Protonation simulative solution

Alternatively, suppose you want to determine which heteroatom in a molecule is protonated first as pH is lowered. Or conversely, you may want to know which is the most acidic proton in a compound (even if it is a hydrocarbon, for example). In such cases, you can obtain optimized geometries for the parent molecule Z and its conjugate acid ZH+ (or conjugate base Z ) for each site of proton attachment or removal. Simply take the differences in total energy (obtained quantum mechanically), E(ZH+)-E(Z) [or E(Z ) E(Z)], and you have a theoretical assessment of the relative gas-phase acidity (basicity). (The electronic energy of a proton is zero because it has no electron.) Of course, these energy differences do not account for solvation, but if the two protonation (or deprotonation) sites are very similar, the vacuum results may suffice. Alternatively, you can turn on implicit (continuum) solvation in your calculation and obtain energies of the simulated solution species. 

Ab initio MD studies were carried out to help understand the elementary processes that occur at the metal-solution interface [77]. At temperatures less than 300 K, acetic acid decomposed on Pd, leaving an adsorbed acetate intermediate along with a proton in solution. Above 300 K, however, surface acetate recombines with a proton in solution to form acetic acid. Acetic acid is then displaced from the surface by water. Once the acetic acid finds its way into solution, it redissociates to form acetate and protons in solution that are now more efficiently stabilized by water. A series of snapshots that portray some of the images from the simulation is shown in Figure 13. These results were further corroborated with a more conventional transition-state search approach, which showed that desorption of acetate from the surface was an activated process. The process is quite complicated, involving the simultaneous breaking of the acetate-metal bond, the formation of an... 

Figure 13 Snapshots from an ab initio MD simulation (T = 300 K) of acetic acid on Pd(l 11) in the presence of water, (a) Acetate forms at the surface along with an H5O2+ intermediate adjacent to the acetate layer (b) acetate species and protons react at the surface to form acetic acid (c) water displaces acetic acid from the surface (d) water adsorbs to the surface (e) acetic acid rotates in solution toward the water layer (f) acetic acid dissociates in solution to form acetate anions and protons in solution. (Adapted from Ref. [77].)...

It is obvious that so many variables make a simulative solution a heroic endeavor unless some of them can be obtained by independent experiments. Considering the fact that any application of the proton pulse in an enzymic system must deal with appreciable buffer capacity of the protein or substrates, I shall demonstrate the general procedure of a simulative solution for a buffered solution. 

Figure 50. Visualization of the buffer proton cycle through the simulative solution of the indicator response to a proton pulse. A simulative solution for a three-component system, 8-hydroxypyrene-1,3,6-trisulfonate (lOOpJW) Bromo Cresol Green (50jiAf) and ImM imi-dazol (pH 5.91). The rate constants of the partial reactions are listed in Table VIII. (a) Free...

In molecular mechanics and molecular dynamics studies of proteins, assig-ment of standard, non-dynamical ionization states of protein titratable groups is a common practice. This assumption seems to be well justified because proton exchange times between protein and solution usually far exceed the time range of the MD simulations. We investigated to what extent the assumed protonation state of a protein influences its molecular dynamics trajectory, and how often our titration algorithm predicted ionization states identical to those imposed on the groups, when applied to a set of structures derived from a molecular dynamics trajectory [34]. As a model we took the bovine... 

The second separation method involves n.O.e. experiments in combination with non-selective relaxation-rate measurements. One example concerns the orientation of the anomeric hydroxyl group of molecule 2 in Me2SO solution. By measuring nonselective spin-lattice relaxation-rat s and n.0.e. values for OH-1, H-1, H-2, H-3, and H-4, and solving the system of Eq. 13, the various py values were calculated. Using these and the correlation time, t, obtained by C relaxation measurements, the various interproton distances were calculated. The distances between the ring protons of 2, as well as the computer-simulated values for the H-l,OH and H-2,OH distances was commensurate with a dihedral angle of 60 30° for the H-l-C-l-OH array, as had also been deduced by the deuterium-substitution method mentioned earlier. 

In recent years, a class of methods has been developed for molecular dynamics simulations to be performed with an external pH parameter, like temperature or pressure [18, 43, 44, 70], These methods treat the solution as an infinite proton bath, and are thus referred to as constant pH molecular dynamics (PHMD). In PHMD, conformational dynamics of a protein is sampled simultaneously with the protonation states as a function of pH. As a result, protein dielectric response to the... 

Borgis D, Hynes JT (1991) Molecular-dynamics simulation for a model nonadiabatic proton transfer reaction in solution. J Chem Phys 94 3619-3628... 

The CH cation 1, protonated methane, is the parent of hypercoordinated carbocations containing a five coordinated carbon atom. It is elusive in solution and has not been observed by NMR spectroscopy but gas-phase infrared investigations have shown its fluxional structure which has been proven by ab initio molecular dynamic simulation.18... 

Meanwhile, computational methods have reached a level of sophistication that makes them an important complement to experimental work. These methods take into account the inhomogeneities of the bilayer, and present molecular details contrary to the continuum models like the classical solubility-diffusion model. The first solutes for which permeation through (polymeric) membranes was described using MD simulations were small molecules like methane and helium [128]. Soon after this, the passage of biologically more interesting molecules like water and protons [129,130] and sodium and chloride ions [131] over lipid membranes was considered. We will come back to this later in this section. 

The 3H chemical shifts, coupling constants, temperature coefficients, exchange rates and inter-residual ROEs of the hydroxyl protons of various synthetic type II trisaccharides, analogues of (3-D-Galp-(l - 4)-p-D-GlcpNAc-(l - 2)-a-D-Man-(l - 0)(CH2)7CH3, were reported and interpreted,8 assisted with molecular dynamic simulations, to deduce key information on the conformational behavior of these important molecules in aqueous solution. 

With the RPA model it has been possible to simulate many sets of CPA/alumina data mentioned in the literature [18], with the same set of unadjusted parameters (PZC, K and K2, OH density). Since pH shifts in the presence and the absence of CPA adsorption on alumina [23] and PTA adsorption on silica [19] are similar, it can be concluded that metal and proton transfer are independent in these systems. Thus the pH shift model can be used in concert with the RPA model not only to predict metal uptake, but also to compute final pH from the initial pH of the contacting solutions [18,28],... 

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