Charge and energy redistribution in sulfonamides undergoing conformational changes. Hybridization as a controlling influence over conformer stability

Abstract

The redistribution of charge and electronic kinetic energy was studied during rotation about the S—N bonds of sulfonamide and fluorosulfonamide. The rotational potentials and electronic topological features of both compounds were evaluated at the HF/6-3 1G* level of theory and their electron densities partitioned into atomic contributions using FASTINT, an updated version of the PROAIM program. The results indicate that the stability of each rotamer is strongly dependent upon the hybridization of the sulfonamide nitrogen. The hybridization of the nitrogen was determined by examination of the positions and magnitudes of the electrostatic and Laplacian minima in the nonbonded region of the sulfonamide nitrogen atom. Independent assessments of hybridization were made using nitrogen pyramidalization altitudes. The rotational barriers in these compounds were found to arise mainly from energetic penalties resulting from adding electrons to already electron-rich sulfonyl oxygens while removing electron density from other more electronegative atoms. The fluorine-substituted analogue provided an example in which the sulfur and oxygen atoms were much less electron rich, causing an enhancement of the nitrogen rehybridization effects. The extent of covalent bonding between pertinent pairs of atoms in sulfonamide and fluorosulfonamide was assessed throughout the rotational pathway using the BONDER program. In contrast with much existing dogma, all of these findings were consistent with the same general model of charge and energy flow that has been shown to determine the internal rotational barriers in amides. Key words: sulfonamide, electron density analysis, rotational barrier, hybridization, atoms-in-molecules calculations.

Rotaxane or Pseudorotaxane? Effects of Small Structural Variations on the Deslipping Kinetics of Rotaxanes with Stopper Groups of Intermediate Size

“…40 kJ/ mol. [27] This difference is in line with the 1 H NMR spectra of, for example, dimethyl acetamide and dimethyl methanesulfonamide. While the former shows slow exchange of the amide methyl groups, resulting in two separate signals for both, the latter gives only one signal, due to an exchange that is fast on the NMR timescale.…”

Quantum Dots of Indium Nitrides

“…This process, in which N atoms play a role of electron charge sinks, is revealed as "belts" of electron charge filling the molecular volume and "embracing" the molecular surface (roughly, in the regions neighbouring nitrogen atoms). The above results obtained by the first-principle many body quantum theoretical computations is in an excellent agreement with well-known experimental observations that demonstrate a charge-redistribution role of nitrogen atoms via hybridization of their AOs as a leading factor of bonding and stability of both inorganic and organic nitrogen-containing molecules [73,74].…”

Experiment stands corrected: accurate prediction of the aqueous pKavalues of sulfonamide drugs using equilibrium bond lengths

“…Now that we have presented the results of model construction and validation, we may take this opportunity to analyse the nature of the AIBL-p K a relationships derived here, starting with the Pr-BSA series we label “ S1 ”. Breneman and Weber60 have previously studied the charge and energy redistribution of sulfonamide (HSO 2 NH 2 ) and fluorosulfonamide (FSO 2 NH 2 ) molecules as they undergo conformational change. At a modest level of theory [HF/6-31G(d)], the authors analyzed the charge and energy of the sulfur atom and amine group of these two species during rotation around each of their interlinking S–N bond.…”