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A series of phosphonoamidates and phosphonoamidines derivatives have been prepared with high yields and their conformations were determined. All compounds were characterized by IR, NMR Spectroscopy (1H, 13C, and 31P) and in some cases by elemental analysis and evolution study by 31P-NMR in an external lock with D2O. A DFT calculations studies was performed to identify the stability of all forms (Cis and Trans) (Syn and Anti) at the B3LYP/6-311G** level. The most stable geometry with an Anti-conformation. A comparison with the experimental results validates the level of theory. The biological activity of dimethyl cyclohexyl carbamoylphosphonate (MAmP) and diethyl cyclohexyl carbamoylphosphonate (EAmP) was evaluated. Only the association of ethyl group with phosphorus in amide gives antimicrobial capacity against S. aureus. The evaluation of the analgesic activity following a thermal stimulus showed that the rats treated with the MAmP do not present any sensation of pain. The MAmP molecule had a dose-dependent significant analgesic activity comparable to morphine effect. The hot plate test showed that the EAmP had a significant analgesic effect less than morphine and MAmP. The new compounds at low dose treatment cause an increase in the sensation of pain following a chemical stimulation that induces inflammation. So the EAmP and the MAmP can be morphemic molecules. The morphine mediates a proinflammatory phenotype and induces hyperalgesia. The MAmP was characterized by analgesic activity comparable to morphine and the EAmP was characterized by specific antimicrobial activity against S. aureus.

The crystal structure of dimethylphenylcarbamothioylphosphonate (MThmP) was obtained by reacting via one-pot synthesis without solvent at room temperature. The crystal structure of MThmP was determined by X-ray analysis (XRD). Two forms (a & b) were showed on the component MThmP which was crystallized in the monoclinic system with P21/c space group. In the first molecule (Form a), the Hirshfeld surface analysis indicates that the major contributions for the crystal packing are H⋯H (40.6%), H⋯O (24.6%)and C⋯H (18.4%) interactions. In the second crystal (Form b), the Hirshfeld surface analysis indicates the different percentage interactions: H⋯H (43.1%), H⋯O (23.3%) and C⋯H (17.8%) interactions. A DFT calculation study was performed to identify the stability of the two structures. A Fukui functions, electrostatic potential surfaces and LUMO-HOMO energy were computed in this work. Geometries of reactants, transition states and products were optimized at the B3LYP/6-311+G(d,p) level. The nucleophilic and electrophilic binding site regions were elucidated using the molecular electrostatic potential (MEP). The pharmacological studies showed that MThmP gives a significant analgesic effect less than morphine with aggravation of inflammatory state. In addition, MThmP had a potential antioxidant activity.