Tautomeric intramolecular proton transfer

Figure 8-4. Schematic picture of tautomeric intramolecular proton transfer in malonaldehyde...

Tliere are several reasons for this great interest in the tautomerism of porphyrins (which could justify its own review) (1) their biological significance, (2) their applications in material science ( hole burning is related to their tautomerism), (3) the simplicity of the system (annular tautomerism involving intramolecular proton transfer both in solution and in the solid state), and (4) the possibility of elucidating the kinetic processes in great detail. 

The optical properties of the 8-o-PhOH-purine adducts have provided insight into their ground-state structures at the nucleoside level. These adducts have the ability to phototautomerize, through an excited-state intramolecular proton transfer (ESIPT) process, to generate the keto form. This tautomerization depends on the presence of a intramolecular hydrogen (H)-bond between the phenolic OH and the imine nitrogen (N-7). Figure 14 shows normalized absorption and emission spectra for 8-o-PhOH-dG and 8-o-PhOH-dA in aqueous buffered water and hexane. In water, 8-o-PhOH-dG shows only enol emission at 395 nm, while 8-o-PhOH-dA shows enol emission at 374 nm and phenolate emission at 447 nm. In hexane, both adducts show keto emission at 475 nm 8-o-PhOH-dA also shows a small amount of enol emission and no phenolate emission. These results show that in water, the intramolecular H-bond... 

There may be two proton transfers in the carbonic anhydrase II-catalyzed mechanism of CO2 hydration that are important in catalysis, and both of these transfers are affected by the active-site zinc ion. The first (intramolecular) proton transfer may actually be a tautomerization between the intermediate and product forms of the bicarbonate anion (Fig. 28). This is believed to be a necessary step in the carbonic anhydrase II mechanism, due to a consideration of the reverse reaction. The cou-lombic attraction between bicarbonate and zinc is optimal when both oxygens of the delocalized anion face zinc, that is, when the bicarbonate anion is oriented with syn stereochemistry toward zinc (this is analogous to a syn-oriented carboxylate-zinc interaction see Fig. 28a). This energetically favorable interaction probably dominates the initial recognition of bicarbonate, but the tautomerization of zinc-bound bicarbonate is subsequently required for turnover in the reverse reaction (Fig. 28b). 

Bensaude et al. (78T2259) have used T-jump relaxation spectrophotometry to determine the rates of protonation and deprotonation of 3(5)-methyl-5(3)-phenylpyrazole anion (416") and cation (416H ), respectively. This study is a fundamental cornerstone in understanding annular tautomerism in azoles. The nondissociative intramolecular proton transfer in azoles is not observed (78T2259 86BSF429). 

DFT calculations on the Mg(L—H)(L) complex reveal how water and acetonitrile can be lost (Scheme 9). Thus intramolecular proton transfer tautomerizes the neutral acetamide ligand in 48 into the hydroxyrmine form in 49, which can then dissociate via another intramolecular proton transfer to yield the four-coordinate adduct 50, which now contains both water and acetonitrile ligands. It is this complex that is the direct precursor to water and acetonitrile loss. Note that the reaction shown in Scheme 9 is a retro-Ritter reaction and involves fragmentation of the neutral rather than the anionic acetamide ligand, which is a bidentate spectator ligand. 

Tautomeric equilibrium in aqueous cw-malonaldehyde, see reaction 1 in Figure 8-4, is a prototypical reaction extensively studied in the gas phase but still relatively unknown in solution. In fact, despite the large number of NMR experiments [52,53,54] and quantum chemical calculations [55] with the polarized continuum model (PCM), [1] the actual stability of czT-malonaldehyde is not well clarified, although the trans isomer should be the predominant form in water. Secondly, the involvement of the light proton in the reaction may in principle provide relevant quantum effects even in condensed phase. All these complications did not prevent this reaction to be used as a prototypical system for theoretical studies of intramolecular proton transfer in condensed phase by several investigators [56,57,58,59,60] including ourselves. 

The presence of the ortho-hydroxy group is essential for the observation of both types of chromisms, and the mechanism involves intramolecular proton transfer via a six-membered-ring transition state, producing enol-keto tautomeric species, with the spectra of the keto forms showing a bathochromic shift (Scheme 16). 

Dynamics in the solid state include processes of an intramolecular proton transfer the tautomerism of porphyrin [10] or the intramolecular proton transfer in cyclic AW-bisaryl formamidine dimers [11] was studied by means of CP MAS NMR. 

The species H2Ar, HAl", andAl correspond to the forms H2B,HB andB of ordinary dibasic acids of the formula H2B. Certainly, there is also an equilibrium of intramolecular proton transfer, i.e., a tautomeric equilibrium HAl HAl. However, its equilibrium constant is so large that the concentration of HAl is very small. In ethanol-water mixtures as solvent, the respective equilibrium constants of glycine, L-alanine, L-valine, L-leucine, L-phenylalanine, L-isoleucine, L-methionine, and L-serine are aU between 10 and 10 [8]. 

Before analysis of the interactions of the nucleic acid bases with the clay minerals in the presence of water and cation one needs to understand the individual interactions of NAs with isolated water and with a cation. Such theoretical study was performed for 1 -methylcytosine (MeC) [139]. The study revealed influence of water and cation in the proton transfer for this compound. This leads to the formation of imino-oxo (MeC ) tautomer. Topology of the proton transfer potential surface and thermodynamics of stepwise hydration of MeCNa+ and MeC Na+ complexes is further discussed. The one dimensional potential energy profile for this process followed by the proton transfer with the formation of hydrated MeC Na+ is presented in Fig. 21.2. One-dimensional potential energy profile for amino-imino proton transfer in monohydrated N1-methylcytosine (this represents the situation when tautomerization is promoted by a single water molecule without the influence of Na+ cation) and for the case of pure intramolecular proton transfer (tautomerization is not assisted by any internal interactions) is also included. The most important features of this profile do not depend on the presence or absence of Na+ cation. All the potential energy curves have local minima corresponding to MeC and MeC. However, the significant difference is observed in the relative position of local minima and transition state, which results in a different thermodynamic and kinetic behavior for all presented cases (see Fig. 21.2). 

Proton transfer is one of the simplest of all elementary chemical processes, the kinetics of which play an important role in many biological processes. Many examples of tautomerism (the equilibrium between two different isomers) involve proton transfer. Of the many systems studied the photon-stimulated Excited State Intramolecular Proton Transfer (ESIPT) in 3-hydroxyfiavone (3-HF) (C15 Hio O3), which is an important plant compound, has many desirable features, making it an ideal model system. 

Transformations of this type play an important role in the mechanism of quite a few reactions, in particular, it is they which lie at the root of the intramolecular tautomerism [52]. It is therefore not surprising that the theoretical investigation of the intramolecular proton transfers is represented by a wide range of calculations of methodological importance. Particularly thoroughly was studied the reaction of the 1,5-proton shift in 3-oxy-2-propenal (cis-enol of malonal-dehyde) XI which affords one of the most significant examples of the degenerate intrachelate tautomerism. 

Proton transfer is another type of reaction of great interest to chemists, especially to biochemists, for it occurs quite often in biological systems. For an illustration, we chose the study of Zhang et al. on the intramolecular proton transfer for the tautomerization of foramidine NH2-CH=NH. The mechanism of the gas-phase tautomerization is shown in Figure 5. 

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