title: 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 nonacid-catalyzed keto-enol tautomerization of related molecules. The presence of HOCl reduced the barrier by 4.5 kcal/mol in relation to the gas phase, consistent with the well-known principle that keto-enol tautomerization can be acid- or base-catalyzed. The 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.
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, USA.
authors.forename: Cassian
authors.initials: C
authors.lastname: D'Cunha
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Morozov
authors.forename: David C
authors.initials: DC
authors.lastname: Chatfield
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D002384:Catalysis; D003198:Computer Simulation; D003517:Cyclopentanes / Q000737:chemistry*; D006997:Hypochlorous Acid / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry*
chemical_list: D000438:Alcohols; D003517:Cyclopentanes; D007659:Ketones; D014867:Water; D006997:Hypochlorous Acid; C017848:4-cyclopentene-1,3-dione
references.citation: J Biol Chem. 1970 Jun;245(12):3129-34
references.pmid: 5432803
references.citation: J Comput Chem. 2010 Mar;31(4):671-90
references.pmid: 19575467
references.citation: Phys Rev B Condens Matter. 1988 Jan 15;37(2):785-789
references.pmid: 9944570
references.citation: J Med Chem. 2004 Dec 30;47(27):6673-80
references.pmid: 15615516
references.citation: J Biol Chem. 1982 May 10;257(9):5030-7
references.pmid: 7068675
references.citation: J Phys Chem B. 1998 Apr 30;102(18):3586-616
references.pmid: 24889800
references.citation: Chem Soc Rev. 2012 Apr 21;41(8):3025-38
references.pmid: 22278388
references.citation: J Phys Chem B. 2012 Nov 1;116(43):12905-14
references.pmid: 23020548
references.citation: J Phys Chem B. 2005 Jul 7;109(26):12966-75
references.pmid: 16852609
references.citation: J Phys Chem A. 2007 Mar 8;111(9):1659-66
references.pmid: 17298039
references.citation: Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 2000 Jul;62(1 Pt A):579-87
references.pmid: 11088494
references.citation: J Phys Chem B. 2008 Jan 24;112(3):997-1006
references.pmid: 18171045
references.citation: Chem Rev. 2005 Sep;105(9):3197-219
references.pmid: 16159150
references.citation: J Comput Chem. 2003 Jun;24(8):939-47
references.pmid: 12720314
references.citation: Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697
references.pmid: 9895674
references.citation: Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9135-9
references.pmid: 8415667
references.citation: J Comput Chem. 2009 Jul 30;30(10):1545-614
references.pmid: 19444816
references.citation: J Phys Chem A. 2007 Jul 5;111(26):5720-8
references.pmid: 17555303
references.citation: J Phys Chem B. 2006 May 18;110(19):9674-80
references.pmid: 16686518
references.citation: Chemphyschem. 2006 Jun 12;7(6):1229-34
references.pmid: 16683282
references.citation: J Chem Theory Comput. 2007 Jul;3(4):1249-66
references.pmid: 26633199
references.citation: J Phys Chem A. 2012 Apr 19;116(15):3836-45
references.pmid: 22439915
references.citation: J Chem Phys. 2012 Apr 7;136(13):134107
references.pmid: 22482540
references.citation: Biophys J. 2011 Feb 16;100(4):1066-75
references.pmid: 21320452
references.citation: J Chem Phys. 2005 May 1;122(17):174506
references.pmid: 15910044
references.citation: Biochemistry. 2013 May 28;52(21):3688-701
references.pmid: 23634952
references.citation: Phys Chem Chem Phys. 2006 Jul 21;8(27):3172-91
references.pmid: 16902710
references.citation: Biochim Biophys Acta. 2006 Aug;1764(8):1325-39
references.pmid: 16870515
references.citation: J Phys Chem A. 2006 Dec 28;110(51):14013-7
references.pmid: 17181363