Intramolecular Natural Energy Decomposition Analysis: Applications to the Rational Design of Foldamers

Abstract

We describe an intramolecular version of the natural energy decomposition analysis (NEDA), with the aim of evaluating interactions between molecular fragments across covalent bonds. The electronic energy in intramolecular natural energy decomposition analysis (INEDA) is divided into electrical, core, and charge transfer components. The INEDA method describes the fragments using the nonfragmented electronic density, and, therefore, there are no limitations in how to choose the boundary orbital. We used INEDA to evaluate the interaction energies that give origin to barriers of rotation around C C (C C ) and N C (N C ) bonds in arylamide-foldamer building blocks. We found that differences of barrier height between models with different ortho-aryl substituents stem from charge transfer and core interactions. In three-center hydrogen-bond (H-bond) models with an NH proton donor H-bound to two electronegative ortho-aryl substituents, the interaction energy of the three-center system is larger than in either of the two-center H-bond subsystem alone, indicating an increase of overall rigidity. The combination of INEDA and NEDA allows the evaluation of intermolecular and intramolecular interactions using a consistent theoretical framework. © 2018 Wiley Periodicals, Inc.

Intramolecular Repulsion Visible Through the Electrostatic Potential in Disulfides: Analysis via Varying Iso-density Envelopes

“…Therefore, energy decomposition analyses (EDA) and symmetry-adapted perturbation theory (SAPT) approaches have been used extensively to study intermolecular interactions 8−11 but have only occasionally extended to intramolecular interactions. 12 In this study, we will be presenting an approach that does not require separating a molecule into parts. For further reading on EDA and SAPT, we also refer to the references given in the cited papers.…”

“…In this contribution, we are focusing upon intramolecular interactions, which are difficult to quantify because unlike intermolecular interactions, there is only one molecular species involved which cannot be straightforwardly separated into interacting fragments. Therefore, energy decomposition analyses (EDA) and symmetry-adapted perturbation theory (SAPT) approaches have been used extensively to study intermolecular interactions − but have only occasionally extended to intramolecular interactions . In this study, we will be presenting an approach that does not require separating a molecule into parts.…”

A journey toward the heaven of chemical fidelity of intermolecular force fields

“…Various energy decomposition analysis (EDA) techniques are currently being used in theoretical chemistry to get practical insights into the intermolecular and intramolecular noncovalent interaction energies. [38][39][40] One of the most commonly used techniques in non-covalent force field development is symmetry-adapted perturbation theory (SAPT) and its extension to DFT known as SAPT (DFT). 41 Few recent reviews have outlined the theory of SAPT and its applicability in force field development.…”

“…The newly developed quantum chemical methods that can deconvolute the total intermolecular interaction energy into various physically significant components helped researchers in formulating new force fields. Various energy decomposition analysis (EDA) techniques are currently being used in theoretical chemistry to get practical insights into the intermolecular and intramolecular non‐covalent interaction energies 38–40 . One of the most commonly used techniques in non‐covalent force field development is symmetry‐adapted perturbation theory (SAPT) and its extension to DFT known as SAPT (DFT) 41 .…”