The base matrix of the resin is styrene divinylbenzene which is chemically compatible with organic solvents at low concentrations.
Chelex 100 resin is not damaged by 100% organics, but it IS affected.
1) The functional group will lose its polarity and metals won't exchange onto the resin:
2) Chelex 100 resin will not work as an ion exchanger in 100% organic solvent.
3) In studies, Chelex 100 resin removed metal ions well in either 20 or 40% ethanol. End users should verify the efficiency of metal ion removal with the sample being treating. Perhaps doing a specific assay for the metal ions would help quantitate the metal content of the buffers before and after treatment. A batch overnight treatment of the solutions would remove metal ions more efficiently than a one hour treatment, particularly in the ethanol solutions.
Note, ethanol will shrink the resin beads and decrease the porosity of the resin, and this would decrease the efficiency of the exchange, particularly for larger metallic ions. Thus a solution of 40% ethanol will require a longer incubation time to remove all of the metal ions. Increasing the Chelex treatment time would allow more time for ion exchange to occur.
Stryrene divinylbenzene and iminodiacetic acid (the functional group) can leach from the resin, and this would be increased with the higher concentration of ethanol. The recommendation is to wash the resin with 100% ethanol and then equilibrate in aqueous solution immediately before using the resin. If the failure to aggregate is due to something leaching from the resin, this experiment should eliminate this possibility.
Also, the carboxyl groups on the resin have a very high selectivity for hydrogen ions, and will exchange hydrogen ions from water, resulting in an increased pH. There is no solution for this except to try equilibrating the resin using the protocol in the instruction manual (this doesn't work very well) or to adjust the pH of the buffer after the Chelex treatment.. The functional group will lose its polarity and metals won't exchange onto the resin. Studies have indicated the resin is still functional in 20% methanol and ethanol.
Organic solvents such as DMSO or DMF might also affect the selectivity of the resin slightly for divalent cations and would reduce the interaction between small hydrophobic molecules and the resin matrix. The resin may also swell upon exposure to the chemicals, but it won't melt or dissolve.