Transcript Carbamazepine Polymorphs

Data Mining with DDView+
and the PDF-4 Databases
Carbamazepine Polymorphs
Some slides of this tutorial have sequentially-layered
information that is best viewed in ‘Slide Show’ mode
This is one of three example-based tutorials for using
the data mining capabilities of DDView+ with the
PDF-4+ database and it covers the following topic:
• Carbamazepine Polymorphs
– a PDF-4/Organics application
– investigating polymorphic forms of an active
pharmaceutical ingredient (API)
Two other similar tutorials for data mining exist and
cover the following topics:
• CIGS Photovoltaics
– solid solution / cell parameter relationship
• FeO Non-stoichiometric Oxides
– sorting out temperature and stoichiometric effects
on cell parameters
Carbamazepine Polymorphs
• An example for the PDF-4/Organics 2008
database that answers the following
questions:
– How many polymorphs are known to exist?
– How do I distinguish these polymorphs by
XRPD?
Carbamazepine Polymorphs
• Search for PDF entries:
– Empirical Formula: C15H12N2O
• Note that this is not unique to carbamazepine
– Name: carbamazepine
• By itself, this name search will also include
hydrates, solvates, derivatives
– Elements: Only {C, H, N, O}
• This could be performed, but really is a
redundancy if the empirical formula search
given above is performed
Results Table Preferences
• Useful information for sorting out polymorphic forms
should be in the results table for retrieved entries
• A plot of space group vs. reduced cell volume can
often provide relevant groupings for polymorph
differentiation
• Another useful plot would be any of the reduced cell
edge lengths vs. reduced cell volume
• Suggested fields for results table:
- PDF #
- Empirical Formula
- Quality Mark
- Compound Name
- Common Name
- International Space Group
- Space Group Number
- Reduced cell a
- Reduced cell b
- Reduced cell c
- Reduced cell volume
Specifying Results Table Preferences for
Carbamazepine Polymorphs Search
Selected Fields:
Use these buttons
to move a selected
item up or down in
the listed order for
the results table.
Prepare the
‘Selected Fields’
list for this exercise
as illustrated here.
Available Fields:
Use these buttons to move selected items between the
‘Available Fields’ list of 60 items and the ‘Selected Fields’
list of items that will be displayed in the results table.
Entering the Empirical Formula Search Criterion
Empirical Formula criteria is
entered on the ‘Elements’ tab
of the ‘Search’ window.
There should be no space between
each element and its ‘subscript’, and
one space before entering each
subsequent element.
These elements can be entered in
any order using the ‘Contains
Elements’ option, but must match
the order of the formula on the PDF
card if the ‘Contains Phrase’ option
is used.
Entering the ‘Carbamazepine’ Name Search Criterion
The name criterion is entered
on the ‘Names’ tab
Since ‘carbamazepine’ may appear as
either a ‘Compound Name’ or ‘Common
Name’, the criterion is best entered in the
‘All Names’ category. Because it is a
single word, it does not matter if ‘Contains
Words’ or ‘Contains Phrase’ is selected.
The search can now be performed.
Carbamazepine Polymorphs
• 17 hits in PDF-4/Organics 2008 database
– 12 have cell parameter and space group information
– 5 different space group designations (1,2,14,15,148)
Carbamazepine Polymorphs
• To illustrate groupings related to space groups and reduced cell
volumes given in the results table, the following is performed to
create the appropriate graph:
Enter ‘RedCellVol’ for the
X-axis field, and SG # for
the Y-axis field
Space Group / Reduced Cell Volume Groupings for 12 Carbamazepine PDF Entries
R-3
C2/c
P21/n
The groupings
suggest that the
likely number of
known polymorphs
for carbamazepine
is 3, 4, or 5.
Note the groupings have
an approximate 2:3:4
‘Reduced Cell Volume’
ratio. The Z values for the
unit cells in each group
will almost assuredly have
the same ratio.
P-1
P1
Carbamazepine – Another View:
a-axis Length vs. Reduced Cell Volume
Beta (6)
Form IV (1)
Alpha (1)
Gamma (4?)
Here, the groupings have been labeled based on information
from the ‘Compound Name’ or ‘Comments’ field from at least
one member of the group.
Carbamazepine – Comparing XRD Data
•
•
•
To sort out all the entries, including those without unit cell information,
the X-ray powder diffraction (XRPD) patterns themselves can be used
With DDView+, the user can overlay simulated XRPD patterns based on
individual PDF entry data
Example – overlay simulated XRPD patterns for entry 00-033-1566
(reported as alpha form but without cell parameters) and entry 00-0431998 (reported as alpha form with cell parameters included)
Double click anywhere on
these ‘Results’ table rows to
open the corresponding PDF
entries (or right-click and
select ‘Open PDF Card’)
Overlaying Simulated XRPD Patterns for Comparison
This icon, when clicked,
displays an XRPD pattern
simulated from the peak list
of the current PDF entry.
• To overlay an XRPD
pattern from another
entry, use the ‘Plots’ drop
dropdown menu and select
‘Add Full Trace …’.
• Enter the PDF entry
number for the pattern to
be overlaid: ‘00-043‘00-0431998’.
• Once the PDF # has been
entered, click ‘OK’ to
overlay the requested
XRPD pattern.
Additional XRPD patterns
can be overlaid using the
‘Plots’/’Add Full Trace …’
option
α-Carbamazepine Pattern Comparison
These two patterns show a similar set of peaks, at
roughly similar positions, indicating polymorphic
similarity. Intensities are somewhat dissimilar but
could be explained by sample thickness: red pattern
from thin layer, blue pattern from thick sample.
The comments section for entry 00-033-1566 indicates that this
is a deleted pattern, having been replaced by 00-043-1998.
Mis-assigned Polymorphic Form
Entry 00-043-1988 (red pattern)
was also labeled as the α-form
by its author. However, one
can see from the comparison
with a known α-form pattern
(top graph – blue) and a known
γ-form pattern (bottom graph –
blue), that this entry is actually
for a γ-carbamazepine.
Overlaying Many XRPD Patterns
Using ‘Ctrl-Click’, one can select multiple entries from the
‘Results’ window and overlay their XRPD patterns on one graph.
Here, all the reported α-form entries have been selected.
A ‘Right-Click’ on one of these selected
entries brings up the menu shown here. The
‘Open Diffraction Pattern’ choice will prepare
the desired graph of overlaid patterns.
Overlay of Reported α-Carbamazepine Patterns
on One Graph
The result clearly shows the obvious difference between the 00043-1988 XRPD pattern (blue) and the other two.
One can use this technique to determine which XRPD patterns
among the 17 entries are similar, including those without
polymorphic form or space group designations. Results of such
a determination are shown on the next slide.
Grouping of Similar XRPD Patterns for 17 Carbamazepine PDF Entries
One can overlay the simulated patterns for all 17 PDF entries to establish four groups of similar
patterns. Note: Several entries with no space group or polymorphic form information have been
reasonably assigned to one of these four groups.
9 entries
2 entries
7 reported as β-form
2 reported as α-form
5 reported SG as P21/n
1 reported SG as R-3
1 reported SG as P2 /c
1
5 entries
1 reported as γ-form
1 misreported as α-form
3 reported SG as P-1
1 reported SG as P1
1 entry
1 reported as Form IV
1 reported SG as C2/c
Carbamazepine - Cell vs. Space Group
17 PDF Entries (12 Experimental, 5 Calculated from Single Crystal data)
Alpha
Gamma
Beta
Form IV
Revisiting the ‘Cell vs. Space Group’
graph, all 17 entries can be assigned to
one of these four groupings, based on
similarity of their XRPD patterns.
Carbamazepine Polymorphs
• Crystallographic and powder diffraction data
suggest 4 known polymorphic forms
• Data mining and display capabilities of
DDView+ give users the ability to categorize
the database entries
• The user’s own pattern can be compared
with the known polymorph patterns to
ascertain polymorphic form
Thank you for viewing our
tutorial. Additional tutorials are
available at the ICDD web site
(www.icdd.com).
International Centre for Diffraction Data
12 Campus Boulevard
Newtown Square, PA 19073
Phone: 610.325.9814
Fax: 610.325.9823