Thank you for all the answers I am starting to get!
In the meantime, could I please also ask you to suggest to me papers that
would be a good reference to put in my publication?
Thank you again!
Eli =)


On Thu, November 29, 2007 4:21 pm, Fischmann, Thierry wrote:
> Dear Eli,
>
> I work in a pharmaceutical company and go through many diverse compounds.
> My extensive experience with Br and Cl is that they easily get cleaved by
> X-ray. I've done a lot of experiments to address the problem: radical
> scavengers (fail: it does not look like the process is radical-mediated),
> energy dependence (fails: in fact cleavage occurs at the home Cu 1.54Å
> source), and fast data collection (success at the expense of data quality,
> but often mandatory).
>
> Cleavage happens much more readily if the halogen is exposed to solvent.
> In fact I have "the ultimate proof" that this is a determinant factor: a
> chiral compound which changes binding orientation when the chirality is
> inversed, and the halogen either exposed to solvent or buried depending on
> chirality. That atom is connected to a non-chiral, planar moiety,
> therefore its chemical environment is the same in each enantiomer. However
> cleavage is very fast in the solvent-exposed conformation, and very slow
> in the opposite orientation.
>
> Solutions:
> -	Collect your data very quickly (example: after running a strategy, 1
> second exposure for 1 degree sweep at the synchrotron, for a total sweep
> of 100 deg). The cleavage is clearly dose-dependent.
> -	Re-scale your data after discarding data collected at the end. Often
> (but not always) these data add redundancy but do little to completeness.
> Try to discard as much data as possible while keeping the completeness
> reasonable. I wouldn't be surprised that the #1 structure would do much
> better in terms of Cl occupancy if you could get by with 50% of the data.
> #2 may be a more tricky case.
>
> As far as publication is concerned, I wouldn't show the Cl for #2, but I
> would show it for #1 if there is no indication that the binding pose has
> moved due to cleavage. That is the case for my compounds.
>
> Good luck!
> Thierry
>
>
> -----Original Message-----
> From: CCP4 bulletin board [mailto:[log in to unmask]] On Behalf Of
> Sabini, Elisabetta
> Sent: Thursday, November 29, 2007 04:41 PM
> To: [log in to unmask]
> Subject: [ccp4bb] "Finding Chlorine" =)
>
> Dear all,
>
> I am refining two structures which have in the active site a ligand
> containing a covalent bond between a carbon and a chlorine atom.
>
> I collected the data at APS, SERCAT ID-22.
>
> Because of radiation damage I tried different occupancy values for the
> chlorine atom and structure number #1 is best with occupancy 0.2 while
> structure #2 seems to be happy with occupancy 0 (occupancy for the rest of
> the ligand is 1).
>
> I checked by mass spec if my compound has the molecular weight expected
> with a chlorine atom and it does, so the original compound was correct.
>
> Can radiation damage make the chlorine completely disappear?
>
> Do the different occupancy values I get depend also on the resolution?
> In fact:
>
> Structure # 1 (OCC=0.2) refined to 1.8A (Rfact/Rfree=20/25%)
> Structure # 2 (OCC=0.0) refined to 2.5A (Rfact/Rfree=23/33%)
>
>
> When I make the figures for publication, do I draw the ligand with or
> without chlorine?
>
> Thanks,
>
> Eli =)
>
>
> --
> Elisabetta Sabini, Ph.D.
> Research Assistant Professor
> University of Illinois at Chicago
> Department of Biochemistry and Molecular Genetics
> Molecular Biology Research Building, Rm. 1108
> 900 South Ashland Avenue
> Chicago, IL 60607
> U.S.A.
>
> Tel: (312) 996-6299
> Fax: (312) 355-4535
> E-mail: [log in to unmask]
> *********************************************************************
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>
>


-- 
Elisabetta Sabini, Ph.D.
Research Assistant Professor
University of Illinois at Chicago
Department of Biochemistry and Molecular Genetics
Molecular Biology Research Building, Rm. 1108
900 South Ashland Avenue
Chicago, IL 60607
U.S.A.

Tel: (312) 996-6299
Fax: (312) 355-4535
E-mail: [log in to unmask]