A Quantitative Scale for the Extent of Conjugation of the Amide Bond. Amidity Percentage as a Chemical Driving Force

Abstract

The amide bond may be considered as one of the most important chemical building blocks, playing an important role not only in living organisms but in organic chemistry as well. The exact description and precise quantification of the amide bond strength is difficult, requiring a particular type of theoretical investigation. The present paper suggests a novel, yet simple, method toward quantifying amide bond strength on a linear scale, defined as the "amidity scale". This is achieved using the computed enthalpy of hydrogenation (DeltaHH2) of the compound examined. In the present conceptual work, the DeltaHH2 value for dimethylacetamide is used to define perfect amidic character (amidity=+100%), while azaadamantane-2-on represents complete absence of amidic character (amidity=0%). The component DeltaHH2 values were computed at differing levels of theory, providing a computational and quasi-"method-independent" measure of amidity. A total of 29 well-known amides were examined to demonstrate the "scoring" accuracy of this methodology. For the compounds examined, a correlation has been made between the computed amidity percentage and their common COSNAR resonance energy values, proton affinities, and reactivity in a nucleophilic addition reaction. Selected chemical reactions were also studied. It has been shown that the change of the amidity value, during acyl transfer reactions, represents a thermodynamic driving force for the reaction.

Energy Managements in the Chemical and Biochemical World, as It may be Understood from the Systems Chemistry Point of View

“…In simpler cases, where the number and the types of the σ and the π-bonds do not change the resonance energy is turned out to be a reliable measure of the overall relative energetic of the process. In order to measure it, a novel concept and therefore a novel discipline was defined, wherein molecules are [10] carbonylicity, [13] olefinicity, [15] each of which in a surrogate thermodynamic function, contributing to the characterization of the mechanisms by which Nature fine-tunes and stores reaction energies to attain hyper-efficiency.…”

“…The ∆H H2 (AM) value for dimethylacetamide (19) is used to define perfect amidic character (Eq. 8.; AM % = +100%), while azaadamantane-2-on (20) represents complete absence of amidic character (AM % = 0%) [10]. The amidicity value is transformed to the resonance enthalpy [H RE (AM); Eq.…”

“…Note that the two set of values represent different scales, than the amidicity is a special section of the carbonylicity scale. Amidicity percentage for example is able to predict whether a transamidation reaction is taking place under the given conditions or not [10][11][12] and it can also point out the most reactive amide bond of a molecule. It was shown that carbonyl groups exhibiting a lower amidicity value are more reactive toward nucleophilic reagents (like amines) than carbonyl groups having a larger value.…”

“…17. In the following part, this new methodology is applied on the field of peptide chemistry, especially for the peptide bond formation [10]. ∆AM (%) = AM%(product) -AM%(starting material)…”

“…Taking into consideration of all of these criteria, it seems nearly impossible to model even a simple acylation reaction. It was demonstrated earlier that the computation of one or a few, easily and quickly computable quantum mechanical (QM) descriptors, such as aromaticity [6][7][8][9], amidicity [10][11][12], carbonylicity, [13,14] olefinicity, [15][16][17] and others can predict properly and somewhat quantitatively certain reactivity and selectivity issues. The global and complex view of these descriptors was defined as the concept of systems chemistry [18], wherein molecules are described as strategically located functional components within molecular frameworks, 'valued' at more than their components' sum, acting in unison to effect efficient energy management.…”