Molecular electrostatic potentials MEPs

Bonaccorsi ct al. [204 defined for the first time the molecular electrostatic potential (MEP), wdicli is dearly tfie most important and most used property (Figure 2-125c. The clcctro.static potential helps to identify molecular regions that arc significant for the reactivity of compounds. Furthermore, the MEP is decisive for the formation of protein-ligand complexes. Detailed information is given in Ref [205]. 

In the present work, we shall investigate the problem of the amount of correlation accounted for in the DF formalism by comparing the molecular electrostatic potentials (MEPs) and dipole moments of CO and N2O calculated by DF and ab initio methods. It is indeed well known that the calculated dipole moment rf these compounds is critically dependent on the level of theory implemented and, in particular, that introduction of correlation is essential for an accurate prediction [13,14]. As the MEP property reflects reliably the partial charges distribution on the atoms of the molecule, it is expected that the MEP will exhibit a similar dependence and that its gross features correlate with the changes in the value of dipole moment when switching from one level of theory to the other. Such a behavior has indeed been reported recently by Luque et al. [15], but their study is limited to the ab initio method and we found it worthwhile to extend it to the DF formalism. Finally, the proton affinity and the site of protonation of N2O, as calculated by both DF and ab initio methods, will be reported. 

The stereoelectronic features produce actions at a distance by the agency of the recognition forces they create. These forces are the hydrophobic effect, and the capacity to enter ionic bonds, van der Waals interactions and H-bonding interactions. The most convenient and informative assessment of such recognition forces is afforded by computahon in the form of MIFs, e.g. lipophilicity fields, hydrophobicity fields, molecular electrostatic potentials (MEPs) and H-bonding fields (see Chapter 6) [7-10]. 

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. 

Physicochemical properties rather than reactivities were also explored. Molecular electrostatic potential (MEP) was calculated for the [l,2,4]triazolo[4,3- ]pyridine fragment 23, according to the CHELPG algorithm. This afforded a prediction of its H-bond acceptor ability in view of the synthesis of p38 MAP kinase inhibitors <2005JME5728>. Tautomerism was also examined for compound 24, also postulated as two possible acyclic structures. The ab initio self-consistent field (SCF)-calculated energies support 24a as the most stable tautomer <1999MRC493>. 

Note that recently Ayers and coworkers have shown how the Molecular Electrostatic Potential (MEP)... 

A (truncated) multipole expansion is a computationally convenient single-center formalism that allows one to quantitatively compute die degree to which a positive or negative test charge is attracted to or repelled by die molecule that is being represented by the multipole expansion. This quantity, die molecular electrostatic potential (MEP), can be computed exactly for any position r as... 

From a wave function, one can also calculate the molecular electrostatic potential (MEP), which is an energy of attraction or repulsion experienced by a hypothetical unit charge as it moves in the vicinity of a molecule (54). The MEP gives clues to how one molecule looks to another as they approach. Hence, MEPs can be studied to reveal how two reactants might approach each other. 

In the last series of azapentalenes (the less experimentally known) we have studied bimanes (248-251) [189, 190] and mesoionic derivatives 222-246. Only the last compound 256, being a polymorph of dinitrogen, has been studied much [191-201], We have calculated (Fig. 7) the molecular electrostatic potentials (MEPs) of compounds 222 and 256 [202],... 

Fig. 7 Molecular electrostatic potentials (MEP) of compounds 252 (left) and 256 (right). Yellow and brown parts correspond to positive and negative regions, respectively...

In this work the use of molecular electrostatic potential (MEP) maps for similarity studies is reviewed in light of the latest results. First, methods of obtaining MEP maps is overviewed. The methodology, reliability and the efficiency of calculations based on semi-empirical as well as ab initio methods are discussed in detail. Point-charge models and multipole expansion methods which provide MEP maps of satisfactory quality are evaluated critically. Later on, similarity indices of various kinds are analyzed, compared and examples of their use are shown. Finally, the last section lists and summarizes software packages capable of calculating MEP map based similarity indices. 

The molecular electrostatic potential (MEP) is a rigorously defined quantum mechanical property. The electrostatic potential (EP) at a point r in the... 

The symbol V is often associated with the electrical potential in the literature, but U is employed here so as not to conflict with the volume descriptor. Another aspect of chemical reactivity involves the molecular electrostatic potential (MEP). The MEP is the interaction energy between a unit point charge and the molecular charge distribution produced by the electrons and nuclei. The electrostatic potential, U r), at a point, r, is defined by Eq. [13]. 

The descriptors developed to characterize the substrate chemotypes are obtained from a mixture of molecular orbital calculations and GRID probe-pharmacophore recognition. Molecular orbital calculations to compute the substrate s electron density distribution are the first to be performed. All atom charges are determined using the AMI Hamiltonian. Then the computed charges are used to derive a 3D pharmacophore based on the molecular electrostatic potential (MEP) around the substrate molecules. 

Methods to Reproduce the Molecular Electrostatic Potential (MEP). The electrostatic potential surrounding the molecule that is created by the nuclear and electronic charge distribution of the molecule is a dominant feature in molecular recognition. Williams reviews (42) methods to calculate charge models to accurately represent the MEP as calculated by ab initio methods by use of large basis sets. The choice between models (monopole, dipole, quadrapole, bond dipole, etc.. Fig. 3.12) depends on the accuracy with which one desires to reproduce the MEP. This desire has to be balanced by the increased complexity of the model and its resulting computational costs when implemented in molecular mechanics. 

A general method, proposed by Politzer and coworkers, to estimate physico-chemical properties depending on noncovalent interactions [Brinck et ai, 1993 Murray et al., 1993 Politzer etal., 1993 Murray et al., 1994]. This is based on molecular surface area in conjunction with some statistically-based quantities related to the - molecular electrostatic potential (MEP) at the - molecular surface. The electron isodensity contour surface [0.001 a.u. contour of Q(r)j is taken as the molecular surface model. 

Molecular interaction fields obtained by calculating electrostatic interaction energy Eel between probe and target in each grid point. Besides the - molecular electrostatic potential (MEP), the most common energy function for electrostatic interactions is the Coulomb potential energy function defined as ... 

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