Why is solubility phe > tyr ?
aealbb1 at peabody.sct.ucarb.com
Thu Jun 13 21:32:14 EST 1996
Davy Kalonia wrote:
> The free energy of solubilization (del G) depends on three factors.
> The energy of crystallization for Tyr is much larger than that of Phe,
> ie. the O..H--O interaction and stacking of the hydrophobic rings
> results in stronger interaction in the solid state. Thus more energy
> must be provided to move the molecules from a solid_solid state to a
> solvent_solid state. Thus poor solubility for tyr.
Quite correct, but it's not just hydroxy groups that have this effect; methoxy
groups can have the same effect. There are several synthetic tricks that
structural chemists can use to make compounds that are easier to crystallize for
X-ray structural analysis. One of the tricks is to use phenyl rings; they stack
beautifully. In this case, both phe and tyr have benzene rings, so that isn't it.
However, beyond this, another common trick is to attach hydroxy or methoxy groups
to the phenyl ring. Very often they really make for excellent crystallization,
because they really increase the lattice energy. In grad school, I tried to get
two rather different reactions to give crystals for quite some time. When I
changed the ligands in both (very different ligands) from having a phenyl to a
having a dimethoxyphenyl, I got x-ray quality, analytically pure crystals in the
NMR tubes I did the reactions in. Without any effort at all. Just left em there
and came in the next day, and handed the tubes to the crystallographer.
The argument about hydroxy groups and hydrogen bonding makes a lot of sense.
However, methoxy groups obviously don't have the same option. It's also hard for
me to believe it's simple polarity--typical crystal stacking with phenyl rings is
in a direction orthogonal to the benzene ring, and the dipole of a methoxyphenyl
is in the plane of the ring. Any crystallographers out there have a good
explanation as to why methoxy groups seem unique in making phenyl-containing
compounds much more crystalline?
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