Synthesis, crystal structure and biological activity of new phosphoester-p-substituted-methylparabens

Abstract

Bis(4-(methoxycarbonyl)phenyl)phosphonate and bis(4-(methoxycarbonyl)phenyl) phosphate were prepared from the reaction of p-hydroxybenzoate with phenyl phosphonic dichloride and with phenyl dichlorophosphate, respectively, in the presence of CuCl as catalyst. The structure of the synthesized compounds was elucidated by FTIR, 1H NMR,13C NMR and 31P NMR spectroscopy. The assignments for the 1H, 13C and 31P chemical shifts are based on 1D and 2D NMR homo- and heteronuclear correlations (H,H-COSY (Correlation Spectroscopy), H,C-HMQC (Heteronuclear Multiple Quantum Correlation and H,C-HMBC (Heteronuclear Multiple Bond Correlation)) and 31P-13C couplings. The synthesized compounds revealed good solubility in common organic solvents. The crystal structure of the products was investigated by single-crystal X-ray diffraction, while the purity of the bulk product was confirmed by powder X-ray diffraction. The antimicrobial effect of the non-phosphoester-functionalized and phosphoester-functionalized p-hydroxybenzoate disc samples was investigated. Antimicrobial activities were evaluated against bacterial strains of Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and fungi Candidaalbicans ATCC 10321 used in this research. The non-phosphoester-functionalized p-hydroxybenzoate exhibit good antibacterial and antifungal effect compared to phosphoester-functionalized p-hydroxybenzoates. The synthesized compounds were screened in vitro for their cytotoxicity on primary Albino Rabbit dermal fibroblasts, by the 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) protocol. The results showed clearly that the synthesized phosphoesters promote cell viability and they have the potential to be developed into economical and reliable additives for skin cosmetics and pharmaceuticals.