Water molecular electrostatic potential

Electrostatic isopotential (EIP) minima186 often identify sites and ease of metabolism by epoxide hydrase, an enzyme responsible for the conversion of epoxides to diols by the addition of water. Molecular electrostatic potential energy calculations also are probably the best means of identifying positions of epoxidation and, possibly, metabolism in general. In the case of aflatoxin B for example, EIP maxima and minima calculated by the CNDO/2 method all lie close to the known sites of metabolism and, in particular, the formation of the carcinogenic 2,3-epoxide is readily predicted.189... 

To make an accurate FEP calculation, a good description of the system is required. This means that the parameters for the chosen force field must reproduce the dynamic behaviour of both species correctly. A realistic description of the environment, e.g. size of water box, and the treatment of the solute-solvent interaction energy is also required. The majority of the parameters can usually be taken from the standard atom types of a force field. The electrostatic description of the species at both ends of the perturbation is, however, the key to a good simulation of many systems. This is also the part that usually requires tailoring to the system of interest. Most force fields require atom centered charges obtained by fitting to the molecular electrostatic potential (MEP), usually over the van der Waals surface. Most authors in the studies discussed above used RHF/6-31G or higher methods to obtain the MEP. 

A speculative proposal was made thirty years ago by Schmid and Krenmayr77, namely that a nitrosyl ion solvated, but not covalently bonded, by a water molecule may be involved in these systems. This hypothesis was investigated theoretically in 1984 by Nguyen and Hegarty78 who carried out ab initio SCF calculations of structure and properties employing the minimal STO-3G basis set, a split-valence basis set plus polarization functions. Optimized geometries of six planar and two nonplanar forms were studied for the nitrosoacidium ion. The lowest minimum of molecular electrostatic potential... 

The quality of the force fields is assessed by comparing the molecular electrostatic potentials, in the vicinity of the molecule, based on the force field and quantum chemical reference calculations. The electrostatic potential is the most suitable observable for such a comparison since it enters directly in the PE potential operator. To probe the electrostatic potential, a grid was constructed around the water molecule, see Ref. [6] for details concerning the construction of this grid. The electrostatic potential, due to the multipoles, at the flth grid point was calculated according to... 

Figure 3.1 The RMSD of the molecular electrostatic potential due to the multipoles of a water molecule as a function of the distance from the molecular van der Waals surface. The distance from the surface is given as the factor scaling the van der Waals radii. The RMSD is in a.u. Results from Ref. [6].

Figure 3.36. Molecular electrostatic potential for water. Positive potential superimposed on right surrounding hydrogens. Negative potential on left surrounding oxygen.

Luque and Orozco (Orozco et al., 1994 1995 Luque et al., 1994) have supplemented MNDO, PM3, and AMI versions of PCM with a careful analysis of all factors involved in the calculation (i.e. scaling factors for semiempirical molecular electrostatic potentials, cavity radii for neutral, cationic and anionic solutes) using a variety of methods (Monte Carlo, QM/MM, and FEP simulations), to check the conclusions. Parametrization has been mainly determined for water solutions, but it has been recently extended to chloroform (Luque et al. (1995)) and CCU.In the remarkable number of publications of this group, only partially quoted here, there is a good wealth of information useful for further studies. 

Figure 4 Molecular electrostatic potential of water molecule, represented as a contour plot with intervals of 0.025 au. Red contours indicate regions of negative potential and blue represents positive, (a-b) Potential generated from full electron density, in and perpendicular to the molecular plane, respectively (c d) potential generated from point charges situated at three atomic positions (e-f) potential generated from point charges and dipoles situated at three atomic positions. (See color plate at end of chapter.)...

These studies indicate that the sequence of duplexes and the accessibility of bases are the dominant factors that determine the binding pattern of the labile metal ions to DNA, and that the molecular electrostatic potential further affects the metal binding. Of importance for this chapter is that in all of the reported solution and solid-state structures, the 3d transition metal ions coordinate to the N7 of a G nucleobase and complete their octahedral coordination sphere with water molecules or with phosphate groups from adjacent nucleotides within the duplexes. Thus they do not form direct interstrand bridges. 

Whereas Eq.(5.58) serves for the determination of local interactions between cluster models of a zeolite and interacting molecules, analytical expressions are needed for the interaction potential if one wishes to compute vibrational frequencies for purpose of comparison with experiment or if the potentials are to be used in Monte Carlo or molecular-dynamics simulation calculations. Sauer and co-workers developed such analytical potentials for the water-silica interaction system. The method makes use of the molecular electrostatic potential (MEP) maps and the functional form of EPEN/2 (Empirical Potential based on interactions of Electrons and Nuclei). EPEN/2 potential functions consist of a point-charge interaction term and... 

In the previous section the adsorption concept was entered of adsorption molecular electrostatic potential and it was remarked that the first and rather acceptable approximation could be obtained by its help for constructing hydrate cover of any type of solid surface. However, within the framework of notions on MESP it is also possible to predict some other important properties of adsorption complexes of polar molecules on silica surface. Thus, it was shown in [ 137] that hydrophility of the hydroxylated surface of silicion dioxide could be explained by availability of local minima of the p potential within the subsurface region created by the atoms of surface functional groups and solid substrate. Here in water this approach was applied to explain adsorption properties of completely chlorinated, aminated, and hydrogenated surfaces [128]. 

Fig. 14.14. Molecular electrostatic potential (MEP) represents the electrostatic interaction of the positive unit diarge (probe) with molecule A. (a) the coordinate system and the vectors used in Eq. (14.34) (b) the equipotential surfaces V (r) for the water molecule (c) another way of showing the MEP one computes V/ ir) on the molecular surface (defined somehow). In more expensive books this is shown by coloring the surface using a certain convention color <-> MEP. Such information is usefiil, because the role of the MEP is to predict the site of attack of another molecule, which is able to approach the surface. MEP in a.u. means the interaction of a proton with the molecule. It is seen that the proton will attack the region of the oxygen atom, while an attack of CI would happen from the side of the hydrogens.

Despite these fairly accurate dipole moments, DFT molecular electrostatic potential fitted charges are most likely not appropriate for simple additive molecular mechanical force fields. For these types of force fields to be accurate in aqueous environments, a priori polarization of molecules is required. The DFT charges are too gas phase-like, and initial tests indicate that the charges are too small and their electrostatic interactions with prepolarized water molecules (such as the SPC, TIP3P, and TIP4P water models ) are too weak. On a brighter note, as nonadditive, polarizable, force fields become more popular, the ability to accurately reproduce gas phase dipole moments will be extremely desirable. 

The reactivity modification or the reaction rate control of functional groups covalently bound to a polyelectrolyte is critically dependent on the strength of the electrostatic potential at the boundary between the polymer skeleton and the water phase ( molecular surface ). This dependence is due to the covalent bonding of the functional groups which fixes the reaction sites to the molecular surface of the polyelectrolyte. Thus, the surface potential of the polyion plays a decisive role in the quantitative interpretation of the reactivity modification on the molecular surface. 

Haeberlein, M., Brinck, T. Prediction of water-octanol partition coefficients using theoretical descriptors derived from the molecular surface area and the electrostatic potential. J. Chem. Soc. 

Brinck, T., J. S. Murray, and P. Politzer. 1993. Octanol/Water Partition Coefficients Expressed in Terms of Solute Molecular Surface Areas and Electrostatic Potentials. J. Org. Chem. 58, 7070. 

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