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choderalab / itctools

Tools for setting up ITC experiments in an automated fashion using the Tecan EVO and Auto-iTC 200.
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Aspirin and Naproxen Solubility #28

Closed bas-rustenburg closed 9 years ago

bas-rustenburg commented 9 years ago

I looked up our stock, seems that we have naproxen as a powder. I looked up the solubility for our particular item: Soluble in DMSO, dimethyl formamide and 100% ethanol. Should we be worried? It does not mention water.. but it seems rather polar. (carboxylic acid group etc.)

This page suggests low solubility. http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+22204-53-1

Issue might also occur with aspirin, not sure.

jchodera commented 9 years ago

Good point:

Practically insoluble in water and freely soluble in alcohol."

jchodera commented 9 years ago

This may be relevant: http://onlinelibrary.wiley.com/doi/10.1002/ceat.201200510/abstract

bas-rustenburg commented 9 years ago

We might be able to use DMSO to increase the solubility. Otherwise... get sodium salts next time?

On Mon, Nov 17, 2014 at 11:33 PM, John Chodera notifications@github.com wrote:

This may be relevant: http://onlinelibrary.wiley.com/doi/10.1002/ceat.201200510/abstract

— Reply to this email directly or view it on GitHub https://github.com/choderalab/itctools/issues/28#issuecomment-63421525.

jchodera commented 9 years ago

We should probably get the sodium salt: http://www.sigmaaldrich.com/catalog/product/sigma/m1275?lang=en&region=US

jchodera commented 9 years ago

We can't use DMSO without dialyzing the protein again against the buffer with added DMSO. Otherwise, the heats of mixing will be too large.

bas-rustenburg commented 9 years ago

The heats of mixing of DMSO can't possibly be that big... oh wait.

For aspirin I did a calculation based on... http://www.acros.com/DesktopModules/Acros_Search_Results/Acros_Search_Results.aspx?search_type=CAS&SearchString=50-78-2 solubility 3.3 g/L

In [10]: (conc / mw).in_units_of(unit.mole / unit.liter) Out[10]: Quantity(value=0.018333333333333333, unit=mole/liter) This is the solubility.

This paper uses.. 30 mM aspirin. http://omicsonline.org/2157-7544/2157-7544-2-107.php?aid=1592

Trying to figure out their matching HSA concentration.

On Mon, Nov 17, 2014 at 11:37 PM, John Chodera notifications@github.com wrote:

We can't use DMSO without dialyzing the protein again against the buffer with added DMSO. Otherwise, the heats of mixing will be too large.

— Reply to this email directly or view it on GitHub https://github.com/choderalab/itctools/issues/28#issuecomment-63421780.

bas-rustenburg commented 9 years ago

Do you think we should cancel the booking? I'm thinking whether we can do an alternative experiment instead tomorrow. Maybe some host guest measurements.

Either way, we should probably make the solutions before booking ITC next time... hadn't looked into this until I started planning for tomorrow.

On Mon, Nov 17, 2014 at 11:47 PM, Bas Rustenburg < bas.rustenburg@choderalab.org> wrote:

The heats of mixing of DMSO can't possibly be that big... oh wait.

For aspirin I did a calculation based on... http://www.acros.com/DesktopModules/Acros_Search_Results/Acros_Search_Results.aspx?search_type=CAS&SearchString=50-78-2 solubility 3.3 g/L

In [10]: (conc / mw).in_units_of(unit.mole / unit.liter) Out[10]: Quantity(value=0.018333333333333333, unit=mole/liter) This is the solubility.

This paper uses.. 30 mM aspirin. http://omicsonline.org/2157-7544/2157-7544-2-107.php?aid=1592

Trying to figure out their matching HSA concentration.

On Mon, Nov 17, 2014 at 11:37 PM, John Chodera notifications@github.com wrote:

We can't use DMSO without dialyzing the protein again against the buffer with added DMSO. Otherwise, the heats of mixing will be too large.

— Reply to this email directly or view it on GitHub https://github.com/choderalab/itctools/issues/28#issuecomment-63421780.

jchodera commented 9 years ago

The heats of mixing of DMSO can't possibly be that big... oh wait.

It's enormous, even for very small mismatches. This is why we need to add DMSO to the buffer first and dialyze against the buffer, rather than try to correct the DMSO concentrations of macromolecule and ligand solutions.

Do you think we should cancel the booking?

Might be a good idea if there is no penalty.

Either way, we should probably make the solutions before booking ITC next time... hadn't looked into this until I started planning for tomorrow.

An excellent idea.

jchodera commented 9 years ago

Aspirin is supposedly soluble in water to 3 mg/mL ~ 20 mM. We'd want to stay well under that, so 5-10 mM at most. http://en.wikipedia.org/wiki/Aspirin

bas-rustenburg commented 9 years ago

It's enormous, even for very small mismatches.

Yes, as demonstrated by our mixing experiments. We should redo those sometime soon as well. Fixed yet another bug in my latest pull request.

Might be a good idea if there is no penalty.

Canceled. No cost as far as I can tell (got pop-up last time I canceled, warning it would still cost money). Website says bookings within 48 hours are not restricted, so I think we're safe.

bas-rustenburg commented 9 years ago

Aspirin is supposedly soluble in water to 3 mg/mL ~ 20 mM. We'd want to stay well under that, so 5-10 mM at most

Yeah, 18 mM is what my calculation gave as the solubility of aspirin. Hopefully by the end of tomorrow we'll have the experiment designed and we can schedule making the solutions. If that goes well, we can schedule the ITC.

bas-rustenburg commented 9 years ago

Canceled. No cost as far as I can tell

Just wanted to confirm, 

Full charge for this session
    0
jchodera commented 9 years ago

I've also ordered a number of other ligands. See deliveries spreadsheet.

bas-rustenburg commented 9 years ago

I think we can close this, as we are aware of the problem and have ordered salts for a few of the compounds. (Ibuprofen and naproxen if I remember correctly)

bas-rustenburg commented 8 years ago

Referring @MehtapIsik to our discussion here.