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From Molecule to Crystal
The Problem of Crystal Engineering
Gautam R. Desiraju
Solid State and Structural Chemistry Unit
Indian Institute of Science
Bangalore 560 012
What is Crystal Engineering?
It is the design of organic and metal-organic solids
Molecular Solids
The understanding of intermolecular interactions in the context of
crystal packing and in the utilisation of such understanding in the
design of new solids with desired physical and chemical properties
(Desiraju, 1989)
Crystal Engineering
The question
Given the molecular structure of an organic compound, what is
its crystal structure?
In other words, how do molecules recognize one another?
Why do we start with molecules?
O
H5C6
H O
C6H5
O H
O
Towards greater complexity
O
H3C
O H
O
H O
O
H3C
O H
CH3
Crystal Engineering
The problem
The behaviour of a functional group in a molecule during crystallization
depends on the nature and positioning of all the other functional groups
in the molecule.
Therefore crystal structures are not related to molecular structures
(functional groups) in simple ways. They are emergent properties.
Hydrocarbon residues also count as functional groups in
supramolecular chemistry.
Crystal Engineering
A second problem
One → Few → Many → Crystal
We do not know how molecular crystals are built up. Are small
clusters formed which increase in an orderly way to give larger
clusters? Or are the events more irregular?
A simplification is required
Supramolecular synthons
are structural units within
supermolecules which
can be formed and/or
assembled by known or
conceivable synthetic
operations involving
intermolecular interactions
Desiraju (1995)
Even more complexity
Br
O
O
H
O
O
H
Br
Br
O
O
H
S. S. Kuduva et al., J. Am. Chem. Soc, 121, 1936, 1999
The Weak Hydrogen Bond
D. Das et al, Cryst. Growth & Des., 3, 675, 2003
D. Das and G. R. Desiraju, Chem. Asian J., 1, 231, 2006
The weak hydrogen bond is
an interaction X–H···Y wherein
a hydrogen atom forms a bond
between two structural moieties
X and Y, of which one or even
both are of moderate to low
electronegativity
C–H···O
C–H···N
O–H···π
C–H··· π
Os–H···O
C–H···Ni
Degrees of complexity
Supramolecular
Synthons
Maximise information density
With weak interactions both
size and complexity increase
ome supramolecular synthons
O
N
O
O
Cl
C N
H C
N
N C
Cl
H C
N
H
N
C
O
C
H
N
H
O
N
H
N
N
H
H
O
H
O
O
N
H
O
N
O
N
O
G. R. Desiraju, Angew. Chem. Int. Ed. Engl., 34, 2311, 1995
Br
Supramolecular retrosynthesis
O
I
O
I
N
O
O
I
N
O
O
I
N
O
N
O
O
N
I
N
O
O
O
I
O
N
O
O
I
N
O
V. R. Thalladi et al., Chem. Comm., 401, 1996
I
Polymorphism
Kinetics and Thermodynamics
G. R. Desiraju, Nature Mat., 1, 77, 2002
Efavirenz polymorphs
A: Thermodynamic;
B and C: Kinetic
S. Mahapatra et al., Cryst. Growth Des. 10, 3191, 2010
Phenylacetylene polymorphs
T. S. Thakur et al., Cryst. Growth Des. 10, 4246, 2010
Lower level objects may
not be the best models for
higher entities
Universality in the behavior of complex
systems often reveals itself in forms that are
essentially independent of the details of
microscopic dynamics. A representative
paradigm of complex behavior in nature is
cooperative evolution, seen in structural
chemistry as self-assembly and
crystallisation (chemical sociology). The
interaction of individuals gives rise to a wide
variety of collective phenomena that
strongly differ from individual dynamics
such as demographic evolution, cultural
and technological development, and
economic activity.
Crystal Engineering
The Holistic Crystal
Students, Post-docs
DST, BASF, Rigaku
Indian Institute of Science
IIAP, AvH Stiftung