Computational Analysis of 1,2-Dialkynylpyrrole Analogues

Bondoc, Joshua
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Computational chemistry can be used to quickly predict the properties of molecules. We are interested in studying the potential of 1,2-dialkynylpyrroles to undergo a thermal Bergman cyclization-triggered rearrangement to reactive diradical intermediates that display cytotoxic activity. These diradical intermediates have garnered much interest in the scientific community as potential anti-tumor drugs. A (U)B3LYP hybrid functional with a 6-31G** basis set was used to predict the electronic energies of each intermediate and transition state in the reaction. The electronic energies were used to construct a reaction coordinate that quantified the energy gap between these intermediates and transition states. The goal of this experiment was to create an analogue of a 1,2-dialkynylpyrrole that maximized the energy gap between the diradical singlet and the retro Bergman transition state while simultaneously minimizing the energy gap between the diradical singlet and the diradical triplet. An analogue that produced a diradical with these properties would be long lived and reactive. We discovered that the addition of electron withdrawing groups to the C3 carbon of the starting 1,2-dialkynylpyrrole lowered the singlet-triplet gap and increased the energy barrier for the retro Bergman transition state. Electron withdrawing groups placed in close proximity to the retro Bergman cleavage site may affect the energies of the bonding and antibonding orbitals associated with that bond. This study provides insight into the further optimization of diradicals to be used for therapeutic applications.
computational chemistry, radicals, chemistry, cancer, Gaussian, quantum, B3LYP, DFT, density functional theory, Honors College
Bondoc, J. (2018). Computational analysis of 1,2-dialkynylpyrrole analogues (Unpublished thesis). Texas State University, San Marcos, Texas.