S S S S S S S SSS S S S S S S S SS

RRSS

RRSS

SS

RRSS

RRSS

RR RR RR RR RR

RR

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

RRSS

S S S S S S S S SSS S S S S S S S SSS S S S S S S S SS

S S S S S S S S SSS S S S S S S S SSS S S S S S S S SSS S S S S S S S SS

Tailor-made additive R to inhibit nucleation of R,S and R nuclei but…

…2D nucleation of R,S


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

Existence of structural relationships between chiral and

racemic phases (2D layer)

Resolution of Resolution of RRacemic Mixturesacemic 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

Design of Polar StructuresDesign of Polar Structures

• Design of 2D polar layers by crystal engineering

D

A

2D polar layerBuilding block

S. George et al., NJC, 2003V. Videnova-Adrabinska et al., J. Mater. Chem., 2000


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

D

A

2D polar layerBuilding block

3D daughter phases


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

Variation of the building block(Substituants)

D

AR Stable polar phases

C. Gervais, submitted to Mol. Cryst. Liq. Cryst. & Poster

Help in Structure PredictionHelp in Structure Prediction

• When polymorphism is of importance (drugs, pigments…):

Known mother phase

Daughter phase 1 Daughter phase 3Daughter phase 2

Verification of Structural Purity

C. Gervais, G. Coquerel, Acta Cryst B. 2002, 58, 662 & Poster


• Complementary tool to ab initio methods:

Rank1234

…

Daughter phases

Xth

Structure Xth has to be taken into consideration

ConclusionConclusion


Polymorphism

Lamellar epitaxy

Twinning

?



Polymorphism

Lamellar epitaxy

Twinning

DCP model

12H, -aminoacids, hexahelicene…

71H, TNT, ZNPPA…

TNT, ZNPPA…

Many examples!

Kuleshova, Cryst. Reports. 2002 & 2003


Particular phenomena for chiral and polar

compounds

Crystal structures

Twins and epitaxies

Mother phase Daughter phases


Particular phenomena for chiral and polar

compounds

Crystal structures

Twins and epitaxies

For the moment, it’s not automatic !


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


• 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…)

Thanks To: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 !

For further information and For further information and examples, see Poster … examples, see Poster … Gérard Coquerel and me!Gérard Coquerel and me!


Form I: P21/a (Z’=2)

a = 14.517Åb = 9.710Åc = 20.875Å = 110.14Å

Modafinil crystallises in various polymorphic forms and solvates

BUT...


• Form III detected experimentally • X-ray powder diffraction (XRPD) pattern closely

similar to that of form I

BUT… Twinned crystals with dendritic growth

Great difficulty to resolve the structure by Single Crystal X-ray diffraction

Application of the DCP model


20m


Form I (P21/a, Z’=2)


Form I (P21/a, Z’=2)

Hydrophilic PF (one molecule)

Hydrophobic PF (two independent molecules)

The two molecules of the asymmetric unit have close conformations


Hydrophobic PF Regeneration of anH-bond network


Hydrophobic PF Pna21 with Z’=2


Hydrophilic PF


Hydrophilic PF Suppression of symmetries contained in the PF


Hydrophilic PF Pna21 with Z’=2


Hydrophilic slice(one molecule)

Hydrophobic slice (two molecules)

Daughter Phase Pna21

Z’=2

Regeneration of the H-bond network

Suppression of symmetries


Form III

Daughter Phase

Good match between the XRPD patterns


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

Pna21 , Z’=2

Crystal packing match with the daughter phase generated

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

the derived crystal packing model: a way to predict crystal structures and structural phenomena...

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