Critical deprotonation model

Examples of models that have been proposed in an attempt to link the above steps into a coherent mechanism include the membrane model, the secondary structure model, the critical deprotonation model, the percolation model, the critical ionization model, and the stone wall model, to mention but a few. In the following sections, we briefly review the aspects of these models. 

The choice of cluster model size is critical. It is essential that the cluster model be neutral and not subjected to optimization constraints. Both these restrictions have been shown to lead to artifactual behavior. Small clusters cannot be used to investigate concentration dependence, and if this dependence is to be considered, a larger model must be used. Similarly, a cluster should not be so small that it artificially constrains the spatial extent of the adsorbate complex or transition state. The acidity of the cluster—quantified by the deprotonation energy—is found to change as a function of cluster size. The deprotonation energy of a 3T atom cluster terminated with hydro-... 

Protonation State. At optimal pH for enzymatic activity ( 5-6) [101, 102, 105], the Asp dyad can in principle exist in three protonation states, a deprotonated, a mono-protonated or a doubly protonated form. Because hydrogen atoms cffe invisible in the X-ray structure, evidence for a specific protonation state must be inferred indirectly by spectroscopic or titration measurements. Up to now, the existence of the doubly protonated, neutral form hfree enzyme. The existence of the deprotonated, doubly negative form is supported by a recent NMR study [102] at pH 6. However, this study has been subjected to criticism [106] and it is not conclusive. Our ab initio simulations of this form show that the Asp dyad is unstable even in the ps timesccde because of the strong Asp-Asp repulsion, which turns out to be -t-30 kcal/mol as estimated with a simple electrostatic model [100]). Thus, our calculations do not support the existence of this form. 

Bale) and Divisek based a quantitative re-evaluation of critically selected data on the equilibrium or rest potentials of the so-called y-NiOOH a-Ni(OH)2 systems on the assumption that these systems consist of homogeneous solid solutions with the end-members Ni(OH)2 and Ni02 xH20. Whereas the Ni(ll) component is considered to be completely undissociated, the Ni(IV) component fully deprotonates to give and Ni02 (x-1)H20 0H. While these authors convincingly describe the redox behaviour of Ni(ll, IV) oxide hydroxides, the stoichiometric and structural characterisation of the hypothetical end-members is still lacking. So the thermodynamic quantities derived from this model were not accepted for the present review. 

How to determine protonation modes in reaction centers of enzymes is a very important issue in biochemistry [1-8], The protonation is obviously related to the catalytic activities of active side chains of amino residues the protonation and deprotonation to side chains of charged acids such as Glu, Asp, Arg, Lys, and His yield Brpnsted-Lowry acids and bases, catalyzing various chemical reactions. Also in metalloenzymes and these model systems, protonations are often critical parts of the reaction mechanisms. For instance, in (1) the water-oxidizing center (WOC) in photosystem II [9-14], (2) the Mn dimeric center in catalase [15-21], and (3) the Mn center in Mn superoxide dismutases (MnSODs)[22,23], the following reactions proceed, respectively ... 

The picture is more complicated when a molecule has more than one ioniz-able center. Some drugs have two, three, and even four such centers, and some are amphoteric. The two acidic drugs shown in Figure 4.9 have two acidic proton sites each, the model for these types of molecules is H2SO4. The relative values of the pKg s reflect which site will deprotonate first. The larger the Kg, the stronger the acid is the smaller the pKj, the weaker the acid. Consequently, the site with the smaller pKg value will dissociate first. To ensure that the molecules remain deprotonated and neutral for extraction, the smaller pKg is the critical one. To extract phenobarbital, a pH of 5.2 is needed, whereas an extraction of salicylic acid requires a more acidic pH of 2.5. Similar arguments apply for dibasic molecules. 

---