Synthesis, Characterization and Antibacterial Studies of Mono and Binuclear Copper (II) Complexes of 1, 10 Phenantroline using Ethylenediamine as Spacer

Copper is a biologically important element, and several enzymes that rely on it to function have been discovered. However, drug-resistant bacteria are a major problem in the medical world, which causes high mortality rates and increases in health care costs, economic losses. The multidirectional effort has been put to overcome the concern as well as discover new drug molecules. In this aspect, the complexation of organic compounds with metal ions increases the therapeutic potency of the organic compounds. Herein, mono [Cu(Phen)2Cl]Cl.H2O, and binuclear [Cu2(en)(Phen)4]Cl4 complexes were synthesized and characterized with the help of ICP‑OES, FT‑IR, and UV‑Vis spectroscopic techniques. The synthesized complexes are proposed with square pyramidal geometries. Moreover, the complexes are characterized by molar conductance measurement, melting point measurement, solubility test, and halide test. Based on the in vitro antibacterial testing, both complexes are biologically active in all studied microorganisms, including the most drug-resistant Klebsiella pneumonia, Surprisingly, the complexes are water-soluble, and the solubility of the synthesized complexes could be viewed as a potential therapeutic application following in vivo cytotoxicity studies. Keywords: 1, 10‑phenanthroline, ethylenediamine, Cu (II) complexes, and antibacterial activities DOI: 10.7176/CMR/14-4-02 Publication date:October 31st 202

Synthesis, Characterisation, and Solution Behaviour of Ag(I) Bis(Phenanthroline‑Oxazine) Complexes and the Evaluation of their Biological Activity Against the Pathogenic Yeast Candida Albicans

Three Ag(I) bis(phenanthroline-oxazine) complexes with varying lipophilicity were synthesised and characterised. The solution stoichiometry of 1:2 Ag(I):ligand was determined for each complex by the continuous variation Job\u27s plot method using NMR spectroscopy. NMR studies were also carried out to investigate the fluxional behaviour of the Ag(I) complexes in solution. The biological activity of the silver(I) complexes and the corresponding ligands towards a clinical strain of Candida albicans MEN was studied using broth microdilution assays. Testing showed the choice of media and the duration of incubation were key determinants of the inhibitory behaviour towards Candida albicans, however, the difference between freshly prepared and pre-prepared solutions was insignificant in minimal media. The activity of the metal-free ligands correlated with the length of the alkyl chain. In minimal media, the methyl ester phenanthroline-oxazine ligand was effective only at 60 μM, limiting growth to 67% of the control, while a 60 μM dose of the propyl ester analogue limited fungal growth at \u3c 20% of the control. MIC50 and MIC80 values for the propyl and hexyl ester analogues were calculated to be 45 and 59 µM (propyl), and 18 and 45 µM (hexyl). Moreover, in a study of activity as a function of time it was observed that the hexyl ester ligand maintained its activity for longer than the methyl and propyl analogues; after 48 h a 60 μM dose held fungal growth at 24% of that of the control. Complexation to Ag(I) was much more effective in enhancing biological activity of the ligands than was increasing the ester chain length. Significantly no difference in activity between the three silver(I) complexes was observed under the experimental conditions. All three complexes were substantially more active than their parent ligands against Candida albicans and AgClO4 and the three silver(I) bis(phen-oxazine) complexes have MIC80 values of \u3c 15 μM. The ability of the silver(I) complexes to hold fungal growth at about 20% of the control even after 48 h incubation at low dosages (15 μM) showcases their superiority over the simple silver(I) perchlorate salt, which ceased to be effective at dosages below 60 μM at the extended time point

Synthesis of substituted 2-vinyl and 2-phenylbenzimidazoles and progress towards the synthesis of natural products ht-13-A and ht-13-B

Synthesis of 2-alkenyl and 2-arylbenzimidazoles, having a variety of functional groups, has been accomplished via a novel palladium-catalyzed reductive N-heteroannulation of 2-nitro- N-alkyl or N-benzyl benzenamines. The cyclization precursors are readily prepared from commercially available compounds by a variety of methods. In addition, the first total synthesis of ht-13-A has been studied. The key steps of the synthesis are a Mitsunobu reaction, an intramolecular Heck reaction, and a reductive N-heteroannulation

Zn thiosacharinates: From ionic to polymeric structures. Synthesis, characterization and cell proliferation inhibition studies

A series of Zn thiosacharinates complexes with nitrogen donor co-ligands were synthesized: [Zn(tsac)2(o-phen)], [Zn(tsac)2(TMDP)]n, [(4,4′-bipy)H2][Zn(tsac)4] [Zn(tsac)2(2,2′-bipy)], [Zn(tsac)2(2,2′-bquin)], (tsac, thiosaccharinate anion: 1,1-dioxo-1,2-benzisothiazole-3-thiolato, C7H4NO2S2−, o-phen: 1,10′-phenantroline, TMDP: trimethylenedipyridine, 2,2′-bipy: 2,2′-bipyridine, 4,4′-bipy: 4,4′-bipyridine, 2,2′-bquin: 2,2′-biquinoline). They were fully characterized by means of FTIR, 13C and 1H NMR, elemental analysis and conductivity measurements. Three of them, [Zn(tsac)2(o-phen)], [(4,4′-bipy)H2][Zn(tsac)4], [Zn(tsac)2(TMDP)]n were also characterized by X-ray single crystal diffractometry and their crystal structures are described herein. DFT geometry optimization for the [Zn(tsac)2(o-phen)] complex was performed and its vibrational spectra was predicted. Moreover, we studied the effects of the five complexes on cell proliferation, thus providing preliminary evidence for their therapeutic potential as anti-cancer drugs.Fil: Delgado, Fermin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Freire Espeleta, Eleonora. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Baggio, Ricardo. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: González Pardo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Dorn, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Dennehy, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

Synthesis of new organic analytical reagents

The investigation of the preparation of three organic compounds, 2.2-bipyrimidyl, 1.4-bis-(cyclohexoxy)-2.3-butanedionedioxime, and 2.2-thenilodioxime, analogs of useful analytical reagents in the specific or selective separation and/or determination of divalent metal ions has been carried out

Investigating the Formation Process of Sn-Based Lead-Free Nanoparticles with a Chemical Reduction Method

Nanoparticles of a promising lead-free solder alloy (Sn3.5Ag (wt.%, SnAg) and Sn3.0Ag0.5Cu (wt.%, SAC)) were synthesized through a chemical reduction method by using anhydrous ethanol and 1,10-phenanthroline as the solvent and surfactant, respectively. To illustrate the formation process of Sn-Ag alloy based nanoparticles during the reaction, X-ray diffraction (XRD) was used to investigate the phases of the samples in relation to the reaction time. Different nucleation and growth mechanisms were compared on the formation process of the synthesized nanoparticles. The XRD results revealed different reaction process compared with other researchers. There were many contributing factors to the difference in the examples found in the literature, with the main focus on the formation mechanism of crystal nuclei, the solubility and ionizability of metal salts in the solvent, the solid solubility of Cu in Ag nuclei, and the role of surfactant on the growth process. This study will help define the parameters necessary for the control of both the composition and size of the nanoparticles

Kinetics of the ligand exchange reactions between bidentate ligands and rriethylenetetramine nickelate (II) and synthesis of boron (III) subphthalocyanines with various boron substitutions

Part 1. The kinetics of the ligand exchange reaction between 5-methyl-1,10-phenanthroline and triethylenetetramine nickel (II) were studied spectrophotometrically over the pH range of 5.2 to 8.0 at 25oC. A ternary complex Ni(Trien)(5MP) forms within a few seconds and subsequently reacts with 5MP to form Ni(5MP)3. The reaction is first-order with respect to: [5MP], [Ni(Trien)(5MP)] and [H+]. The rate law is given by: k dt d[Ni(trien)] = ( − MP Ni(trien)(5MP) + kH, 5MP Ni(trien)(5MP) [H+]) [Ni(trien)][5mp] where: 5MP is 5-methyl-1,10-phenanthroline and k is the first order rate constant that has units of 1/time. kH, 5mp Ni(trien)(5mp) = 9.78 X 104 M-2 s-1 and k5mp Ni(trien)(5mp) = 9.42 X 10-3 M-2 s-1 Part 2. Axial substitution on boron (III) subphthalocyanines (SubPcs) were investigated. The Boron subphthalocyanines BsubPcCl and BsubPcOH were synthesized. These derivatives were then used to prepare BsubPcSiHx3, BsubPcBu, and BsubPcOSi(CH2CH2CH2CH3)3. This study represents the first synthesis of axial substitution on boron subphthalocyanine with a tributylsiloxy group. The products were characterized by infrared spectroscopy, 1H nuclear magnetic resonance analysis, and high resolution mass spectroscopy

The Generation of Novel Metal-Folate- Phenanthroline Complexes and Phenanthroline-Folate Conjugates with Potential as Chemotherapeutic Agents

The folate receptor (FR) was identified in 1986 and has been established as a ‘molecular Trojan Horse’ target for the uptake of folate-conjugated organic molecules into cells. The FR is overexpressed in many malignancies, including those of the ovary, uterus, breast, cervix, and prostate, yet it is reportedly under-expressed in normal healthy cells. This difference in expression and the high affinity/specificity of folate towards the folate receptor presents a promising drug delivery system. The aim of this research was to utilise folic acid as a targeting moiety and generate simple metal folate and novel folate-phenanthroline complexes with cytotoxic properties. A challenging set of chemical objectives were set and resulted in the successful generation of simple metal-folate and metal-folate-phen complexes (metal = Cu2+, Mn2+, Fe3+ and Zn2+). In contrast to reports in the literature, NMR and IR evidence indicates that the folate ligand coordinates the metal centre via a tridentate ONO {α-COO-, γ-COO-, and Namide} binding mode. A challenging six-stage synthetic route yielded the novel folate-ethylenediamine-imidazole-phen (FIMP-et) ligand and the novel complexes [Cu(FIMP-et)2(H2O)2].(ClO4)2.4.5H2O and [Mn(FIMP-et)3].(ClO4)2.9H2O were subsequently isolated in high yield and purity. The complexes generated were then utilised in a series of biological studies using cellular models expressing the folate receptor. Our results suggest that the effects mediated by these complexes are not dependent on folate receptor expression. Western blot analysis and live cell analysis identified that [Cu(fol)(phen)(H2O)].3H2O, with or without the inclusion of folic acid, induced expression of proteins associated with proteasomal inhibition and apoptosis. In contrast, [Mn(fol)(phen)(H2O)].4H2O was ineffective in inducing proteasomal inhibition. Interestingly [Mn(fol)(phen)(H2O)].4H2O induces cell death through a mechanism independent of proteasomal inhibition, which may involve ROS-induced autophagy. This work advances the field of medicinal inorganic chemistry and has identified novel mechanisms of action for metal folate targeted inorganic complexes as potential chemotherapeutic agents, through proteasomal inhibition and ROS-induced autophagy