X=Y=ZH Systems as potential 1,3-dipoles. Part 58: Cycloaddition route to chiral conformationally constrained (R)-pro-(S)-pro peptidomimetics

Imines of (1S,9S)-t-butyl-9-amino-octahydro-6,10-dioxo-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate undergo thermal (toluene, 110°C) or LiBr-DBU catalysed (MeCN, room temperature) regio- and stereo-specific cycloaddition to a range of chiral dipolarophiles giving enantiopure spiro-cycloadducts in excellent yield. The reactions proceed via intermediate NH azomethine ylides and litho azomethine ylides, respectively and results in the multiplication of chiral centres from 2 (one of which is lost in the process) to 5.     

Infrared-visible sum frequency generation spectroscopic study of molecular orientation at polystyrene/comb-polymer interfaces

Surface-sensitive infrared-visible sum frequency generation spectroscopy (SFG) in total internal reflection geometry has been used to study the structure of poly(vinyl n-octadecyl carbamate-co-vinyl acetate) (PVNODC) or poly(octadecyl acrylate) (PA-18) in contact with a deuterated or hydrogenated polystyrene (dPS or hPS) layer. SFG spectra from the PVNODC (or PA-18)/hPS interface show methyl and methylene peaks corresponding to PVNODC (or PA-18) and phenyl peaks corresponding to the PS. Analysis suggests that the methyl groups are tilted at angles less than 30 degrees with respect to the surface normal. The presence of a strong methylene peak suggests the PVNODC alkyl side chains contain more gauche defects at the PS/PVNODC interface in comparison to PVNODC (or PA-18)/air interfaces. On heating, the SFG intensity from the PS/PA-18 interface drops sharply near the bulk melting temperature (T(m)) of PA-18. Interestingly, a similar drop in SFG signal is also observed for the PS phenyl groups. This demonstrates the ability of the phenyl group at the PS/PA-18 interface to rearrange itself upon the solid-to-liquid transition of the PA-18 alkyl side chain, at a temperature well below the bulk PS glass transition temperature. For PS/PVNODC interfaces, the drop in SFG intensity is gradual and in agreement with the three broad transitions of PVNODC observed in the bulk.     

Chemical, sensory and microbiological changes of gamma irradiated coconut cream powder

A study was carried out to determine optimum decontamination dose for a locally manufactured coconut cream powder. Samples were gamma irradiated (0–15 kGy) and ageing process was achieved using GEER oven at 60 °C for 7 days, which is equivalent to one-year storage at room temperature. Iodine value (IV), ranging from 4.8 to 6.4, was not affected by radiation doses and storage, however peroxide value and thiobarbituric acid (TBA) generally increased with radiation doses. In most samples, peroxide value (meq/kg) reduced after storage, whilst the TBA (mg malonaldehyde/kg), indicator for product quality, slightly increased. The sensory evaluation conducted using 25 taste panellists indicated that scores on odour, creamy taste and overall acceptance for all irradiated samples at more than 5 kGy were significantly lower (P<0.05) than the control. However, the panellists could not detect any significant differences among the irradiation doses (P>0.05). All stored products were significantly different in colour, creamy taste, odour and overall acceptance (P<0.05) when compared to the non-stored non-irradiated control. Microbiological count of the samples prior to irradiation was in the range of 1×10²–1.7×10³ cfu/g with no detection of Salmonella sp. and Escherichia coli. No microbial colonies were detected after irradiation. Based on the TBA and overall sensory acceptance, gamma irradiation of 5 kGy was found to be the optimum dose and lower doses can be considered to decontaminate coconut cream powder.     

An accurate expression for radial distribution function of the Lennard-Jones fluid

A simple and accurate expression for radial distribution function (RDF) of the Lennard-Jones fluid is presented. The expression explicitly states the RDF as a continuous function of reduced interparticle distance, temperature, and density. It satisfies the limiting conditions of zero density and infinite distance imposed by statistical thermodynamics. The distance dependence of this expression is expressed by an equation which contains 11 adjustable parameters. These parameters are fitted to 353 RDF data, obtained by molecular dynamics calculations, and then expressed as functions of reduced distance, temperature and density. This expression, having a total of 65 constants, reproduces the RDF data with an average root-mean-squared deviation of 0.0152 for the range of state variables of 0.5  T^*  5.1 and 0.35  ρ^*  1.1 (T^*=kT/ε and ρ^* = ρσ³ are reduced temperature and density, respectively). The expression predicts the pressure and the internal energy of the Lennard-Jones fluid with an uncertainty that is comparable to that obtained directly from the molecular dynamics simulations.     

Palladium(II) and platinum(II) complexes of Schiff bases derived from 2,6-diacetylpyridine and S-methyldithiocarbazate and the X-ray crystal structure of the [Pd(mdapsme)Cl] complex

Condensation of 2,6-diacetylpyridine (dap) with S-methyldithiocarbazate (smdtc) in a 1:2 molar ratio yields a bicondensed pentadentate Schiff base (H₂dapsme) which reacts with K₂MCl₄ (M = Pd^II, Pt^II) giving stable complexes of empirical formula, [M(dapsme)] · 0.5Me₂CO. These complexes have been characterized by a variety of physico-chemical techniques. Condensation of dap with smdtc in a 1:1 molar ratio also yields the bicondensed Schiff base (H₂dapsme) as the major product, but a mono-condensed one-armed Schiff base (Hmdapsme) is also obtained as a minor product. The latter reacts with K₂PdCl₄ in an EtOH–H₂O mixture yielding a crystalline complex of empirical formula, [Pd(mdapsme)Cl], the crystal structure of which has been determined by X-ray diffraction. The complex has a distorted square-planar structure in which the ligand is coordinated to the palladium(II) ion as a uninegatively charged tridentate chelating agent via the pyridine nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom; the oxygen atom of the acetyl group does not participate in coordination.     

Synthesis and pharmacological activity of 4-(4'-(chlorophenyl)-4-hydroxypiperidine) derivatives

A new series of 4-(4'-chlorophenyl)-4-hydroxypiperidine derivatives (2-5), substituted at nitrogen, were synthesized and tested as potential analgesic compounds as well as evaluated for their effect on hypotensive activity. Results showed that all the derivatives exhibit significant analgesic activity in male Wistar rats at a dose of 50 mg/kg of body weight after intramuscular injection, when tested by thermal stimuli (tail flick test). Pethidine was used as reference drug. Compounds 2, 3 and 5 produced reduction in blood pressure in normotensive rat.     

Organotin(IV) derivatives as biocides: An investigation of structure by IR, solution NMR, electron impact MS and assessment of structure correlation with biocidal activity

A brief account is given of the synthesis, structural chemistry and the antibacterial, antifungal and cytotoxic effects of organotin complexes of 2-[(2,4-dichloroanilinocarbonyl)]benzoic acid. The unimolar and bimolar substitution products have been characterized by elemental analysis and spectral studies, including IR, ¹H NMR, ¹³C NMR, ¹¹⁹Sn NMR, and mass spectra. The data support the binding of the oxygen atom to the tin atom in [R₂Sn(OOCR’)₂] and [R₃Sn(OOCR’)] (R = Me, Bu, and Ph, R’ = 2-[(2,4-dichloroanilinocarbonyl)]benzoic acid). Based on these studies, with a coordination number of four, a distorted tetrahedral geometry has been proposed for the resulting derivatives in solution. The free ligand (R’/COOH) and its respective tin complexes were tested in vitro against a number of microorganisms to assess their biocidal properties and to correlate them with the structures of the derivatives.     

Ab initio Computational Modeling of Glyphosate Analogs: Conformational Perspective

A historical perspective on the application of conformational analysis to structure-based ligand design approach is presented. The application of isodensity molecular electrostatic potential surfaces with the conformational energy surfaces (CES) have allowed us to reach pertinent conclusions for aiding synthetic and biochemical studies. Here we illustrate such an application on the modeling of the potent analogs of an important, environmentally stringent herbicidal compound glyphosate by constructing conformational energy surfaces. The systems were modeled by substituting F, Cl, and NH— OH moiety to the position of pharmacophoric nitrogen center in glyphosate structure. All the calculations were thoroughly performed with ab initio MO theory at Hartree–Fock method using 3-21G(d) basis functions. On the basis of the results, we identified the bioactive conformations for N-fluoro-glyphosate, N-chloro-glyphosate, and N-hydroxyamino-glyphosate as (−38^∘, 77^∘), (−61^∘, 111^∘), and (−167^∘, −169^∘), respectively. Geometry optimization of certain selected conformations of these compounds using hybrid DFT method with 6–31+G(d) basis functions provides nearly equal values of φ and ψ. Moreover, the results indicate that the global minimum structures of N-fluoro and N-chloro analogs of glyphosate show cyclic conformation whereas the N-hydroxyamino-glyphosate global minimum structure shows spyrocyclic and zig-zag conformation. Also, the predicted bioactive conformation of N-hydroxyamino analog optimally overlaps with glyphosate backbone in EPSPS complex with 0.1 Å RMSD value. However, the other two compounds slightly deviate from the backbone of glyphosate with RMSD of 0.92 Å for N-fluoro-glyphosate and 0.83 Å for N-chloro-glyphosate. The linear N-hydroxyamino-glyphosate exhibits relatively more number of intermolecular hydrogen bond interactions as compared to the other two analogs. Further, comparison of CES of previously studied glyphosate analogs such as N-hydroxy-glyphosate (2.2 μM) and N-amino-glyphosate (0.61 μM) with the present systems reveals the order of activity as: N-hydroxyamino-glyphosate > N-fluoro-glyphosate > N-chloro-glyphosate based on CES flexibility. Also, the calculated heats of formation of N-fluoro-glyphosate, N-chloro-glyphosate, and N-hydroxyamino-glyphosate are −288, −209, and −288 kcal/mol, respectively, which clearly indicate that the N-hydroxyamino and N-fluoro analogs of glyphosate are thermodynamically more stable than N-amino-glyphosate (−278 kcal/mol).     

N-Levulination of Guanosine

A procedure have been developed for the synthesis of the N-levulinoyl derivative of guanosine.