A Quantum Theory of Atoms-in-Molecules Perspective and DFT Study of Two Natural Products: Trans-Communic Acid and Imbricatolic Acid

2017 ◽  
Vol 70 (3) ◽  
pp. 328 ◽  
Author(s):  
Sarvesh Kumar Pandey ◽  
Mohammad Faheem Khan ◽  
Shikha Awasthi ◽  
Reetu Sangwan ◽  
Sudha Jain

The topological features of the charge densities, ρ(r), and the chemical reactivity of two most biologically relevant and chemically interesting scaffold systems i.e. trans-communic acid and imbricatolic acid have been determined using density functional theory. To identify, characterize, and quantify efficiently, the non-covalent interactions of the atoms in the molecules have been investigated quantitatively using Bader's quantum theory of atoms-in-molecules (QTAIM) technique. The bond path is shown to persist for a range of weak H···H as well as C···H internuclear distances (in the range of 2.0–3.0 Å). These interactions exhibit all the hallmarks of a closed-shell weak interaction. To get insights into both systems, chemical reactivity descriptors, such as HOMO–LUMO, ionization potential, and chemical hardness, have been calculated and used to probe the relative stability and chemical reactivity. Some other useful information is also obtained with the help of several other electronic parameters, which are closely related to the chemical reactivity and reaction paths of the products investigated. Trans-communic acid seems to be chemically more sensitive when compared with imbricatolic acid due to its experimentally observed higher half-maximal inhibitory concentration (bioactivity parameter) value, which is in accordance with its higher chemical reactivity as theoretically predicted using density functional theory-based reactivity index. The quantum chemical calculations have also been performed in solution using different solvents, and the relative order of their structural and electronic properties as well as QTAIM-based parameters show patterns similar to those observed in gas phase only. This study further exemplifies the use and successful application of the bond path concept and the quantum theory of atoms-in-molecules.

2017 ◽  
Vol 17 (11) ◽  
pp. 5845-5857 ◽  
Author(s):  
Marcos A. P. Martins ◽  
Leticia V. Rodrigues ◽  
Alexandre R. Meyer ◽  
Clarissa P. Frizzo ◽  
Manfredo Hörner ◽  
...  

2021 ◽  
Author(s):  
David Dohan

The present article is directed at the chem- ical community. It aims to convey the ba- sic concepts and breadth of applications: the current status and trends of approximation methods (local density and generalized gra- dient approximations, hybrid methods) and the new light which DFT has been shedding on important concepts like electronegativity, hardness, and chemical reactivity index.


2020 ◽  
Vol 21 (4) ◽  
pp. 1253 ◽  
Author(s):  
Mohamed E. Elshakre ◽  
Mahmoud A. Noamaan ◽  
Hussein Moustafa ◽  
Haider Butt

In this work, three computational methods (Hatree-Fock (HF), Møller–Plesset 2 (MP2), and Density Functional Theory (DFT)) using a variety of basis sets are used to determine the atomic and molecular properties of dihydrothiouracil-based indenopyridopyrimidine (TUDHIPP) derivatives. Reactivity descriptors of this system, including chemical potential (µ), chemical hardness (η), electrophilicity (ω), condensed Fukui function and dual descriptors are calculated at B3LYP/6-311++ G (d,p) to identify reactivity changes of these molecules in both gas and aqueous phases. We determined the molecular electrostatic surface potential (MESP) to determine the most active site in these molecules. Molecular docking study of TUDHIPP with topoisomerase II α and β is performed, predicting binding sites and binding energies with amino acids of both proteins. Docking studies of TUDHIPP versus etoposide suggest their potential as antitumor candidates. We have applied Lipinski, Veber’s rules and analysis of the Golden triangle and structure activity/property relationship for a series of TUDHIPP derivatives indicate that the proposed compounds exhibit good oral bioavailability. The comparison of the drug likeness descriptors of TUDHIPP with those of etoposide, which is known to be an antitumor drug, indicates that TUDHIPP can be considered as an antitumor drug. The overall study indicates that TUDHIPP has comparable and even better descriptors than etoposide proposing that it can be as effective antitumor drug, especially 2H, 6H and 7H compounds.


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