Theoretical Study of HOCl-Catalyzed Keto–Enol Tautomerization of β-Cyclopentanedione in an Explicit Water Environment

Abstract

The mechanism of acid-catalyzed keto-enol tautomerization of β-cyclopentanedione (CPD) in solution is studied computationally. Reaction profiles are first calculated for a limited solvation environment using ab initio and density functional methods. Barrier heights for systems including up to one hydration shell of explicit water molecules depend strongly on the number of waters involved in proton transfer, and to a lesser but significant extent on the number of waters forming hydrogen bonds with waters in the proton transfer chain (each such water reduces the barrier by 4.4 kcal/mol on average). Barriers of 8-13 kcal/mol were obtained when a full or nearly full hydration shell was present, consistent with calculations for non-acid-catalyzed keto-enol tautomerization of related molecules. The presence of HOCl reduced the barrier by 4.5 kcal/mol viz-a-viz the gas phase, consistent with the well-known principle that keto-enol tautomerization can be acid or base catalyzed. Reaction was also modeled beginning with snapshots of reactant conformations taken from a 300 K molecular dynamics simulation of CPD, HOCl and 324 explicit waters. Reaction profiles were calculated at a QM/MM level with waters in the first hydration shell either fixed or energy minimized at each step along the reaction coordinate. A substantial variation in barrier height was observed in both cases, depending primarily on electrostatic interactions (hydrogen bonding) with first-hydration-shell waters and to a lesser extent on electrostatic interactions with more distant waters and geometric distortion effects. For the lowest barriers, the extent of barrier reduction by waters involved in proton transfer is consistent with the limited-solvation results, but further barrier reduction due to hydrogen-bonding to waters involved in proton transfer is not observed. It is postulated that this is because highly flexible structures such as extensive hydrogen bonding networks optimal for reaction are entropically disfavored and so may not contribute significantly to the observed reaction rate.

Competing Intramolecular vs. Intermolecular Hydrogen Bonds in Solution

“…In a real, dilute solution the solute is surrounded by solvent molecules all around. Except for the simplest modeling cases like the partial solvation of γ-amino-butyric acid with 2–5 water molecules [ 76 ] or consideration of 3–8 water molecules during the HOCl catalyzed tautomerization of β-cyclopentadione [ 77 ], a considerably larger number of water molecules is generally required for reasonable modeling of the solvation sphere even for a small organic molecule. An impressive example was provided by Lu [ 78 ], who optimized the geometry of the Al(H 2 O) 6 3+ ·12 H 2 O hydrate at the B3LYP/6-31+G(d,p) level in a water continuum by the PCM method.…”

Relaxation dynamics of photoexcited resorcinol: internal conversion versus H atom tunnelling

“…Such a process would likely need to overcome, or tunnel through a barrier before tautomerisation could occur. 77,78 Previous experiments have placed the vibrational modes that would likely mediate the KET mechanism, which include the O-H bend, at B1300 cm À1 in the ground state of resorcinol. 33,35 A similar excess energy would be expected for the O-H bend in the 1 1 pp* excited state which is in fairly good agreement with the onset of t 2 (>1900 cm À1 ).…”

How the Proximal Pocket May Influence the Enantiospecificities of Chloroperoxidase-Catalyzed Epoxidations of Olefins

“…Along with its native function of halogenating organic substrates using chloride, bromide and iodide ions [ 2 , 3 , 4 ], CPO is also capable of many promiscuous activities, including peroxidase, catalase and cytochrome P450 (P450) types of reactions [ 1 ]. CPO-catalyzed reactions are of biotechnological and environmental importance [ 5 ], therefore attracting current research interest on both the experimental [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ] and theoretical sides [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. The catalytic cycle requires a two-electron oxidation of the ferric heme center, using hydrogen peroxide or other suitable peroxide, and the glutamic acid side chain (E 183 ) in the distal pocket as a general acid-base catalyst, to form Compound I (CPO-I), a highly reactive oxyferryl porphyrin π-cation radical intermediate [ 15 , 20 , 22 , 23 ].…”