Short Historical Overview of Tautomerization Dynamics

The study of prototropic tautomerization is intimately related to the study of proton transfer reactions. The study of the dynamics of proton transfer is as old as the study of reaction kinetics itself Indeed, the first reactions studied, that is, the inversion of sugar by Wilhehny in 1850 [65], involves a proton transfer as the elementary step in the reaction. In the first studies on the dynamics of tautomerization, primarily keto-enol tautomerization in acetone-like compounds were studied, which is a slow process involving a number of reaction steps of which the acid catalyzed keto-enol conversion was taken as the rate determining one [66]. In the past century, since 1910, nearly 2000 papers have been published on the kinetics of tautomerization, and in the first 60 years most of those were devoted to the ground-state reactions of the keto-enol type involving a C atom. Until the mid-1950s, only a handful of papers can be found this was obviously due to experimental hmitations. Two things are needed a method to start the reaction, and a method to follow it. In Dawson s experiments [66], the rate could be influenced by the amount of acid present, and the reaction could be followed because the enol produced 

One of the topics much under discussion in the early years of kinetics research was the nature of the two tautomeric forms, or where the proton actually resided. Laar [35] had proposed a so-caUed oscillatory model, where a hydrogen atom vibrates continuously between the two possible positions. Other early observations include dielectric effects the polarity of the solvent could help release a proton from one position, thus making a transfer possible [1]. Although a tautomerization reaction is not an ionization (Section 1.1), an ionization step does play a crucial role, and may in many cases be the rate-determining step. 

The third type of experiment is photolysis, where the product is one of a tautomer pair [2, 7, 75]. Again, almost aU reactions studied are keto-enol tautomerizations where the proton transfer is not direct but in a number of steps via the solvent Since the first step is often an ionization (proton transfer to solvent molecule), which is thought to be diffusion-controlled [67], it does give some insight into proton transfer reactions, but exact elucidation is hard, since often there are numerous possibiHties for reaction mechanisms and roles of solvent molecules and internal vibrations [76, 77]. In view of the lack of understanding of proton transfer reactions, it would be much better to have a simpler and more direct way to initiate intramolecular proton transfer. This possibility is offered by looking at intramolecular proton transfer reactions in the excited state, which can be initiated much faster and followed on a much shorter timescale than ground-state reactions. 

The dashed arrow indicates the excited-state proton transfer. There are a few cases of dual emission from both the normal (E) and tautomeric (T) forms. Salicylic acid is not one of them in most solvents. 

This observation has led to many other cases in which a large red shift is found, and where ESIPT is invoked to explain this. Since absorption and emission wavelengths can be modified by substituents at various places in the ring system, and there is a considerable dependence on the solvent or other environment (protein, membranes), many reporter systems have been designed on the basis of this idea. Salicylic acid and the related ortHo-hydroxybenzaldehyde derivatives have attracted most attention in the literature for fundamental research, but there are a few other groups of ESIPT molecules that have attracted attention as well. 

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