Molecular electrostatic potential features

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]. 

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

The applications of NN to solvent extraction, reported in section 16.4.6.2., suffer from an essential limitation in that they do not apply to processes of quantum nature therefore they are not able to describe metal complexes in extraction systems on the microscopic level. In fact, the networks can describe only the pure state of simplest quantum systems, without superposition of states. Neural networks that indirectly take into account quantum effects have already been applied to chemical problems. For example, the combination of quantum mechanical molecular electrostatic potential surfaces with neural networks makes it possible to predict the bonding energy for bioactive molecules with enzyme targets. Computational NN were employed to identify the quantum mechanical features of the... 

As an alternative to describing molecules by their structural features (substruc-tural elements, functional groups) and similarly to CoMFA, this approach uses field points to describe the van der Waals and electrostatic minima and maxima that surround molecules and compares these field points. The field points that are used are derived from molecular electrostatic potential descriptors. The XED model is marketed by Cresset Biomolecular and forms the basis for the proprietary virtual screening technology FieldPrint [95]. 

In this section, we present and discuss some of the computed results that we have obtained for Groups IV-VII. These include relevant features of molecular electrostatic potentials (Table 6.1) and key properties of a-hole-bonded complexes (Table 6.2). All of the data in these tables are taken from our own work, some of it unpublished, so as to ensure consistency in procedure. 

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. 

Gasteiger, J., Li, X., Rudolph, C.J., Sadowski, J. and Zupan, J. (1994a). Representation of Molecular Electrostatic Potentials by Topological Feature Maps. J.Am.Chem.Soc., 116,4608—4620. 

Some General Features of Atomic and Molecular Electrostatic Potentials... 

In contrast, certain other parameters that are computed from analyses of molecular shape-encoded space-filling and electrostatic potential features can also yield good models of activity however, their computation requires detailed conformational analyses. 

Because all of these electronic aspects of aromaticity are ultimately derived from the electron distribution, we might ask whether representations of electron density reveal any special features in aromatic compounds. The electron density of the IT electrons can be mapped through the MESP (molecular electrostatic potential, see Section 1.4.5). The MESP perpendicular to the ring is completely symmetrical for benzene, as would be expected for a delocalized structure and is maximal at about... 

Murray, Politzer, and their co-workers have developed several descriptors based on features of the molecular electrostatic potential surface (EPS) that can be used to characterize a variety of chemical and physical properties, including pK s [26,199,231]. In studies of the acidities of substituted azoles and anilines they showed that values of the most negative surface potentials (Vrma) and the minimum local ionization energy on the molecular surface (Is,min) showed strong correlations (r 0.97) with the pK s of these compounds. Later, Ma et al. [27] found that Is,jjn and several other EPS descriptors provided good models of the pK variations in substituted phenols and benzoic acids. Sakai and co-workers [232] have shown that Vmin yields an excellent fit (r = 0.996) for the aqueous pK s of a set of 22 amines. These studies demonstrate that features of the molecular electrostatic potential surfaces of acids can offer useful guides for pK, estimatioa... 

Several workers have employed features of the molecular electrostatic potential surface to study the pK s of amines. Nagy, Novak, and Aszasz [340] found good linear correlations between the pK s of pyridines, anilines, and aliphatic amines and the minima of the electrostatic potentials for these compounds. They used the CNDO/2 method [341] as well as a bond-increment method with data from Perrin s 1972 compilation [342] for their study. Using the bond-increment approach they found the following relationships ... 

Clark and co-workers [493] have used DFT and MP2 computations along with natural bond orbital (NBO) analysis and features of the molecular electrostatic potential (MEP) surface (EPS) to explain why DMSO is such a good solvent. The MEP study revealed a number of strongly positive and negative regions that encourage intermolecular interactions, while the NBO analysis showed that the supposed S=0 double bond in (0113)280 is actually a coordinate covalent S+ 0 single bond. 

We stress again that decompositions and corrections not based on the use of physical observables have a degree of arbitrariness, and that different definitions may be accepted, when employed in a coherent way. With this point in view, a CP correction to Ees could be acceptable. This proposal introduces, however, some features in the interpretation of the reaction act and potentially destroys the use of molecular electrostatic potentials as indicators of chemical reactivity. 

If one takes the bond length pattern (Table 4.1) as a topological criterion for radialene-Uke character, one may find it to some extent in the geometry of coran-nulene (154). This is supported by calculations of the molecular electrostatic potential, which show five minima at the bonds exocychc to the central ring and another five at the peripheral double bonds of the six-membered rings [115]. These structural features, with rather localized double bonds, are also reflected in fullerene Cgg, which consists of three corannulene substructures. Notably, the chemical reactivity of Cgg is dominated by addition reactions at a 6-6 bond (connecting two six-membered rings) [116], and it fits into this picture that the first addition of dichlorocarbene to corannulene also occurs at a radial (6-6) C=C bond [117]. 

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