How crystals are made and why this really matters
Mike Zaworotko
Bernal Professor of Crystal Engineering & SFI Research Professor
University of Limerick
23rd February 2015 1st Brasil-Ireland Science Week
My 2 cents worth
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Addressing human disease and environmental
sustainability trump all else.
The “right chemistry” is at the heart of both
matters.
Individual research groups and individual countries
cannot solve the big problems alone – we are all
“wearing the green”.
Being “competitive” is not enough – the rewards
do not go to the runners-up.
Some immediate low cost, low risk but high reward
opportunities are crystal clear.
The Basics: Compounds form Crystals
solution
supersaturated solution
crystal
The vast majority of substances form one or more crystalline solids
that exhibit a regular repeating array of molecules that extends in 3D.
This brings purity, consistency and easy processing.
First some ancient history – 2000+ years ago
D- and L- quartz: chiral crystals
The original “crystal”, named after the Greek
word κρύσταλλος (krystallos) meaning clear ice
(thought at time to be a hard version of ice)
Pasteur’s spontaneous resolution
experiment in 1848 started the
field of stereochemistry
More recently: the dawn of modern science
The discovery of x-ray diffraction?
J. Watson
F. Crick
R. Franklin
D. Hodgkin
M. Perutz
J.D. Bernal
K. Lonsdale
W.L. Bragg and W.H.
Bragg, 1912: Nobel Prize
for Physics in 1915
Max von Laue
discovered x-ray
diffraction (CuSO4,
ZnS) in 1912: Nobel
Prize for Physics in
1914
John D. Bernal, 1901-1971
Born Nenagh, Co. Tipperary, Ireland
Student of W.H. Bragg
Stalin Peace Prize, 1953
Determined structure of graphite, 1924
Two students won Nobel Prizes
(Hodgkin, Perutz), Crick was a Perutz student
Credited with idea of first database (CSD, 1950’s)
Recognized CO2 and climate change (1950’s)
J.D. Bernal
Proc. Royal Soc., 1924, 749-773.
But ... the situation in 1988
Crystal engineering was an oxymoron
“One of the continuing scandals in the physical
sciences is that it remains in general impossible to
predict the structure of even the simplest crystalline
solids from a knowledge of their chemical
composition”
John Maddox editorial, Nature, 1988, 335, 201.
“… a large part of the scandal remains”
Philip Ball editorial, Nature, 1996, 381, 648
“Whenever people agree with me I always feel I must be
wrong” Oscar Wilde
Why does design of crystalline materials matter?
Finesse
Faith
Force
Now for some geography: 11/2013-present
40 million Euro over 6 years
30 PIs
30 post docs
60 Ph.D. students
Hosted by University of Limerick
7 other Irish institutions
17 industry partners
12 international partners
Bernal Building
University of Limerick
“Starship
Enterprise”
Courtesy SSPC
Anthony Maher
Application 1: Pharmaceutical Materials
Polymorph 1
A $30 billion
patent
(Zantac®)
Form 2 is:
• Novel
• Not obvious
• Has utility
Polymorph 2
Early Drug Discovery and Development
3 stages: Molecules to Materials to Medicines
Pre-formulation
Objective Formulation
Molecules
Materials
Medicines
Medicinal Chemistry
Drug Substance(s)
Drug Product
le
Optimize properties
APIof drug substance to enable or
Excipients
Pharmaceutical
improveActive
performance
of
drug product.
Ingredient
To make better medicines through a low cost, low risk
but high reward approach
Universidade Federal do Ceara
Instituto de
Fisica de Sao
Carlos,
Universidade de
Sao Paulo
Alejandro Ayala, Beatriz Bezerra, Renato Carneiro,
Javier Ellena, Pierre Fechine, Alcemira Oliveira
A Catch-22
Why has the pharmaceutical
industry failed to address
neglected diseases?
Financial incentives for the
developed world
• Need high prices to cover
development + provide
profits
• Patent protection needed
• Patient reimbursement
schemes needed
Financial incentives for the
developing world
• High prices cannot be
sustained
• Patent protection not
enforced or discouraged
• Little or no reimbursement
See poster 7 for more details
Application 2: Porous Materials
• Desiccants
• Catalysts/Catalyst Supports
• Molecular Sieving
• Separation or Storage of Gases
• Purification of Liquids
• Drug Delivery
• Pollution Control
• Sensors
• Respiratory Protection
14
Why should we care?
Industry uses around 1/3 of
world energy production
Commodity purification
uses >10% of world energy
Distillation alone uses >5%
of world energy production
Porous sorbents also used
in heat pumps
Publications, citations on coordination polymers
WebofScience® search on “coordination polymers”
The main reason for the
inflection point?
India is also in on the act
The most cited chemists in India both work in solid state chemistry:
C.N.R. Rao (h-index = 110, about 40 chemists >100)
G.R. Desiraju (h-index = 70)
Energy-related applications of CO2 capture
CO2 is an impurity in
natural gas and NG storage
is a challenge
CO2 is a bye-product of
coal combustion
Natural gas (most abundant)
Published November 2012
Selectivity is a critical parameter for CO2 capture
Relationship between cost of CO2 capture, CO2 selectivity, and
working CO2 capacity for solid sorbents
Merel, J., Clausse, M. & Meunier, F.
Ind. Eng. Chem. Res. 47, 209-215 (2008)
mmo-2: 298K single component isotherms + selectivity
mmo-2
11 cm3/g at 0.39 mbar
45 cm3/g at 0.15 bar
Overall goal: task specific materials by design
Finesse
Faith
Force
Think
Globally
Think
Teamwork
The Right Chemistry
Thank you