Solid State NMR Spectroscopy of Boron Compounds
Libor Kobera, Olivia Policianova, Martina Urbanova, Jiri Brus
Institute of Macromolecular Chemistry, Academy of Science of Czech Republic,
Heyrovského nám. 2, 162 06 Praha 6, Czech Republic
Introduction
Results
Very important, for finally using as a medicinal product, is precise description of structural homogeneity and purity.
Excellent tool for structural analysis is solid state NMR spectroscopy. Organoboron compounds description is possible by
NMR measurements of included nuclei such as 13C, 11B etc.
11B
These proteasome inhibitors systems, exhibits not only extensive polymorphism, but boronic acid fragments can
spontaneously undergoes condensation and dehydration forming thus various oligomers.
High sensitivity and abundance of boron nucleus is suitable for measurement and consequently analysis of NMR
spectra. On the other hand, the quadrupolar character of boron atoms complicates detail analysis. Typical 1D MAS NMR
spectra are very complicated and difficult to interpret. However, the solution provides the MQ/MAS NMR experiment and
using of relatively new techniques called biaxial shearing. This combination enhances the spectral resolution and thereby
helps correctly analyze and describe structure units.
11B
3Q/MAS NMR of high Active Pharmaceutical Ingredients
11B
MAS NMR
ISO shearing
MAS NMR
Biaxial ISO shearing
Q shearing
B3
B3’’
B2
Phenyl Boronic Acid
h-API
metallocarborane
ppm
40
30
20
10
0
-10
B3
B2
B3’
Borax
Biaxial Q shearing
B3’’
B3’
-20
B3’
B3
B2
B3
B2
25.0
ppm
20.0
15.0
10.0
5.0
0.0
-5.0
50
ppm
40
30
20
10
0
-10
-20
ppm
20
10
0
-10
-20
-30
-40
ppm
40
30
20
10
0
-10
B3’
-20
ppm
40
30
20
10
0
-10
?
?
-20
Classical & biaxial shearing
B1
B4
B3
B3
B3
B4
ISO shearing
B3
CS
11B
MQ/MAS NMR of borax
Biaxial ISO shearing
Q shearing
CS
A
B3
QIS
A
B3’
Biaxial Q shearing
QIS
B3
CS
B4
A
QIS
CS
B3
B4
A
QIS
ppm
40
30
20
10
0
-10
R2
Monomer
“B1”
11B
3Q/MAS NMR of metallocaborane
Biaxial ISO shearing
Q shearing
Biaxial Q shearing
3Q/MAS NMR of Borax + Phenyl Boronic Acid + (2-methylpropyl) boronic acid
physical mixture
ISO shearing
Borax
PBA
Biaxial ISO shearing
Q shearing
B3
B1
Biaxial Q shearing
?
?
-20
R1
11B
B2
B2
B4
B4
ISO shearing
B3’
Dimer
“B2”
R3
Conclusion
R3
R1
R1
Trimer
“B3”
R1
R2
R2
R1
R1
Four possible schemes was demonstrated on this poster which may be valuable for shearing 2D MQ/MAS
NMR spectra. Examination of peaks contours under different shearing schemes helps to interpret the 2D
MQ/MAS NMR spectra. The suggestion arises that the choice of shearing factor should be made
on a case-by-case basis. Where distinct chemical sites are well resolved, as for many model
compounds, ISO-shearing is the best choice. Amorphous or disordered materials,
on the other hand, typically give a distribution of chemical shift and/or quadrupolar parameters,
and it can be more difficult to interpret MQMAS spectra to identify distinct chemical sites.
Where the distribution of chemical shifts leads to greater inhomogeneous linewidths than
the second-order quadrupolar broadening, eliminating chemical shift in the
indirect dimension by Q-shearing can lead to apparently sharper spectra
and therefore enhanced ability to distinguish dissimilar sites.
Additional shearing in the directly detected dimension (biaxial shearing)
can provide further cosmetic modifications of the spectra which
may aid interpretation by helping to identify and
characterize independent chemical sites.
(2-MP)BA
The research was supported by Grant 2B08021, MSM 2008-2011