NMR studies of solvent-assisted proton transfer in a biologically relevant Schiff base

Toward a distinction of geometric and equilibrium H-bond isotope effects

Shasad Sharif, Gleb S. Denisov, Michael D. Toney, Hans Heinrich Limbach

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

The tautomeric equilibrium in a Schiff base, N-(3,5-dibromosalicylidene)- methylamine 1, a model for the hydrogen bonded structure of the cofactor pyridoxal-5′-phosphate PLP which is located in the active site of the enzyme, was measured by means of 1H and 15N NMR and deuterium isotope effects on 15N chemical shifts at variable temperature and in different organic solvents. The position of the equilibrium was estimated using the one-bond 1J(OHN) and vicinal 3J(H αCNH) scalar coupling constants. Additionally, DFT calculations of a series of Schiff bases, N-(R1-salicylidene)-alkyl(R 2)amines, were performed to obtain the hydrogen bond geometries. The latter made it possible to investigate a broad range of equilibrium positions. The increase of the polarity of the aprotic solvent shifts the proton in the intramolecular OHN hydrogen bond closer to the nitrogen. The addition of methanol and of hexafluoro-2-propanol to 1 in aprotic solvents models the PLP-water interaction in the enzymatic active site. The alcohols, which vary in acidity and change the polarity around the hydrogen bond, also stabilize the equilibrium, so that the proton is shifted to the nitrogen.

Original languageEnglish (US)
Pages (from-to)3375-3387
Number of pages13
JournalJournal of the American Chemical Society
Volume128
Issue number10
DOIs
StatePublished - Mar 15 2006

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Proton transfer
Schiff Bases
Isotopes
Protons
Hydrogen
Hydrogen bonds
Nuclear magnetic resonance
Nitrogen
Catalytic Domain
Pyridoxal Phosphate
Deuterium
Chemical shift
Propanol
Acidity
Discrete Fourier transforms
Organic solvents
Amines
Methanol
Phosphates
Alcohols

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

NMR studies of solvent-assisted proton transfer in a biologically relevant Schiff base : Toward a distinction of geometric and equilibrium H-bond isotope effects. / Sharif, Shasad; Denisov, Gleb S.; Toney, Michael D.; Limbach, Hans Heinrich.

In: Journal of the American Chemical Society, Vol. 128, No. 10, 15.03.2006, p. 3375-3387.

Research output: Contribution to journalArticle

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