Tore Brinck

Statistically-based interaction indices derived from molecular surface electrostatic potentials: a general interaction properties function (GIPF)

Abstract A number of physical properties determined primarily by non-covalent interactions can be expressed quantitatively in terms of molecular surface area plus three statistically-based quantities obtained from the surface electrostatic potential: Π, a measure of local polarity; σ 2 tot , which indicates the variability of the potential on the surface; v , a measure of the balance between positive and negative regions. In the applications discussed, these quantities and the area are obtained through ab initio computations. The various specific relationships can be summarized through a general interaction properties function (GIPF), property = f (area, Π, σ 2 tot , v ) the functional form of which depends upon the property of interest.

Correlations between molecular electrostatic potentials and some experimentally-based indices of reactivity

Abstract The key role that electrostatics plays in molecular reactive behavior is demonstrated in this work, which surveys and further explores correlations that we found between the molecular electrostatic potential V(r) calculated by an ab initio SCF-MO approach (a gas-phase property) and experimentally-based indices of reactivity (derived from solution studies). In our relationships involving negative V(r), we find in all cases that spatial minima (Vmin) provide correlations of higher quality than surface minima (VS, min ). Relationships between Vmin and the hydrogenbond-acceptor parameter β, and VS,max and the hydrogen-bond-donor parameter α, confirm the physical validity of the empirically-derived solvatochromic parameters α and β. Correlations between the Vmin of NH2-X molecules and the substituent constants σI, and σI + σR (when σR>0) for the substituents X show how electrostatic properties reflect the electron-attracting tendencies of substituent groups. Whereas good relationships exist between the pKa, values of some limited groups of molecules and their conjugate base Vmin, we find that the average local ionization energy Ī(r) is better suited as a general measure of aqueous acidity.

Quantitative determination of the total local polarity (charge separation) in molecules

We introduce a polarity index Π that is proposed as a measure of the charge separation in a molecule. Π can be viewed as the average deviation of the electrostatic potential on the surface of the molecule. It permits a quantitative assessment of total local polarity, even in a molecule that has zero dipole moment. In support of our formulation of Π, we show that it is related to an empirical polarity-polarizability parameter and also to the dielectric constant.

Radial behavior of the average local ionization energies of atoms

The radial behavior of the average local ionization energy I(r) has been investigated for the atoms He–Kr, using ab initio Hartree–Fock atomic wave functions. I(r) is found to decrease in a stepwise manner with the inflection points serving effectively to define boundaries between electronic shells. There is a good inverse correlation between polarizability and the ionization energy in the outermost region of the atom, suggesting that I(r) may be a meaningful measure of local polarizabilities in atoms and molecules.

Applications of calculated local surface ionization energies to chemical reactivity

Abstract A recently introduced property, the average local ionization energy I ( r ), is discussed in relation to chemical reactivity. I ( r ), is defined within the framework of self-consistent-field molecular-orbital (SCF-MO) theory and is interpreted as the average energy required to remove an electron from any point r in the space of a molecule. A survey of applications of ab initio SCF I ( r ), computed on molecular surfaces defined by the 0.002 e bohr −3 contour of the electronic density is presented. The positions at which the surface I ( r ), has its lowest values ( I S,min ) are indicative of sites most reactive toward electrophiles. An excellent correlation was found between the ring carbon ( I S,min ) of monosubstituted benzenes and the Hammett constants. For a large variety of carbon, oxygen and nitrogen acids, we have shown that good correlations exist between p K a and the conjugate base ( I S, min ) Finally, a good relationship is demonstrated to exist between the conjugate base ( I S,min ) of substituted acetic acids and the inductive substituent constants σ i (which were derived from the p K a values). ( I S, min ) found near the C-C bond midpoints of the three-membered ring portions of saturated strained hydrocarbons are interpreted as reflecting the σ aromaticity of these rings.

The use of the electrostatic potential at the molecular surface in recognition interactions: Dibenzo- p -dioxins and related systems

An ab initio self-consistent-field molecular orbital approach was used to compute the electrostatic potentials of dibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), two analogues of the latter, and two isomeric benzoflavones on a three-dimensional molecular surface corresponding to the contour of constant electronic density equal to 0.002 electrons/bohr3. The results are discussed in relation to the biological activities of the respective molecules. It is shown that the electrostatic potential graphically depicted on the molecular surface is well suited for the study of recognition interactions, such as are believed to be involved in the initial receptor-mediated step leading to toxicity in the dibenzo-p-dioxins. The surface potential has the advantage of clearly showing steric features that may play a role in understanding the recognition process being investigated.

Some proposed criteria for simulants in supercritical systems

Abstract There is a need for identifying realistic simulants of toxic compounds, to be used in investigating the possible disposal of the latter through oxidation in supercritical water. We have computed several molecular properties, related to size and to interaction tendency, for a group of three toxic molecules and five proposed simulants; the calculations were carried out at the ab initio HF/STO-5G ∗ //HF/STO-3G ∗ level. Two of these properties, the molecular volume and the sum of the variances of the positive and negative electrostatic potentials on the molecular surface, were used to quantitatively predict supercritical solubility. On the basis of these factors, 1,5-dichloropentane is a very promising simulant for sulfur mustard.