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I've just remembered another approach that I've heard suggested, although I don't know anyone who has tried it. Dissolve plenty of the small molecule in paraffin or silicone oil, and use this mixture to cover the drop. This can be used with regular vapor diffusion or (probably better) microbatch-under-oil. The oil acts as a reservoir that contains excess small molecule that (you hope) will be fed into the crystals. Patrick Shaw Stewart -- [log in to unmask] Douglas Instruments Ltd. DouglasHouse, EastGarston, Hungerford, Berkshire, RG177HD, UK Directors: Peter Baldock, Patrick Shaw Stewart, James Smith http://douglas.co.uk <http://douglas.co.uk/> or http://www.douglasinstruments.com <http://www.douglasinstruments.com/> Tel: 44 (0) 148-864-9090 US toll-free 1-877-225-2034 Regd. England 2177994, VAT Reg. GB 480 7371 36 ________________________________ From: CCP4 bulletin board [mailto:[log in to unmask]] On Behalf Of Green, Todd Sent: 22 January 2007 20:40 To: [log in to unmask] Subject: crystal friendly solvents that are useful for dissolving hydrophobic small molecules? Hello All, I am trying to soak some crystals with a small molecule that is quite hydrophobic. I am having trouble with solubilty of the small molecule. It will dissolve up to about 1 mM in 100 % DMSO, but precipitates at concentrations of less than 15 micromolar when the DMSO concentration is below 20 percent in my crystal growth solutions(which are peg 4k, low pH, low salt). Can anyone suggest solvents other than DMSO which might help dissolve the inhibitor and might be somewhat friendly to my crystals. Thanks in advance- Todd Green