Hi Herman and Tim, Thank you Tim for a comprehensive answer! Personally, we are collecting data using the rotation method (traditional "microED" style data collection) and processing our data with DIALS, which cannot perform the dynamical refinement Tim discussed. We therefore cannot determine the absolute configuration based strictly on the intensities.
We can of course determine the relative stereochemistry (as is possible with X-rays). Basically if you know the handedness of one site, you can use it to infer the chirality of all of the other chiral centers in the molecule. We have been suggesting to our clients that they attempt co-crystallization with small chiral molecules which can then serve as the chirality reference. We have had one client successfully accomplish this for one compound, but hopefully others will attempt this as well. I personally have minimal experience with small molecule crystallization techniques, but some reading suggested that first searching the CSD for compounds that tend to co-crystallize with your compound of interest may be a good way to start. And though not every structure will be able to help weigh in on chirality, there is still a lot of value in these structures for those in the chemistry field. People working in solid formulations are especially interested in ED structures because unlike (most) protein crystallographers, they are actually very interested in the lattice and the forces that drive packing. Additionally, using an ED structure to simulate a powder diffraction pattern can be helpful for those optimizing large-scale synthesis reactions as they can now use X-ray powder diffraction and a comparison with the simulated pattern to determine the relative purity of their sample or to detect small amounts of contaminants. The list goes on. And as Tim said, hopefully further advances allow for more straightforward/routine determination of the absolute stereochemistry. Cheers, Jessica On Mon, Jul 20, 2020 at 5:34 AM Schreuder, Herman /DE < herman.schreu...@sanofi.com> wrote: > Thank you Tim, I had the same impression. > I am afraid that our chemists will have to wait a little longer before > they routinely can get absolute configurations from electron diffraction. > > Best Herman > > -----Ursprüngliche Nachricht----- > Von: Tim Gruene <tim.gru...@univie.ac.at> > Gesendet: Montag, 20. Juli 2020 14:21 > An: Schreuder, Herman /DE <herman.schreu...@sanofi.com> > Cc: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> > Betreff: Re: [EXTERNAL] chirality with electron diffraction > > EXTERNAL : Real sender is tim.gru...@univie.ac.at > > > > Dear Herman, > > no, I don't think this is routine, yet! > First of all, instrument manufacturers need to catch up. What's on the > market is quite behind what is possible - although, I don't have the > instrument I'd love to have, but at least the meta data transfer to the > image headers only works when you work with a native CCD camera (stone age, > I know), not with a hybrid pixel detector. > > Secondly, Lukas Palatinus' software is, as far as I know, not yet > compatible with the rotation method, i.e. when you use XDS or DIALS or > mosflm, etc, you cannot use his software for dynamic refinement. I also > understand that dynamic refinement is quite time consuming. Lukas is > working on this, though. > > Best wishes, > Tim > > On Mon, 20 Jul 2020 10:36:49 +0000 > "Schreuder, Herman /DE" <herman.schreu...@sanofi.com> wrote: > > > Hi Tim, > > > > thank you for your reply. The 1998 Schenk paper is "new" to me, I had > > seen this one: > > https://science.sciencemag.org/content/sci/364/6441/667.full.pdf The > > background of my question was about the status in practice: Is it > > possible to routinely determine the absolute configuration of small > > molecules by electron diffraction, or is it something that in theory > > can be done, but only difficult in practice? > > > > Best, > > Herman > > > > > > > > -----Ursprüngliche Nachricht----- > > Von: Tim Gruene <tim.gru...@univie.ac.at> > > Gesendet: Montag, 20. Juli 2020 11:03 > > An: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK>; Schreuder, Herman /DE > > <herman.schreu...@sanofi.com> Betreff: [EXTERNAL] chirality with > > electron diffraction > > > > EXTERNAL : Real sender is tim.gru...@univie.ac.at > > > > > > > > Dear Herman, > > > > The absolute configuration can be determined, although very > > differently from X-ray ccrystallography. > > > > So far, two different experimental approaches have been published: > > Ma, Oleynikov, Terasaki (2017), https://doi.org/10.1038/nmat4890 > > > > and Brazda et al (2019), 10.1126/science.aaw2560 > > > > The former is based on imaging, the latter is based on dynamical > > refinement: Jansen, Tang, Zandbergen, Schenk (1998), > > https://doi.org/10.1107/S0108767397010489 > > > > There is a very interesting paper by Burmester and Schroeder Scanning > > Microscopy Vol. 11, 1997 (Pages 323-334). According to this paper, the > > anomalous signal in ED is actually stronger than in X-ray > > crystallography. As far as I know, this has not been pursued further. > > > > Best wishes, > > Tim > > > > P.S.: This is a response to your email to Jessica Bruhns in the thread > > 'quote source inquiry'. This thread has reached an overflow, so I took > > the liberty to adjust the subject. > > > > -- > > -- > > Tim Gruene > > Head of the Centre for X-ray Structure Analysis Faculty of Chemistry > > University of Vienna > > > > Phone: +43-1-4277-70202 > > > > GPG Key ID = A46BEE1A > > > > -- > -- > Tim Gruene > Head of the Centre for X-ray Structure Analysis Faculty of Chemistry > University of Vienna > > Phone: +43-1-4277-70202 > > GPG Key ID = A46BEE1A > > ######################################################################## > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 > > This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a > mailing list hosted by www.jiscmail.ac.uk, terms & conditions are > available at https://www.jiscmail.ac.uk/policyandsecurity/ > -- Jessica Bruhn, Ph.D Principal Scientist NanoImaging Services, Inc. 4940 Carroll Canyon Road, Suite 115 San Diego, CA 92121 Phone #: (888) 675-8261 www.nanoimagingservices.com ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
