Anesthetic activity and the electrostatic potential (revisited).

A survey of the fascinating history of anesthetics and the many critical findings that have improved our understanding of anesthetic activity is followed by an expanded analysis of the electrostatic potentials of 27 molecules and two noble gases with anesthetic activities ranging from high to totally inactive. We again find that an intermediate value for the internal charge separation (polarity) Π appears to be an important factor in anesthetic activity. Other electrostatic potential features that favor high anesthetic activity include the presence of at least one strongly positive site on the molecule and regions of weakly to moderately negative electrostatic potential. For 14 molecules with consistent anesthetic activity data, we find a reasonable multivariable correlation that reflects the above features and also includes a measure of molecular size, reflecting the polarizability. The commonalities found in the electrostatic potential data for the active anesthetics suggest that anesthetics interact via their positive and/or negative sites in noncovalent reversible interactions with target sites, perhaps in brain proteins.

The average local ionization energy as a tool for identifying reactive sites on defect-containing model graphene systems.

In a continuing effort to further explore the use of the average local ionization energy [Formula: see text] as a computational tool, we have investigated how well [Formula: see text] computed on molecular surfaces serves as a predictive tool for identifying the sites of the more reactive electrons in several nonplanar defect-containing model graphene systems, each containing one or more pentagons. They include corannulene (C20H10), two inverse Stone-Thrower-Wales defect-containing structures C26H12 and C42H16, and a nanotube cap model C22H6, whose end is formed by three fused pentagons. Coronene (C24H12) has been included as a reference planar defect-free graphene model. We have optimized the structures of these systems as well as several monohydrogenated derivatives at the B3PW91/6-31G* level, and have computed their I(r) on molecular surfaces corresponding to the 0.001 au, 0.003 au and 0.005 au contours of the electronic density. We find that (1) the convex sides of the interior carbons of the nonplanar models are more reactive than the concave sides, and (2) the magnitudes of the lowest I(r) surface minima (the I S, min) correlate well with the interaction energies for hydrogenation at these sites. These I S, min values decrease in magnitude as the nonplanarity of the site increases, consistent with earlier studies. A practical benefit of the use of I(r) is that a single calculation suffices to characterize the numerous sites on a large molecular system, such as graphene and defect-containing graphene models.