Proton transfer rate-determining

Van der Spoel,D., Berendsen, H.J.C. Determination of proton transfer rate constants using ab initio, molecular dynamics and density matrix evolution calculations. Pacific Symposium on Biocomputing, World Scientific, Singapore (1996) 1-14. 

Finally, in many cases the acidity equilibria cannot be measured but the rate of proton transfer or transmetallation can be measured to give an ionic or ion pair kinetic acidity. Studies using the rates of proton transfer have included the use of isotopes such as tritium and deuterium5,6. The rate is then used to calculate the Brpnsted slope, a, by plotting the logarithm of the proton transfer rate against the pK, as determined by the equilibrium acidity, for a series of compounds. From this plot, the approximate pKa of an unknown compound can be determined by comparison of the same type of compounds. 

The radical anion pathway (e-c-P-d-p Scheme 2) requires a rate-determining protonation after cyclization, i.e., a slow protonation of a hard oxyanion. However, such proton transfer rates are usually diffusion controlled, so this seems unlikely [32,33], On the other hand, the carbanion closure (e-P-d-c-p) portrayed in Scheme 4 requires a very reasonable suggestion that the ratedetermining step corresponds to protonation of the soft, weakly basic radical anion 42, prior to cyclization [32-35] this is the preferred mechanism. One must use caution, however, realizing that these conclusions are drawn for the particular set of substrates which were examined. In some cases, radical anion cyclization remains a viable option. 

Physically, dv appears as a broadening of the spectral lines. It has been found that the study of NMR band shapes provides a powerful tool for the measurement of proton-transfer rates through the determination of state lifetimes, related to St. Nuclei such as H and have been studied. This allows the simultaneous determination of different rates of proton exchange. NMR methods are particularly valuable for degenerate equilibria, for which AWJ. and AVj are useless. 

The ionic resistance of a polymer electrolyte membrane is an important parameter in determining the mobility of protons through the membrane and the corresponding voltage loss across the membrane. Currently, the most commonly used membranes in PEM fuel cells are Nafion membranes produced by DuPont. However, these membranes are limited to low-temperature uses (usually below 80°C) because membrane dehydration at high temperatures can lead to reduced water content and then a lower proton transfer rate, resulting in a significant decrease in conductivity. The relationship between conductivity and the diffusion coefficient of protons can be expressed by the Nemst-Einstein equation ... 

The time scale of the classical temperatine-jnmp experiment ( 1 qs) as originally pioneered by Eigen has been shortened to nanoseconds and very recently to approximately 5 ps using lasers. The classical temperatnre-jump experiment has found only limited application to biological systems, in spite of its great success in determining, for example, proton transfer rates or keto-enol isomerizations. An important reason for its limited apphcation to enzyme research, apart from experimental difficulties such as optical artifacts as a result of the temperature-jump, is the relatively small deviation from equihbrium AG = AH —... 

The rate of initial electron transfer from A,7V-dimethylaniline to [Fe(phen)3] + is diffusion-limited. This is followed by the rate-determining proton transfer from the radical cation to pyridine to give the deprotonated a-amino radical which is rapidly oxidized by a second equivalent of [Fe(phen)3] + to yield the product iminium ion. Kinetic isotope effects [kii/kjf) for the proton transfer were determined from the J3/tfo ratios of the products derived from p-substituted A-methyl-A-trideuteromethylanilines. The k /kx) value first increases and then decreases with increasing pAa of p-substituted A,A-dimethylaniline. Such a bell-shaped isotope effect profile is typical of proton-transfer reactions [82, 85]. The maximum kn/fco value is determined as 8.8 which is much larger than the corresponding value for the demethylation of the same substrate by cytochrome P-450 (2.6) [79]. 

Quantitative determination of proton-transfer rates to radical anion EGBs derived from carbonyl compounds (Sec. III.B.2) is problematic using voltammetric methods, since the protonated EGB is not undergoing further reduction at the potential of radical anion formation (cf. Sec. III.B.2). this may lead to reversibility of the proton transfer. 

As a consequence of the limitations just mentioned, attempts to characterize the kinetic basicity of preparatively used EGBs by determination of proton-transfer rates have mainly been done on the first-mentioned group of radical anions, particularly radical anions derived from azobenzenes, and the group of dianions derived from activated alkenes. At the same time, these type of measurements have been used to compare kinetic and thermodynamic acidities of weak organic acids. 

STEP 1 Add a proton. A rate-determining proton transfer from HI to the carbon-carbon double bond gives a 3° carbocation intermediate ... 

However, although PTR-MS is loosely based on estabhshed measurements of proton transfer rate coefficients these cannot be applied directly as an absolute method for quantification of an analyte because of the presence of the electric field in the drift mbe. For exothermic proton transfer, a reaction rate coefficient of 2 X 10 cm s is often used in PTR-MS to estimate trace analyte concentrations. However, the rate coefficients for proton transfer have been measured under thermal conditions (e.g., SIFT) and vary between 1 x 10" and 8 x 10 cm s. It is therefore necessary to resort to calibration proceditres using permeation mbes or calibrated mixtures of analytes at the operational field strength of the instrument to determine the absolute analyte concentration in a sample. 

The acid decomposition of alkyldithiocarbamates from parent amines with pA N < 10 occurs through dithiocarbamate anion and a zwitterion intermediate the specific acid catalysis rate constant = 2 3 a/( 3 + -2). Fast -protonation and rate-determining C-N breakdown is believed to account for the behaviour of the dithiocarbamic conjugate acid of EbisDTC anion whereas for that of GlyDTC the -protonation is slower than C-N breakdown and can benefit from the increased efficiency of intramolecular proton transfer (through a water molecule). 

A kinetic study of the acid-catalysed loss of alkoxide and thiolate ions from alkoxide and thiolate ion adducts, respectively, of benzylidene Meldrum s acid, methoxy-benzylidene Meldrum s acid, and thiomethoxybenzylidene Meldrum s acid has been reported. The reactions appear to be subject to general acid catalysis, although the catalytic effect of buffers is weak and the bulk of the reported data refers to H+ catalysis. a-Carbon protonation and, in some cases, protonation of one of the carbonyl oxygens to form an enol compete with alkoxide or thiolate ion expulsion. This scenario rendered the kinetic analysis more complex but allowed the determination of p/fa values and of proton-transfer rate constants at the a-carbon. In conjunction with the previously reported data on the nucleophilic addition of RO and RS ions to the same Meldmm s acid derivatives, rate constants for nucleophilic addition by the respective neutral alcohols and thiols could also be calculated. ... 

The resulting AH radical is more easily reduced than anthracene, and therefore is rapidly reduced and protonated again to yield AH2. The initial protonation is rate-determining for the overall two-electron transfer, and so both electron transfers are observed in a single voltanmietric wave, which may be shifted to more positive potentials by accelerating the protonation process, e.g. by elevating the concentration of phenol. 

If experimental values of the polarizability and/or the dipole moment of the neutral molecule are unavailable, as is the case for many molecules, then these quantities can be calculated from ab initio or density functional theory (DFT) quantum chemical calculations. Zhao and Zhang have provided a comprehensive evaluation of this approach by carrying out calculations on 78 hydrocarbons and 58 non-hydrocarbons [31], A quite modest level of theory (DFT with the B3LYP functional and a 6-31G(d,p) Gaussian basis set) gave polarizabilities and dipole moments which yielded good agreement with experiment (where such values were available). The calculated dipole moments and polarizabilities were then employed in ADO calculations to obtain thermal rate coefficients. For most molecules, the predicted proton transfer rate coefficient was within 25% of the value determined from SIFT measurements. 

Clearly the transmission is an important quantity to take into account for any quantitative analysis. In particular it is important to know how the transmission varies with miz for a given instrument. The transmission curve for a PTR-MS instrument can be determined in two ways. One option is to add selected compounds with different masses and known concentrations which are then detected following proton transfer. The relative ion signals from each compound can then be equated with the relative ion transmission values at the respective mJz values. However, this approach assumes no fragmentation and equal proton transfer rate coefficients. The latter issue can be avoided by separately calibrating the instrument for each of the compounds using one of the procedures discussed in Chapter 4. 

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