Dianions proton transfers

This variation from the ester hydrolysis mechanism also reflects the poorer leaving ability of amide ions as compared to alkoxide ions. The evidence for the involvement of the dianion comes from kinetic studies and from solvent isotope effects, which suggest that a rate-limiting proton transfer is involved. The reaction is also higher than first-order in hydroxide ion under these circumstances, which is consistent with the dianion mechanism. 

As for the acetyl phosphate monoanion, a metaphosphate mechanism has also been proposed 78) for the carbamoyl phosphate monoanion 119. Once again, an intramolecular proton transfer to the carbonyl group is feasible. The dianion likewise decomposes in a unimolecular reaction but not with spontaneous formation of POf as does the acetyl phosphate dianion, but to HPOj and cyanic acid. Support for this mechanism comes from isotopic labeling proof of C—O bond cleavage and from the formation of carbamoyl azide in the presence of azide ions. 

When the EGB is an anion or a dianion, irreversible follow-up reaction of the deprotonated substrate, S , is the only way by which an unfavorable proton transfer equilibrium can be driven toward products. A disadvantage is that when the follow-up reaction of S is with an added electrophile, competing reaction between the EGB and the electrophile is often observed. Or - if the EGB is a dianion - the monoprotonated form may react with the electrophile. 

Two types of electrogenerated carbon bases have commonly been used (1) dianions derived from activated alkenes, and (2) carbanions formed by reductive cleavage of halogen compounds or by direct reduction of weak carbon acids. In both cases, the efficiency of the proton transfer reaction relies on a thermodynamically favored proton transfer or a fast follow-up reaction of the deproto-nated substrate. 

Fig. 16 Free energy/reaction coordinate diagram for proton transfer from the 4,6-bis(phenylazo)resorcinol monoanion to give the dianion in the presence of 2-methylphenol buffers at a 1 1 buffer ratio and at buffer concentrations of (a) 0.001 and (b) 0.10mol" dm. ...

Proton transfer may proceed directly or via a six-membered cyclic transition state involving a molecule of water. A calculation of the intermediate zwitter-ionic concentration for the hydrolysis of methyl phosphate monoanion, based on the pKa values for methanol and methyl phosphate dianion, predicts the first-order rate coefficient for zwitterion decomposition to be ca. 10 sec-1 at 100°C. This value is in good agreement with the observed rate of hydrolysis and, considering the assumptions involved, with the rate of P-O bond fission of the presumed zwitterionic intermediate (2) formed in the Hg(II) catalyzed solvolysis of phosphoenolpyruvic acid, a model reaction for pyruvate kinase10. 

The possible mechanistic pathways can be shown using horizontal changes for electron transfer and vertical ones for proton transfer (Scheme 1). This scheme has been generalized and truncated to show only the reduction of A to AH2. Pyridine reduction would be extended from this scheme to reflect the six electrons and six protons involved. Of course, protonated monocationic species would probably be important only in acidic electrolytes, whereas dianions would normally be formed only in aprotic electrolytes at high junction potentials. The dication, AH22+ is an unlikely species when A is pyridine. 

Fluorescence properties of lumazine (3) and its 1- and 3-methyl derivatives were studied in aqueous solution and in dependence of the pH to obtain information about the possible tautomeric forms of the various ionic species. Emissions were found for the neutral form at 380 nm, the monoanion at 467 nm, the dianion at 483 nm, and the cation at 505 nm. From similar emissions of 3-methyllumazine (but different ones of the 1-methyl isomer), it was concluded that the emitting species is the A(8)-H phototautomer (34) resulting from an N-l to N-8 proton transfer in the excited state (Scheme 4) <87MI 718-08). 

Nitro-attached ketone dianions generally suffer from rapid proton transfer during the alkylation process. However, the reaction conditions have been optimized by using HMPA or TMEDA, which enhanced the reactivity of the dianions toward the alkylating agents19. Examples are shown in Table 10. 

Similar steps have been proposed for other acylphosphates " . Reaction (1) could involve a cyclic transition state including proton transfer. For the dianion, elimination of cyanic acid, viz. 

For the first reaction step we also examine the most plausible pathway for an unprotonated mechanism (T 2-> P3-> P4, with total charge -3 on the reacting fragments). In this case there is no proton transfer between the nucleophile and the phosphate group and the negatively charged cysteine reacts directly with the phosphorus atom of the dianionic substrate. 

We have employed the EVB method to study the energetics of nucleophile activation by proton transfer to a dianionic substrate in both LMPTP and human PTPIB. The two valence bond states O, and O2 used in the calculations are shown in Figure 3. These states represent the reactants and products for the reaction where a proton is transferred from the cysteine residue to the phenyl phosphate dianion. Starting coordinates for the protein simulations were the structure of bovine liver LMPTP in complex with sulfate and human PTPIB (C215S mutant) in complex with phosphotyrosine (PDB entries IPHR [5] and IPTV [9] respectively). 

Figure 11. Calculated energetics of proton transfer between the catalytic cysteine and the dianionic phosphate group of the substrate in LMPTP and PTPIB.

Most—if not all—of the preparative results just presented for reduction of 12 can be rationalized within the RR mechanism when effects of hydrogen-bonding and proton transfer are taken into account. Under conditions with very low proton donor concentrations DPSCC measurements on 12a-b in DMF indicate that the initial dimerization step is reversible with a large equilibrium constant, and the rate-determining step is protonation (or cyclization) of the dimer dianion [10,11]. Assuming this mechanism, the equilibrium constants for the dimerization were determined = 109 for 12a and = 53.1... 

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