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 alpha-CD or beta-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 alpha-CD. This is attributed to the small cavity size of alpha-CD which sustains only partial inclusion. Upon the addition of gamma-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 gamma-CD. This interaction is a result of the large cavity size of gamma-CD which does not support a stable complex. The largest caging effect was observed in 2,6-di-O-methyl-beta-CD (DMbeta-CD) which is an indication of a more hydrophobic environment around the guest. The large hydrophobicity of DMbeta-CD is due to the presence of the two methyl groups in the beta-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.
authors: Department of Chemistry, Faculty of Science, Sultan Qaboos University, P.O. Box 36, Muscat, Postal Code 123, Sultanate of Oman. abouzied@squ.edu.om
authors: Osama K
authors: OK
authors: Abou-Zied
authors: Othman I K
authors: OI
authors: Al-Shihi
mesh_terms: D003505:Cyclodextrins / Q000737:chemistry*; D007536:Isomerism; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D011728:Pyridones / Q000737:chemistry*; D012997:Solvents; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D003505:Cyclodextrins; D011725:Pyridines; D011728:Pyridones; D012997:Solvents; D014867:Water