Historically, Hammett constants have been extremely effective in describing the influence of substituents on chemical reactivity and other physical and chemical properties, whereas variables derived from quantum chemical calculations have generally been less effective. Taking the experimental pK(a)s of substituted anilines as a representative physicochemical property, five ab initio quantum chemical indices are compared for effectiveness as one-parameter regression descriptors for pK(a). All of the tested descriptors performed well for a set of 19 mono-, 13 di-, and 4 trisubstituted anilines, and two performed somewhat better than the traditional Hammett sigma constants. Among the calculated quantities, the best representation of the aniline pK(a)s is produced by the minimum average local ionization energy on the molecular surface.

Noncovalent interactions are predominantly electrostatic in nature.It follows that an effective tool for their investigation and elucidation is the electrostatic potential on the molecular surface. We have shown that a variety of condensed phase macroscopic properties can be expressed quantitatively in terms of certain site-specific and global statistical quantities that characterize the overall pattern of the surface potential. We are now extending this approach to interactions in biological systems. Several applications will be discussed, including initial qualitative studies of dioxins, a series of anticonvulsants and some tetracyclines, the nucleotide bases, and a recent quantitative treatment of the anti-HIV activities of three groups of reverse transcriptase inhibitors.

To help understand and predict nanotube interactions, the electrostatic potentials on both the outer and the inner surfaces of 10 single-walled model systems have been computed at the Hartree−Fock STO-5G//STO-3G level. All structures were optimized computationally. Both carbon and boron/nitrogen tubes were studied, including the open and closed (5,5) and the open (6,1), (7,1), and (8,1), plus fullerene for comparison. Hydrogen atoms were introduced at the ends of the open tubes, to satisfy the unfulfilled valencies. The surface potentials were characterized in terms of both site-specific and global properties: positive and negative extrema and average values, average deviation, positive and negative variances, and electrostatic balance. The all-carbon systems, the closed (5,5) and fullerene, are very weakly positive on most of the outer and all of the inner surfaces, the latter potentials being somewhat stronger. In contrast, the open carbon tubes with charge-donating hydrogens at the ends are slightly negative on the outer lateral surfaces and somewhat less so on the inner, except for the narrowest, the (6,1), which is positive inside. The boron/nitrogen tubes have much stronger and more variable surface potentials than do the carbon; there are characteristic patterns of positive and negative sites on the outer lateral surfaces, while the inner ones are markedly positive. A general feature of all of the systems studied, both carbon and boron/nitrogen, is that stronger potentials are associated with regions of higher curvature.

ABSTRACT:The electrostatic potentials and average local ionization energies computed on the molecular surfaces of four tetracyclines have been investigated with the objective of identifying common features as well as subtle differences that may be related to their biological activities. The four are the parent molecule tetracycline, chlortetracycline, oxytetracycline, and doxycyline. The calculations were carried out at the HF/STO-3G * //STO-3G * level. Our electrostatic potential results show that each molecule has a large negative region that extends along its lower portion, consistent with its ability to complex Ca 2+ and Mg 2+ ions. Although the surface electrostatic potentials of the four tetracyclines show many similarities, our statistical measure of local polarity allows us to label doxycycline as the one with the lowest degree of local polarity, consistent with its longer half-life in vivo. The regions in the tetracyclines with the most reactive electrons are the amide nitrogen lone pairs and certain carbons of the outermost rings.