A theoretical aspect of mechanism of proton transfer from water to aromatic heterocyclic anions in microsolvated state and aqueous state as well as effect of substitution on them
Adyasa Priyadarsini and Bhabani S. Mallik*
Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy-502285, Telangana, India
Heterocyclic compounds are those in which the ring atoms contain oxygen, nitrogen, and sulfur and also can be aromatic. Nowadays heterocycles containing nitrogen are extensively used for pharmacological research as they are biologically active and can be used for bio mimicking1. Water oxidation catalysts contain heterocyclic compounds as ligands. In biological systems, we have water as a primary solvent along with various physical conditions. Thus understanding the solvation of aromatic heterocyclic anion is our main aim. We have explored proton transfer from water in aromatic heterocyclic anions (AHAs), such as pyrrolide, pyrrazolide, benzimmidazolide, indolide and effect of substitution on the process. We carried out first principle simulation of all the aqueous solutions, radial distribution function analysis, free energy calculation to establish the transition state2 and metadynamics3 simulation using collective variables. Form the gas phase calculation we find out that in case of pyrrolide 3 water molecules are sufficient for proton transfer and for rest of the anions at least 4 waters molecules are required for the process. The hydroxyl anion generated after proton transfer is stabilized by the cooperative effect of neighboring water molecules. By substituting ring hydrogen by an electron withdrawing group for e.g. CN- and Br- at suitable site drastically effects the proton transfer as they withdraw electron density from the heteroatom. Even presence of 4 water molecules for the cooperative effect could not initiate the proton transfer. Water in general one of the weakest acid with pKa = 14. But this process is a fast reaction and change of acidity of the hydroxyl group in the close vicinity of AHAs aids the reaction4. Extensive study of hydration of anions which act as stable intermediate in several reactions can be used to understand the gap between microsolvation and aqueous solution reactions.
References:
1. Yamauchi, M., Katayama, S. & Watanabe, T. Studies on the syntheses of heterocyclic compounds containing benzopyrone. Part 6. Biomimetic total synthesis of citromycetin. J. Chem. Soc. Perkin 1 0, 395-398 (1987).
2. Theoretical Calculations in Reaction Mechanism Studies. studylib.net Available at :https://studylib.net/doc/18222298/theoretical-calculations-in-reaction-mechanism-studies.
3. F. G., et.al Using metadynamics to understand the mechanism of calmodulin/target recognition at atomic detail. - PubMed - NCBI. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16877506.
4. Biswas, S. & Mallik, B. S. A delicate case of unidirectional proton transfer from water to an aromatic heterocyclic anion. Phys. Chem. Chem. Phys. 18, 29979-29986 (2016).