Boris Galabov

In this work, we comparatively assess the utility of electrostatic potential at nuclei (V_n) and several frequently used atomic partial charge schemes for describing hydrogen-bond basicity. This is accomplished with a total of 114 examples across four classes of molecules: ketones, ethers, nitriles, and substituted pyridine derivatives. Density functional theory calculations at the CPCM//PBE0-D3/def2-TZVPP level were employed to evaluate reactivity descriptors for the most basic site in each molecule. The effectiveness of the descriptors was assessed through their correlation with experimental basicity data. Three widely used partial charge models—Hirshfeld, CM5, and NPA—were considered. Strong correlations between both V_n and partial charges with basicity were observed across all four molecular classes. Notably, the electrostatic potential at the nucleus (V_n) consistently exhibits stronger correlations with the experimental pK_HB values than the partial charge models, highlighting its robustness as a quantitatively reliable descriptor of basicity across diverse organic systems. Both descriptors display inherent system dependence, and meaningful correlations with basicity are observed primarily within individual classes of compounds.

Atomic partial charges have been described as proxy variables, vague conceptor noumenon (in contrast to phenomenon). Still, these quantities find wide application in chemistry, physics, and biology research. In this study, we assess the physical relevance of the partial charges concept by examining the correspondence between theoretically derived charges and experimentally measured vibrational frequency shifts of the methanol OH stretching mode Δν(OH)_exp induced by hydrogen bonding with variously substituted nitriles. The Δν(OH)_exp shifts in 4-fluorophenol upon hydrogen bonding with mono- and disubstituted pyridines have been shown to correlate nearly perfectly with an alternative atom-centered theoretical parameter─the electrostatic potential at the basic nitrogen in the respective monomers. We explore the correspondence between the Δν(OH)_exp shifts for methanol complexes with nitriles and the partial charges at the CN nitrogen derived from different models. The theoretical charges are evaluated using several frequently used density functionals─B3LYP, ωB97X-D, PBE, PBE0, M06, and M06-2X combined with the aug-cc-pVTZ basis set. The effects of the basis set choice were also considered. Applications of the different density functionals revealed remarkable consistencies for both the magnitude of estimated charges and the strength of correlations with the Δν(OH)_exp shifts. Altogether, the results obtained provide clear support for the physical significance of the partial charges concept.

Density functional theory is employed in understanding the reactivity in the TiCl ₄ catalyzed Friedel–Crafts benzylation of benzene with substituted benzyl chlorides in nitromethane solvent.

Recent advances in quantifying nucleophilic reactivities in chemical reactions and intermolecular interactions of aromatic molecules are reviewed. This survey covers experimental (IR frequency shifts induced by hydrogen bonding) and theoretical (modeling of potential energy surfaces, atomic charges, molecular electrostatic potential) approaches in characterizing chemical reactivity. Recent advances in software developments assisting the evaluation of the reactive sites for electrophilic aromatic substitution are briefly discussed.

Theoretical computations of charge density parameters are juxtaposed to experimental spectroscopic shifts induced by hydrogen bonding for a series of 21 substituted in the aromatic ring ethyl and methyl benzoates. Strong correlations between atomic charges at the proton accepting atom and the shifts of methanol O–H frequencies are established. Hirshfeld, Charge Model 5 (CM5), and natural population analysis (NPA) atomic charges are evaluated using ωB97X‐D/6‐311++G(3df,2pd) and MP2/6‐311++G(3df,2pd) computations. The results obtained reveal the power of hydrogen bond measurements in characterizing the variations of electron densities at the proton accepting center within a series of structurally related molecules. The limits of application of the approach are outlined.

The reactivity trends for two basic organic reactions – addition of bromine to a CC double bond in alkenes and electrophilic aromatic benzylation of alkyl‐ and halobenzenes – are rationalized using both experimental and theoretical quantities. Literature kinetic data are employed. The shifts of phenol O–H stretching frequency upon π‐hydrogen bonding (Δ ν (OH) _exp ) with the nucleophilic reactants are shown to provide a quantitative measure of the reactivity for the considered reactions. Very good correlations between Δ ν (OH) _exp and theoretically estimated charge density parameters (atomic charges and shifts of molecular electrostatic potential) show that the O–H frequency shifts reflect the variations of nucleophilic properties in the reaction centers upon structural changes. The Δ ν (OH) _exp shifts perform much better in quantifying reactivity trends than usually employed experimental quantities, such as gas‐phase basicities and proton affinities.

The shifts of phenol O-H stretching vibration frequencies [Δν(OH)_exp] upon π-hydrogen bonding with aromatic compounds is proposed as a spectroscopic probe of the reactivity of aromatic substrates towards electrophiles. A single infrared spectrum reflecting the Δν(OH)_exp shift for an aromatic species in a reference solvent (CCl₄ in this study) provides a good estimate of reactivity. The methodology is applied in rationalizing reactivity trends for the BF₃ catalyzed nitration by methylnitrate in nitromethane of 20 aromatic reactants, including benzene, 11 methylbenzenes, several monoalkyl benzenes, the four halobenzenes, and anisole. Literature kinetic data¹ are employed in the analysis. Very good correlations between relative rates of nitration and Δν(OH)_exp are obtained. The approach is best applied to reactions, where the initial interactions between the reactants controls the rates. A new theoretical quantity, the shifts (with respect to benzene) of the molecular electrostatic potential at 1.5 Å over the centroid of the aromatic ring [ΔV(1.5)] is defined and shown to provide a good description of substituent effects on properties of the aromatic species. B3LYP density functional and MP2 ab initio methods combined with the 6-311++G(3df,2pd) basis set are employed in evaluating the ΔV(1.5) values.

The performance of four frequently employed population analysis methods is assessed by comparisons with experimentally derived properties of monosubstituted benzene derivatives. The analysis is based on the expected dependence between site reactivities and electron densities at the respective ring carbon atoms. The correspondence between charges obtained from Mulliken, NPA, Hirshfeld, and QTAIM approaches and the σ⁰_m and σ⁰_p aromatic substituent constants is examined. The series of molecules investigated includes benzene and 18 monosubstituted derivatives. The atomic charges are derived using the B3LYP, ωB97X-D density functional and MP2 MO methods combined with the 6-311++G(3df,2pd) basis set. A quantitative correspondence between Hirshfeld charges and σ⁰ constants is established. Application of Møller–Plesset second-order perturbation theory (MP2) wave functions appears to be essential in obtaining a more realistic electron density distribution. NPA and QTAIM charges provide in most cases a satisfactory description of the substituent effects. The net transfer of charges between substituents and the aromatic ring is assessed.

The potential energy surfaces for the S_N2 reactions of allyl and propyl chlorides with 21 anionic and neutral nucleophiles was studied by using ωB97X‐D/6‐311++G(3df,2pd) computations. The “allylic effect” on S_N2 barriers was observed for all reactions, and compared with propyl substrates, the energy barriers differed by −0.2 to −4.5 kcal mol⁻¹ in the gas phase. Strong correlations of the S_N2 net activation barriers with cation affinities, proton affinities, and electrostatic potentials at nuclei demonstrated the powerful influence of electrostatic interactions on these reactions. For the reactions of anionic (but not neutral) nucleophiles with allyl chloride, some of the incoming negative charge (0.2–18 %) migrated into the carbon chains, which would provide secondary stabilization of the S_N2 transition states. Activation strain analysis provided additional insight into the allylic effect by showing that the energy of geometric distortion for the reactants to reach the S_N2 transition state was smaller for each allylic reaction than for its propyl analogue. In many cases, the interaction energies between the substrate and nucleophile in this analysis were more favorable for propyl chloride reactions, but this compensation did not overcome the predominant strain energy effect.

Density functional theory computations with the B3LYP/6‐311++G(2df,2p) method and IR spectroscopy are employed in investigating the properties of twenty π‐hydrogen bonded complexes between substituted phenols and hexamethylbenzene. All complexes possess T‐shaped structures. The methyl hyperconjugative effects on interactions energies and OH stretching frequencies are estimated via comparisons with previously reported theoretical and experimental results for analogous phenol complexes with benzene. The theoretical computations provide excellent quantitative predictions of the OH stretching frequency shifts (Δν_OH) resulting from the hydrogen bonding. The Δν_OH shifts in the hexamethylbenzene complexes are approximately twice as large as the corresponding shifts for the benzene complexes. Hirshfeld charges, electrostatic potential at nuclei values, and molecular electrostatic potential maps are employed in gaining insights into the mechanisms of methyl hyperconjugative effects on complex formation.