(560in) An Investigation into the Catalytic Cycle of Cytochrome P-450 Involving 1-n-Alkyl-3-Methylimidazolium Cations As Substrate

Ionic liquids have been projected as ‘green’ chemicals due to their environmentally benign characteristics like inherent low vapor pressure and flammability. As compared to conventional industrial solvents, their extremely low vapor pressures translate to the fact that they have negligible role in air emissions. These liquids can also be flexibly designed in order to tune their physical properties. Thousands of possible combinations of cations and anions are possible for such a design process. Out of the several ionic liquid classes, imidazolium-based ionic liquids have been one of the most widely utilized in diverse applications. Suitable variants of these types of ionic liquids have been applied to many processes in the chemical industry. Though being proved to be highly effective in driving complex industrial processes, experimental investigations have raised questions on their environmental degradability. Thus, it becomes imperative to include rational design into their synthesis. From an experimental point of view, considerable efforts have been put in this direction but molecular level details have not been explored in detail computationally. The present work aims to provide physical insight into the phenomena of ionic liquid biodegradability to aid in the future design of these solvents.

Cytochrome P-450 has been identified and widely studied for their role in oxidation of a wide variety of molecules in aerobic and anaerobic environments. Thus, it was deemed necessary to capture the effects of the cytochrome’s active site molecule on imidazolium-based ([C_nmim]⁺) cations to develop a computational framework for their biodegradability. For this, the enzymatic center of the P-450 molecule (heme) was modeled as an iron porphyrin molecule with an Fe-based center conjugated with the amino acid residue cysteine (FePCys) at its proximal side. The cations were included in the model as a potential substrate for the P-450 enzyme in complexation with the underlying porphyrin molecule. This interaction was modeled using DFT calculations by adapting a purely quantum mechanical framework at the M06 level of theory. To include the conformational effects, two different conformations of the ionic liquid cation, namely, tail up and tail down conformations, were considered in this work varying the 1-n-alkyl chain on the cation progressively along the homologous series (n =2,4,6,8,10). To provide insight into the dynamics of the substrate while binding to the active site molecule (FePCys) and further, different steps of the catalytic cycle were modeled using a synchronous approach. Result and discussion would describe the energetics and properties evaluated from the interaction between FePCys and ionic liquid cation from the binding, reduction and subsequent dioxygen insertion processes in the cycle. Also, key analysis of the interaction strength and thermodynamics of the system derived from each step would be included to provide further insight into the protein-ligand model.