The underlying cause for polymorphism in acyglycerols has puzzled researchers for more than 150 years. For the last 50 years or so, the subcell concept has been used to describe and understand this phenomenon. In general, there is a correlation between the crystal structure of the various polymorphs and the packing of the polymethylene chains (reflected in the subcell). This occurs because, for acylglcyerols, higher-melting polymorphs form due to an increase in packing efficiency for the polymethylene chains (i.e. packing efficiency increases α < β′ < β) . These same concepts are used to understand polymorphism in waxes and alkanes, and when applied to acylglycerols, they work reasonably well (i.e. as a rule of thumb). They are, however, of limited use in understanding more complex or exceptional polymorphic behaviors. In fact, progress in answering more difficult research problems is hindered, rather than helped, by the current reliance on the subcell concept.
In this work we provide a more fundamental understanding for polymorphism in acylglycerols. Using a stereochemical approach, we are able to provide solutions and mechanisms for research questions that have challenged (and remained unanswered) by many previous workers.
10. Homochirality – required for evolution of life
• predictable and reproducible molecular and
supramolecular structure
- efficient function of natural enzymes, transfer and storage
of genetic information in nucleic acids
• “… a detailed knowledge of the stereochemistry of
intermolecular and interionic organization is
ultimately required for understanding the molecular
processes that characterize life.”
Stewart, M. V.; Arnett, E. M. In Topics in Stereochemistry; Allinger, N. L., Eliel, E. L., Wilen, S.
H., Eds.; John Wiley & Sons: New York, 1982; Vol. 13.
10
11. “Perhaps Looking-glass milk isn’t good to drink…”
D-carbohydrates
L-amino acids
D-ribose DNA & RNA
sn-3 phospholipid
L-carbohydrates
D-amino acids
L-ribose DNA & RNA
sn-1 phospholipid
11
12. Polymorphism influences the physical
properties of many foods
Butter
β′
Margarine
β′
Chocolate
βV and βVI
12
13. (2002), Science, 295, 2410-2413
“The fundamental difficulty for this field is that
molecular crystals are held together by a multitude
of weak interactions, a huge number of free energy
minima (polymorphs) exist within a few
kilojoules/mol of the global minimum.”
13
40. Triacylglycerols –
Space Group Assignments
Compound
β′ forms
8 / 13 compounds
β forms
33 / 34 compounds
Space group
S# a
C2 / I2
one
P1
both
a. S# ≡ number of stereoisomers in the unit cell determined by the lack or
presence of a reflective symmetry operation for the designated space group.
40
42. 1-Monoacylglycerols Space Group Assignments
Compound
Enantiomer
sn-C11Br:0-OH-OH
sn-HO-HO-18:0
Racemic Mixture
rac-18:0-OH-OH
rac-16:0-OH-OH
Form Space
group
Z
Z′
E# a
Reference
β′
β′
P21
P212121
4
8
2
2
one
one
1
2
β1
β2
P21/m
Am
8
8
both 3
both 3
a. E# ≡ number of enantiomers in the unit cell determined by the lack or
presence of a reflective symmetry operation for the designated space group.
1. Larsson, K. Acta Crystallographica 1966, 21, 267.
2. Goto, M.; Kozawa, K.; Uchida, T. Bulletin of the Chemical Society of Japan 1988, 61, 1434.
3. Larsson, K. Arkiv fur Kemi 1964, Band 32, 29.
42
43. “It has thus been proved that the crystal form earlier known as the β′
form is optically active, and that the racemic form is separated into
antipode crystals on rapid crystallization. … A single-crystal analysis of
the β1 form, earlier known as the β form, has shown that it is a racemic
form. “ [Larsson, 1964, Arkiv for Kemi, 23, 35]
“The β′ form of a racemic mixture, however, is isomorphous with the
β′ form of optically active 1-monoglyceride, so obviously the two
antipodes separate into D- and L-crystals.” [Hernquist in Garti and Sato,
1988]
“Single-crystal analysis of the β1 form of racemic monostearin shows
that this form contains both enantiomers in the same
crystal.” [Hernquist in Garti and Sato, 1988]
For racemic mixtures of 1(3)-MAG in the β form “… alternative
distribution of D- and L- molecules in the unit cell.” “… mirror
symmetry relating the associated molecules.” [Larsson, 1964, Arkiv for
Kemi, 23, 35]
43
46. 1,2-Diacylglycerols Space Group Assignments
Form
Space group
Z
E# a
Reference
sn-HO-12:0-12:0
β′
P21
2
one
1
sn-16:0-16:0-OH
β′
P21
2
one
2-5
Compound
Enantiomers
Racemic Mixture
rac-16:0-16:0-OH
α
subcell plane group:
p6m
—
6
electron diffraction
a. E# ≡ number of enantiomers in the unit cell determined by the lack or
presence of a reflective symmetry operation for the designated space group.
1.
2.
3.
4.
5.
6.
Pascher, I.; Sundell, S.; Hauser, H. Journal of Molecular Biology 1981, 791.
Albon, N.; Baret, J. F. Journal of Physical Chemistry 1984, 88, 6333.
Dorset, D. L.; Pangborn, W. A. Chemistry and Physics of Lipids 1988, 48, 19.
Mo, F.; Hauback, B. C.; Albon, N. Journal of Physical Chemistry 1993, 97, 6083.
Han, G. W.; Ruble, J. R.; Craven, B. M. Chemistry and Physics of Lipids 1994, 71, 219.
Dorset, D. L. Chemistry and Physics of Lipids 1974, 13, 133.
46
47. “The respective IR spectra of both the α- and β′-polymorphic forms of
rac-PP(OH) are indistinguishable from the spectra of the
corresponding polymorphs of sn-PP(OH). This is indicative of identical
structure and environment between the sn- and rac-PP(OH) in their
respective polymorphic forms. ”[Shannon et al. 1992]
“However, both X-ray diffraction patterns (including X-ray small angle
diffraction) and the infrared absorption spectra were almost the same
between (R)- and (RS)-forms irrespective of their crystalline forms. ”
[Iwahashi et al, 1984]
“Melting temperatures for the racemic 1,2-DGs are systematically 6°C
lower than those for the corresponding [enantiopure] 1,2DGs.” [Kodali et al 1990]
47
48. 2-Monoacylglycerol
• is the only achiral class of acylglycerols
• crystallizes in a symmetric configuration
• no reported polymorphism
48
49. *
Bredikhin, A. A.; Bredikhina, Z. A.; Zakharychev, D. V. Mendeleev Communications 2012, 22, 171
49
50. *
“The fact that the secondary
hydroxyl is directly bound to
the chiral centre ensures the
sensitivity of the crystal packing
to chirality effects.”
Bredikhin, A. A.; Bredikhina, Z. A.; Zakharychev, D. V. Mendeleev Communications 2012, 22, 171
50
52. Exact same behavior is seen for acylglycerols
1,2-DAG
1,3-DAG
α
TAG and 1-MAG
*
*
solid solution
*
conglomerate
racemic compound
Bredikhin, A. A.; Bredikhina, Z. A.; Zakharychev, D. V. Mendeleev Communications 2012, 22, 171
52
62. Observations / Conclusions / Future Work
• Absolutely no way stereochemistry is not
involved in the polymorphism of acylglycerols
– suggesting that acylglycerols behave like all other
molecules with a stereocenter
– the most important factor (?)
62
63. Observations / Conclusions / Future Work
• Acylglycerols (fats & oils / metabolism)
– scalemic mixtures occur in nature
• frequently <—> rarely ?
– crystallization POS in cocoa butter / POO in palm
63
64. Observations / Conclusions / Future Work
• encapsulated bioactives / drug delivery /
sensor technologies
– homochiral bioactives / homochiral membranes /
homochiral enzymes / homochiral active sites
64
