In vitro anti-bacterial and time kill evaluation of binuclear tricyclohexylphosphanesilver(I) dithiocarbamates, {Cy3PAg(S2CNRR′)}2

Abstract

Four binuclear phosphanesilver(I) dithiocarbamates, {cyclohexyl 3 PAg(S 2 CNRR′)} 2 for R = R′ = Et (1), CH 2 CH 2 (2), CH 2 CH 2 OH (3) and R = Me, R′ = CH 2 CH 2 OH (4) have been synthesised and characterised by spectroscopy and crystallography, and feature tri-connective, μ 2 -bridging dithiocarbamate ligands and distorted tetrahedral geometries based on PS 3 donor sets. The compounds were evaluated for anti-bacterial activity against a total of 12 clinically important pathogens. Based on minimum inhibitory concentration (MIC) and cell viability tests (human embryonic kidney cells, HEK 293), 1-4 are specifically active against Gram-positive bacteria while demonstrating low toxicity; 3 and 4 are active against methicillin resistant S. aureus (MRSA). Across the series, 4 was most effective and was more active than the standard anti-biotic chloramphenicol. Time kill assays reveal 1-4 to exhibit both time-and concentration-dependent pharmacokinetics against susceptible bacteria. Compound 4 demonstrates rapid (within 2 h) bactericidal activity at 1 and 2 × MIC to reach a maximum decrease of 5.2 log 10 CFU/mL against S. aureus (MRSA). While the R = Cy and Ph derivatives exhibited specific activity against Gram-positive bacteria, the R = Et compound showed broad range activity against both Gram-positive and Gram-negative bacteria [23]. Also, based on time kill studies the R = Cy and Ph compounds were bactericidal whereas the R = Et compound was bactericidal and

Crystal structure of bis[μ2-(N-(2-hydroxyethyl)-N-methylcarbamodithioato-κS:κS,κS′)]-bis(triethylphosphine-P)-di-silver(I), C20H46Ag2N2O2P2S4

“…The O-bound H atoms were refined with O-H = 0.84 ± 0.01 Å, and with 1.5Ueq(O). [5]. The remaining R 3 PAg(S 2 CNR′R′′) structures have the dithiocarbamate ligands lying to opposite sides of the central Ag 2 S 2 plane [5][6][7][8][9][10][11].…”

Crystal structure of bis[μ2-(pyrrolidine-1-carbodithioato-κS:κS,κS′)]-bis(triethylphosphine-κP)disilver(I), C22H46Ag2N2P2S4

“…In connection with recent anti-bacterial screening and pharmacokinetic studies of binuclear phosphanesilver(I) dithiocarbamates, {Cy 3 PAg(S 2 CNRR′)} 2 , complementary crystallographic studies revealed a novel conformation for one of the derivatives [5]. The common feature of the solid-state structures are µ 2 -bridging dithiocarbamate ligands and a central Ag 2 S 2 core, with the distinction arising in terms of the relative disposition of the dithiocarbamate ligands.…”

Crystal structure of catena{di-aqua-sodium-[N-(hydroxyethyl), N-isopropyl-dithiocarbamato]}n, [C6H16NNaO2S2]n

“…During the course of structural investigations related to crystal engineering considerations [5,6] and putative biological activities of metal dithiocarbamates ( − S 2 CNR 2 ), e.g. anti-tumour [7] and anti-bacterial [8], occasionally, crystals of alkali metal salts of the dithiocarbamate anions have been isolated and characterised by X-ray crystallography [9,10]. In continuation of a long-term interest in such structural chemistry [11] The molecular structures of the constituents of (I) are shown in the figure (upper view: 70% displacement ellipsoids).…”