Synthesis and Characterization of Ligand-Stabilized Silver Nanoparticles and Comparative Antibacterial Activity against E. coli.

Silver is a well-established antimicrobial agent. Conjugation of organic ligands with silver nanoparticles has been shown to create antimicrobial nanoparticles with improved pharmacodynamic properties and reduced toxicity. Twelve novel organic ligand functionalized silver nanoparticles (AgNPs) were prepared via a light-controlled reaction with derivatives of benzothiazole, benzoxazine, quinazolinone, 2-butyne-1,4-diol, 3-butyne-1-ol, and heptane-1,7-dioic. UV-vis, Fourier-transform infrared (FTIR) spectroscopy, and energy-dispersive X-ray (EDAX) analysis were used to confirm the successful formation of ligand-functionalized nanoparticles. Dynamic light scattering (DLS) revealed mean nanoparticle diameters between 25 and 278 nm. Spherical and nanotube-like morphologies were observed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Seven of the twelve nanoparticles exhibited strong antimicrobial activity and five of the twelve demonstrated significant antibacterial capabilities against E. coli in a zone-of-inhibition assay. The synthesis of functionalized silver nanoparticles such as the twelve presented is critical for the further development of silver-nanoconjugated antibacterial agents.

Cobalt(III)- and rhodium(III)-porphyrin complexes for the effective degradation of fentanyl: Biological inactivation and mechanistic insights.

Cobalt(III) and rhodium(III) complexes containing the water-soluble porphyrin ligand meso-tri(4-sulfonatophenyl)mono(4-carboxyphenyl)porphine (C1S3TPP), [Rh(C1S3TPP)]Nax•nH2O (1) and [Co(C1S3TPP)]Nax•nH2O (2) were prepared from the direct reaction of free porphyrin and metal chloride salts in refluxing MeOH/DMF or EtOH/H2O. Compounds 1 and 2 were characterized using UV-vis and 1H NMR spectroscopies, and high-resolution mass spectrometry. Cell culture based assays of opioid receptor activation showed that while the rhodium complex reduced fentanyl opioid activity 113-fold to an IC50 value of 1.7 µM, the cobalt complex reduced fentanyl activity by 160-fold to an IC50 value of 2.4 µM. An oxidative mechanism for fentanyl breakdown is proposed.

Investigation of copper oxidation states in plasmonic nanomaterials by XAS and Raman spectroscopy.

Plasmonic core-shell-isolated nanoparticles are promising nanoplatforms for photocatalysis and for low detection analysis. This paper describes the characterization of a 2,2'-bipyridine phosphonate functionalized Ag@TiO2 nanocomposite which complexes copper ions by enhanced Raman spectroscopy and X-ray absorption (XANES and EXAFS). We distinguished Cu(i) from Cu(ii) complexes using shell-isolated nanoparticle enhanced Raman (SHINERS) combined with XAS spectroscopy.

Functionalized core-shell Ag@TiO2 nanoparticles for enhanced Raman spectroscopy: a sensitive detection method for Cu(ii) ions.

This paper demonstrates the use of surface plasmon resonance of core-shell Ag@TiO2 particles in SHINERS experiments. A copper(ii) complex grafted onto Ag@TiO2 surface was probed by Raman spectroscopy using resonance excitation profiles vs. excitation wavelengths (514, 633 and 785 nm) to tune the Raman signals. Enhancement factors of the SHINERS assembly have been estimated and compared to the SERS effect of unmodified silver NPs colloidal dispersions. Finally, the grafting of the copper(ii) complex onto Ag@TiO2 was advantageously compared to the grafting onto Ag@SiO2 shell.

Surface modification of plasmonic noble metal-metal oxide core-shell nanoparticles.

A comprehensive survey on the methods for the surface modification of plasmonic noble metal-metal oxide core-shell nanoparticles is presented. The review highlights various strategies for covalent attachment and electrostatic binding of molecules and molecular ions to core-shell nanoparticles with a focus on plasmonically active silver and gold nanoparticles encapsulated by SiO2 and TiO2 shells.

Synthesis of a Reactive Oxygen Species-Responsive Doxorubicin Derivative.

A heterobifunctional reactive oxygen species (ROS)-responsive linker for directed drug assembly onto and delivery from a quantum dot (QD) nanoparticle carrier was synthesized and coupled to doxorubicin using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)/sulfo⁻NHS coupling. The doxorubicin conjugate was characterized using ¹H NMR and LC-MS and subsequently reacted under conditions of ROS formation (Cu2+/H2O2) resulting in successful and rapid thioacetal oxidative cleavage, which was monitored using ¹H NMR.

Non-photochemical catalytic hydrolysis of methyl parathion using core-shell Ag@TiO2 nanoparticles.

Highly water-dispersible core-shell Ag@TiO2 nanoparticles were prepared and shown to be catalytically active for the rapid degradation of the organothiophosphate pesticide methyl parathion (MeP). Formation of the hydrolysis product, p-nitrophenolate was monitored at pH 7.5 and 8.0, using UV-Vis spectroscopy. 31P NMR spectroscopy confirmed that hydrolysis is the predominant pathway for substrate breakdown under non-photocatalytic conditions. We have demonstrated that the unique combination of TiO2 with silver nanoparticles is required for catalytic hydrolysis with good recyclability. This work represents the first example of MeP degradation using TiO2 doped with AgNPs under mild and ambient conditions. Analysis of catalytic data and a proposed dark mechanism for MeP hydrolysis using core-shell Ag@TiO2 nanoparticles are described.

Kinetic analysis of the hydrolysis of methyl parathion using citrate-stabilized 10 nm gold nanoparticles.

"Ligand-free" citrate-stabilized 10 nm gold nanoparticles (AuNPs) promote the hydrolysis of the thiophosphate ester methyl parathion (MeP) on the surface of gold as a function of pH and two temperature values. At 50 °C, the active surface gold atoms show catalytic turnover ∼4 times after 8 h and little turnover of gold surface atoms at 25 °C with only 40% of the total atoms being active. From Michaelis-Menten analysis, k(cat) increases between pH 8 and 9 and decreases above pH 9. A global analysis of the spectral changes confirmed the stoichiometric reaction at 25 °C and the catalytic reaction at 50 °C and mass spectrometry confirmed the identity of p-nitrophenolate (PNP) product. Additional decomposition pathways involving oxidation and hydrolysis independent of the formation of PNP were also seen at 50 °C for both catalyzed and un-catalyzed reactions. This work represents the first kinetic analysis of ligand-free AuNP catalyzed hydrolysis of a thiophosphate ester.

Crystal structure of catena-poly[[chlorido-(4,4'-dimethyl-2,2'-bi-pyridine-κ(2) N,N')copper(II)]-µ-chlorido].

The title compound, [CuCl2(C12H12N2)] n , was obtained via a DMSO-mediated dehydration of Cu(4,4'-dimethyl-2,2'-bi-pyridine)-copper(II)·0.25H2O. The central Cu(II) atom is coordinated in a distorted trigonal-bipyramidal geometry by two N atoms of a chelating 4,4'-dimethyl-2,2'-bi-pyridine ligand [average Cu-N = 2.03 (3) Å] and three Cl atoms, one terminal with a short Cu-Cl bond of 2.2506 (10) Å, and two symmetry-equivalent and bridging bonds. The bridging Cl atom links the Cu(II) ions into chains parallel to [001] via one medium and one long Cu-Cl bond [2.3320 (10) and 2.5623 (9) Å]. The structure displays both inter- and intra-molecular C-H⋯Cl hydrogen bonding.

Attaching high charge density metal ions to surfaces and biomolecules. Reaction chemistry of hypodentate cobalt diamine complexes.

Hypodentate diamine cobalt(III) pentammine complexes [Co(NH3)5(NH2(CH2)(n)NH3)](ClO4)4 (8: a: n = 3; b: n = 4; c: n = 6; d: n = 8) have been synthesized via the reaction of [Co(NH3)5(OTf)](OTf)2 (TfOH = CF3SO3H) with the corresponding diamines. The analogous t-boc protected diamine complexes [Co(NH3)5(NH2(CH2)(n)NHt-boc)](ClO4)3 (7a-d) were prepared in 4-26% yield. Low yields for the formation of 7a-d are due to competing side reactions which also gave [Co(NH3)6](3+). Complexes 7a-d were deprotected using trifluoroacetic acid to give the corresponding hypodentate diamine complexes [Co(NH3)5(NH2(CH2)(n)NH3)](CF3CO2)0.5(ClO4)3.5 (9a-d). HBTU coupling of 8c with N-(t-boc)-L-phenylalanine gave an amino acid functionalized cobalt pentammine complex [Co(NH3)5(NH2(CH2)6NHt-boc)-L-phenylalanine)](ClO4)3 (10). All new complexes were characterized using UV-vis and (1)H NMR spectroscopy, and elemental analysis. Grafting of 8c onto 2.4 mm poly(ethylene-co-acrylic acid) (PEAA) beads was achieved via amide coupling. Complex 8c was coupled to thioctic acid via amide coupling and the resulting cobalt disulfide complex [Co(NH3)5(N-(6-aminohexyl)-5-(1,2-dithiolan-3-yl)pentanamide)](ClO4)3 (11) was attached to 10 nm Au nanoparticles. The amount of cobalt loading onto PEAA beads and Au nanoparticles was determined using ICP-MS and EDX.

Synthesis of a 2,2'-bipyridyl functionalized oligovinylene-phenylene using Heck and Horner-Wadsworth-Emmons reactions and X-ray crystal structure of E-(4-(4-bromostyryl)phenyl)(methyl)sulfane.

The synthesis of a new 2,2'-bipyridyl functionalized oligovinylenephenylene (OVP-5) containing a methyl protected thiol using Heck coupling and the Horner-Wadsworth-Emmons reaction and is described. A key step involving a diisopropylcarbodiimide promoted dehydration of a stable ß-hydroxyphosphonate intermediate was identified. The structure of precursor E-(4-(4-bromostyryl)phenyl)(methyl)sulfane was determined using X-ray crystallography.

Accelerating the initial rate of hydrolysis of methyl parathion with laser excitation using monolayer protected 10 nm Au nanoparticles capped with a Cu(bpy) catalyst.

Using a low power green laser, we have demonstrated a rate acceleration of ~2-fold for the hydrolysis of methyl parathion by irradiating the plasmon absorption band of Au nanoparticles capped with a Cu(bpy) catalyst.

Oxidation of trimethoprim by ferrate(VI): kinetics, products, and antibacterial activity.

Kinetics, stoichiometry, and products of the oxidation of trimethoprim (TMP), one of the most commonly detected antibacterial agents in surface waters and municipal wastewaters, by ferrate(VI) (Fe(VI)) were determined. The pH dependent second-order rate constants of the reactions of Fe(VI) with TMP were examined using acid-base properties of Fe(VI) and TMP. The kinetics of reactions of diaminopyrimidine (DAP) and trimethoxytoluene (TMT) with Fe(VI) were also determined to understand the reactivity of Fe(VI) with TMP. Oxidation products of the reactions of Fe(VI) with TMP and DAP were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Reaction pathways of oxidation of TMP by Fe(VI) are proposed to demonstrate the cleavage of the TMP molecule to ultimately result in 3,4,5,-trimethoxybenzaldehyde and 2,4-dinitropyrimidine as among the final identified products. The oxidized products mixture exhibited no antibacterial activity against E. coli after complete consumption of TMP. Removal of TMP in the secondary effluent by Fe(VI) was achieved.

Poly[aqua(µ-vinyl-phospho-nato)cadmium].

The title compound, [Cd(C(2)H(3)O(3)P)(H(2)O)](n), was obtained from vinyl-phospho-nic acid and cadmium nitrate. The vinyl groups project into the inter-lamellar space and the structure is held together via van der Waals forces. The Cd(2+) ion is six-coordinate and the geometry is best described as distorted octa-hedral, with O-Cd-O angles falling within the range 61.72 (13)-101.82 (14)°. Five of the coordinated oxygen atoms originate from the phospho-nate group and the sixth from a bound water molecule. Cd-O distances lie between 2.220 (3) and 2.394 (2) Å. The water mol-ecule is hydrogen bonded to a phospho-nate oxygen atom.

Cobalt Complexes as Antiviral and Antibacterial Agents.

Metal ion complexes are playing an increasing role in the development of antimicrobials. We review here the antimicrobial properties of cobalt coordination complexes in oxidation state 3+. In addition to reviewing the cobalt complexes containing polydentate donor ligands, we also focus on the antimicrobial activity of the homoleptic [Co(NH3)6]3+ ion.

Antiviral properties of cobalt(III)-complexes.

We have investigated the potential antiviral activity of three cobalt(III) compounds. Two compounds, Co(III)-cyclen-methylbenzoic acid and its methyl ester derivative, are based on the macrocyclic chelator, cyclen, and were synthesized in our laboratory. Both compounds have been shown to bind tightly to nucleic acids and to hydrolyze phosphodiester bonds. However, neither compound exhibited any significant antiviral activity in an in vitro model of Sindbis virus replication. In contrast, a third compound, Co(III)hexammine, significantly inhibited Sindbis virus replication in baby hamster kidney (BHK) cells in a dose- and time-dependent manner. In plaque assays, the incubation of Co(III)hexammine with Sindbis virus resulted in a dose-dependent decrease in virus replication when measured at both 24 and 48-h post-infection. Over the concentration range of 0-5mM Co(III)hexammine, the IC(50) for the inhibition of viral replication was determined to be 0.10+/-0.04mM at 48h. Additionally, when BHK cell monolayers were pretreated with Co(III)hexammine for 6h prior to Sindbis infection, optimal cellular morphology and plasma membrane integrity were observed at 0.6-1.2mM Co(III)hexammine. Analysis by flow cytometry confirmed that Co(III)hexammine mediated a concomitant dose-dependent increase in BHK cell viability and a decrease in the percentage of Sindbis virus-infected cells (IC(50)=0.13+/-0.04mM). Our findings demonstrate for the first time that Co(III)hexammine possesses potent antiviral activity. We discuss our findings within the context of the ability to further functionalize Co(III)hexammine to render it a highly specific antiviral therapeutic reagent.

RNA hydrolysis and inhibition of translation by a Co(III)-cyclen complex.

Metal ion-chelator catalysts based on main-group, lanthanide, or transition metal complexes have been developed as nonenzymatic alternatives for the hydrolysis of the phosphodiester bonds in DNA and RNA. Cobalt (III), with its high-charge density, is known for its ability to hydrolyze phosphodiesters with rate constants as high as 2 x 10(-4) s(-1). We have developed a kinetically inert Co(III)-cyclen-based complex, Co(III)-cycmmb that is very potent in inhibiting the translation of RNA into protein. Contact time as short as 10 min is sufficient to achieve the complete inhibition of the translation of a concentrated luciferase RNA solution into the enzyme in a cell-free translation system. The inhibition appears to proceed through two pathways. The first pathway involves the kinetic or substitutional inertness of Co(III) for the RNA template at short contact times. This interaction is mediated through the kinetic inertness of Co(III) for the phosphate groups of the nucleotides, as well as coordination of Co(III) to the nitrogenous bases. The second pathway occurs at longer contact times and is mediated by the hydrolysis of the phosphodiester backbone. This report represents the first demonstrated use of a metal-chelate complex to achieve the inhibition of the translation of RNA into protein. This Co(III) system can be useful in its present nonsequence-specific form as a novel viral decontamination agent. When functionalized to recognize specific nucleic acid sequences, such a system could potentially be used in gene-silencing applications as an alternative to standard antisense or RNAi technologies.

Carboxylic acid functionalized cobalt(III) cyclen complexes for catalytic hydrolysis of phosphodiester bonds.

4-(1,4,7,10-Tetraazacyclotetradec-1-yl)methylbenzoic acid (cycmba, 1) has been synthesized, as a step towards the eventual development of sequence-specific hydrolytic complexes. A cobalt(III) complex of 1, [Co(cycmba)Cl2]Cl.1.5H2O (.1.5H2O) was found to be active against both an activated phosphodiester compound, bis(nitrophenyl)phosphate (BNPP), and supercoiled DNA. The presence of the benzoate group depresses the rate of hydrolysis of the ligand-Co(III) system at neutral pH, as confirmed by the kinetics results of a methyl ester analog. The ability of (2.1.5H2O) to bind to solid substrates and remain active was also demonstrated by attachment of the molecule to agarose beads.

Coordination chemistry of the water-soluble ligand TPPTP and formation of a [Mo(CO)5(m-TPPTP)] monolayer on an alumina surface.

Phosphonate and phosphonic acid functionalized phosphine complexes of platinum(II) were prepared via direct reaction of the ligands with K2PtCl4 in water. Either cis or trans geometries were found depending on the nature of the ligand. The crystal structure of P(3-C6H4PO3H2)3.2H2O (6b) (triclinic, P1, a = 8.3501(6) A, b = 10.1907(6) A, c = 14.6529(14) A, alpha = 94.177(6) degrees, beta = 105.885(6) degrees, gamma = 108.784(5) degrees, Z = 2) shows a layered arrangement of the phosphonic acid. The phosphonodiamide complex cis-[PtCl2(P[4-C6H4PO[N(CH3]2]]3)2].3H2O (10) was synthesized in 89% yield and hydrolyzed to the phosphonic acid complex using dilute HCl. Aqueous phase and silica gel supported catalytic phosphonylation of phenyl triflate using palladium phosphine complexes was achieved. A molybdenum complex, Mo(CO)5[P3-C6H4PO3H2)3] (11), was synthesized in situ and grafted to an alumina surface. XPS, RBS, and AFM studies confirm the formation of a monolayer of 11 on the alumina surface.