Synthesis and Structure Insights of Two Novel Broad-Spectrum Antibacterial Candidates Based on (<i>E</i>)-<i>N</i>′-[(Heteroaryl)methylene]adamantane-1-carbohydrazides

• Main Authors: Lamya H. Al-Wahaibi, Natalia Alvarez, Olivier Blacque, Nicolás Veiga, Aamal A. Al-Mutairi, Ali A. El-Emam
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Molecules
• Subjects: adamantane-1-carbohydrazides; antibacterial activity; crystal structure; DFT; Hirshfeld surface analysis; IR
• Online Access: https://www.mdpi.com/1420-3049/25/8/1934

Two new <i>N</i>′-heteroarylidene-1-carbohydrazide derivatives, namely; <i>E</i>-<i>N</i>′-[(pyridine-3-yl)methylidene]adamantane-1-carbohydrazide (<b>1</b>) and <i>E</i>-<i>N</i>′-[(5-nitrothiophen-2-yl)methylidene]adamantane-1-carbohydrazide (<b>2</b>), were produced via condensation of adamantane-1-carbohydrazide with the appropriate heterocyclic aldehyde. Both compounds were chemically and structurally characterized by ¹H-NMR, ¹³C-NMR, infrared and UV-vis spectroscopies, and single crystal X-ray diffraction. The study was complemented with density functional theory calculations (DFT). The results show an asymmetrical charge distribution in both compounds, with the electron density accumulated around the nitrogen and oxygen atoms, leaving the positive charge surrounding the N-H and C-H bonds in the hydrazine group. Consequently, the molecules stack in an antiparallel fashion in the crystalline state, although the contribution of the polar contacts to the stability of the lattice is different for <b>1</b> (18%) and <b>2</b> (42%). This difference affects the density and symmetry of their crystal structures. Both molecules show intense UV-Vis light absorption in the range 200–350 nm (<b>1</b>) and 200–500 nm (<b>2</b>), brought about by π → π* electronic transitions. The electron density difference maps (EDDM) revealed that during light absorption, the electron density flows within the π-delocalized system, among the pyridyl/thiophene ring, the nitro group, and the <i>N</i>′-methyleneacetohydrazide moiety. Interestingly, compounds <b>1</b> and <b>2</b> constitute broad-spectrum antibacterial candidates, displaying potent antibacterial activity with minimal inhibitory concentration (MIC) values around 0.5–2.0 μg/mL. They also show weak or moderate antifungal activity against the yeast-like pathogenic fungus <i>Candida albicans</i>.