Amorphous Organic Solids and
Their Crystallization
Ye Sun, Lei Zhu, Ting Cai, Erica Gunn, Caleb
Brian, Mariko Hasebe, Travis Powell, Tian Wu,
Hanmi Xi, Melgardt de Villliers, Mark Ediger,
and Lian Yu
University of Wisconsin – Madison
School of Pharmacy & Dept. of Chemistry
With thanks to: NSF, Abbott, PRF,
AstraZeneca
Organic glasses have special applications
Drug delivery
Food
Glasses are more
soluble than crystals
Bio-preservation
In sugar glasses
Shirota 2005
In amber
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From yesterday’s workshop
• Glasses (amorphous solids) are made by
cooling liquids, as well as by including milling,
drying hydrates, vapor deposition, …
• Solidity does not mean no mobility.
Glasses relax
Glasses can crystallize
This talk
(1) Engineering organic glasses
(2) Crystal growth in organic glasses – bulk
(3) Crystal growth in organic glasses –
surface
A glass is a “living thing” – it relaxes over time
OTP
Longer
annealing
T annealing
= 233 K
Can a glass be
made at such a
low energy that
virtually no
relaxation occurs
on storage?
Heat capacity of OTP glass annealed for up to 10 hrs at 233 K (Tg
– 13 K). Longer annealing leads to lower energy and higher “heat
of melting”.
Xi, H.; Sun, Y.; Yu, L. J. Chem. Phys. 2009, 130, 094508.
Vapor deposition can produce stable glasses
Substrate
Vapor
VD glasses can be 14 J/g
lower in energy than
ordinary glasses – a level
reached only after very long
aging (perhaps 106 years)
Swallen, Ediger, et al. Science 2007, 315, 353
Zhu & Yu Chem. Phys. Lett. 2010, 499, 62
Glasses are generally isotropic, but anisotropy
can be introduced by cooling liquids in E field
Eich, M. et al. J. Opt. Soc. Am. B 1989, 6, 1590 – 1597.
Vapor deposition can yield anisotropic glasses
XRD
Ellipsometry
2D detector
VD glass film
Asymmetric
scattering indicates
“layered” structure
Dawson, Ediger, Yu et
al. PNAS 2009 ; Dawson
et al. J. Phys. Chem. B
2011
This talk
(1) Engineering organic glasses
(2) Crystal growth in organic glasses – bulk
(3) Crystal growth in organic glasses –
surface
J. Chem. Educ. 2000, 77, 846
But glasses do crystallize!
Amorphous indomethacin
crystallizes in days 
30 ºC (Tg - 12 ºC)
O
CO2H
N
O
Cl
Yoshioka et al. J. Pharm. Sci. 1994, 83, 1700
Well known kinetic pattern of crystal growth in onecomponent liquids
-4
glass
Tg
-7
liquid
Tm
-8
-5
-6
Log u, (m/s)
-9
Thermodynamic
control
-7
-10
-11
uD
-8
-9
-12
Diffusion
controlled
growth
OTP
-13
-10
Log D, (cm2/s)
-3
The pattern was
predicted by
Wilson and
Frenkel
-14
-11
▲ log u Magill & Li (1973)
□ log D Mapes et al. (2006)
○ log D Fujara et al. (1992)
-12
-15
-16
-13
220
240
260
280
T, K
300
320
340
A new, fast growth mode emerges near Tg
-3
-7
Tg
Tm
-8
-5
Log u, (m/s)
-6
-7
-9
“GC growth”
Not controlled by
bulk diffusion
-10
-11
-8
-12
Diffusion
controlled
growth
-9
-13
-10
-14
-11
▲ log u Magill & Li
● log u Hikima et al.
□ log D Mapes et al.
○ log D Fujara et al.
-12
-15
-16
-13
220
240
260
• First observed for
OTP by Greet and
Turnbull in 1967
280
T, K
300
320
340
Log D, (cm2/s)
-4
• Studied by Oguni
and coworkers
since 1995
• Unknown for
inorganic and
polymeric glass
formers
OTP
Many organic liquids
show emergence of GC
growth near Tg
Shtukenberg, A.; Freundenthal,
J.; Gunn, E.; Yu, L.; Kahr, B.
Crystal Growth & Design 2011,
11, 4458
Two substances not showing GC growth
cordierite
Nascimento & Zanotto 2010
Studying crystal growth with polymorphs:
From the same liquid/glass, which polymorph
grows, and which does not?
Polymorphs of ROY
O
N
O
N
H
N
(1) R P-1
mp 106.2 oC
= 21.7°
(2) ON P21/c
mp 114.8oC
= 52.6°
C

S
ROY
CH3
(3) Y P21/c
mp 109.8 oC
= 104.7°
J. Am. Chem. Soc.
2000, 122, 585
(4) OP P21/c
mp 112.7 oC
= 46.1°
(5) YN P-1, mp 99 ºC
= 104.1°
(7) RPL
(6) ORP Pbca
mp 97 ºC, = 39.4°
R
100 m
R05
Y04
Y04
(8) Y04
L
L
a
6
Some ROY polymorphs
show GC growth;
some do not
R
JACS 2005a
JACS 2001
(9) YT04 P21/c (10) R05
mp 106.9oC
 = 112.8°
JACS 2005b
T, K
220 240 260 280 300 320 340 360 380
Tg fibers
GC growth
(compact
spherulites)
R
Tt
4
OP
Log u, (m/s)
2
y shift
+11
YT04
0
-2
+8
Y
-4
YN
+ = R05
+5
ON
-6
+2
-8
No GC growth
b
YT04 GC
growth
Tt
-3
-4
YT04
fibers
-5
-6
-7
-8
-9
Y. Sun et al. J. Phys. Chem. B 2008
L. Yu. Acc. Chem. Res. 2010
ON (No GC growth)
220 240
260 280 300 320 340
T, K
360 380
-10
-11
Log u, (m/s)
-10
Polymorphs that grow in glasses are more
isotropically packed and “liquid-like”
4
3
2
1
0
3 3
No GC growth
Radial
distribution
functions
GC growth
Number of molecules
2
ON
4
5
6
7
8
9
10
4
5
6
7
8
9
10
4
5
6
7
8
9
10
4
5
6
7
8
9
10
4
5
6
7
8
9
10
6
7
8
9
10
YN
1
0
3
4
3
2
1
0
4 3
3
2
1
0
3 3
2
1
Y
OP
R
0
4 3
3
2
1
0
3
YT04
4
5
r, Ǻ
Explanations for GC growth – still imperfect
•  relaxation. But the process is
absent in ROY and aged away in OTP
(Hikima et al. 1995; Sun et al. 2008)
• Cluster growth. But has difficulty
explaining the abrupt onset, termination
(Hikima et al. 1995)
glass
• Tension from densification. But fibers
grow rapidly above Tg; no “autocatalysis”
(Konishi & Tanaka 2007)
crystal
(denser)
• Solid-state transition similar to polymorphic
conversion and grain-boundary migration. But no
predictive power (Sun et al. 2008)
This talk
(1) Engineering organic glasses
(2) Crystal growth in organic glasses – bulk
(3) Crystal growth in organic glasses –
surface
Crystal growth
in the bulk
Crystal growth at
the free surface
crystal
glass
crystal
glass
“Whereas in many metallic glasses nucleation has been
observed to be enhanced at the surface, growth rates
are usually quite comparable with those in the bulk.”
Koster (Mat. Sci. & Eng. 1988, 97, 233)
[For silicate glasses,] “The crystal growth velocities of
crystals in the volume and of the surface layer in the
glass volume, as well as of isolated crystals on the glass
surface are equal.” Diaz-Mora et al. (J. Non-Crystalline
Solids 2000, 273, 81)
Organic glasses can grow crystals faster at the
surface than in the bulk
Crystal growth rate of
IMC ( polymorph)
Log u, m/s
bulk
surface
O
CO2H
N
O
Tg
T, °C
Cl
Indomethacin
(IMC)
Wu, T.; Yu, L. J. Phys. Chem. B 2006, 100, 15694; Pharm. Res. 2006, 23, 2350
What do surface crystals
look like?
a
200µm
1500nm
b
2µm
IMC crystals at Tg – 2C
Surface crystals rise above glass
surface by 100 – 1000 nm, as they
grow laterally
c
Ye Sun et al. PNAS 2011, 108, 5990
051
040
032
022
Bulk
glass
020
021
10000
Counts (arb.
Unit)
Surface
crystals
Surface crystals are so
thin that they diffract
weakly. Can we do
better with GADDS?
0
IMC
5
10
20
2degree
30
Effect of PVP on crystal growth in NIF glasses
Ting Cai et al. Pharm. Res. 2011, 28,
2458
Polymer dopants can strongly inhibit bulk crystal
growth, but their effect on surface growth is less
Crystal growth in NIF glass at Tg – 12 ºC
-8
Surface
log u (m/s)
-9
-10
Bulk
CH3
-11
H
N
CH3
OCH3
O
NO2
H3CO
O
NIF
-12
0
1
2
3
4
5
% w/w PVP-K15
Ting Cai et al. Pharm. Res. 2011, 28, 2458
Surface crystallization can be inhibited with a
nanocoating
Layer-by-layer
coating
Uncoated
IMC glass
7 d at 40 ºC
15 mm
+ +- +- +- +-
PDDA
PSS
- - - - + + + + +
Coated with
10 nm gold
or 2–30 nm
polymer
+
+- +- +- +
- -
PDDA
IMC glass
7 d at 40 ºC
200μm
PSS
- - - - + + + + +
200μm
Wu, Sun, Li, de Villiers, and Yu. Langmuir 2007, 23, 5148
Explanations for fast surface crystal growth
• Tension from crystal growth is relaxed at surfaces
(Schmelzer 1993)
• Surface mobility and opportunity for upward
growth (Sun et al. 2011)
The latter model better explains inhibition by
nanocoating and upward growth of surface crystals
Tension-release model tested with polymorphs
Form I
Form III
number of molecules
Form I
Form III
Model predicts
positive slope
Form IV
Form IV
distance (Å)
Gunn, E.; Guzei, I. A.; Yu, L. Cryst. Growth Des. 2011, 11, 3979-3984
Surface diffusion is fast on IMC glasses
log D, m2/s
-13
b
Ds (surface)
-15
-17
Dv (bulk)
Tg
-19
-21
290
300
310
320
330
340
350
T, K
Mobile surface
Glass
L. Zhu et al. Phys. Rev. Lett. 2011, 106, 256103
Summary
• XRD plays a key role in studying amorphous
solids and glasses
• Organic glasses can be “engineered” into have
different structures and properties
• Organic liquids develop fast modes of crystal
growth as they solidify to glasses
in the bulk
at the surface
• The phenomena are unknown or uncommon
for non-organic glasses