Synthesis and antibacterial studies of new cadmium,silver and zinc dithiophosphonates.

Abstract

A variety of dithiophosphonate and bis(dithiophosphonate) compounds were synthesised from the reaction between a dithiophosphetane disulfide dimer, [P(4-C6H4OMe)S(S)]2, commonly referred to as Lawesson’s Reagent (LR), and alcohols. The LR was symmetrically cleaved by nucleophilic attack from primary or secondary alcohols, as well as diols. The alcohols used include isosorbide, 1, 4 cyclohexanol, 2-hexanol, isomannide, 2-butene 1, 4-diol, 2-methyl-cyclohexanol and 2-methyl- 3 hexanol. The reaction of alcohols with LR resulted in the replacement of the P ̶ S bond by a P ̶ O bond due to the oxophilic nature of the phosphorous atom and consequent formation of dithiophosphonic acids (pKa ~ 3-4) which were then readily deprotonated by ammonia gas to form the corresponding ammonium dithiophosphonate and bis(dithiophosphonato) ligand salts of the form NH4[S2PR(OR’)] and (NH4)2[S2PR(OR’O)PS2R] respectively where (R = 4-C6H4OMe, and R’ = a spacer portion from a diol). The ligands were further reacted with aqueous metal nitrate salts of zinc(II), cadmium(II) and silver(I) precipitating copious amounts of dinuclear complexes with yields of at least 70% in most instances. The characterisation of the compounds was achieved using solubility, stability, colour, melting point and several techniques which included FT-IR, mass spectrometry, 1H-NMR, 13C-NMR, 2D-NMR and 31P-NMR and SC-XRD. The 31P-NMR spectra revealed singlet peaks indicative of a single phosphorous centre or equivalent phosphorous centres which were typically in the range ca. 90-110 ppm, values which are consistent with dithiophosphonate chemical shifts. Crystals of Cd(II) [3B] and Zn(II) [3C] complexes were successfully grown and subjected to single-crystal XRD analyses. The structures of the cadmium(II) and zinc(II) complexes were confirmed by SC-XRD as dinuclear complexes with an inversion centre within the molecular structure and comprising three ring structures including an eight-membered ring consisting of the metal, sulfur and phosphorus atoms, The dinuclear core M2S4P2 formed via bridging of the ligands with the two metal centres and with a distorted tetrahedral geometry around the metal atoms. The Zn(II) and Cd(II) dinuclear metalcomplexes had formulae of [Zn2{S2PR(OCH2HC=CHCH2O)PS2R}2] and [Cd2{S2PR(OCH2HC=CHCH2O)PS2R}2], respectively, where (R =4-C6H4OMe). The synthesised dithiophosphonate ligands and complexes were subsequently investigated as antimicrobial agents against Methicillin resistant Staphylococcus Aureus, Staphylococcus Aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia Coli and Salmonella Typhimurium bacterial strains. In general, the metal complexes were found to be more efficacious than the ammonium salts against these virulent bacterial strains. Silver(I) complexes were the most effective, consistent with the general observation that silver is a good antibacterial agent while cadmium generally had poor effectiveness. The most susceptible bacteria was Klebsiella pneumoniae, while the most resistant bacterial strains were Salmonella Typhimurium and Escherichia Coli. Most compounds, especially ammonium salts, were ineffective against these two bacterial strains in particular Salmonella Typhimurium. In general, each of the synthesised compounds had some degree of antibacterial activity against at least two strains.