Nickel(II) Complexes of Pentadentate N5 Ligands as Catalysts for Alkane Hydroxylation by Using m‐CPBA as Oxidant: A Combined Experimental and Computational Study

A new family of nickel(II) complexes of the type [Ni(L)(CH₃CN)](BPh₄)₂, where L=N‐methyl‐N,N′,N′‐tris(pyrid‐2‐ylmethyl)‐ethylenediamine (L1, 1 ), N‐benzyl‐N,N′,N′‐tris(pyrid‐2‐yl‐methyl)‐ethylenediamine (L2, 2 ), N‐methyl‐N,N′‐bis(pyrid‐2‐ylmethyl)‐N′‐(6‐methyl‐pyrid‐2‐yl‐methyl)‐ethylenediamine (L3, 3 ), N‐methyl‐N,N′‐bis(pyrid‐2‐ylmethyl)‐N′‐(quinolin‐2‐ylmethyl)‐ethylenediamine (L4, 4 ), and N‐methyl‐N,N′‐bis(pyrid‐2‐ylmethyl)‐N′‐imidazole‐2‐ylmethyl)‐ethylenediamine (L5, 5 ), has been isolated and characterized by means of elemental analysis, mass spectrometry, UV/Vis spectroscopy, and electrochemistry. The single‐crystal X‐ray structure of [Ni(L3)(CH₃CN)](BPh₄)₂ reveals that the nickel(II) center is located in a distorted octahedral coordination geometry constituted by all the five nitrogen atoms of the pentadentate ligand and an acetonitrile molecule. In a dichloromethane/acetonitrile solvent mixture, all the complexes show ligand field bands in the visible region characteristic of an octahedral coordination geometry. They exhibit a one‐electron oxidation corresponding to the Ni^II/Ni^III redox couple the potential of which depends upon the ligand donor functionalities. The new complexes catalyze the oxidation of cyclohexane in the presence of m‐CPBA as oxidant up to a turnover number of 530 with good alcohol selectivity (A/K, 7.1–10.6, A=alcohol, K=ketone). Upon replacing the pyridylmethyl arm in [Ni(L1)(CH₃CN)](BPh₄)₂ by the strongly σ‐bonding but weakly π‐bonding imidazolylmethyl arm as in [Ni(L5)(CH₃CN)](BPh₄)₂ or the sterically demanding 6‐methylpyridylmethyl ([Ni(L3)(CH₃CN)](BPh₄)₂ and the quinolylmethyl arms ([Ni(L4)(CH₃CN)](BPh₄)₂, both the catalytic activity and the selectivity decrease. DFT studies performed on cyclohexane oxidation by complexes 1 and 5 demonstrate the two spin‐state reactivity for the high‐spin [(N5)Ni^II?O^.] intermediate (ts1_hs, ts2_doublet), which has a low‐spin state located closely in energy to the high‐spin state. The lower catalytic activity of complex 5 is mainly due to the formation of thermodynamically less accessible m‐CPBA‐coordinated precursor of [Ni^II(L5)(OOCOC₆H₄Cl)]⁺ ( 5 a ). Adamantane is oxidized to 1‐adamantanol, 2‐adamantanol, and 2‐adamantanone (3°/2°, 10.6–11.5), and cumene is selectively oxidized to 2‐phenyl‐2‐propanol. The incorporation of sterically hindering pyridylmethyl and quinolylmethyl donor ligands around the Ni^II leads to a high 3°/2° bond selectivity for adamantane oxidation, which is in contrast to the lower cyclohexane oxidation activities of the complexes.     

Excimer laser forward transfer of mammalian cells using a novel triazene absorbing layer

We present a novel laser-based approach for developing tissue engineered constructs and other cell-based assembly's. We have deposited mesoscopic patterns of viable B35 neuroblasts using a soft direct approach of the matrix assisted pulsed laser evaporation direct write (MAPLE DW) process. As a development of the conventional direct write process, an intermediate layer of absorbing triazene polymer is used to provide gentler and efficient transfers. Transferred cells were examined for viability and proliferation and compared with that of as-seeded cells to determine the efficacy of the process. Results suggest that successful transfers can be achieved at lower fluences than usual by the incorporation of the intermediate absorbing layer thus avoiding any damage to cells and other delicate materials. MAPLE DW offers rapid computer-controlled deposition of mesoscopic voxels at high spatial resolutions, with extreme versatility in depositing combinations of natural/synthetic, living/non-living, organic/inorganic and hard/soft materials. Our approach offers a gentle and efficient transfer of viable cells which when combined with a variety of matrix materials allows development of constructs and bioactive systems in bioengineering.     

Two-dimensional differential adherence of neuroblasts in laser micromachined CAD/CAM agarose channels

Laser micromachining of hydrophobic gels into CAD/CAM patterns was used to develop differentially adherent surfaces and induce the attachment of B35 rat neuroblasts that would later form engineered nerve bundles. Narrow channels, 60-400 μm wide, were micromachined in a 2% agarose gel using an ArF laser, and subsequently filled with an extracellular matrix gel. Upon the addition of 1 ml of a 2 × 104 cells/ml neuroblast suspension, the cells selectively adhered to the ECM-lined channels in a non-confluent manner and we monitored their growth at various time points. The adherent neuroblasts were fluorescently imaged with a propidium iodide live/dead assay, which revealed that the cells were alive within the channels. After 72 h growth, the neuroblasts grew, proliferated, and differentiated into nerve bundles. The fully grown 1 cm long nerve bundle organoids maintained an aspect ratio on the order of 100. The results presented in this paper provide the foundation for laser micromachining technique to develop bioactive substrates for development of three-dimensional tissues. Laser micromachining offers rapid prototyping of substrates, excellent resolution, control of pattern depth and dimensions, and ease of fabrication.     

Development and validation of a HPLC method for simultaneous quantitation of gatifloxacin, sparfloxacin and moxifloxacin using levofloxacin as internal standard in human plasma: application to a clinical pharmacokinetic study

A highly selective, sensitive and accurate HPLC method has been developed and validated for the estimation of three fluoroquinolones (FQs) viz., gatifloxacin (GFC), sparfloxacin (SFC) and moxifloxacin (MFC) with 500 microL human plasma using levofloxacin (LFC) as an internal standard (IS). The sample preparation involved simple liquid-liquid extraction of GFC, SFC, MFC and IS from human plasma with ethyl acetate. The resolution of peaks was achieved with phosphate buffer (pH 2.5)-acetonitrile (80:20, v/v) at a flow rate of 1 mL/min on a Kromasil C(18) column. The total chromatographic run time was 18.0 min and the simultaneous elution of GFC, SFC, MFC and IS occurred at approximately 10.8, 12.8, 17.0 and 6.0 min, respectively. The method proved to be accurate and precise at linearity range of 100-10,000 ng/mL with a correlation coefficient (r) of > or =0.999. The limit of quantitation for each of the FQs studied was 100 ng/mL. The intra- and inter-day precision and accuracy values found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of 400 mg GFC tablet.     

Synthetic,spectroscopic and thermal aspects of some heterochelates

The present article describes the synthesis, structural features and thermal studies of heterochelates of the type [M(SB)(benen)(H₂O)]·nH₂O [where H₂SB=(Z)-2-(2,2,2-trifluoro-1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)ethylideneamino)benzoic acid, benen=bis(benzylidene)ethylenediamine and M=Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and VO(IV)]. The Schiff base (H₂SB) have been characterized on the basis of elemental analysis, IR, ¹H and ¹³C NMR. The heterochelates have been characterized on the basis of elemental analyses, magnetic measurements, solid state conductivity measurements, IR, reflectance spectra, and thermal studies. The FAB mass spectrum of [Co(SB)(benen)(H₂O)] has been carried out. The kinetic parameters such as order of reaction (n) and the energy of activation (E _a) have been reported using Freeman-Carroll method. The pre-exponential factor (A), the activation entropy (ΔS ^#), the activation enthalpy (ΔH ^#) and the free energy of activation (ΔG ^#) have been calculated.     

Rapid resolution of carbohydrate isomers by electrospray ionization ambient pressure ion mobility spectrometry-time-of-flight mass spectrometry (ESI-APIMS-TOFMS)

Carbohydrates are an extremely complex group of isomeric molecules that have been difficult to analyze in the gas phase by mass spectrometry because (1) precursor ions and product ions to successive stages of MS(n) are frequently mixtures of isomers, and (2) detailed information about the anomeric configuration and location of specific stereochemical variants of monosaccharides within larger molecules has not been possible to obtain in a general way. Herein, it is demonstrated that gas-phase analyses by direct combination of electrospray ionization, ambient pressure ion mobility spectrometry, and time-of-flight mass spectrometry (ESI-APIMS-TOFMS) provides sufficient resolution to separate different anomeric methyl glycosides and to separate different stereoisomeric methyl glycosides having the same anomeric configuration. Reducing sugars were typically resolved into more than one peak, which might represent separation of cyclic species having different anomeric configurations and/or ring forms. The extent of separation, both with methyl glycosides and reducing sugars, was significantly affected by the nature of the drift gas and by the nature of an adducting metal ion or ion complex. The study demonstrated that ESI-APIMS-TOFMS is a rapid and effective analytical technique for the separation of isomeric methyl glycosides and simple sugars, and can be used to differentiate glycosides having different anomeric configurations.     

Stereoselective synthesis of novel C-3 functionalized 3-sulfonyl-β-lactams: Promising biologically active heterocyclic scaffolds

An efficient and operationally simple strategy for the stereoselective synthesis of novel C-3 functionalized 3-sulfonyl-β-lactam heterocycles is described. The C-3 functionalized 3-phenyl/benzylsulfonyl-β-lactams 3/3′, 5/5′ has been synthesized via Michael addition using different Michael acceptors on trans-3-phenyl/benzylsulfonyl-β-lactams 2(a–f) using K₂CO₃ as a base and acetonitrile/DMF as solvents. The reaction furnished exclusively cis-β-lactam adducts 3(a–r) using sterically less hindered Michael acceptors. Further, the effect of steric bulk and chiralilty of Michael acceptors was explored to achieve target C-3 functionalized β-lactams 3(s-u)/3′(s-u) and 5(a–c)/5′(a–c). The structural and stereochemical analysis of novel β-lactams were carried out using FT-IR, NMR (¹H, ¹³C, ¹H-¹H COSY, ¹H-¹³C COSY and ¹³C DEPT-135), elemental analysis (CHNS), mass spectrometry (EIMS and LCMS) in representative cases and single crystal X-ray crystallographic studies (3e). The cis or trans configuration of the Michael acceptor (E) at C-3 was assigned with respect to C4-H.     

Assessment of PHB with varying hydroxyvalerate content for potential packaging applications

Poly-(hydroxybutyrate) (PHB) is biodegradable aliphatic polyester that is produced by a wide range of microorganisms. Basic PHB has relatively high glass transition and melting temperatures. To improve flexibility for potential packaging applications, PHB is synthesized with various co-polymers such as poly-(3-hydroxyvalerate) (HV) leading to a decrease of the glass transitions and melting temperatures. In addition, the HV broadens the processing window since there is improved melt stability at lower processing temperatures. In this study, PHB synthesized with different valerate contents (5%, 12%, and 20%) and varying in molecular weights were characterized. All PHBV materials displayed a glass transition between −10 and 20 °C. The two melting transitions found for Aldrich 5%, 12%, and Tianan 20%, resulted from crystals formed during cooling of the samples. The complex viscosity decreased with increasing temperature due to a decrease in molecular weights of the samples. These results suggest that processing the co-polymer below 160 °C would be beneficial with low screw speed. The mechanical results indicate all PHBV materials had high elastic modulus and flexural strength with low tensile strength and elongation at break. The WVTR results indicated the polymer to be very hydrophilic, resulting in higher water transmission rates.     

Synthesis, spectroscopic characterization and DNA nuclease activity of Cu(II) complexes derived from pyrazolone based NSO-donor Schiff base ligands

Two neutral mononuclear Cu(II) complexes have been prepared in EtOH using Schiff bases derived from 4-toluoyl pyrazolone and thiosemicarbazide. Both the ligands have been characterized on the basis of elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. The molecular geometry of one of these ligands has been determined by single crystal X-ray study. It reveals that these ligands exist in amine-one tautomeric form in the solid state. Microanalytical data, Cu-estimation, molar conductivity, magnetic measurements, IR, UV-Visible, FAB-Mass, TG-DTA data and ESR spectral studies were used to confirm the structures of the complexes. Electronic absorption and IR spectra of the complexes suggest a square-planar geometry around the central metal ion. The interaction of complexes with pET30a plasmid DNA was investigated by spectroscopic measurements. Results suggest that the copper complexes bind to DNA via an intercalative mode and can quench the fluorescence intensity of EB bound to DNA. The interaction between the complexes and DNA has also been investigated by agarose gel electrophoresis, interestingly, we found that the copper(II) complexes can cleave circular plasmid DNA to nicked and linear forms.     

Evaluation and solubility improvement of Carvedilol: PSC[n]arene inclusion complexes with acute oral toxicity studies

The aqua phobic molecules that are practically insoluble in aqueous media demonstrate a staggeringly slow intrinsic dissolution rate. In this work, we exemplify the utility of calixarenes as a tool to form inclusion complexes with Carvedilol (CDL). It is poorly water soluble drug. CDL is a Biopharmaceutical Classification System (BCS) Class II drug and it is a nonselective β-adrenegenic blocking agent with α1-blocking activity. It is mainly used in the management of hypertension. The maximum complexation of the drug was accomplished after 48?h of stirring with para sulphonato calix[4]arene (PSC[4]arene) and para sulphonato calix[6]arene (PSC[6]arene) in water and evaporation of water to acquire solid complexes. The study includes characterisation of both the complexes—physical mixtures of drug and PSC[4]arene and PSC[6]arenes by different methods like Fourier-transform infra red spectroscopy, differential scanning calorimetry and powder X-ray diffraction, proton nuclear magnetic resonance. This studies shows that there is electrostatic interaction between drug and PSC[n]arenes. The complexation was determined by phase solubility study. The prepared complexes exhibited improved in vitro dissolution profile and decreased in vivo acute oral toxicity compared to the pure drug.