Characterization of Heterocyclic Rings through Quantum Chemical Topology

Abstract

Five-membered rings are found in a myriad of molecules important in a wide range of areas such as catalysis, nutrition, and drug and agrochemical design. Systematic insight into their largely unexplored chemical space benefits from first principle calculations presented here. This study comprehensively investigates a grand total of 764 different rings, all geometry optimized at the B3LYP/6-311+G(2d,p) level, from the perspective of Quantum Chemical Topology (QCT). For the first time, a 3D space of local topological properties was introduced, in order to characterize rings compactly. This space is called RCP space, after the so-called ring critical point. This space is analogous to BCP space, named after the bond critical point, which compactly and successfully characterizes a chemical bond. The relative positions of the rings in RCP space are determined by the nature of the ring scaffold, such as the heteroatoms within the ring or the number of π-bonds. The summed atomic QCT charges of the five ring atoms revealed five features (number and type of heteroatom, number of π-bonds, substituent and substitution site) that dictate a ring's net charge. Each feature independently contributes toward a ring's net charge. Each substituent has its own distinct and systematic effect on the ring's net charge, irrespective of the ring scaffold. Therefore, this work proves the possibility of designing a ring with specific properties by fine-tuning it through manipulation of these five features.

A topological assessment of the electronic structure of mesoionic compounds

“…NNCS and NSS were comparable to pyrrole and thiophene, respectively, in relation to ρ RCP and ∇ 2 ρ RCP ; NOO was very similar to furan with respect to ∇ 2 ρ RCP , but ρ RCP mean value was about 7% smaller than its aromatic analogue. These results agree with the previous study on the effect of the heteroatom on the RCP variables . Nevertheless, the mesoionic ring ellipticities were much larger than the aromatic reference compounds.…”

“…Electron density, Laplacian, and Ellipticity in the RCPs were analyzed. The mean values for the properties for each ring type are shown in Table ; the individual values for the mesoionic compounds are shown in Supporting Information Tables S1–S3 and for the reference aromatic compounds in Table S4 in the Supporting Information section.…”

“…Quantities such as |V|/G, | λ 1 |/ λ 3 and the delocalization index ( δ A , B ) also give some insight into the nature of chemical interactions. Finally, second‐order saddle points, called ring critical points (RCP), are found inside the cyclic structures and their properties are also used to characterize the ring structures …”

Theoretical study of electron-attracting ability of the nitro group: classical and reverse substituent effects

“…Another fruitful field of research seems to be comparison of the cSAR characteristics of the substituent with quantum topological molecular descriptors of the substituents [44,45] and of the transmitting moiety (ring) [46].…”

Characterization of Local Aromaticity in Polycyclic Conjugated Hydrocarbons Based on Anisotropy of π‐Electron Density

“…[45][46][47] It is worth noting that successful application of the pelectron density anisotropy (despite its seeming simplicity) to explain aromatic character in non-equilibrium distorted benzene and heterocyclic compounds is a surprising finding because in principle, any changes in the molecular symmetry or the atom types around the RCP should strongly affect the electron density and its topological properties at the RCP. [48,49] In the other word, the isotropical or anisotropical distribution of 1 p on the planes parallel to the molecular ring are correctly preserved for above mentioned systems, despite a noticeable polarization in the p-electron density distribution caused by the geometrical distortions and the presence of heteroatoms in molecular rings.…”