Caging and solvent effects on the tautomeric equilibrium of 3-pyridone/3-hydroxypyridine in the ground state

A study in cyclodextrins and binary solvents

Osama K. Abou-Zied, Othman I K Al-Shihi

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18 Citations (Scopus)

Abstract

The tautomeric equilibrium between 3-pyridone (3Py) and 3-hydroxypyridine (3HP) shows characteristic absorption peaks for the zwitterion form of 3Py in water that may be used as a probe of the hydrophobic nature inside macromolecules such as proteins and other biologically related systems. We studied this equilibrium in the ground state in aqueous cyclodextrins (CDs) and in binary solvent mixtures of 1,4-dioxane and water by absorption spectroscopy, and by ab initio calculations. Upon the addition of α-CD or β-CD to an aqueous solution of the 3Py/3HP system, the absorbance intensity of the zwitterion tautomer decreases with a concomitant increase in the intensity of the enol tautomer of 3HP. The results reflect the nature of the tautomeric equilibrium and point to the hydrophobic environment inside the CD cavities. The effect of inclusion is noticeably less in the case of α-CD. This is attributed to the small cavity size of α-CD which sustains only partial inclusion. Upon the addition of γ-CD, the intensity of the zwitterion tautomer slightly increased over that in water which is attributed to the direct interaction between the charged sides of the tautomer with the outer primary or secondary hydroxyls of the glycopyranose units of γ-CD. This interaction is a result of the large cavity size of γ-CD which does not support a stable complex. The largest caging effect was observed in 2,6-di-O-methyl- β-CD (DMβ-CD) which is an indication of a more hydrophobic environment around the guest. The large hydrophobicity of DMβ-CD is due to the presence of the two methyl groups in the β-CD derivative which reduce the amount of water inside the cavity upon encapsulation. In the binary mixtures of 1,4-dioxane and water, the change in the absorbance intensity of the enol and the zwitterion tautomers was analyzed quantitatively and three water molecules were found to solvate the polar centers of each tautomer. Ab initio calculations of the solvation of both tautomers by two and three water molecules were performed at the MP2/6-31++G(d,p) level. The calculations show that three water molecules are necessary to solvate the polar centers of each tautomer in a water network pattern. The results presented here suggest that the 3Py/3HP system represents a potentially useful new photophysical probe for supramolecular structures, particularly those involving inclusion.

Original languageEnglish
Pages (from-to)5377-5383
Number of pages7
JournalPhysical Chemistry Chemical Physics
Volume11
Issue number26
DOIs
Publication statusPublished - 2009

Fingerprint

Pyridones
Cyclodextrins
tautomers
Ground state
ground state
zwitterions
Water
water
cavities
inclusions
Molecules
3-hydroxypyridine
molecules
probes
hydrophobicity
Solvation
macromolecules
Hydrophobicity
Binary mixtures
binary mixtures

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Physics and Astronomy(all)

Cite this

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title = "Caging and solvent effects on the tautomeric equilibrium of 3-pyridone/3-hydroxypyridine in the ground state: A study in cyclodextrins and binary solvents",
abstract = "The tautomeric equilibrium between 3-pyridone (3Py) and 3-hydroxypyridine (3HP) shows characteristic absorption peaks for the zwitterion form of 3Py in water that may be used as a probe of the hydrophobic nature inside macromolecules such as proteins and other biologically related systems. We studied this equilibrium in the ground state in aqueous cyclodextrins (CDs) and in binary solvent mixtures of 1,4-dioxane and water by absorption spectroscopy, and by ab initio calculations. Upon the addition of α-CD or β-CD to an aqueous solution of the 3Py/3HP system, the absorbance intensity of the zwitterion tautomer decreases with a concomitant increase in the intensity of the enol tautomer of 3HP. The results reflect the nature of the tautomeric equilibrium and point to the hydrophobic environment inside the CD cavities. The effect of inclusion is noticeably less in the case of α-CD. This is attributed to the small cavity size of α-CD which sustains only partial inclusion. Upon the addition of γ-CD, the intensity of the zwitterion tautomer slightly increased over that in water which is attributed to the direct interaction between the charged sides of the tautomer with the outer primary or secondary hydroxyls of the glycopyranose units of γ-CD. This interaction is a result of the large cavity size of γ-CD which does not support a stable complex. The largest caging effect was observed in 2,6-di-O-methyl- β-CD (DMβ-CD) which is an indication of a more hydrophobic environment around the guest. The large hydrophobicity of DMβ-CD is due to the presence of the two methyl groups in the β-CD derivative which reduce the amount of water inside the cavity upon encapsulation. In the binary mixtures of 1,4-dioxane and water, the change in the absorbance intensity of the enol and the zwitterion tautomers was analyzed quantitatively and three water molecules were found to solvate the polar centers of each tautomer. Ab initio calculations of the solvation of both tautomers by two and three water molecules were performed at the MP2/6-31++G(d,p) level. The calculations show that three water molecules are necessary to solvate the polar centers of each tautomer in a water network pattern. The results presented here suggest that the 3Py/3HP system represents a potentially useful new photophysical probe for supramolecular structures, particularly those involving inclusion.",
author = "Abou-Zied, {Osama K.} and Al-Shihi, {Othman I K}",
year = "2009",
doi = "10.1039/b823405a",
language = "English",
volume = "11",
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journal = "Physical Chemistry Chemical Physics",
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T1 - Caging and solvent effects on the tautomeric equilibrium of 3-pyridone/3-hydroxypyridine in the ground state

T2 - A study in cyclodextrins and binary solvents

AU - Abou-Zied, Osama K.

AU - Al-Shihi, Othman I K

PY - 2009

Y1 - 2009

N2 - The tautomeric equilibrium between 3-pyridone (3Py) and 3-hydroxypyridine (3HP) shows characteristic absorption peaks for the zwitterion form of 3Py in water that may be used as a probe of the hydrophobic nature inside macromolecules such as proteins and other biologically related systems. We studied this equilibrium in the ground state in aqueous cyclodextrins (CDs) and in binary solvent mixtures of 1,4-dioxane and water by absorption spectroscopy, and by ab initio calculations. Upon the addition of α-CD or β-CD to an aqueous solution of the 3Py/3HP system, the absorbance intensity of the zwitterion tautomer decreases with a concomitant increase in the intensity of the enol tautomer of 3HP. The results reflect the nature of the tautomeric equilibrium and point to the hydrophobic environment inside the CD cavities. The effect of inclusion is noticeably less in the case of α-CD. This is attributed to the small cavity size of α-CD which sustains only partial inclusion. Upon the addition of γ-CD, the intensity of the zwitterion tautomer slightly increased over that in water which is attributed to the direct interaction between the charged sides of the tautomer with the outer primary or secondary hydroxyls of the glycopyranose units of γ-CD. This interaction is a result of the large cavity size of γ-CD which does not support a stable complex. The largest caging effect was observed in 2,6-di-O-methyl- β-CD (DMβ-CD) which is an indication of a more hydrophobic environment around the guest. The large hydrophobicity of DMβ-CD is due to the presence of the two methyl groups in the β-CD derivative which reduce the amount of water inside the cavity upon encapsulation. In the binary mixtures of 1,4-dioxane and water, the change in the absorbance intensity of the enol and the zwitterion tautomers was analyzed quantitatively and three water molecules were found to solvate the polar centers of each tautomer. Ab initio calculations of the solvation of both tautomers by two and three water molecules were performed at the MP2/6-31++G(d,p) level. The calculations show that three water molecules are necessary to solvate the polar centers of each tautomer in a water network pattern. The results presented here suggest that the 3Py/3HP system represents a potentially useful new photophysical probe for supramolecular structures, particularly those involving inclusion.

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