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The Competing Mecha...
The Competing Mechanisms of Phosphate Monoester Dianion Hydrolysis
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- Duarte, Fernanda (author)
- Uppsala universitet,Struktur- och molekylärbiologi,Science for Life Laboratory, SciLifeLab,Univ Oxford, Chem Res Lab, 12 Mansfield Rd, Oxford OX1 3TA, England.;Univ Oxford, Phys & Theoret Chem Lab, S Parks Rd, Oxford OX1 3QZ, England.
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- Barrozo, Alexandre (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för cell- och molekylärbiologi
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- Åqvist, Johan (author)
- Uppsala universitet,Beräkningsbiologi och bioinformatik,Science for Life Laboratory, SciLifeLab
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- Williams, Nicholas H. (author)
- Univ Sheffield, Dept Chem, Sheffield S3 7HF, S Yorkshire, England.
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- Kamerlin, Shina C. Lynn (author)
- Uppsala universitet,Struktur- och molekylärbiologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2016-08-15
- 2016
- English.
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 138:33, s. 10664-10673
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https://uu.diva-port... (primary) (Raw object)
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https://pubs.acs.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Despite the numerous experimental and theoretical studies on phosphate monoester hydrolysis, significant questions remain concerning the mechanistic details of these biologically critical reactions. In the present work we construct a linear free energy relationship for phosphate monoester hydrolysis to explore the effect of modulating leaving group plc on the competition between solvent- and substrate-assisted pathways for the hydrolysis of these compounds. Through detailed comparative electronic-structure studies of methyl phosphate and a series of substituted aryl phosphate monoesters, we demonstrate that the preferred mechanism is dependent on the nature of the leaving group. For good leaving groups, a strong preference is observed for a more dissociative solvent-assisted pathway. However, the energy difference between the two pathways gradually reduces as the leaving group pK(a) increases and creates mechanistic ambiguity for reactions involving relatively poor alkoxy leaving groups. Our calculations show that the transition-state structures vary smoothly across the range of pK(a)s studied and that the pathways remain discrete mechanistic alternatives. Therefore, while not impossible, a biological catalyst would have to surmount a significantly higher activation barrier to facilitate a substrate-assisted pathway than for the solvent-assisted pathway when phosphate is bonded to good leaving groups. For poor leaving groups, this intrinsic preference disappears.
Subject headings
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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