Tautomers description

Quinone oximes and nitrosoarenols are related as tautomers, i.e. by the transfer of a proton from an oxygen at one end of the molecule to that at the other (equation 37). While both members of a given pair of so-related isomers can be discussed separately (see, e.g., our earlier reviews on nitroso compounds and phenols ) there are no calorimetric measurements on the two forms separately and so discussions have admittedly been inclusive—or very often sometimes, evasive—as to the proper description of these compounds. Indeed, while quantitative discussions of tautomer stabilities have been conducted for condensed phase and gaseous acetylacetone and ethyl acetoacetate, there are no definitive studies for any pair of quinone oximes and nitrosoarenols. In any case. Table 4 summarizes the enthalpy of formation data for these pairs of species. 

Table VI collects the theoretical quantities appropriate to the description of the tautomeric stability of cytosine, computed by methods including both -n- and cr-electrons. We have added to it the results of a 77-SCF MO approach (including cr-polarization effects) on heats of atomization of different tautomeric forms of cytosine. Bodor et al.liB have related the heat of atomization to the stability of the tautomers, and found that the most stable structure of the molecule is the amine-lactam 2 having the greatest heat of atomization (59.707 eV). They predict on this basis the following order of stability 2 > 3 > 6 > 1.

Such tautomeric equilibria, which may be crucial for the understanding and appropriate description of phase equilibria, can technically be treated in the same way as conformational equilibria in COSMO-RS. Unfortunately, we must be aware that the total energy differences between the tautomers may be in error by 8 kJ/mol or even more, if we calculate them on our default DFT/COSMO level. To gain an accurate description of such phenomena, it is therefore necessary to correct the COSMO energy differences either by comparison with higher level QM calculations, or by treating them as adjustable parameters. 

A few chapters of the current volume describe different state-of-the-art experimental techniques used to unravel photophysical and photochemical properties of complex molecular systems. These chapters are especially tailored for the scholarly description of electronic excited state properties of nucleic acid bases and related species predicting different tautomeric distributions and possible nonra-diative deactivation processes. It is interesting to note that guanine provides particularly challenging case to discuss. Recent theoretical and experimental investigations show the existence of relatively significantly less stable imino tautomers in the... 

Successful virtual screening relies on an appropriate and correct description of the molecules being screened two particular sources of error are protonation state and tautomeric form. Oellien et have developed an exhaustive tautomer enumeration approach based on a set of 21 predefined transforms. The group do not attempt to say which tautomer is favoured, only that every form is represented. Databases built using all tautomers show better performance especially when screened with pharmacophore queries, as the bias introduced by most compound registration tools as to the correct tautomer is removed. 

A description of both the allenyl and propargylic tautomers is included here because there is convincing evidence that the former often contains a significant contribution from a propargylic resonance structure (see Section V). 

Fig. 2.67. IR spectrum of heated cyanamide vapor. The underlined approximate descriptions refer to absorptions due to the HNCNH tautomer [1688].

The effect of the solvent is usually modelled either by the use of the Onsager s self consistent reaction field (SCRF) [20] or by the polarizable continuum method (PCM) [21]. With regard to the relative stability of cytosine tautomers in aqueous solution, these methods provided results [14,15] which, in spite of some discrepancies, are in reasonable agreement with experimental data [3]. However, continuum-based methods do not explicitly take into consideration the local solvent-solute interaction which is instead important in the description of the proton transfer mechanism in hydrogen-bonded systems. A reasonable approach to the problem was recently proposed [22,23] in which the molecule of interest and few solvent molecules are treated as a supermolecule acting as solute, while the bulk of the solvent is represented as a polarizable dielectric. 

In the gas phase the neutral form is energetically favored, while in condensed phases, such as solutions in polar solvents and crystals, the ionic form is more stable. Glycine and alanine are zwitterionic in water solutions and their description is a rather challenging task for continuum solvation models. In the following we summarize the results of a study we have published on Theochem on structures and energies of tautomers of glycine and alanine in the framework of the lEF version of the Polarizable Continuum Model. 

The authors assumed that the catalytically active species might be a copper(I) complex originating from reduction by the silyl dienolate 214. As a consequence, the aldol reaction was performed with the chiral copper(I) complex [Cu(OfBu)-(S)-270], and identical results in terms of the stereochemical outcome were obtained. In addition, the reaction was followed by react IR. The study led to evidence of a copper(I) enolate as the active nucleophile, and the catalytic cycle also shown in Scheme 5.77 was proposed. The reaction of the copper(I) complex Cu(OiBu)-(S)-270 with silyl dienolate 214 represents the entry into the catalytic cycle. Under release of trimethylsilyl triflate, the copper enolate 272 forms, whose existence is indicated by in situ IR spectroscopy. Its exact structure remains unclear, but the description as O-bound tautomer is plausible. Upon reaction with the aldehyde, the copper aldolate 273 is generated, which is then silylated by means of the silyl dienol ether 214 to give the (isolable) silylated alcohol 274 from which the aldol product 271 is liberated during the acidic workup [132b]. 

In this chapter, we considered a few of the problems, and even fewer solutions, encountered when searching for a theoretical description of the rate of a tautomer-ization reaction. It should be obvious by now that it is not a solved problem by any standard. There are many technical issues that we did not discuss at all, but in addition there are problems of a fundamental nature that hamper real progress. Although in cases where the rate problem can be considered classical a consistent picture can be painted for a tautomerization reaction taking place in a polarizable environment, it is also clear that there are a number of facets that are extremely problematic. In particular, for those aspects where the quantum mechanics of the problem starts playing a role, no internally consistent description has been found. That is not due to the lack of trying we have given some examples of attempts all of which turn out to fail at one level or another, both for equilibrium as well as dynamical situations. 

Frequently, energy differences are quite small and hence require very accurate calculations which can be fiendishly difficult Thus, the choice of an appropriate electronic structure procedure is very important. Furthermore, environmental influences (solvent) have a profound effect on the position of tautomeric equilibria. Consequently, a proper description of solvation is essential. Alternatively, some property that might be useful to distinguish between tautomers could be... 

The lifetime is independent of temperature between 40 and 160 K however, above 160 K the hfetime becomes shorter, with the relative quantum yield decreasing as the temperature increases (see Table 68.5). These data make it possible to calculate the temperature-dependent nonradiative rates, which yield an activation energy of 3.7 kcal/mol, implying the existence of the excited zwitterions as well as the tautomer form. Nevertheless, interpretation of these experiments is comphcated by thermal and solvent effects, thus a proper description of the formation of the blue emission has not been unambiguously estabhshed. In order to eliminate these problems, supersonic jet excitation spectroscopy was found to provide new information regarding the spectra of the isolated molecule and dynamics at different excess vibrational... 

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