Excluding hyperconjugation from the Z conformational preference and investigating its origin: formic acid and beyond

Abstract

Carboxylic acids, esters, secondary amides, and related molecules share a thermodynamic preference for the Z arrangement of their X[double bond, length as m-dash]C-Y-R moiety. This conformational predisposition is known as the Z effect and its most common explanation invokes the hyperconjugation from a Y lone pair to the σCX* orbital. In this work, we present clear topological evidence that hyperconjugation is not responsible for the Z preference. Diverse tools defined within the quantum chemical topology framework (such as, for example, atomic and electron localization function populations or the interacting quantum atoms energy decomposition) were used to analyse the evolution of formic acid from the E conformer towards the Z conformation. The results highlight the important role of the π resonance in the barrier between conformers and they also indicate that the hyperconjugative interaction lacks a leading role. Concretely, in an X[double bond, length as m-dash]C-Y-R structure, the XR interaction seems to be the key to understanding the preference for the Z arrangement of the moiety. Interestingly, our proposed explanation can be extended to a wide range of molecules presenting the same conformational preference, such as proteins or peptide nucleic acids.

Rotational Spectroscopy of 2‐Furoic Acid and Its Dimer: Conformational Distribution and Double Proton Tunneling

“…The current results are common for most carboxylic acids, especially where there are no strong intramolecular H‐bonds or close contacts to stabilize the trans‐ COOH conformers. The cis ‐COOH conformational preference has been called the Z effect, although its origin is still being debated [37,38] . To map out the different non‐covalent intramolecular interactions in FA and THFA, noncovalent interaction (NCI) analyses [39] were performed and the results are provided in Figure 3.…”

“…The cis-COOH conformational preference has been called the Z effect, although its origin is still being debated. [37,38] To map out the different non-covalent intramolecular interactions in FA and THFA, noncovalent interaction (NCI) analyses [39] were performed and the results are provided in Figure 3. Clearly, the much stronger intramolecular OH•••O ring interaction in THFA I and II than in FA III is responsible for the strong preference of trans-COOH configuration in THFA.…”

Electron Density Analysis on the Alpha Acidity of Nitriles

“…We The variation experienced by the most significant BCP properties for the compounds in this series is summarized in Table 3. C  -R bonds display an opposite behavior when we compare compounds enclosing electron donors (6), where the C  -R bond is slightly weaker in the anion, and electron acceptors (5), where it gets stronger. According to these properties, fluorine (see compound 10) also behaves as an electron donor.…”

“…In this context, we acknowledge the very good services provided by RM in Chemistry [3,4]. Even, different possibilities to supply resonance structures with more reliable and quantitative weighting coefficients obtained making use of modern tools of electron density topological analysis can be explored [5]. Nevertheless, since the publication of the seminal paper by Wiberg and Laidig on the electronic origin of the esther and amide resonance [6], it is not possible to deny that a large amount of inconsistencies between RM predictions and computed evolutions of electron densities have been reported [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26].…”

Fermi and Coulomb correlation effects upon the interacting quantum atoms energy partition

“…These conditions have enabled QTAIM to address many different chemical processes and systems on the same footing [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] . In similar fashion, the IQA approach has recently been applied to the study of transition metal-ligand interactions [25][26][27] , bonding between electronegative atoms [28] , the transferability of different species inside oligopeptides [29] , the formation of water clusters [30,31] and the conformational arrangement of carboxylic acids [32] .…”