Molecular modeling of acrylamide derivatives: the case of N-acryloylaminoethoxyethanol versus acrylamide and trisacryl.

Molecular mechanics (for evaluation of total energies of individual structures of monomers and oligomers) and molecular dynamics (for evaluating dynamic dependencies of structural features) were used for obtaining information on some unique chemical behavior of a novel N-substituted acrylamide (N-acryloylaminoethoxyethanol; AAEE) vs. conventional acrylamide and trisacryl (N-acryloyl-2-amino-2-hydroxymethyl-1,3-propane diol, an extremely hydrophilic derivative; Tris-A). As free monomers, Tris-A degrades with zero-order and acrylamide with first-order kinetics, whereas AAEE is highly resistant to hydrolysis. It is found that Tris-A (and its dideoxy derivative) is constantly forming hydrogen bonds between the -OH groups and the carbonyl of the amido group (bond distances of 1.64 to 1.70 A); this activates a mechanism of "N-O acyl transfer" which leads to quick degradation of the amido bond even under mildly alkaline conditions. Conversely, AAEE (which also contains an omega-OH group increasing its hydrophilicity) has no tendency to form H-bonds with the amido carbonyl, thus being resistant to the above degradation mechanism. In fact, the oxygen in the ethoxy moiety of the N-substituent chain acts as a preferential partner for H-bond formation with the omega-OH group. In the oligomeric state, it is found that Tris-A (tetrameric and dodecameric structures were simulated) tends to form inter-residue H-bonds (approximately parallel to the growing chain) competing with the intra-residue H-bonds (folding onto the amido carbonyl and approximately perpendicular to the oligomer chain), thus greatly increasing its stability.(ABSTRACT TRUNCATED AT 250 WORDS)