The ring-opening polymerizations of the
dilactones glycolide and the S,S- and S,R-stereoisomers of
lactide were studied using quantum mechanical methods.
The ring strain and the conformational distribution of these
cyclic monomers and of the polymers were calculated, and
the effect of the medium on the polymerization was predicted,
for both bulk and solution. The polymerizability of
the three monomers in the gas phase, that is, nonpolar
medium, is much greater than that of d-valerolactone or
1,4-dioxan-2-one. This difference vanishes in the polar
medium chloroform, which is attributed to the fact that,
while all of these monomers possess polar cis-lactone
bonds, the three dilactones possess small dipole moments.
The data are combined to give polymerization enthalpy and
free energy values. The four stereoregular lactide polymers
did not differ significantly in energy. Accordingly, the
ability to synthesize any one of these rests on catalyst
specificity (‘‘polymer chain-end control’’). Although
introduction of sterically demanding methyl groups into
glycolide is expected to favor coiled conformations and
decrease polymerizability, this was not found to be the
case. Good agreement of calculated values with experimental
data from the literature was achieved.
1-Aminocyclopropanecarboxylic acid (Ac3c) is a constrained a amino acid residue that exhibits peculiar conformational characteristics. The aim of the present study is to provide a deeper understanding of these features to be used as guidance to decide when to choose Ac3c as a building block for the design of peptide and protein surrogates. The whole Ramachandran plot of the Ace-Ac3c-NCH3 dipeptide was investigated at the Hartree-Fock level using a 6-31G(d) basis set and the most favorable structures were assessed on this surface by energy minimization. These results were subsequently used as a reference to generate specific molecular mechanics parameters for Ac3c compatible with the parm94 set of the AMBER force field. The effect of water as a solvent on the conformational profile of the dipeptide was also assessed using the Miertus-Scrocco-Tomasi self-consistent reaction-field model at the Hartree-Fock level using a 6-31G(d) basis set and using the AM1 semiempirical method. The conformational profile of the Ac3c dipeptide can be characterized by two symmetric low-energy regions for values of f around ± 80° with a wide range of values for ¿ ranging from -40 to 180°. with the lower areas located at low values of ¿. Solvent effects do not alter the features of the conformational map, but a shift of the two absolute minima to (f, ¿)values near ( ±90°, 0°) can be observed. These results are in accord with all experimental evidence and with the known tendency of Ac3c to induce ß-turn conformations in peptides.