Synthesis, Structure and Biological Activity of 2-Methyl-5-nitro-6-phenylnicotinohydrazide-Based Hydrazones

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Computational Chemistry

Background:

• Hydrazides and hydrazones exhibit diverse biological activities, making them valuable synthetic targets.
• Nicotinohydrazide derivatives are of interest due to their potential pharmacological applications.

Purpose of the Study:

• To synthesize novel 2-methyl-5-nitro-6-phenylnicotinohydrazide-based hydrazones.
• To characterize the synthesized compounds using spectroscopic and computational methods.
• To investigate the isomeric composition and conformational preferences of the synthesized hydrazones.

Main Methods:

• Synthesis of substituted hydrazones from 2-methyl-5-nitro-6-phenylnicotinohydrazide and aldehydes.
• Structural elucidation using Nuclear Magnetic Resonance (NMR) spectroscopy.
• Density Functional Theory (DFT) calculations for conformational analysis and energy estimation.

Main Results:

• Successful synthesis of target hydrazone compounds.
• NMR data indicated the presence of four isomers (Z-I, Z-II, E-I, E-II) in all synthesized compounds.
• DFT calculations accurately predicted the Gibbs free energy and rotamer ratios (approximately 3:2 for E-isomer), aligning with experimental NMR findings.
• Preliminary screening of antibacterial and antifungal activities was conducted.

Conclusions:

• The synthesized nicotinohydrazide-based hydrazones exist as complex mixtures of four isomers.
• Computational modeling provides valuable insights into the conformational landscape and isomeric distribution.
• Further investigation into the biological activities of these specific isomers is warranted.