Organic Chemistry has evolved continuously as the backbone for the
sustainability of different disciplines such as medicinal chemistry, chemical biology,
biochemistry, biotechnology, material science, polymers, and nanotechnology. The
beauty of organic reactions lies in their unique structural framework, reactivity, and
selectivity, interesting stuff for molecular modelling research. However, theoretical
interpretations of organic reactions have not been able to keep pace with the everincreasing
efficiency of computational chemistry software along the last two decades.
This is probably due to the popular use of the Frontier Molecular Orbital (FMO) theory
to study the course of organic reactions during the last 40 years, in spite of its failure
and criticism in several cases. In 2016, Domingo proposed a new theory, called
“Molecular Electron Density Theory (MEDT)” to study molecular reactivity of
organic reactions, which is backed up by the use of quantum chemical tools. This
theory proposes the decisive role of electron density changes in the reactivity of
organic molecules, being opposed to FMO concepts. MEDT has been successfully
applied to rationalize the experimental outcome of several Diels-Alder reactions,
sigmatropic rearrangements, electrocyclic reactions, and [3+2] cycloaddition reactions.
MEDT covers the detailed analysis of Conceptual DFT (CDFT) indices, exploration of
the Potential Energy Surface (PES), calculation of the global electron density transfer
(GEDT), topological analysis of the Electron Localization Function (ELF) and
Quantum Theory of Atoms in Molecules (QTAIM), and Non-Covalent Interactions
(NCI) with the aid of molecular modelling software. MEDT correlates the changes in
electron density along a reaction path with the activation energies and establishes the
polar character associated with the reorganization of the molecular mechanism to reach
a meaningful insight into the reactivity of organic molecules. MEDT can be applied to
study the mechanism, reactivities and selectivities of organic reactions, particularly
those showing chemo-, regio-, and stereoselectivities in the synthesis of biologically
active products. This chapter aims to provide a detailed description of the basic
theoretical concepts covered by MEDT to design a precise computational model of an
organic reaction. Some applications of MEDT have also been illustrated in the
concluding section for ready reference.
Keywords: Bond Critical Points, Bonding Evolution Theory, Conceptual DFT,
Electron Density, Topology, Electron Localization Function, Global Electron
Density Transfer, Intrinsic Reaction Coordinate, Laplacian, Molecular Electron
Density Theory, Non-Covalent Interactions, Potential Energy Surface, Quantum
Theory of Atoms in Molecules, Transition States Structures.