To further elucidate the effect of thionation on the polymer dynamics in solution, we performed molecular dynamics simulations on small 20-mers, serving as model systems to study the impact of increasing degrees of thionation (0 -100%). In line with the observed solubility issues, upon full thionation the modeling results in formation of a compact globule (Figure ). In contrast, PEtOx can be seen rapidly transitioning between various coiled conformations throughout the simulations, thus showing the largest fluctuations regarding radii of gyration (Figure ) and median values of solvent-accessible surface areas (Figure ). To investigate hydrogen bonding, we first calculated radial distribution functions (RDFs) of water oxygens around polymer oxygen and sulfur atoms (Figure ), respectively. The peak of the first hydration shell of PEtOx at 0.29 nm noticeably broadens and decreases in intensity upon insertion of the first thioamide elements (25%); upon additional insertions (75 -100%) the peak shifts to a maximum at 0.36 nm for 100% thionation, indicating weaker hydrogen bonding with larger donor-acceptor distances.