Transcript No Slide Title

Organic Molecule Identification Using 1D Proton & Carbon Spectra
Reinhard
*
Dunkel
and Xinzi Wu, ScienceSoft LLC, Sandy, UT
NMR is an important technique to elucidate unknown organic molecules.
But a full structure elucidation relies on sufficient sample and several
spectroscopic techniques. This procedure is normally performed by an
experienced spectroscopist. The success rate of automated structure
elucidation systems remains limited.
This poster describes an alternative approach: dereplication. Given most
published small organic molecules, full structure elucidation is replaced by
the identification of structures from this collection best matching available
NMR data. The dereplication can be applied using limited NMR data and
can be reliably automated.
Method and Results
The dereplication approach is tested using 179 datasets. In order to obtain
representative placements for unknown molecules, the known shifts for the
correct structures are removed and do not contribute to predicted shifts.
Undecoupled 19F and 31P, low field strength, too small a chosen sweep
width, and imperfect shimming are represented among these sample
datasets.
The top graph shows the percentages of times the correct structure is
identified at the top (1st) FindIt position among the 6.3 million candidate
structures given various combinations of proton (1H), carbon (13C), HSQC
or DEPT-135 (13CH), and/or molecular formula (MF). The bottom graph
shows the percentages by which the correct structure is within the top ten
placement. The percentages range from 56% to 98% in the top graph, and
79% to 100% in the bottom graph.
Only protonated carbon shifts are detected from an HSQC spectrum, which
leads to the weakest FindIt structure matching results, as information for
quaternary carbons is missing. However, an HSQC spectrum can be
acquired using an indirect detection probe with a much smaller sample than
required for a 1D carbon spectrum.
NMRanalyst: Automatic NMR Data Analysis
The acquisition of NMR data is largely automated. The processing and
interpretation of acquired data need to be equally automated. Spectrometer
software provides some processing. The NMRanalyst software adds
automatic baseline and phase correction. It models resonances in 1D and
spin systems in multidimensional spectra for detection. It can generate a
clean list of numerical descriptions for the NMR data with minimal user
interaction.
NMRanalyst
can
analyze
1,1-ADEQUATE,
2DINADEQUATE, DQF-COSY, HMBC, HSQC, HETCOR, NOESY, ROESY,
and TOCSY spectra and is at least as sensitive as the visual inspection by a
spectroscopist for all the supported spectral types.
FindIt: Dereplication of an Unknown Molecule
The NMRanalyst FindIt module contains over 6.3 million structures from
NIH PubChem (http://nihroadmap.nih.gov). It matches the predicted carbon
and proton shifts for the structures in this collection to the observed carbon
and proton shifts analyzed and extracted by NMRanalyst. It reports the best
structures consistent with the NMR data. Structures not in PubChem can be
added to the FindIt structure database. Even if the correct structure is not in
the FindIt collection, best matches may still be similar to the unknown
molecule. Identifying the FindIt best matches takes only minutes on a
modern PC.
Taxol Example Using Proton and Carbon Spectra
The 8.3 mg Paclitaxel in CDCl3 datasets were acquired by Dr. Dimitris
Argyropoulos, Varian Deutschland GmbH, on a Varian INOVA 500 MHz
spectrometer using a Cold Probe.
Percentages Correct Structure Identified as Best Match
Quinine Example Using HSQC Instead of 1D Carbon
The
1D
proton
spectrum
is
not
shown, but is used
due to its nearly
quantitative
properties. The ~200
µg quinine in CDCl3
spectra were acquired
on an AV 400 MHz
by Dr. Till Kühn,
Bruker BioSpin.
Percentages Correct Structure Identified Within Top 10 Matches
Conclusions
Proton and carbon NMR shifts sufficiently describe a small organic
molecule and can be used to identify the molecule among millions of
candidate structures. The freely available PubChem structure collection
provides a great foundation for the described dereplication system.
Commonly acquired 1D proton and carbon survey spectra are sufficiently
informative for the dereplication. This approach can be reliably automated
and can be used for fast compound identification, where a full structure
elucidation may not be practical.
The results reported in this poster were obtained with NMRanalyst 3.4. The
software with FindIt module is available for RH Linux (Enterprise 4, 3 and
Linux 9) and MS Windows (XP and 2000). For commercial availability,
please ask or see www.ScienceSoft.net.
Work in Progress
NMRanalyst 3.5 beta contains over 8 million PubChem structures. To
make use of all available information, all known shifts (including the ones
for the tested datasets) are used and contribute to predicted shifts. By now
230 sample datasets have been tested with NMRanalyst 3.5 beta. Analyzed
spectra and best matching structures for the evaluated datasets are
accessible from www.ScienceSoft.net.
Acknowledgements
This work was made possible by NIH SBIR Phase II grant 5 R44
MH061652. Datasets were contributed by Heinz Kolshorn (University of
Mainz), Dimitris Argyropoulos, Ronald Crouch, Péter Sándor, Igor Goljer
(Varian, Inc.), Till Kühn (Bruker BioSpin), Charles G. Fry (University of
Wisconsin - Madison), Shi Bai (University of Delaware), Charles L.
Mayne (University of Utah), FID Archive, AIST, and WebSpectra.
http://www.ScienceSoft.net