Kinetics and Mechanism of Electron Transfer Reaction of an Adipato Bridged Iron(III)-Salen Complex with Dithionite Ion in Perchloric Acid Medium

Redox kinetics of the reaction of an adipato bridged iron(III)-salen complex, [(Fe(salen))2adi] with dithionite ion, S2O42–, was investigated in perchloric acid at I = 0.05 mol dm–3 (NaClO4) and T = 29 ± 1 °C. Spectrophotometric titrations indicated consumption of one mole of S2O42– per mole of [(Fe(salen))2adi] reduced. Under pseudo-first order conditions of [S2O42–] above ten-fold excess of concentration of [(Fe(salen))2adi], observed rates increased with increase in [S2O42–] and second order rate constants were fairly constant (0.285 ± 0.01 dm3 mol–1 s–1) indicating first order dependence of the rate on [(Fe(salen))2adi]. A plot of logkobs versus log[S2O42–] was linear and gave a slope of 1.0 indicating first order dependence of the rate on [S2O42–]. The reaction rate increased with increase in [H+] within 3 × 10–3 mol dm–3 ≤ [H+] ≤ 14 × 10–3 mol dm–3. The reaction was unaffected by variation of ionic strength and dielectric constant of the medium. Addition of anion and cation did not catalyze the reaction. The reaction has been analyzed on the basis of an inner-sphere mechanism mediated by proton transfer

Experimental and In-Silico Investigation of Anti-Microbial Activity of 1-Chloro-2-Isocyanatoethane Derivatives of Thiomorpholine, Piperazine and Morpholine.

The Antibiogram properties of 1-chloro-2-isocyanatoethane derivatives of thiomorpholine (CTC), piperazine (CPC) and morpholine (CMC) were evaluated by the approved agar well diffusion, the minimum inhibitory concentration (MIC) and in silico techniques. A total of fourteen microbial cultures consisting of ten bacteria and four yeast strains were used in the biological study while affinity of the compounds for DNA gyrase, a validated antibacterial drug target, was investigated by docking method. Results indicate that both thiomorpholine and piperazine had zero activity against the Gram negative organisms tested. With morpholine, similar result was obtained except that cultures of Escherichia coli (ATCC 15442) and Salmonella typhi (ATCC 6539) presented with weak sensitivity (7-8 mm) as shown by the inhibition zone diameter (IZD) measurement. The Gram positive organisms were more sensitive to morpholine than the other compounds. The highest IZD values of 15-18 mm were achieved except for Streptococcus pneumoniae (ATCC 49619) in which mobility of the compound stopped after 12 mm. S. pneumoniae was resistant to both thiomorpholine and piperazine. The yeast strains were not sensitive to any of the studied compounds investigated. The MIC tests evaluated against a reference antibiotic show that while morpholine was most active at 4 μg.ml-1 against both B. cereus ATCC (14579) and B. subtilis, the least active compound was thiomorpholine which inhibited S. aureus (ATCC 25923) at 64 μg.ml-1. The three compounds demonstrated high affinity for the target protein (DNA gyrase) ranging from -4.63 to -5.64 Kcal/mol and even showed better ligand efficiencies than three known antibiotics; chlorobiocin, ciprofloxacin and tetracycline. This study identified the studied compounds as potential antibiotic leads with acceptable physicochemical properties and gave the molecular basis for the observed interactions between the compounds and the target protein which can be harnessed in structural optimization process

Synthesis of hiomorpholine piperazine and and morpholine derivatives of 1-chloro-2-isocyanatoethane.

<p>Synthesis of hiomorpholine piperazine and and morpholine derivatives of 1-chloro-2-isocyanatoethane.</p

Binding conformations of the compounds (a) CTC, (b) CPC, (c) CMC and (d) is the solid surface representation of the protein binding site with all the three compounds in it.

<p>For subfigures a, b and c; the protein residues and ligands are in line and stick representations respectively. The atoms are in their standard colors for both the protein residues and ligands i.e. oxygen atom is in red color, chlorine atom in green color, hydrogen atom in white color, sulphur atom in yellow color etc. Polar contacts are shown in dash lines.</p

Inhibition zone diameter (IZD) of the effect of CTC, CPC and CMC on the test isolates.

<p>Inhibition zone diameter (IZD) of the effect of CTC, CPC and CMC on the test isolates.</p

<i>In-silico</i> inhibitory potential of the three compounds against DNA gyrase.

<p><i>In-silico</i> inhibitory potential of the three compounds against DNA gyrase.</p

Minimum inhibitory concentration (MIC, μg.ml^-1) of the effect of compounds.

<p>Minimum inhibitory concentration (MIC, μg.ml^-1) of the effect of compounds.</p

Binding conformations of the (a) native ligand (chlorobiocin) and (b) ciprofloxacin showing interactions with DNA gyrase active site residues similar to those observed in Fig 2a, 2b and 2c.

<p>Binding conformations of the (a) native ligand (chlorobiocin) and (b) ciprofloxacin showing interactions with DNA gyrase active site residues similar to those observed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170150#pone.0170150.g002" target="_blank">Fig 2a, 2b and 2c</a>.</p