Synthesis of Computationally Designed Mesoionic NL2(+) Systems and Their Medicinal Applications

Posted: 11 Feb 2020 Last revised: 16 Feb 2020

See all articles by Gurudutt Dubey

Gurudutt Dubey

Government of India - National Institute of Pharmaceutical Education and Research (NIPER)

Shruti Awari

Independent

Prasad V. Bharatam

Independent

Date Written: February 9, 2020

Abstract

In the past decade, a novel class of compounds has been recognized containing an unusual electronic configuration at N+ center. These species have been investigated theoretically as well as experimentally for the presence of L→N+←L (where L is an electron donating ligand) bonds within the molecule. As a result, N+ possesses two lone pairs of electrons with (+1) oxidation state. These compounds are called divalent N(I) compounds and can be represented as NL2(+). This character is already present in marketed drug such as Metformin HCl, Cycloguanil HCl, Ebrotidine HCl etc. Recently published compounds were found active against Trypanothione Reductase (TR) enzyme. Mesoionic compounds are different class of heterocycles having a non-benzenoid aromatic character. They have unusual structural, chemical properties and five to seven membered ring size. Mesoionic compounds are dipolar in nature in which negative and positive charges are present together in the ring system and cannot be represented in a complete covalent form. Out of these, a five membered mesoionic compound, 1,2,3-triazole is reported with anti-leishmanial property and therefore, chosen as one of the ligand (L) for NL2(+) systems. Herein, mesoionic 1,2,3-triazole based divalent N(I) compounds were designed using Density Functional Theory (DFT) calculations. First of all their structural and electronic parameters were established to confirm the presence of divalent N(I) nature and then their mesoionic properties were established by Natural Bond Orbital (NBO) analysis and Nucleus-Independent Chemical Shifts (NICS) calculation. Then a series of compounds was subjected for molecular docking analysis followed by MMGBSA against Trypanothione Reductase enzyme. Based on quantum chemical analysis, the selective compounds were synthesized and characterized by NMR, Mass spectroscopy and single crystal X-ray analysis.

Keywords: Nitreone, Divalent N(I) compounds

JEL Classification: Y2

Suggested Citation

Dubey, Gurudutt and Awari, Shruti and Bharatam, Prasad V., Synthesis of Computationally Designed Mesoionic NL2(+) Systems and Their Medicinal Applications (February 9, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3534892

Gurudutt Dubey (Contact Author)

Government of India - National Institute of Pharmaceutical Education and Research (NIPER) ( email )

India

Shruti Awari

Independent ( email )

Prasad V. Bharatam

Independent ( email )

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