Naturally-occurring nitro compounds

Naturally-occurring nitro compounds display great structural diversity, and a wide range of biological activities. This review summarizes current information on the structures of naturally-occurring nitro compounds and on the biosynthesis of the nitro group.     

Targeted quantitative bioanalysis in plasma using liquid chromatography/high-resolution accurate mass spectrometry: an evaluation of global selectivity as a function of mass resolving power and extraction window, with comparison of centroid and profile modes

There is a growing interest in exploring the use of liquid chromatography coupled with full-scan high resolution accurate mass spectrometry (LC/HRMS) in bioanalytical laboratories as an alternative to the current practice of using LC coupled with tandem mass spectrometry (LC/MS/MS). Therefore, we have investigated the theoretical and practical aspects of LC/HRMS as it relates to the quantitation of drugs in plasma, which is the most commonly used matrix in pharmacokinetics studies. In order to assess the overall selectivity of HRMS, we evaluated the potential interferences from endogenous plasma components by analyzing acetonitrile-precipitated blank human plasma extract using an LC/HRMS system under chromatographic conditions typically used for LC/MS/MS bioanalysis with the acquisition of total ion chromatograms (TICs) using 10 k and 20 k resolving power in both profile and centroid modes. From each TIC, we generated extracted ion chromatograms (EICs) of the exact masses of the [M + H](+) ions of 153 model drugs using different mass extraction windows (MEWs) and determined the number of plasma endogenous peaks detected in each EIC. Fewer endogenous peaks are detected using higher resolving power, narrower MEW, and centroid mode. A 20 k resolving power can be considered adequate for the selective determination of drugs in plasma. To achieve desired analyte EIC selectivity and simultaneously avoid missing data points in the analyte EIC peak, the MEW used should not be too wide or too narrow and should be a small fraction of the full width at half maximum (FWHM) of the profile mass peak. It is recommended that the optimum MEW be established during method development under the specified chromatographic and sample preparation conditions. In general, the optimum MEW, typically ≤ ±20 ppm for 20 k resolving power, is smaller for the profile mode when compared with the centroid mode.     

Rational design of a Tn antigen mimic

A novel Tn antigen mimic, in which the natural underlying amino acid has been replaced by the non-natural α-methylserine analogue, is reported. This derivative exhibits a similar affinity for a natural lectin as for the natural Tn and retains the bioactive conformation observed in the Tn-containing glycopeptides with anti-MUC1 antibodies.     

Viscoelastic and shear viscosity studies of colloidal silica particles dispersed in monoethylene glycol (MEG), diethylene glycol (DEG), and dodecane stabilized by dodecyl hexaethylene glycol monoether (C12E6)

Silica dispersions stabilized by a nonionic surfactant, dodecyl hexaethylene glycol monoether (C 12E 6), were studied using rheological measurements. The viscosity-shear rate flow behavior of silica in monoethylene glycol (MEG) is shear thinning at low shear rates, leading to a Newtonian plateau at high shear rates for all dispersions studied. All rheological properties showed an increase above a critical surfactant concentration. The dispersions were stable at low levels of C 12E 6 concentrations because of electrostatic repulsions as deduced from the zeta potentials of silica that were on the order of about -30 to -65 mV in monoethylene glycol (MEG). Instability on further addition of C 12E 6 to the silica particles, a phenomenon normally obtained with high-molecular-weight polymers, was observed in MEG. Viscoelatic measurements of silica in monoethylene glycol at various surfactant concentrations showed a predominantly viscous response at low frequency and a predominantly elastic response at high frequencies, indicative of weak flocculation. Instability is explained in terms of hydrophobic and bridging interactions. Restabilization observed at high surfactant concentration was due to the steric repulsion of ethoxy groups of micellar aggregates adsorbed on silica particles. The study also revealed that the presence of trace water introduced charge repulsion that moderated rheological measurements in glycol media and introduced the charge reversal of silica particles in dodecane.     

Additional Minor Phytoecdysteroids of Serratula wolffii

Three new and one known ecdysteroids were identified in the MeOH extract of the roots of Serratula wolffii. The new compounds isolated were (11α)‐11‐hydroxyshidasterone ( 1 ), (2β,3α,5β,14β,22R)‐2,3,20,22,25‐pentahydroxycholest‐7‐en‐6‐one ( 2 ), and (2β,3α,5β,22R)‐2,3,20,22,25‐pentahydroxycholest‐7‐en‐6‐one ( 3 ), together with the known ponasterone A ( 4 ). This latter compound was now better characterized than earlier. The structures of compounds 1 – 4 were established by extensive spectroscopic techniques, including one‐ and two‐dimensional NMR methods.     

Luminescent Di‐ and Polynuclear Organometallic Gold(I)–Metal (Au2, {Au2Ag}n and {Au2Cu}n) Compounds Containing Bidentate Phosphanes as Active Antimicrobial Agents

The reaction of new dinuclear gold(I) organometallic complexes containing mesityl ligands and bridging bidentate phosphanes [Au₂(mes)₂(μ‐LL)] (LL=dppe: 1,2‐bis(diphenylphosphano)ethane 1 a , and water‐soluble dppy: 1,2‐bis(di‐3‐pyridylphosphano)ethane 1 b ) with Ag⁺ and Cu⁺ lead to the formation of a family of heterometallic clusters with mesityl bridging ligands of the general formula [Au₂M(μ‐mes)₂(μ‐LL)][A] (M=Ag, A=ClO₄^?, LL=dppe 2 a , dppy 2 b ; M=Ag, A=SO₃CF₃^?, LL=dppe 3 a , dppy 3 b ; M=Cu, A=PF₆^?, LL=dppe 4 a , dppy 4 b ). The new compounds were characterized by different spectroscopic techniques and mass spectrometry The crystal structures of [Au₂(mes)₂(μ‐dppy)] ( 1 b ) and [Au₂Ag(μ‐mes)₂(μ‐dppe)][SO₃CF₃] ( 3 a ) were determined by a single‐crystal X‐ray diffraction study. 3 a in solid state is not a cyclic trinuclear Au₂Ag derivative but it gives an open polymeric structure instead, with the {Au₂(μ‐dppe)} fragments “linked” by {Ag(μ‐mes)₂} units. The very short distances of 2.7559(6) Å (Au? Ag) and 2.9229(8) Å (Au? Au) are indicative of gold–silver (metallophilic) and aurophilic interactions. A systematic study of their luminescence properties revealed that all compounds are brightly luminescent in solid state, at room temperature (RT) and at 77 K, or in frozen DMSO solutions with lifetimes in the microsecond range and probably due to the self‐aggregation of [Au₂M(μ‐mes)₂(μ‐LL)]⁺ units (M=Ag or Cu; LL=dppe or dppy) into an extended chain structure, through Au? Au and/or Au? M metallophilic interactions, as that observed for 3 a . In solid state the heterometallic Au₂M complexes with dppe ( 2 a – 4 a ) show a shift of emission maxima (from ca. 430 to the range of 520‐540 nm) as compared to the parent dinuclear organometallic product 1 a while the complexes with dppy ( 2 b–4 b ) display a more moderate shift (505 for 1 b to a max of 563 nm for 4 b ). More importantly, compound [Au₂Ag(μ‐mes)₂(μ‐dppy)]ClO₄ ( 2 b ) resulted luminescent in diluted DMSO solution at room temperature. Previously reported compound [Au₂Cl₂(μ‐LL)] (LL dppy 5 b ) was also studied for comparative purposes. The antimicrobial activity of 1–5 and Ag[A] (A=ClO₄^?, SO₃CF₃^?) against Gram‐positive and Gram‐negative bacteria and yeast was evaluated. Most tested compounds displayed moderate to high antibacterial activity while heteronuclear Au₂M derivatives with dppe ( 2 a – 4 a ) were the more active (minimum inhibitory concentration 10 to 1 μg mL^?1). Compounds containing silver were ten times more active to Gram‐negative bacteria than the parent dinuclear compound 1 a or silver salts. Au₂Ag compounds with dppy ( 2 b , 3 b ) were also potent against fungi.     

Investigation of solid surfaces modified by Langmuir-Blodgett monolayers using sum-frequency vibrational spectroscopy and X-ray photoelectron spectroscopy

Langmuir-Blodgett (LB) monomolecular layers of alkylhydroxamic acids and alkylphosphonic acids on copper and iron substrates have been studied by X-ray photoelectron spectroscopy (XPS) and sum-frequency vibrational spectroscopy. According to the XPS results, the structures of the hydroxamic acid and phosphonic acid Langmuir-Blodgett films are very similar: the thickness of the layer of the hydrocarbon tails is typically 1.9-2.1 nm, while the layer of headgroups is about 0.3-0.35 nm thick. The tilt angle of the carbon chains is estimated to be 20-30 degrees with respect to the sample surface normal, and the molecules are connected to the substrate via their headgroups. Analysis of the P 2p and N 1s lines indicates the presence of deprotonated headgroups. The substrate Cu 2p line includes a component which can be assigned to Cu(2+) ions in a thin Cu(OH)(2) layer. The deposition of LB layers led to significant decrease of the hydroxide-related signal, which indicates that binding of the headgroups to the surface is accompanied by the elimination of water molecules. The sum-frequency spectra also clearly indicate that well-ordered monolayers can be formed by the Langmuir-Blodgett technique. Since the non-resonant background from the metal substrates renders the analysis of the spectra more difficult, model system samples on glass were prepared. It was found that the alkyl chains of the adsorbed acids predominantly adopt the all-trans conformation and form an ordered structure. Upper limits for the mean tilt angle of the terminal methyl groups are approximately 10-20 degrees.     

Improvement of the properties of CSD-processed (Pb0.76Ca0.24)TiO3 thin films by control of the solution chemistry

Ferroelectric (Pb_0.76Ca_0.24)TiO₃ thin films were prepared on platinized Si substrates by chemical solution deposition (CSD). Two different synthetic strategies were adopted to optimize the functionality of the resulting perovskite films: (1) tailoring the schedule of the solution synthesis and (2) chemical selectivity of the calcium precursor. The choice of an appropriate synthetic procedure led to homogeneous sols constituted by a single distribution of particles, as revealed by dynamic light scattering (DLS). Stronger polymeric structures in the sol network are believed to prevent atomic diffusion of metal cations during crystallization at higher temperatures, and perovskite films with a uniform compositional profile and without any detrimental interface with the electrode were measured by Rutherford backscattering spectroscopy (RBS). On the other hand, phase formation and microstructure of crystalline films were strongly affected by the calcium compound used, i.e. calcium acetate or calcium acetylacetonate. The single decomposition mechanism of the last one, with absence of intermediate carbonates, resulted in the prompt crystallization of the perovskite phase (375°C) and an enhanced grain-growth mechanism that led to dense films formed by larger grains. Consequently, the optimized ferroelectric (Pb_0.76Ca_0.24)TiO₃ films showed superior electrical properties: maximum values of dielectric constant nearly doubled and a relative increase in the remanent polarization being ∼40% (P _r =23 μC/cm²). The potential application of these films in functional microelectronic devices is also demonstrated.     

Conformation of glycomimetics in the free and protein-bound state: structural and binding features of the C-glycosyl analogue of the core trisaccharide alpha-D-Man-(1 --> 3)-[alpha-D-Man-(1 --> 6)]-D-Man

The conformational properties of the C-glycosyl analogue of the core trisaccharide alpha-D-Man-(1 --> 3)-[alpha-D-Man-(1 --> 6)]-D-Man in solution have been carefully analyzed by a combination of NMR spectroscopy and time-averaged restrained molecular dynamics. It has been found that both the alpha-1,3- and the alpha-1,6-glycosidic linkages show a major conformational averaging. Unusual Phi ca. 60 degrees orientations for both Phi torsion angles are found. Moreover, a major conformational distinction between the natural compound and the glycomimetic affects to the behavior of the omega(16) torsion angle around the alpha-1 --> 6-linkage. Despite this increased flexibility, the C-glycosyl analogue is recognized by three mannose binding lectins, as shown by NMR (line broadening, TR-NOE, and STD) and surface plasmon resonance (SPR) methods. Moreover, a process of conformational selection takes place, so that these lectins probably bind the glycomimetic similarly to the way they recognize the natural analogue. Depending upon the architecture and extension of the binding site of the lectin, loss or gain of binding affinity with respect to the natural analogue is found.