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. 2023 Oct 13;12(10):1858.
doi: 10.3390/antiox12101858.

Coumarin N-Acylhydrazone Derivatives: Green Synthesis and Antioxidant Potential-Experimental and Theoretical Study

Dušica M Simijonović  1 , Dejan A Milenković  1 , Edina H Avdović  1 , Žiko B Milanović  1 , Marko R Antonijević  1 , Ana D Amić  2 , Zana Dolićanin  3 , Zoran S Marković  1   4
Affiliations

Coumarin N-Acylhydrazone Derivatives: Green Synthesis and Antioxidant Potential-Experimental and Theoretical Study

Dušica M Simijonović et al. Antioxidants (Basel). .

Abstract

Coumarin N-acylhydrazone derivatives were synthesized in the reaction of 3-acetylcoumarin and different benzohydrazides in the presence of molecular iodine as catalyst and at room temperature. All reactions were rapidly completed, and products were obtained in good to excellent yields. It is important to emphasize that four products were reported for the first time in this study. The obtained compounds were subjected to evaluation of their in vitro antioxidative activity using DPPH, ABTS, and FRAP methods. It was shown that products with a catechol moiety in their structure are the most potent antioxidant agents. The thermodynamic parameters and Gibbs free energies of reactions were used to determine the most probable mechanism of action. The results of in silico examination emphasize the need to take solvent polarity and free radical species into account when examining antiradical action. It was discovered by using computational approaches that HAT and SPLET are competitive molecular pathways for the radical scavenging activity of all compounds in polar mediums, while the HAT is the dominant mechanism in non-polar environments.

Keywords: DFT; antioxidant activity; coumarin N-acylhydrazone derivatives; green synthesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of some coumarin derivatives with clinical application.
Scheme 1
Scheme 1
Synthesis of coumarin N-acylhydrazone derivatives: 3-acetylcoumarin (1), benzoyl hydrazide (2), iodine as catalyst (10 mol%), absolute ethanol, and room temperature (RT).
Scheme 2
Scheme 2
The suggested mechanism for formation of coumarin N-acylhydrazone derivatives.
Figure 2
Figure 2
Optimized geometries of investigated compounds, 3a–3f at M06-2X/6-311++G(d,p) level of theory in methanol (SMD solvation model). Legend: gray—carbon atom, white—hydrogen atom, red—oxygen atom, blue—nitrogen atom.
Figure 3
Figure 3
The possible reaction mechanism: HAT and SET-PT, between DPPH radical and investigation compounds 3a–3f (A–OH).
Figure 4
Figure 4
The possible reaction mechanism: HAT and SET-PT, between ABTS radical cation and investigated compounds 3a–3f (A–OH).
See this image and copyright information in PMC

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