Hi 

Just to echo what has been said before, and expand a little.

(*) 5mm NMR tubes are wonderful for growing small molecule crystals in the way Artem describes - partly because they have _extremely_ smooth interior surfaces with few nucleation points - so you tend to get fewer, bigger crystals. You could also leave the NMR tube sealed, and having run your spectrum at room temperature, just “bung it in the ‘fridge or freezer” for a couple of weeks. I’ve grown 1st-class crystals by just forgetting the (sealed) nmr tube on my bench for a week or so...

(*) PX beamlines are possibly not the best for small molecules because you really want to get the high resolution data - say ~0.7Å; a lab-based diffractometer in a Chemistry department will do this routinely. If you can only grow “tiny" crystals (say << 0.1mm), then you may benefit from a synchrotron, but even then a good, modern set-up in a Chem lab would possibly still do the job.

(*) I'm being a little picky here, but you don’t use SHELXL to solve structures - it’s for refinement. You want one of the structure solution programs like SHELXD, SHELXS or SHELXT. If you’re a masochist you could try to get hold of an old copy of SHELX-76 and pick your own triplets to solve or try to find the heavy atoms “by hand” from thelist of peaks in a Patterson map, and also use the same program to refine - but I really, really, wouldn’t recommend it unless you don’t have better things to do and don’t mind arguing with referees about why you used a program that hasn’t really been developed since Jimmy Carter was POTUS!

There are other solutions to solving and refining small molecule structures - some I’ve used are Crystals (from the Oxford lab), SIR (in various flavours, from Bari), OLEX (from Durham) and Crysalis-Pro (from Rigaku). All work, each is slightly different, all are acceptable to all of the major journals.

HTH

Harry

> On 1 Jun 2020, at 23:31, Peat, Tom (Manufacturing, Parkville) <[log in to unmask]> wrote:
> 
> Hello Jiyuan, 
> 
> One small point to note- as Artem says, small molecule crystals are often generated out of solvents and these same solvents often melt the standard protein crystallisation plates, so be careful what you put into a plastic plate. 
> 
> As Artem mentioned, synchrotrons are generally overkill for small molecule structures (although there are exceptions). In this case, I would like to plug for the Australian Synchrotron which has a dedicated small molecule crystallographer and a beamline set up for small molecule crystallography (we do some protein crystallography there too!). So there is help available for those that do want to use synchrotrons for small molecule structures. 
> 
> cheers, tom 
> 
> Tom Peat
> Proteins Group
> Biomedical Program, CSIRO
> 343 Royal Parade
> Parkville, VIC, 3052
> +613 9662 7304
> +614 57 539 419
> [log in to unmask]
> 
> From: CCP4 bulletin board <[log in to unmask]> on behalf of Artem Evdokimov <[log in to unmask]>
> Sent: Tuesday, June 2, 2020 8:07 AM
> To: [log in to unmask] <[log in to unmask]>
> Subject: Re: [ccp4bb] Question about small molecule crystallography
>  
> Hi
> 
> A small organic molecule is typically crystallized from organic solvents (or water, if soluble) by means of at least three main techniques:
> 
> 1. slow evaporation of solvent leading to supersaturation and eventual crystallization
> 2. supersaturation at higher temperature followed by gradual drop in temperature causing crystallization
> 3. counter-diffusion of an incompatible solvent to drop solubility of the substance and cause crystallization
> 
> Many times, just leaving an NMR tube with a tiny hole in the plastic cap for a week or so will cause crystals to form.
> 
> Schnobviously, some substances will not crystallize easily - some form oils, amorphous precipitates, etc. and others will form liquid hydrated forms or just plain decompose. If you have any specific questions please don't hesitate to contact me in person. I've spent half of my PhD crystallizing weird small molecules for fun and profit.
> 
> As to how to solve structures of small molecules - any synchrotron is a massive overkill. Just get in touch with a University X-ray lab, many of which still have functional small molecule instruments. SHELX is the software of choice - of course! (I still have the blue/white polka dot SHELX cup, it's one of my more treasured curios).
> 
> Artem
> - Cosmic Cats approve of this message
> 
> 
> On Mon, Jun 1, 2020 at 6:01 PM Jiyuan Ke <[log in to unmask]> wrote:
> Hi Everyone,
> 
> I want to crystallize a small organic molecule. I have very limited experience in small molecule crystallography. I found that the Crystal Screen HT from the Hampton research is good for both small molecule and macromolecule crystallization. Plan to set up a sitting drop screen just like setting up protein crystallization. I don’t know if this is the proper way to do it. Is the MRC sitting drop 2-well plate (HR3-083) used for protein crystallization good for small molecule crystallization? Are there any special plates used for small molecule crystallization? Is room temperature ok or not? 
> 
> For data collection, can I use the beamline for protein crystals to collect data on small molecule crystals? Larger oscillation angle, shorter exposure, reduced beam intensity? 
> 
> For structure determination, is SHELXL the preferred software for solving small molecule structures?
> 
> If anyone has experience in small molecule crystallography, please help.  Thanks!
> 
> Best Regards,
> 
> -- 
> Jiyuan Ke, Ph.D.
> 
> Research Investigator
> H3 Biomedicine Inc.
> 300 Technology Square, Floor 5
> Cambridge, MA 02139
> Phone: 617-252-3923
> Email: [log in to unmask]
> Website: www.h3biomedicine.com
> 
> 
>  
>  
> 
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