Environmental effects on phosphoryl group bonding probed by vibrational spectroscopy

Implications for understanding phosphoryl transfer and enzymatic catalysis

Hu Cheng, Ivana Nikolic-Hughes, Jianghua H. Wang, Hua Deng, Patrick J. O'Brien, Li Wu, Zhong-Yin Zhang, Daniel Herschlag, Robert Callender

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

We have used vibrational spectroscopy to study bonding in monosubstituted dianionic phosphates, both to learn more about basic properties intrinsic to this important class of biological substrates and to assess the ability of vibrational spectroscopy to provide a "sensor" or probe of the local environment experienced by the phosphoryl group. We examined the bonding properties of the phosphoryl group via vibrational spectroscopy for a series of compounds in which the phosphoryl substituent was varied systematically and extensively. A broad linear correlation of the bridging P-O(R) bond length and the pKa of the substituent alcohol was observed. The results indicate that the P-O(R) bond changes by only ∼0.04 Å with alcohol substituents that vary in pKa by ∼12 units, suggesting that phosphoryl group bonding responds in a subtle but regular manner to changes in the local environment. We also determined the effect on the phosphoryl bonding from changes in the solvent environment. Addition of dimethyl sulfoxide (DMSO) elongates the bridging bond, presumably as a result of lessened solvation to the nonbridging oxygens and conservation of bond order to phosphorus. Finally, we have addressed the relationship between groundstate bonding properties and reactivity, as changing the leaving group substituent and adding DMSO have large rate effects, and it was previously proposed that lengthening of the bond to be broken is the cause of the increased reactivity. The results herein suggest, however, that the change in the bridging bond energy is small compared to the changes in energy that accompany the observed reactivity differences. Further analysis indicates that electrostatic interactions can provide a common driving force underlying both bond lengthening and the observed rate increases. We suggest that ground-state distortions of substrates bound to enzymes can provide a readout of the electrostatic active site environment, an environment that is otherwise difficult to assess.

Original languageEnglish (US)
Pages (from-to)11295-11306
Number of pages12
JournalJournal of the American Chemical Society
Volume124
Issue number38
DOIs
StatePublished - Sep 25 2002
Externally publishedYes

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Vibrational spectroscopy
Catalysis
Environmental impact
Spectrum Analysis
Dimethyl sulfoxide
Dimethyl Sulfoxide
Static Electricity
Alcohols
Solvation
Bond length
Substrates
Coulomb interactions
Phosphorus
Ground state
Electrostatics
Conservation
Catalytic Domain
Phosphates
Enzymes
Oxygen

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Environmental effects on phosphoryl group bonding probed by vibrational spectroscopy : Implications for understanding phosphoryl transfer and enzymatic catalysis. / Cheng, Hu; Nikolic-Hughes, Ivana; Wang, Jianghua H.; Deng, Hua; O'Brien, Patrick J.; Wu, Li; Zhang, Zhong-Yin; Herschlag, Daniel; Callender, Robert.

In: Journal of the American Chemical Society, Vol. 124, No. 38, 25.09.2002, p. 11295-11306.

Research output: Contribution to journalArticle

Cheng, Hu ; Nikolic-Hughes, Ivana ; Wang, Jianghua H. ; Deng, Hua ; O'Brien, Patrick J. ; Wu, Li ; Zhang, Zhong-Yin ; Herschlag, Daniel ; Callender, Robert. / Environmental effects on phosphoryl group bonding probed by vibrational spectroscopy : Implications for understanding phosphoryl transfer and enzymatic catalysis. In: Journal of the American Chemical Society. 2002 ; Vol. 124, No. 38. pp. 11295-11306.
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AU - Cheng, Hu

AU - Nikolic-Hughes, Ivana

AU - Wang, Jianghua H.

AU - Deng, Hua

AU - O'Brien, Patrick J.

AU - Wu, Li

AU - Zhang, Zhong-Yin

AU - Herschlag, Daniel

AU - Callender, Robert

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