Page 569 - Carrahers_Polymer_Chemistry,_Eighth_Edition

532 Carraher’s Polymer Chemistry

There are many potential and real applications of self-assembly.
Pharmaceutical chiral drug sales top $100 billion yearly worldwide. More than half of the drugs
on the market are asymmetric molecules with about 90% administered as racemates. In general,
one optical center of a drug will have the desired activity while the other can produce negative side
effects. Because of this the Food and Drug Administration (FDA) in 1992, issued a statement saying
that for every new racemic drug, the two enantiomers must be treated as separate substances that are
required to undergo pharmocokinetic and topological studies.
One direct approach to the separation of chiral compounds is called molecular imprint polymers
(MIPs) that involves the formation of a three-dimensional cavity with the shape and electronic fea-
tures that are complementary to the imprinted or target molecule.
While MIPs are part of the current nanorevolution, it’s roots are found in the antibody formation
theory of Pauling’s. While the particulars were wrong, the general concept is good.
In the formation of MIPs, the target drug is added to a solvent along with selected polymers. It
is important that the liquid, self-assembling polymer(s), and template molecule complement one

another. The specific bonding can be a combination of covalent and noncovalent bonding. Here we
will look at an instance involving only noncovalent bonding. The main secondary bonding interac-
tions include metal–ligand complexations, hydrogen bonding, and ionic, dipolar, hydrophobic, and
pi–pi interactions.
Because most drugs have both polar and nonpolar regions, solvents and vinyl monomers that
contain both polar and nonpolar regions are often employed. Where aromatic rings are present,
polymers such as 4-vinylpyridine and styrene are often utilized because of their ability to “fi t” such
structures, bond through overlap of pi systems, and be readily polymerized via a variety of methods
(such as UV, heat, and use of free radical initiators). Hydrogen bonding solvents are generally dis-
couraged because of their tendency to form strong bonds with the template molecule and after evac-
uation of the template site, with polar portions of the template site. Often dipolar aprotic solvents are
employed that offer both polar and nonpolar sites.

In general, the sequence is

mixing together of the template, polymer, and solvent → self-assembly about the template →
polymerization → extraction of template molecule → grinding, sieving, and column packing.

A number of drugs have been successfully separated using MIPs. Naproxen(TM), (S)-6-methosy-α-

methyl-2-naphthaleneacetic acid, is a nonsteroidal antiinflammatory drug (NSAID) that is adminis-
tered as the “S” enantiomer. Naproxen (16.20) will be used to illustrate the MIP sequence. Naproxen
has both polar and nonpolar domains. It also has a fused-ring aromatic site.
CH 3

O
(16.20)

C OH
H 3
O
Solvents and self-assembling polymer(s) are chosen that have both polar and nonpolar portions. The
polymers and solvents then self-assemble about the target molecule. This arrangement is then exposed
to UV radiation, heat, and/or catalysts that effectively form a polymeric “cocoon” about the target mol-
ecule. After polymerization and the formation of the “cocoon” about the target molecule, the solvent
molecules and target molecule are removed exposing a partially completed cavity with both structural

(both shape and spatial configuration) and electronic characteristics complementing the target mole-
cule. For naproxen the solvent is tetrahydrofurane (THF) and the monomer is 4-vinylpyridine.

9/14/2010 3:43:07 PM
K10478.indb 532 9/14/2010 3:43:07 PM
K10478.indb 532