Modeling the solvent effect in free radical polymerization and deamidation of peptides

Abstract

In the first part of this study, the kinetics free radical polymerization of ethyl methacrylate (EMA) and ethyl α-hydroxy methacrylate (EHMA) in solution is investigated; in the second part the deamidation in three different dipeptides is modeled in solution by using Density Functional Theory (DFT). In the first part of this study, the propagation kinetics of EMA and EHMA has been subjected to a computational study in order to understand their free radical polymerization (FRP) behavior in bulk and in solution. Methacylates are among the most commonly used monomers in FRP and can be used as dental materials, biomaterials, adhesives, optical adhesives, coatings, fiber-optic coatings and in many other areas. The hydroxy-functional methacrylate monomers have drawn attention due to their hydrophilicity, crosslinking sites and functionality for subsequent reactions. The correlation between the calculated propagation rate constants and the experimental results has been reproduced with the MPWB1K/6-311+G(3df,2p) methodology. In the second part of this study, the deamidation reaction mechanism in peptides is investigated. Out of the twenty naturally occurring amino acid residues, two of them, namely Asparagine (Asn) and Glutamine (Gln) are known to be unstable under physiological solvent conditions. The amide group from the backbone of the amino acid residue of Asn and Gln cleaves to form Aspartly (Asp) and Glutamyl (Glu) residues. Peptides and proteins that contain Asn and/or Gln with different primary sequence are known to have very different half-life times for deamidation. Therefore, the effect of the primary sequence on deamidation is studied by choosing three different peptides as models.