Synthesis And Study Of The Physicochemical And Antimicrobial Properties Of New Azo-Calix [6] Arene Derivatives

Abstract

The current study describes the synthesis, structural characterisation and physicochemical and antimicrobial properties of five new azo-calix[6]arene analogues (AC6-1 to AC6-5). Compounds were synthesized through diazotization-coupling reactions on an electron-withdrawing and/or -donating substituted calix[6]arene scaffold decorated with azo aryl groups. FT-IR, ¹H NMR (including heteronuclear single quantum coherence (HSQC) and double-quantum correlation spectroscopy (DQF-COSY)), ¹³C NMR, mass spectrometry, and elemental analysis were used to confirm the structure. The physicochemical parameters were systematically determined, including the melting points (218–248°C), maximum absorbance in UV-Vis λmax (412–448 nm), log P (3.81–4.68) and solubility profiles. Thermogravimetric analysis showed decomposition onset temperatures were in the range of 248°C–279°C which indicated satisfactory stability was achieved across the series. Broth microdilution and agar diffusion methods for the antimicrobial evaluation against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans and Aspergillus niger resulted in minimal inhibitory concentrations (MIC) as low as 2 μg/mL (AC6-5 against S. aureus) and inhibition zones with a length of up to 22.7±0.6 mm. Compound-dependent and organism-dependent variability was confirmed by statistical analysis (two-way ANOVA + Pearson correlation p < 0.001). Compound AC6-5, with its nitro-substituted azo group, showed the strongest biological activity because of an improved electron deficiency and hydrophobicity. These results position azo-functionalized calix[6]arenes as a new class of compounds with tremendous scope for antimicrobial drug discovery in a structural tuneable family.