Exploring Bioconjugation and Bioorthogonal Strategies via Computational Chemistry

In this thesis, A set of computational studies are presented exploring exploring bioconjugation and bioorthogonal strategies. To so we applied the activation strain model (ASM)of reactivity in conjunction with the matching energy decomposition analysis (EDA) and quantitative Kohn-Sham molecular orbital (KS-MO) theory analysis. Through our analyses we teased apart the the activation modes of the retro-Cope reaction and utelized these to promose new reagents for this bioorthogonal reaction. Addtionally, we present a double hierarchical benchmark of the organodichalcogenide bonding motif, accompanied by a DFT perfomance study. Lastly, study teasing apart the bonding mechanism of the organodichalcogenide bond is presented. Here, we find that the Pauli repulsion determines the trends in the Ch–Ch bond strength both for oxidation as for moving to heavier chalcogens.