Open Access Senior Honors Thesis
Polyphenolic compounds containing two gallate groups have been shown to be effective inhibitors of Plasminogen Activator Inhibitor-1 (PAI-1). In this work we use Density Functional calculations to examine energetically-accessible configurations of two digallate compounds exhibiting disparate inhibitory activity toward PAI-1. In addition, we examine the partial charges of potentially acidic protons and the relative stability of the respective conjugate bases of a select group of PAI-1 inhibitors. This analysis was carried out to determine whether such characteristics can be used to distinguish between effective and less effective inhibitors. An examination of the stable configurations of CDE-008 and CDE-056 indicates that the range of distances between gallate rings for the poor inhibitor (CDE-008) does not overlap with the range of distances for the better inhibitor (CDE-056). However, no clear differences were observed in the partial charge distribution or relative stability of conjugate bases for the group of inhibitors examined here.
Spoutz, Patrick, "A Comparative Analysis of the Electronic and Structural Characteristics of Polyphenolic Inhibitos of PAI-1" (2010). Senior Honors Theses. 217.