Monica C. Concha

σ-hole bonding between like atoms; a fallacy of atomic charges

AbstractCovalently bonded atoms, at least in Groups V–VII, may have regions of both positive and negative electrostatic potentials on their surfaces. The positive regions tend to be along the extensions of the bonds to these atoms; the origin of this can be explained in terms of the σ-hole concept. It is thus possible for such an atom in one molecule to interact electrostatically with its counterpart in a second, identical molecule, forming a highly directional noncovalent bond. Several examples are presented and discussed. Such “like-like” interactions could not be understood in terms of atomic charges assigned by any of the usual procedures, which view a bonded atom as being entirely positive or negative. FigureCalculated electrostatic potential on the surface of SCl2. The sulfur is in the foreground, the chlorines are at the back. Color ranges (kcal mol−1): purple negative, blue between 0 and 8, green between 8 and 15, yellow between 15 and 20, red more positive than 20. Note that the sulfur has regions of both positive (red) and negative (purple) electrostatic potential

Halogen bond tunability I: the effects of aromatic fluorine substitution on the strengths of halogen-bonding interactions involving chlorine, bromine, and iodine

AbstractIn the past several years, halogen bonds have been shown to be relevant in crystal engineering and biomedical applications. One of the reasons for the utility of these types of noncovalent interactions in the development of, for example, pharmaceutical ligands is that their strengths and geometric properties are very tunable. That is, substitution of atoms or chemical groups in the vicinity of a halogen can have a very strong effect on the strength of the halogen bond. In this study we investigate halogen-bonding interactions involving aromatically-bound halogens (Cl, Br, and I) and a carbonyl oxygen. The properties of these halogen bonds are modulated by substitution of aromatic hydrogens with fluorines, which are very electronegative. It is found that these types of substitutions have dramatic effects on the strengths of the halogen bonds, leading to interactions that can be up to 100% stronger. Very good correlations are obtained between the interaction energies and the magnitudes of the positive electrostatic potentials (σ-holes) on the halogens. Interestingly, it is seen that the substitution of fluorines in systems containing smaller halogens results in electrostatic potentials resembling those of systems with larger halogens, with correspondingly stronger interaction energies. It is also shown that aromatic fluorine substitutions affect the optimal geometries of the halogen-bonded complexes, often as the result of secondary interactions. FigureSchematic models of halogen bonding complexes studied in this work

Br···O Complexes as Probes of Factors Affecting Halogen Bonding: Interactions of Bromobenzenes and Bromopyrimidines with Acetone.

Halogen bonding is a unique type of noncovalent binding phenomenon in which a halogen atom interacts attractively with an electronegative atom such as oxygen or nitrogen. These types of interactions have been the subject of many recent investigations because of their potential in the development of new materials and pharmaceutical compounds. Recently, it was observed that most halogen bonding interactions in biological contexts involve close contacts between a halogen bound to an aromatic ring and a carbonyl oxygen on a proteins backbone structure. In this work we investigate interactions of substituted bromobenzenes and bromopyrimidines with acetone to ascertain the effects of various substituents upon the strengths of these interactions. It was found that replacement of ring hydrogens in these systems has dramatic effects upon the interaction strengths of the resulting complexes, which have interaction energies between -1.80 and -7.11 kcal/mol. Examination of the electrostatic potentials of the substituted bromobenzene and bromopyrimidine monomers indicates that the addition of substituents has a large influence upon the most positive electrostatic potential on the surface of the interacting bromine and thus modulates these halogen bonding interactions. Results obtained using the symmetry-adapted perturbation theory (SAPT) interaction energy decomposition procedure also indicate that electrostatic interactions play the key role in these halogen bonding interactions. These results have important implications in drug design and crystal engineering. Halogen bonds have been a subject of great interest in these fields because of their unique noncovalent bonding characteristics.

An electrostatic interaction correction for improved crystal density prediction

Recent work by others has shown that the densities of C,H,N,O molecular crystals are, in many instances, given quite well by the formula M/Vm, in which M is the molecular mass and Vm is the volume of the isolated gas phase molecule that is enclosed by the 0.001 au contour of its electronic density. About 41% of the predictions were in error by less than 0.030 g/cm3, and 63% by less than 0.050 g/cm3. However, this leaves more than one-third of the compounds with errors greater than 0.050 g/cm3, or in some instances, 0.100 g/cm3. This may indicate that intermolecular interactions within the crystal are not being adequately taken into account in these cases. Accordingly, the effectiveness of including a second term that reflects the strengths, variabilities and degree of balance of the positive and negative electrostatic potentials computed on the surfaces of the isolated molecules, has been included. The database was selected such that half of the densities predicted by M/Vm had errors larger than 0.050 g/cm3. The introduction of the electrostatic interaction correction produced a marked improvement. Overall, 78% of the predictions are within 0.050 g/cm3 of experiment, with 50% within 0.030 g/cm3. Among those that originally all had errors larger than 0.050 g/cm3, 67% are now less. The reasons for the better performance of the dual-variable formula are analysed.

Blue shifts vs red shifts in σ-hole bonding

Abstractσ-Hole bonding is a noncovalent interaction between a region of positive electrostatic potential on the outer surface of a Group V, VI, or VII covalently-bonded atom (a σ-hole) and a region of negative potential on another molecule, e.g., a lone pair of a Lewis base. We have investigated computationally the occurrence of increased vibration frequencies (blue shifts) and bond shortening vs decreased frequencies (red shifts) and bond lengthening for the covalent bonds to the atoms having the σ-holes (the σ-hole donors). Both are possible, depending upon the properties of the donor and the acceptor. Our results are consistent with models that were developed earlier by Hermansson and by Qian and Krimm in relation to blue vs red shifting in hydrogen bond formation. These models invoke the derivatives of the permanent and the induced dipole moments of the donor molecule. FigureComputed electrostatic potential on the molecular surface of Cl-NO2. Color ranges, in kcal mol−1, are: red, greater than 25; yellow, between 10 and 25; green, between 0 and 10; blue, between −4 and 0; purple, more negative than −4. The chlorine is facing the viewer, to the right. Note the yellow region of positive potential on the outer side of the chlorine, along the extension of the N–Cl bond. The blue region shows the sides of the chlorine to have negative potentials. The calculations were at the B3PW91/6–31G(d,p) level.

Links between surface electrostatic potentials of energetic molecules, impact sensitivities and C–NO2/N–NO2 bond dissociation energies

Earlier work has shown a link—not necessarily a causal relationship—between the impact sensitivities of energetic compounds and the electrostatic potentials on their molecular surfaces. The latter are anomalous in that the positive regions are strikingly dominant, contrary to what is typical of organic molecules. In this work, we show that the presence of several electron-withdrawing NO2 groups and/or aza nitrogens (common features of energetic systems), which is the reason for the anomalously positive surface potentials, also weakens the C–NO2 and/or N–NO2 bonds. Thus, insofar as these are trigger linkages, the rupture of which is a key step in detonation initiation, an approximate correlation between the features of the surface potentials and sensitivity may be expected. A group of eight nitramines is used to demonstrate this. Work is in progress to elucidate the basis for the surface potential–sensitivity link when a non-trigger-linkage mechanism is operative.

Halogen bond tunability II: the varying roles of electrostatic and dispersion contributions to attraction in halogen bonds

AbstractIn a previous study we investigated the effects of aromatic fluorine substitution on the strengths of the halogen bonds in halobenzene…acetone complexes (halo = chloro, bromo, and iodo). In this work, we have examined the origins of these halogen bonds (excluding the iodo systems), more specifically, the relative contributions of electrostatic and dispersion forces in these interactions and how these contributions change when halogen σ-holes are modified. These studies have been carried out using density functional symmetry adapted perturbation theory (DFT-SAPT) and through analyses of intermolecular correlation energies and molecular electrostatic potentials. It is found that electrostatic and dispersion contributions to attraction in halogen bonds vary from complex to complex, but are generally quite similar in magnitude. Not surprisingly, increasing the size and positive nature of a halogen’s σ-hole dramatically enhances the strength of the electrostatic component of the halogen bonding interaction. Not so obviously, halogens with larger, more positive σ-holes tend to exhibit weaker dispersion interactions, which is attributable to the lower local polarizabilities of the larger σ-holes. FigureIn this work we investigate the roles played by electrostatic and dispersion forces in stabilizing halogen bonding interactions.

Sensitivity and the available free space per molecule in the unit cell

AbstractInvoking the known link between impact sensitivity and compressibility, we have expanded upon an earlier preliminary study of the significance of the available free space per molecule in the unit cell, ΔV. We express ΔV as Veff – Vint, where Veff corresponds to zero free space, Veff = molecular mass/density. Vint is the intrinsic gas phase molecular volume. We demonstrate that Vint can be appropriately defined as the volume enclosed by the 0.003 au contour of the molecule’s electronic density; this produces packing coefficients that have the range and average value found crystallographically. Measured impact sensitivities show an overall tendency to increase as ΔV becomes larger. For nitramines, the dependence upon ΔV is rather weak; we interpret this as indicating that a single overriding factor dominates their initiation mechanism, e.g., N-NO2 rupture. (An analogous situation appears to hold for many organic azides.) In addition to the conceptual significance of identifying ΔV as a factor in impact sensitivity, the present results allow rough estimates of relative sensitivities that are not known. FigureImpact sensitivities, h50, plotted against available free space per molecule in the unit cell, ΔV, for 7 nitramines (left) and 14 non-nitramines (right)

Computational investigation of the structures and relative stabilities of amino/nitro derivatives of ethylene

Eight amino and/or nitro derivatives of ethylene have been investigated computationally at the density functional B3P86/631 + G** level. The molecular geometries and relative stabilities reflect the varying roles of ‘push‐pull’ electronic delocalization and intramolecular hydrogen bonding. The same two factors affect, to varying extents, the computed C‐NO2 and C‐NH2 bond dissociation energies, which are also presented, as are the heats of formation, vaporization and sublimation of the three diaminodinitroethylenes. The potential of the latter as energetic compounds is briefly discussed. q 1998 Elsevier Science B.V. All rights reserved

The reaction force : Three key points along an intrinsic reaction coordinate

The concept of the reaction force is presented and discussed in detail. For typical processes with energy barriers, it has a universal form which defines three key points along an intrinsic reaction coordinate: the force minimum, zero and maximum. We suggest that the resulting four zones be interpreted as involving preparation of reactants in the first, transition to products in the second and third, and relaxation in the fourth. This general picture is supported by the distinctive patterns of the variations in relevant electronic properties. Two important points that are brought out by the reaction force are that (a) the traditional activation energy comprises two separate contributions, and (b) the transition state corresponds to a balance between the driving and the retarding forces.