Greetings to all,
If this post does not fit within the realm of the newsgroup, please just
say so ...
We are embarking on some 3D structural determination projects for our
medicinal chemistry. Up until now, we have obtained the necessary
information for 3D modeling through "collaborative" laboratories (i.e.:
inter-proton distances, coupling constants). Since we own a Varian 300
MHz Mercury-Vx which is used primarily for 1D-exp'ts by the synthetic
chemists, we would like to be self-sufficient and try to acquire our own
data for in-house 3D-modeling. I am in charge of developing this
in-house; admittedly I have little experience at obtaining this
information myself and therefore have a few questions. I apologize for
the "basic" nature of these questions; this is my first attempt at
posting to AMMRL and I'll try to make this short ...
We are studying molecules of MWt of around 500 which are poorly soluble
in water. Previous NOESY exp'ts on one of these molecules showed +'ve
and -'ve cross-peaks in MeOH indicating aggregation, while for another
molecule, ROESY spectra for a very dilute sample in water showed +'ve
cross-peaks with ca 3 -'ve cross-peaks between protons which are
separated by more than 3 bonds. In no particular order,
1) What is the significance of these -'ve cross-peaks in ROESY?
Should we use these "contacts" in 3D modeling?
2) For a given sample, do you expect cross-peaks obtained by NOESY
to be also obtained by ROESY (to confirm aggregation issues)?
3) In your expert opinion, should we focus our efforts on ROESY
rather than NOESY?
We are planning to use DMSO for our first tries as our compounds are
readily soluble and thus can use more concentrated samples (shorter acq
times). However, how can we be certain that possible aggregation does
not affect the results obtained, particularly in ROESY?
I have not included any specifics on the instrument set-up, I can answer
these as I interact with the community.
I greatly appreciate any help and/or comments,
Thank you,
Axel Mathieu
Received on Wed Dec 07 2005 - 16:45:49 MST