New carbacylamidophosphates containing nicotinamide: Synthesis, crystallography and antibacterial activity

Abstract

Carbacylamidophosphates are important compounds with unique physicochemical properties and many biological and chemical applications. Here, new derivatives of this class of compounds containing nicotinamide (nia), with the formula (nia)P(O)R2, R=NC4H8 (1), NC5H10 (2), NC6H12 (3), 4-CH3-NC5H9 (4), NC4H8O (5) and N(CH3)(C6H11) (6), were synthesized from the reaction of N-nicotinyl phosphoramidic dichloride with various cyclic aliphatic amines. The characterization and spectroscopic study of the products were carried out by 1H, 13C, 31P NMR and IR spectroscopy, and elemental analysis. For molecules 1–3, with the increasing ring size of the amine groups, from five-to seven-membered, the δ(31P) peaks shift downfield, 3J(P, C)aliphatic decreases, the PO bond gets stronger and the CO bond gets weaker. The 1H NMR spectra of compounds 2 and 6 demonstrated interesting long-range 5JP,H or 7JP,H coupling constants. Long-range coupling of pyridine ring protons with 4J(H,H)=1.6Hz were also detected for molecule 5. The crystal structures of compounds 2–4 and 6 were also determined by X-ray crystallography. The data revealed that the six-membered aliphatic rings in compounds 2, 4 and 6 have a stable chair conformation. The phosphoryl and the carbonyl groups have anti configurations in all crystals, the phosphorus atoms in these structures have a distorted tetrahedral configuration and the environment of most nitrogen atoms is practically planar in all the structures. All the structures form dimers through strong intermolecular PO…HN hydrogen bonds. These dimers connect to each other via various electrostatic weak bonds to produce a 3-D network in each lattice. Moreover, the in vitro antibacterial activities of compounds 1–6 were measured for Staphylococcus aureus and Escherichia coli bacteria in nutrient agar culture medium by the disk method. The antibacterial effect of all the compounds against E. coli was very similar to that of chloramphenicol. Compound 4 showed the most activity toward both tested bacteria and its activity against E. coli was even greater than that of chloramphenicol. The growth inhibitory zone (GIZ) of the synthesized molecules for both bacteria was dependent on the substituent nature of the phosphorus atom in each compound.