Complete spectroscopic structural characterization of novobiocin,isonovobiocin, decarbamylnovobiocin, 2″-(o-Carbamyl)novobiocin,and novobiocin-2″,3″-carbonate

The rigorous structural characterization of novobiocin, is reported using mass spectrometric, infrared and nmr spectroscopic analysis. Complete nmr assignments are reported. Previous reports in the literature had left some quaternary carbon resonances unassigned. Isonovobiocin and decarbamylnovobiocin, although known in the literature for a number of years, have never been completely characterized. Mass spectrometric fragmentation pathways and complete ¹H and ¹³C nmr assignments are reported for these congeners for the first time. The mass spectral fragmentation pathway and nmr assignments are also reported for 2″-(O-carbamyl)novobiocin although the nmr assignments at lower field were reported previously. The structural characterization of novobiocin-2″,3″-carbonate observed in the Test Assay procedure used for Novobiocin is reported for the first time.     

A sensitive two-phase titration of anionic surfactants with a dilute tetraphenylphosphonium chloride solution

A visual indicator method is described for titrations of anionic surfactants with 5 × 10^-5 M tetraphenylphosphonium solution. Two dyes, the hydrophilic neutral red and the hydrophobic tetrabromophenolphthalein ethyl ester, are used as indicator in the presence of 1,2-dichloroethane.     

Optimal homotopy analysis and control of error for solutions to the non-local Whitham equation

The Whitham equation is a non-local model for nonlinear dispersive water waves. Since this equation is both nonlinear and non-local, exact or analytical solutions are rare except for in a few special cases. As such, an analytical method which results in minimal error is highly desirable for general forms of the Whitham equation. We obtain approximate analytical solutions to the non-local Whitham equation for general initial data by way of the optimal homotopy analysis method, through the use of a partial differential auxiliary linear operator. A method to control the residual error of these approximate solutions, through the use of the embedded convergence control parameter, is discussed in the context of optimal homotopy analysis. We obtain residual error minimizing solutions, using relatively few terms in the solution series, in the case of several different kernels and associated initial data. Interestingly, we find that for a specific class of initial data, there exists an exact solution given by the first term in the homotopy expansion. A specific example of initial data which satisfies the condition producing an exact solution is included. These results demonstrate the applicability of optimal homotopy analysis to equations which are simultaneously nonlinear and non-local.     

Novel Copolymers of Styrene. 3. Some Ring-Substituted Butyl 2-Cyano-3-Phenyl-2-Propenoates

Novel trisubstituted ethylenes, ring-substituted butyl 2-cyano-3-phenyl-2-propenoates, RPhCH=C(CN)CO₂C₄H₉ (where R is 2-C₆H₅CH₂O, 3-C₆H₅CH₂O, 4-C₆H₅CH₂O, 4-CH₃COO, 3-CH₃CO, 4-CH₃CO, 4-CH₃CONH, 2-CN, 3-CN, 4-CN, 4-(CH₃)₂N, 4-(C₂H₅)₂N) were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and butyl cyanoacetate, and characterized by CHN analysis, IR, ¹H and ¹³C-NMR. All the ethylenes were copolymerized with styrene (M₁) in solution with radical initiation (ABCN) at 70°C. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, ¹H and ¹³C-NMR. The order of relative reactivity (1/r₁) for the monomers is 4-C₆H₅CH₂O (6.39) > 2-C₆H₅CH₂O (2.06) > 3-CH₃CO (1.86) > 3-C₆H₅CH₂O (1.78) > 4-CH₃COO (1.58) > 3-CN (1.47) > 4-CN (1.21) > 4-(C₂H₅)₂N (1.19) > 4-(CH₃)₂N (1.18) > 2-CN (1.04) > 4-CH₃CO (0.71) > 4-CH₃CONH (0.63). Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200–500°C range with residue (3.6–9.5% wt), which then decomposed in the 500–800°C range.     

Melanosomal damage in normal human melanocytes induced by UVB and metal uptake--a basis for the pro-oxidant state of melanoma

Melanins are ubiquitous catecholic pigments, formed in organelles called melanosomes within melanocytes, the function of which is to protect skin against harmful effects of UV radiation. Melanosomes within melanoma cells are characteristically abnormal, with fragmented melanin and disrupted membranes. We hypothesize that the disruption of melanosomal melanin might be an early event in the etiology and progression of melanoma, leading to increased oxidative stress and mutation. In this report, we examine the effect of a combination of UV treatment and metal ion exposure on melanosomes within melanocytes, as well as their ability to act as pro-oxidants in ex situ experiments, and assay the effects of this treatment on viability and cell cycle progression. UVB exposure causes morphologic changes of the cells and bleaching of melanosomes in normal melanocytes, both significantly enhanced in Cu(II) and Cd(II)-treated cells, as observed by microscopy. The promoted bleaching by Cu(II) is due to its ability to redox cycle under oxidative conditions, generating reactive oxygen species; verified by the observed enhancement of hydroxyl radical generation when isolated melanosomes were treated with both Cu(II) ions and UVB, as assayed by DNA clipping. Single-dose UVB/Cu treatment does not greatly affect cell viability or cell cycle progression in heavily pigmented cells, but did so in an amelanotic early stage melanoma cell line.     

Imaging Photoelectron Circular Dichroism in the Detachment of Mass-Selected Chiral Anions

Photoelectron Circular Dichroism (PECD) is a forward-backward asymmetry in the photoemission from a non-racemic sample induced by circularly polarized light. PECD spectroscopy has potential analytical advantages for chiral discrimination over other chiroptical methods due to its increased sensitivity to the chiral potential of the molecule. The use of anions for PECD spectroscopy allows for mass-selectivity and provides a path to simple experimental schemes that employ table-top light sources. Evidence of PECD for anions is limited, and insight into the forces that govern PECD electron dynamics in photodetachment is absent. Here, we demonstrate a PECD effect in the photodetachment of mass-selected deprotonated 1-indanol anions. By utilizing velocity map imaging photoelectron spectroscopy with a tunable light source, we determine the energy-resolved PECD over a wide range of photon energies. The observed PECD reaches up to 11 %, similar to what has been measured for neutral species.     

Photoisomerization of cis‐1,2‐di(1‐Methyl‐2‐naphthyl)ethene at 77 K in Glassy Media

cis‐1,2‐Di(1‐methyl‐2‐naphthyl)ethene, c‐ 1,1 , undergoes photoisomerization in methylcyclohexane, isopentane and diethyl ether/isopentane/ethanol glasses at 77 K. On 313 nm excitation the fluorescence of c‐ 1,1 is replaced by fluorescence from t‐ 1,1 . Singular value decomposition reveals that the spectral matrices behave as two component systems suggesting conversion of a stable c‐ 1,1 conformer to a stable t‐ 1,1 conformer. However, the fluorescence spectra are λ_exc dependent. Analysis of global spectral matrices shows that c‐ 1,1 is a mixture of two conformers, each of which gives one of four known t‐ 1,1 conformers. The λ_exc dependence of the c‐ 1,1 fluorescence spectrum is barely discernible. Structure assignments to the resolved fluorescence spectra are based on the principle of least motion and on calculated geometries, energy differences and spectra of the conformers. The relative shift of the c‐ 1,1 conformer spectra is consistent with the shift of the calculated absorption spectra. The calculated structure of the most stable conformer of c‐ 1,1 agrees well with the X‐ray crystal structure. Due to large deviations of the naphthyl groups from the ethenic plane in the conformers of both c‐ and t‐ 1,1 isomers, minimal motion of these bulky substituents accomplishes cis → trans interconversion by rotation about the central bond.     

Irradiance,Photofrin® Dose and Initial Tumor Volume are Key Predictors of Response to Interstitial Photodynamic Therapy of Locally Advanced Cancers in Translational Models

The objective of the present study was to develop a predictive model for Photofrin^®-mediated interstitial photodynamic therapy (I-PDT) of locally advanced tumors. Our finite element method was used to simulate 630-nm intratumoral irradiance and fluence for C3H mice and New Zealand White rabbits bearing large squamous cell carcinomas. Animals were treated with light only or I-PDT using the same light settings. I-PDT was administered with Photofrin^® at 5.0 or 6.6 mg kg⁻¹, 24 h drug-light interval. The simulated threshold fluence was fixed at 45 J cm⁻² while the simulated threshold irradiance varied, intratumorally. No cures were obtained in the mice treated with a threshold irradiance of 5.4 mW cm⁻². However, 20–90% of the mice were cured when the threshold irradiances were ≥8.6 mW cm⁻². In the rabbits treated with I-PDT, 13 of the 14 VX2 tumors showed either local control or were cured when threshold irradiances were ≥15.3 mW cm⁻² and fluence was 45 J cm⁻². No tumor growth delay was observed in VX2 treated with light only (n = 3). In the mouse studies, there was a high probability (92.7%) of predicting cure when the initial tumor volume was below the median (493.9 mm³) and I-PDT was administered with a threshold intratumoral irradiance ≥8.6 mW cm⁻².     

Intramolecular and intermolecular contributions to the barriers for rotation of methyl groups in crystalline solids: electronic structure calculations and solid-state NMR relaxation measurements

The rotation barriers for 10 different methyl groups in five methyl-substituted phenanthrenes and three methyl-substituted naphthalenes were determined by ab initio electronic structure calculations, both for the isolated molecules and for the central molecules in clusters containing 8-13 molecules. These clusters were constructed computationally using the carbon positions obtained from the crystal structures of the eight compounds and the hydrogen positions obtained from electronic structure calculations. The calculated methyl rotation barriers in the clusters (E(clust)) range from 0.6 to 3.4 kcal/mol. Solid-state (1)H NMR spin-lattice relaxation rate measurements on the polycrystalline solids gave experimental activation energies (E(NMR)) for methyl rotation in the range from 0.4 to 3.2 kcal/mol. The energy differences E(clust) - E(NMR) for each of the ten methyl groups range from -0.2 kcal/mol to +0.7 kcal/mol, with a mean value of +0.2 kcal/mol and a standard deviation of 0.3 kcal/mol. The differences between each of the computed barriers in the clusters (E(clust)) and the corresponding computed barriers in the isolated molecules (E(isol)) provide an estimate of the intermolecular contributions to the rotation barriers in the clusters. The values of E(clust) - E(isol) range from 0.0 to 1.0 kcal/mol.