Hypervalency in Organic Crystals: A Case Study of the Oxicam Sulfonamide Group

Abstract

The theoretical charge density of the active pharmaceutical ingredient piroxicam (PXM) was evaluated through density functional theory with a localized basis set. To understand the electronic nature of the sulfur atom within the sulfonamide group, a highly ubiquitous functional group in pharmaceutical molecules, a theoretical charge density study was performed on PXM within the framework of Bader theory. Focus is on developing a topological description of the sulfur atom and its bonds within the sulfonamide group. It was found that sulfur d-orbitals do not participate in bonding. Instead, the existence of a strongly polarized ("ionic") bonding structure is found through a combined topological and natural bonding orbital analysis. This finding is in stark contrast to long-held theories of the bonding structure of organic sulfonamide and has important implications for the parametrization of calculations using classical approaches.

Topology vs. thermodynamics in chemical reactions: the instability of PH5

“…Through studies based on the QTAIM approach, the theory of ''hypervalence'' was proven to incorrectly describe the electronic structure of different compounds, such as H 2 SO 4 , PF 5 and sulphonamide groups within oxicams. [12][13][14] In these studies it was shown that there is no expansion of the valence shell with violation of the octet rule as previously proposed by Pauling. 3,11 Nevertheless the ''hypervalency'' theory is still widely evoked in many different chemistry text books, being the easiest way to give an apparently convincing description of chemical bonding, which does not require any knowledge about the quantum mechanics and electronic structure, as for Bader's theory.…”

Revisiting a Historical Concept by Using Quantum Crystallography: Are Phosphate, Sulfate and Perchlorate Anions Hypervalent?

“…For the most part, the concept of hypervalency has been studied based on theoretical wavefunctions . However, quantum crystallographic techniques allow experimental access to wavefunctions and charge densities .…”

Computational Modeling of 2D Materials under High Pressure and Their Chemical Bonding: Silicene as Possible Field-Effect Transistor

“…Thus, an analysis of VSCC for a bonded Si atom can give us an initial indication about the nature of its bonding. If a maximum CP sits along a bond path, − it can be described as a bond maximum (BM), whereas all other maximum CPs are nonbonding maxima (NBM). − As expected, all Si atoms in the silicene monolayer have a BM along their corresponding bond paths (light pink balls in Figure a), but there are no NBMs perpendicular to the xy -plane indicating the residual lone pair of the nonhybridized p z -orbital. This initial analysis confirms a distorted sp 3 geometry instead of distorted sp 2 .…”